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Paroxetine: Drug information

Paroxetine: Drug information
(For additional information see "Paroxetine: Patient drug information" and see "Paroxetine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Suicidal thoughts and behaviors:

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening and for emergence of suicidal thoughts and behaviors. Paroxetine is not approved for use in pediatric patients.

Brand Names: US
  • Brisdelle [DSC];
  • Paxil;
  • Paxil CR;
  • Pexeva [DSC]
Brand Names: Canada
  • ACT PARoxetine [DSC];
  • AG-Paroxetine;
  • APO-PARoxetine;
  • Auro-PARoxetine;
  • BIO-PARoxetine;
  • JAMP-PARoxetine;
  • M-Paroxetine;
  • Mar-PARoxetine;
  • MINT-Paroxetine;
  • NRA-Paroxetine;
  • PARoxetine-10;
  • PARoxetine-20;
  • PARoxetine-30;
  • Paxil;
  • Paxil CR;
  • PMS-PARoxetine;
  • Priva-PARoxetine [DSC];
  • RIVA-PARoxetine;
  • SANDOZ PARoxetine;
  • TARO-PARoxetine;
  • TEVA-PARoxetine
Pharmacologic Category
  • Antidepressant, Selective Serotonin Reuptake Inhibitor
Dosing: Adult

Dosage guidance:

Dosing: Some experts suggest a lower starting dose of 5 to 10 mg once daily (immediate release) or 12.5 mg once daily (extended release) and gradual titration in increments of ≤10 mg (immediate release) or 12.5 mg (extended release), particularly in patients with anxiety who are sensitive to antidepressant-associated overstimulation effects (eg, anxiety, insomnia) (Ref).

Dosage form information: Paroxetine is available as IR and ER formulations; both formulations are dosed once daily but are not interchangeable on a milligram to milligram basis. Where dosing for the ER formulation is not provided for an indication, may convert between formulations using equivalence shown in "Dosing conversions" section below.

Body dysmorphic disorder

Body dysmorphic disorder (off-label use): Dosing recommendations based on expert opinion: Immediate release: Oral: Initial: 20 mg once daily; may increase dose gradually based on response and tolerability in increments of 20 mg/day at intervals of every 2 to 3 weeks to a usual dose of 60 mg/day; doses up to 100 mg/day may be necessary in some patients for optimal response, typically under specialist care. Note: An adequate trial for assessment of effect in body dysmorphic disorder is 12 to 16 weeks, including maximum tolerated doses for at least 3 to 4 of those weeks (Ref).

Generalized anxiety disorder

Generalized anxiety disorder: Immediate release : Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to 50 mg/day (Ref).

Major depressive disorder

Major depressive disorder (unipolar):

Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week to a maximum of 50 mg/day (Ref).

Extended release: Oral: Initial: 25 mg once daily; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week to a maximum of 62.5 mg/day.

Obsessive-compulsive disorder

Obsessive-compulsive disorder: Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to a recommended dose of 40 to 60 mg/day; maximum dose: 60 mg/day (Ref). Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered ≥6 weeks at the maximum tolerated dose (Ref).

Panic disorder

Panic disorder:

Immediate release: Oral: Initial: 10 mg once daily for 3 to 7 days; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to a usual dose of 20 to 40 mg/day (Ref); maximum dose: 60 mg/day.

Extended release: Oral: Initial: 12.5 mg once daily; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week up to a maximum of 75 mg/day.

Posttraumatic stress disorder

Posttraumatic stress disorder: Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week up to 60 mg/day (Ref).

Premature ejaculation

Premature ejaculation (off-label use): Immediate release: Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a usual dosage of 20 mg/day (Ref). Some patients may require up to 40 mg/day for optimal response (Ref); some experts suggest 3- to 4-week titration intervals (Ref).

Premenstrual dysphoric disorder

Premenstrual dysphoric disorder: Note: Some experts prefer selective serotonin reuptake inhibitors (SSRIs) other than paroxetine for this use (Ref).

Continuous daily dosing regimen:

Immediate release (off-label): Oral: Initial: 10 mg once daily; increase to usual effective dose of 20 mg once daily over the first month; in a subsequent menstrual cycle, a further increase to 40 mg/day may be necessary in some patients for optimal response (Ref).

Extended release: Oral: Initial: 12.5 mg once daily; increase to usual effective dose of 25 mg once daily over the first month; in a subsequent menstrual cycle, a further increase to 50 mg/day (based on equivalent IR dose) may be necessary in some patients for optimal response (Ref).

Intermittent regimens:

Luteal phase dosing regimen:

Immediate release (off-label): Oral: Initial: 10 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase to usual effective dose of 20 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 30 mg/day during the luteal phase may be necessary in some patients for optimal response (Ref).

Extended release: Oral: Initial: 12.5 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase to usual effective dose of 25 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 37.5 mg/day (based on equivalent IR dose) during the luteal phase may be necessary in some patients for optimal response (Ref).

Symptom-onset dosing regimen (off-label): Immediate release: Oral: Initial: 10 mg once daily from the day of symptom onset until a few days after the start of menses; over the first month, may increase dose based on response and tolerability up to 20 mg/day; in a subsequent menstrual cycle, a further increase to 30 mg/day may be necessary in some patients for optimal response (Ref).

Social anxiety disorder

Social anxiety disorder:

Immediate release: Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a maximum of 60 mg/day (Ref).

Extended release: Oral: Initial: 12.5 mg once daily; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week up to a maximum of 37.5 mg/day (Ref). Note: Doses up to 75 mg/day (based on equivalent IR dose) may be necessary in some patients for optimal response (Ref).

Vasomotor symptoms associated with menopause

Vasomotor symptoms associated with menopause (alternative agent): Note: Nonhormonal alternative in patients unable or unwilling to take estrogen (Ref).

Immediate release :

Capsule: Oral: 7.5 mg once daily at bedtime.

Tablet (off-label): Oral: 10 to 20 mg once daily at bedtime (Ref).

Extended release (off-label): Oral: 12.5 to 25 mg once daily at bedtime (Ref).

Dosing conversions: Immediate release 10 mg is equivalent to extended release 12.5 mg (Ref).

Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). Reasons for a slower taper (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).

Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).

Switching to or from an MAOI:

Allow 14 days to elapse between discontinuing an MAOI and initiation of paroxetine.

Allow 14 days to elapse between discontinuing paroxetine and initiation of an MAOI.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

CrCl >60 mL/minute: No dosage adjustment necessary (Ref).

CrCl 30 to 60 mL/minute: There are no dosage adjustments provided in manufacturer's labeling; however, AUCs after a single paroxetine dose were approximately 2 times that of individuals with normal function (Ref). Consider a 25% to 50% reduction in initial dose and titrate based on efficacy and tolerability, not to exceed the usual indication-specific maximum recommended dose (refer to dosing in adults) (Ref).

CrCl <30 mL/minute: AUCs after a single paroxetine dose were ~3.5 times that of patients with normal kidney function (Ref).

Immediate release: Initial: 5 to 10 mg/day; increase if needed by increments of no more than 10 mg/day at intervals of at least 1 week based on efficacy and tolerability; maximum dose: 40 mg/day or the indication-specific maximum recommended dose (refer to dosing in adults), whichever is less (Ref).

Extended release: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week based on efficacy and tolerability to a maximum dose of 50 mg/day or the indication-specific maximum recommended dose (refer to dosing in adults), whichever is less (Ref).

Hemodialysis, intermittent (thrice weekly): Not likely to be significantly dialyzable due to large Vd and high protein binding (Ref).

Oral: Dose for CrCl <30 mL/minute (Ref).

Peritoneal dialysis: Not likely to be significantly dialyzable due to large Vd and high protein binding (Ref).

Oral: Dose for CrCl <30 mL/minute (Ref).

CRRT:

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important.

Oral: Dose as for CrCl <30 mL/minute (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration):

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions due to drug accumulation is important.

Oral: Dose as for CrCl <30 mL/minute (Ref).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: There are no dosage adjustments provided in manufacturer's labeling.

Severe impairment:

Immediate release: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day.

Extended release: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week to a maximum of 37.5 mg/day (social anxiety disorder) or 50 mg/day (major depressive disorder, panic disorder).

Dosing: Older Adult

Note: Avoid use (Ref).

Major depressive disorder (unipolar), obsessive-compulsive disorder, panic disorder, social anxiety disorder:

Immediate release: Oral: Initial: 10 mg/day; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a maximum of 40 mg/day.

Extended release: Oral: Initial: 12.5 mg/day; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week to a maximum of 37.5 mg/day (social anxiety disorder) or 50 mg/day (major depressive disorder, panic disorder).

Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered to be ≥6 weeks at the maximum tolerated dose (Ref).

Dosing conversions: Refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Paroxetine: Pediatric drug information")

Dosage guidance:

Dosage form information: Immediate-release paroxetine is available in two salts, hydrochloride (eg, Paxil) and mesylate (eg, Brisdelle, Pexeva); use extra precaution to ensure correct product selection. Paroxetine is available as immediate-release and extended-release formulations; both formulations are dosed once daily but are not interchangeable on a mg to mg basis; based on adult bioavailability data, immediate-release 10 mg is equivalent to extended-release 12.5 mg (Ref).

Major depressive disorder

Major depressive disorder (unipolar): Limited data available:

Note: The use of paroxetine should be reserved for refractory cases when other options are ineffective or unacceptable/intolerable to the patient; therapy should not be initiated in a primary care setting; patients should be closely monitored for adverse effects (eg, suicidal thoughts/behaviors) (Ref). Therapy should be initiated at a low dose and titrated every 1 to 2 weeks based on response and tolerability (Ref).

Children ≥12 years and Adolescents: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; usual reported effective dose: 20 mg/day; maximum daily dose: 60 mg/day (Ref).

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD): Limited data available:

Note: In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary it should be in combination with cognitive behavioral therapy (CBT) and a selective serotonin reuptake inhibitor (SSRI) should be used first line; a preferred agent has not been identified (Ref).

Children ≥7 years and Adolescents <18 years: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; titrate every 7 to 14 days in 10 mg/day increments; mean reported effective dose: 32 mg/day; maximum daily dose: 60 mg/day (Ref).

Social anxiety disorder

Social anxiety disorder: Limited data available:

Note: In pediatric patients, selective serotonin reuptake inhibitor (SSRI) therapy is considered first-line pharmacologic treatment for moderate to severe anxiety disorders in combination with cognitive behavioral therapy (CBT); a preferred SSRI has not been defined; therapeutic selection should be based on pharmacokinetic and pharmacodynamic data, patient tolerability, cost, and unique risks/precautions with specific agents (Ref).

Children ≥8 years and Adolescents <18 years: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; titrate at intervals of at least 7 days in 10 mg/day increments; maximum daily dose: 50 mg/day. Dosing based on a 16-week multicenter, randomized, double-blind, placebo-controlled trial that reported the efficacy of paroxetine in pediatric patients (aged 8 to 17 years) with social anxiety disorder; 163 patients were randomized to receive paroxetine; the overall mean dose was 21.7 mg/day for children and 26.1 mg/day for adolescents (Ref).

Discontinuation of therapy: Consider planning discontinuation of therapy during lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to OCD treatment discontinuation (Ref). To discontinue therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission is sparse, particularly in pediatric patients; however, a general consensus is to taper over several weeks to months and to resume the previous OCD therapy if symptoms worsen; a plan for continued psychotherapy during serotonergic medication discontinuation is recommended (Ref). A unified taper protocol has been reported in adults with OCD in which serotonin reuptake inhibitor monotherapy was tapered over 12 weeks with biweekly psychiatrist visits (Ref). For the treatment of depression, experts suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; agents with a shorter half-life may need to be tapered more conservatively and if intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate; similar principles may also be applicable to OCD therapy discontinuation (Ref).

Switching selective serotonin reuptake inhibitor (SSRI): Evidence for ideal SSRI switching strategies in pediatric patients is sparse; strategies described in pediatric guidelines include a conservative approach (tapering and discontinuing the first SSRI before adding the second) and cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant). While consensus does not exist regarding which approach to utilize, it is important to note that the conservative approach runs the risk for exacerbation of symptoms or discontinuation syndrome; cross-titration may avoid these risks (Ref). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from a monamine oxidase inhibitor. While not as common of a strategy, a direct switch may be considered when switching to another agent in the same or similar class (eg, when switching between 2 SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children ≥7 years and Adolescents: Oral: There are no pediatric-specific recommendations; based on pharmacokinetics in adult patients, plasma concentration is 2 times that seen in normal function in mild to moderate renal impairment (CrCl 30 to 60 mL/minute), and in severe impairment (CrCl <30 mL/minute) mean plasma concentration is ~4 times that seen in normal function; dosing adjustment suggested.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific recommendations; based on pharmacokinetics in adult patients with hepatic dysfunction, plasma concentration is 2 times that seen in normal function; dosing adjustment suggested.

Adverse Reactions (Significant): Considerations
Activation of mania or hypomania

Antidepressants (when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients with unipolar major depressive disorder (MDD) have been reported, as many cases of bipolar disorder present in episodes of MDD (Ref).

Mechanism: Non-dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref).

Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy, but not thereafter (up to 4.6 years) (Ref).

Risk factors:

• Family history of bipolar disorder (Ref)

• Depressive episode with psychotic symptoms (Ref)

• Younger age at onset of depression (Ref)

• Antidepressant resistance (Ref)

• Female sex (Ref)

Bleeding risk

Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants in adult and pediatric patients. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematoma, petechiae, purpuric disease, and epistaxis to cerebrovascular accident, upper GI bleeding (UGIB), intracranial hemorrhage, postpartum hemorrhage, and intraoperative bleeding, although conflicting evidence also exists (Ref).

Mechanism: Possibly via decreased platelet serotonin concentrations and inhibition of serotonin-mediated platelet activation leading to subsequent platelet dysfunction (Ref). SSRIs may also increase gastric acidity, which can increase the risk of GI bleeding (Ref).

Onset: Varied; bleeding risk is likely delayed for several weeks until SSRI-induced platelet serotonin depletion becomes clinically significant (Ref), although the onset of bleeding may be more unpredictable if patients are taking concomitant antiplatelets, anticoagulants, or nonsteroidal anti-inflammatory drugs (NSAIDs). For UGIB, some studies have found risk to be the highest in the first 28 to 30 days (Ref), whereas another study reported a median time of onset of 25 weeks (Ref).

Risk factors:

Concomitant use of anticoagulants and/or antiplatelets (Ref)

Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor) (Ref)

Concomitant use of NSAIDs increases the risk for UGIB (Ref)

Fragility fractures

Limited data from observational studies involving mostly older adults (≥50 years of age) suggest selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of bone fractures (Ref).

Mechanism: Time-related; mechanism not fully elucidated; postulated to be through a direct effect by SSRIs on bone metabolism via interaction with 5-HT and osteoblast, osteocyte, and/or osteoclast activity (Ref). SSRIs may also contribute to fall risk, contributing to the incidence of fractures (Ref).

Onset: Delayed; risk appears to increase after initiation and may continue to increase with long-term use. A meta-analysis found risk of fracture increased from 2.9% over 1 year to 5.4% over 2 years; within 5 years, risk increased to 13.4% (Ref).

Risk factors:

Long-term use may be a risk factor (Ref)

Hyponatremia

Selective serotonin reuptake inhibitors (SSRIs) are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia, including severe cases, predominantly in the elderly (Ref). Hyponatremia is reversible with discontinuation of therapy (Ref).

Mechanism: May cause SIADH via release of antidiuretic hormone (ADH) (Ref) or may cause nephrogenic SIADH by increasing the sensitivity of the kidney to ADH (Ref).

Onset: Intermediate; usually develops within the first few weeks of treatment (Ref).

Risk factors:

Older age (Ref)

Females (Ref)

Concomitant use of diuretics (Ref)

Low body weight (Ref)

Lower baseline serum sodium concentration (Ref)

Volume depletion (Ref)

History of hyponatremia (potential risk factor) (Ref)

Symptoms of psychosis (potential risk factor) (Ref)

Ocular effects

Selective serotonin reuptake inhibitors (SSRIs) are associated with acute angle-closure glaucoma (AACG) in case reports and a case-controlled study. AACG may cause symptoms including eye pain, changes in vision, swelling, and redness, which can rapidly lead to permanent blindness if not treated (Ref). In addition, SSRIs may be associated with an increased risk of cataract development (Ref).

Mechanism: AACG: Unclear; hypothesized SSRIs may increase the intraocular pressure via serotonergic effects on ciliary body muscle activation and pupil dilation (Ref).

Risk factors:

For AACG:

• Females (Ref)

• ≥50 years of age (slight increase) (Ref)

• Hyperopia (slight increase) (Ref)

• Personal or family history of AACG (Ref)

• Inuit or Asian descent (Ref)

Serotonin syndrome

Serotonin syndrome has been reported and typically occurs with coadministration of multiple serotonergic drugs. Only a handful of cases of serotonin syndrome have been reported with paroxetine monotherapy at therapeutic doses, in addition to a case which occurred following paroxetine overdose (Ref). The diagnosis of serotonin syndrome is made based on the Hunter Serotonin Toxicity Criteria (Ref) and may result in a spectrum of symptoms, such as anxiety, agitation, confusion, delirium, hyperreflexia, muscle rigidity, myoclonus, tachycardia, tachypnea, and tremor. Severe cases may cause hyperthermia, significant autonomic instability (ie, rapid and severe changes in blood pressure and pulse), coma, and seizures (Ref).

Mechanism: Dose-related; overstimulation of serotonin receptors by serotonergic agents (Ref).

Onset: Rapid; in the majority of cases (74%), onset occurred within 24 hours of treatment initiation, overdose, or change in dose (Ref).

Risk factors:

• Concomitant use of drugs that increase serotonin synthesis, block serotonin reuptake and/or impair serotonin metabolism (eg, monamine oxidase inhibitors [MAO inhibitors]). Of note, concomitant use of some serotonergic agents, such as MAO inhibitors, are contraindicated.

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRIs) are commonly associated with sexual disorders in both men and women. The following adverse reactions have been associated with SSRI use: Ejaculatory delay, orgasm disturbance, erectile dysfunction, and decreased libido (Ref). Priapism and decreased penile sensation have also been reported (Ref).

Mechanism: Increases in serotonin may affect other hormones and neurotransmitters involved in sexual function, in particular, testosterone's effect on sexual arousal and dopamine's role in achieving orgasm (Ref).

Risk factors:

• Depression (sexual dysfunction is commonly associated with depression; SSRI-associated sexual dysfunction may be difficult to differentiate in treated patients) (Ref)

Suicidal thinking and behavior

Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years) in short-term studies. In adults >24 years, short-term studies did not show an increased risk of suicidal thinking and behavior and in older adults ≥65 years of age, a decreased risk was observed. Although data have yielded inconsistent results regarding the association of antidepressants and risk of suicide, particularly among adults, collective evidence shows a trend of an elevated risk of suicidality in younger age groups (Ref). Of note, the risk of a suicide attempt is inherent in major depression and may persist until remission occurs.

Mechanism: Not established; one of several postulated mechanisms is antidepressants may energize suicidal patients to act on impulses; another suggests that antidepressants may produce a worsening of depressive symptoms leading to the emergence of suicidal thoughts and actions (Ref).

Onset: Varied; increased risk observed in short-term studies (ie, <4 months) in pediatric and young adults; it is unknown whether this risk extends to long-term use (ie, >4 months).

Risk factors:

• Children and adolescents (Ref)

• Depression (risk of suicide associated with major depression and may persist until remission occurs)

Withdrawal syndrome

Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, light-headedness, vertigo, shock-like sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological symptoms (eg, anxiety, agitation, confusion, insomnia, irritability), have been reported, primarily following abrupt discontinuation in adult and pediatric patients (Ref). Withdrawal symptoms may also occur following gradual tapering (Ref).

Mechanism: Withdrawal; due to reduced availability of serotonin in the CNS with decreasing levels of the selective serotonin reuptake inhibitor (SSRI). Other neurotransmission systems, including increased glutamine and dopamine, may also be affected, as well as the hypothalamic-pituitary-adrenal axis (Ref).

Onset: Intermediate; expected onset is 1 to 10 days (following either abrupt or tapered discontinuation) (Ref).

Risk factors:

• Abrupt discontinuation (rather than gradual dosage reduction) of an antidepressant treatment that has lasted >3 weeks, particularly a drug with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)

• Prior history of antidepressant withdrawal symptoms (Ref)

• High dose (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Diaphoresis (5% to 14%)

Endocrine & metabolic: Decreased libido (≤15%) (table 1)

Paroxetine: Adverse Reaction: Decreased Libido

Drug (Paroxetine)

Placebo

Population

Indication

Number of Patients (Paroxetine)

Number of Patients (Placebo)

Comments

0% to 9%

0% to 2%

Females

Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD

1,822

1,340

Multiple placebo-controlled clinical trials evaluating different components of sexual dysfunction

6% to 15%

0% to 5%

Males

Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD

1,446

1,042

Multiple placebo-controlled clinical trials evaluating different components of sexual dysfunction

Gastrointestinal: Constipation (2% to 16%), decreased appetite (1% to 12%), diarrhea (6% to 18%), dyspepsia (2% to 13%), nausea (17% to 26%), xerostomia (3% to 18%)

Genitourinary: Ejaculatory disorder (13% to 28%) (table 2)

Paroxetine: Adverse Reaction: Ejaculatory Disorder

Drug (Paroxetine)

Placebo

Indication

Number of Patients (Paroxetine)

Number of Patients (Placebo)

13% to 28%

0% to 2%

Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD

1,446

1,042

Nervous system: Asthenia (12% to 22%), dizziness (6% to 14%), drowsiness (3% to 24%, less frequent in children and adolescents) (Safer 2006), headache (6% to 27%, including vascular headache), insomnia (7% to 24%), tremor (4% to 11%)

1% to 10%:

Cardiovascular: Chest pain (3%), hypertension (≥1%), palpitations (2% to 3%), tachycardia (≥1%), vasodilation (2% to 4%)

Dermatologic: Pruritus (≥1%), skin rash (2% to 3%)

Endocrine & metabolic: Weight gain (≥1%)

Gastrointestinal: Abdominal pain (4% to 7%), dysgeusia (2%), flatulence (4% to 6%), increased appetite (2% to 4%), nausea and vomiting (4%), vomiting (2% to 3%; more frequent in children [two- to threefold] and adolescents) (Safer 2006)

Genitourinary: Abnormal orgasm (2% to 10%) (table 3), difficulty in micturition (3%), dysmenorrhea (5%), erectile dysfunction (2% to 10%) (table 4), female genital tract disease (2% to 10%), male genital disease (10%), urinary frequency (2% to 3%), urinary tract infection (2%), urination disorder (3%)

Paroxetine: Adverse Reaction: Abnormal Orgasm

Drug (Paroxetine)

Placebo

Population

Indication

Number of Patients (Paroxetine)

Number of Patients (Placebo)

2% to 9%

0% to 1%

Females

Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD

1,822

1,340

Paroxetine: Adverse Reaction: Erectile Dysfunction

Drug (Paroxetine)

Placebo

Dosage Form

Indication

Number of Patients (Paroxetine)

Number of Patients (Placebo)

2% to 9%

0% to 3%

Tablet

Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD

1,446

1,042

5% to 10%

0% to 3%

Tablet, controlled release N/A

Multiple trials in a variety of conditions: MDD, panic disorder, and social anxiety disorder

328

369

Infection: Infection (5% to 6%)

Nervous system: Abnormal dreams (3% to 4%), agitation (3% to 5%), amnesia (2%), anxiety (2% to 5%), chills (2%), confusion (1%), depersonalization (3%), emotional lability (≥1%), fatigue (≤5%), hypomania (≤1%), intoxicated feeling (2%), lack of concentration (3% to 4%), lethargy (≤5%) malaise (≤5%), mania (≤1%), manic reaction (2%), myasthenia (1%), myoclonus (2% to 3%), nervousness (4% to 9%), paresthesia (4%), vertigo (≥1%), yawning (2% to 5%)

Neuromuscular & skeletal: Arthralgia (≥1%), back pain (3% to 5%), myalgia (2% to 5%), myopathy (2%)

Ophthalmic: Blurred vision (4%), visual disturbance (2% to 5%)

Otic: Tinnitus (≥1%)

Respiratory: Pharyngeal edema (2%), pharyngitis (4%), rhinitis (3%), sinusitis (4% to 8%)

<1%:

Cardiovascular: Acute myocardial infarction, angina pectoris, atrial fibrillation, atrioventricular nodal arrhythmia, bradycardia, bundle branch block, edema, heart block, heart failure, hypotension, ischemic heart disease, orthostatic hypotension, peripheral edema, phlebitis, premature ventricular contractions, pulmonary embolism, supraventricular extrasystole, syncope, thrombophlebitis, thrombosis

Dermatologic: Alopecia, dermal ulcer, ecchymoses, eczema, erythema multiforme, erythema nodosum, exfoliative dermatitis, maculopapular rash, skin discoloration, skin hypertrophy, skin photosensitivity, urticaria, vesicobullous dermatitis, xeroderma

Endocrine & metabolic: Adrenergic syndrome, amenorrhea, dehydration, diabetes mellitus, heavy menstrual bleeding, hirsutism, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperphosphatemia, hyperthyroidism, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranges from <1% to as high as 32%) (Gandhi 2017; Jacob 2006), hypothyroidism, increased libido, increased thirst, ketosis, thyroiditis, weight loss

Gastrointestinal: Ageusia, aphthous stomatitis, bloody diarrhea, bruxism, cholelithiasis, colitis, dental bleeding (gums), duodenitis, dysphagia, enteritis, eructation, esophageal achalasia, esophagitis, fecal impaction, fecal incontinence, gastric ulcer, gastritis, gingivitis, glossitis, hematemesis, hiccups, ileitis, intestinal obstruction, melena, oral mucosal ulcer, oral paresthesia, peptic ulcer, peritonitis, rectal hemorrhage, sialadenitis, sialorrhea, stomatitis (including angular) (Verma 2012), tongue discoloration

Genitourinary: Cystitis, dysuria, epididymitis, hematuria, lactation, leukorrhea, mastitis, nocturia, oliguria, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, urolithiasis, uterine hemorrhage, vaginal hemorrhage

Hematologic & oncologic: Anemia (hypochromic, microcytic, normocytic, and iron deficiency), basophilia, eosinophilia, hematoma, hypergammaglobulinemia, leukocytosis, leukopenia, lymphadenopathy, lymphedema, monocytosis, prolonged bleeding time, purpuric disease, thrombocytopenia, thrombocytosis

Hepatic: Hepatic, hyperbilirubinemia, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, jaundice

Hypersensitivity: Angioedema, facial edema, hypersensitivity reaction, tongue edema

Nervous system: Abnormal gait, akathisia, akinesia, altered sense of smell, antisocial behavior, aphasia, ataxia, bulimia nervosa, cerebral ischemia, cerebrovascular accident, choreoathetosis, delirium, delusion, depression with psychosis, drug dependence, dysarthria, euphoria, extrapyramidal reaction, hallucination, hostility, hyperacusis, hyperalgesia, hyperesthesia, hyperreflexia, hypertonia, hyporeflexia, hysteria, lack of emotion, manic depressive reaction, migraine, neuralgia, neuropathy, neurosis, paralysis, paranoid ideation, peripheral neuritis, psychosis, seizure, stupor, suicidal ideation, suicidal tendencies, trismus

Neuromuscular & skeletal: Arthritis, bursitis, dyskinesia, dystonia, fasciculations, gout, hypokinesia, muscle spasm, myelitis, myositis, osteoarthritis, osteoporosis, tenosynovitis, tetany, torticollis

Ophthalmic: Accommodation disturbance, amblyopia, anisocoria, blepharitis, blepharoptosis, cataract, conjunctival edema, corneal ulcer, diplopia, exophthalmos, keratoconjunctivitis, mydriasis, night blindness, nystagmus disorder, photophobia, retinal hemorrhage, visual field defect

Otic: Deafness

Renal: Increased blood urea nitrogen, nephritis, nephrolithiasis

Respiratory: Asthma, bronchitis, dyspnea, epistaxis, hemoptysis, pneumonia, pulmonary edema, pulmonary emphysema, pulmonary fibrosis, stridor

Postmarketing:

Cardiovascular: Torsades de pointes (Wenzel-Seifert 2011), vasculitis (Margolese 2001; Welsh 2006), ventricular fibrillation (Lee 2018), ventricular tachycardia

Dermatologic: Acute generalized exanthematous pustulosis (Mameli 2013), hyperhidrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Ahmed 2008)

Endocrine & metabolic: Galactorrhea not associated with childbirth (Gonzales 2000; Morrison 2001), hyperprolactinemia (Evrensel 2016), porphyria, SIADH (Gandhi 2017), uncontrolled diabetes mellitus

Gastrointestinal: Acute pancreatitis, hemorrhagic pancreatitis

Genitourinary: Preeclampsia, priapism (Ahmad 1995), sexual disorder (Montejo 2019; Montejo-Gonzalez 1997)

Hematologic & oncologic: Agranulocytosis, aplastic anemia, bone marrow aplasia, hemolytic anemia, Henoch-Schönlein purpura, immune thrombocytopenia, pancytopenia

Hepatic: Hepatic failure, hepatic necrosis, hepatotoxicity (Azaz-Livshits 2002; Benbow 1997)

Hypersensitivity: Anaphylaxis, drug reaction with eosinophilia and systemic symptoms, nonimmune anaphylaxis

Nervous system: Aggressive behavior (Nishida 2008; Sharma 2016), anosmia (including hyposmia), cogwheel rigidity, disorientation (Wakeno 2007), Guillain-Barre syndrome, homicidal ideation (Moore 2010), hyperactive behavior (including hyperkinetic muscle activity; more frequent in children [two- to threefold] and adolescents) (Safer 2006), intracranial hemorrhage (Douros 2018), neuroleptic malignant syndrome (with drug interactions) (Tanii 2006; Uguz 2013), restless leg syndrome (Rottach 2008; Sanz-Fuentenebro 1996), restlessness (Naslund 2017), serotonin syndrome (Hudd 2020; Velez 2004), status epilepticus (Taniguchi 2014), withdrawal syndrome (Fava 2015)

Neuromuscular & skeletal: Bradykinesia

Ophthalmic: Acute angle-closure glaucoma (Eke 1997; Kirwan 1997; Lewis 1997), optic neuritis

Renal: Acute kidney injury

Respiratory: Hypersensitivity pneumonitis (Maia 2015), laryngismus, pulmonary alveolitis (allergic), pulmonary hypertension

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any component of the formulation; concurrent use with or within 14 days of monoamine oxidase inhibitors (including linezolid or methylene blue IV); concomitant use with pimozide or thioridazine; pregnancy (Brisdelle only).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Initiation of paroxetine within 2 weeks of pimozide or thioridazine discontinuation.

Warnings/Precautions

Concerns related to adverse effects:

• Akathisia: Inability to remain still due to feelings of agitation or restlessness has been observed with paroxetine and other selective serotonin reuptake inhibitors (SSRIs). Usually occurs within the first few weeks of therapy.

• Anticholinergic effects: Has low potential for sedation and anticholinergic effects relative to cyclic antidepressants; however, among the SSRI class these effects are relatively higher.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; paroxetine has not been systemically evaluated in patients with a recent history of myocardial infarction or unstable heart disease.

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed. However, selective serotonin reuptake inhibitors such as paroxetine are considered the safest antidepressants to use in chronic liver disease because of their relative lack of side effects and high therapeutic index (Mullish 2014).

• Renal impairment: Use with caution in patients with renal impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.

• Seizure disorder: Use with caution in patients with seizure disorder.

Dosage form specific issues:

• Brisdelle: Brisdelle contains a lower dose than what is required for the treatment of psychiatric conditions. Patients who require paroxetine for the treatment of psychiatric conditions should discontinue Brisdelle and begin treatment with a paroxetine-containing medication which provides an adequate dosage.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Product Availability

Pexeva has been discontinued in the United States for >1 year.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as mesylate [strength expressed as base]:

Brisdelle: 7.5 mg [DSC] [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]

Generic: 7.5 mg

Suspension, Oral, as hydrochloride [strength expressed as base]:

Paxil: 10 mg/5 mL (250 mL) [contains fd&c yellow #6(sunset yellow)alumin lake, methylparaben, propylene glycol, propylparaben, saccharin sodium; orange flavor]

Generic: 10 mg/5 mL (250 mL)

Tablet, Oral, as hydrochloride [strength expressed as base]:

Paxil: 10 mg [DSC]

Paxil: 10 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Paxil: 20 mg [DSC]

Paxil: 20 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Paxil: 30 mg [DSC]

Paxil: 30 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Paxil: 40 mg [DSC]

Paxil: 40 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Generic: 10 mg, 20 mg, 30 mg, 40 mg

Tablet, Oral, as mesylate [strength expressed as base]:

Pexeva: 10 mg [DSC], 20 mg [DSC], 30 mg [DSC], 40 mg [DSC]

Tablet Extended Release 24 Hour, Oral, as hydrochloride [strength expressed as base]:

Paxil CR: 12.5 mg [contains fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Paxil CR: 25 mg [DSC]

Paxil CR: 25 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Paxil CR: 37.5 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake]

Paxil CR: 37.5 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Generic: 12.5 mg, 25 mg, 37.5 mg

Generic Equivalent Available: US

Yes

Pricing: US

Capsules (PARoxetine Mesylate Oral)

7.5 mg (per each): $6.60

Suspension (PARoxetine HCl Oral)

10 mg/5 mL (per mL): $1.58

Suspension (Paxil Oral)

10 mg/5 mL (per mL): $2.13

Tablet, 24-hour (PARoxetine HCl ER Oral)

12.5 mg (per each): $0.80 - $5.58

25 mg (per each): $0.86 - $5.82

37.5 mg (per each): $0.92 - $5.99

Tablet, 24-hour (Paxil CR Oral)

12.5 mg (per each): $11.04

25 mg (per each): $11.52

37.5 mg (per each): $11.87

Tablets (PARoxetine HCl Oral)

10 mg (per each): $1.95 - $2.67

20 mg (per each): $2.29 - $2.73

30 mg (per each): $2.70 - $2.83

40 mg (per each): $2.88 - $3.18

Tablets (Paxil Oral)

10 mg (per each): $10.72

20 mg (per each): $11.18

30 mg (per each): $11.52

40 mg (per each): $12.17

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride [strength expressed as base]:

Paxil: 10 mg, 20 mg, 30 mg [contains polysorbate 80]

Generic: 10 mg, 20 mg, 30 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride [strength expressed as base]:

Paxil CR: 12.5 mg [contains fd&c yellow #6(sunset yellow)alumin lake, polysorbate 80, quinoline (d&c yellow #10) aluminum lake]

Paxil CR: 25 mg [contains polysorbate 80]

Administration: Adult

Oral: May be administered without regard to meals. Administer preferably in the morning; when used for vasomotor symptoms of menopause, administer at bedtime. Do not crush, break, or chew ER or IR film-coated tablets. Shake suspension well before use.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER tablets should be swallowed whole. IR tablet, capsule, and oral suspension formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

Administration: Pediatric

Oral: May be administered without regard to meals; administration with food may decrease GI side effects; shake suspension well before use. Paxil should preferentially be administered in the morning. Do not chew or crush immediate- or controlled-release tablet; swallow whole.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 3]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Brisdelle:https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/204516s013lbl.pdf#page=18

Paxil: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020031s082,020710s050lbl.pdf#page=39

Paxil CR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020936s057s064lbl.pdf#page=30

Pexeva: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021299s035s038lbl.pdf#page=18

Use: Labeled Indications

Generalized anxiety disorder (immediate release): Treatment of generalized anxiety disorder.

Major depressive disorder (unipolar) (immediate and extended release): Treatment of unipolar major depressive disorder.

Obsessive-compulsive disorder (immediate release): Treatment of obsessions and compulsions in patients with obsessive-compulsive disorder.

Panic disorder (immediate and extended release): Treatment of panic disorder, with or without agoraphobia.

Posttraumatic stress disorder (immediate release): Treatment of posttraumatic stress disorder.

Premenstrual dysphoric disorder (extended release): Treatment of premenstrual dysphoric disorder.

Social anxiety disorder (immediate and extended release): Treatment of social anxiety disorder, also known as social phobia.

Vasomotor symptoms of menopause (immediate release; 7.5 mg capsule): Treatment of moderate to severe vasomotor symptoms associated with menopause.

Use: Off-Label: Adult

Body dysmorphic disorder; Premature ejaculation

Medication Safety Issues
Sound-alike/look-alike issues:

PARoxetine may be confused with DULoxetine, FLUoxetine, PACLitaxel, piroxicam, pyridoxine, vortioxetine

Paxil may be confused with Doxil, PACLitaxel, Plavix, PROzac, Taxol, Trexall

Pexeva [DSC] may be confused with Lexiva

Older Adult: High-Risk Medication:

Beers Criteria: Paroxetine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its strong anticholinergic properties and potential for sedation and orthostatic hypotension. In addition, use the SSRIs with caution due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Substrate of CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (strong)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Ajmaline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider therapy modification

Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Amphetamines: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities, including serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust dose as needed. Risk C: Monitor therapy

Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Antiplatelet Agents (P2Y12 Inhibitors): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor therapy

Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider therapy modification

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Asenapine: May increase the serum concentration of PARoxetine. Management: Decrease the paroxetine dose by half when used concomitantly with asenapine. Monitor patients receiving this combination closely for signs and symptoms of increased paroxetine toxicity. Risk D: Consider therapy modification

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider therapy modification

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Brexanolone: Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with strong CYP2D6 inhibitors, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder Risk D: Consider therapy modification

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination

Broom: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor therapy

BuPROPion: May enhance the adverse/toxic effect of PARoxetine. Risk C: Monitor therapy

BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

Carvedilol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Chlorpheniramine. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of PARoxetine. Risk C: Monitor therapy

Citalopram: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Citalopram may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

CloZAPine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy

Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of PARoxetine. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of PARoxetine. Risk C: Monitor therapy

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination

Darunavir: May decrease the serum concentration of PARoxetine. Risk C: Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Dextromethorphan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Dextromethorphan. Management: Consider alternatives to this drug combination. The dose of dextromethorphan/bupropion product should not exceed 1 tablet once daily. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DULoxetine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). DULoxetine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of DULoxetine. Management: Monitor for increased duloxetine effects/toxicities and signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperthermia, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy

Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Fenfluramine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Fesoterodine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

Flecainide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Flecainide. Risk C: Monitor therapy

FLUoxetine: May enhance the antiplatelet effect of PARoxetine. FLUoxetine may enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. FLUoxetine may increase the serum concentration of PARoxetine. PARoxetine may increase the serum concentration of FLUoxetine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes), bleeding, and increased SSRI toxicities when these agents are combined. Risk C: Monitor therapy

FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of FluPHENAZine. Risk C: Monitor therapy

Fosamprenavir: May decrease the serum concentration of PARoxetine. The active metabolite amprenavir is likely responsible for this effect. Risk C: Monitor therapy

Galantamine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy

Gefitinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Risk C: Monitor therapy

Gepirone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Gilteritinib: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor. Risk D: Consider therapy modification

Haloperidol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy

Iboga: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iboga. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor and monitor for increased iloperidone toxicities, including QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Indoramin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy

Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Levomethadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lofexidine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Lofexidine. Risk C: Monitor therapy

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Maprotiline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Maprotiline. Risk C: Monitor therapy

Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Risk X: Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Methadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Methadone: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Methadone. Risk C: Monitor therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Metoclopramide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for toxicity when combined. Risk D: Consider therapy modification

Metoprolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoprolol. Risk C: Monitor therapy

Mexiletine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mexiletine. Risk C: Monitor therapy

Mivacurium: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Nefazodone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Oliceridine: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Oliceridine. Management: Monitor for increased opioid effects (eg, respiratory depression, sedation) and for serotonin syndrome/serotonin toxicity when these agents are combined. Risk C: Monitor therapy

Olmutinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may diminish the therapeutic effect of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for decreased therapeutic response (eg, analgesia) and opioid withdrawal when coadministered with SSRIs that strongly inhibit CYP2D6. Additionally, monitor for serotonin syndrome/serotonin toxicity if these drugs are combined. Risk C: Monitor therapy

Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Perhexiline: PARoxetine may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of PARoxetine. Risk C: Monitor therapy

Perphenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy

Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pitolisant: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. Risk D: Consider therapy modification

Pravastatin: May enhance the adverse/toxic effect of PARoxetine. Specifically, blood glucose elevations may occur with the combination. Risk C: Monitor therapy

Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Primaquine. Risk C: Monitor therapy

Procyclidine: PARoxetine may increase the serum concentration of Procyclidine. Risk C: Monitor therapy

Propafenone: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Propranolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propranolol. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Rasagiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid combination

RisperiDONE: CYP2D6 Inhibitors (Strong) may increase the serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Safinamide: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of other Selective Serotonin Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of other Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

Selegiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Risk X: Avoid combination

Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

Sertindole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Sertindole. Management: Consider alternatives to this combination when possible. If combined, consider using lower doses of sertindole and monitor the ECG closely for evidence of QTc interval prolongation. Risk D: Consider therapy modification

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider therapy modification

Tamsulosin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Thioridazine. Risk X: Avoid combination

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy

Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy

Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Tolterodine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy

TraMADol: Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may enhance the adverse/toxic effect of TraMADol. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may diminish the therapeutic effect of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes), seizures, and decreased tramadol efficacy when these agents are combined. Risk C: Monitor therapy

Tricyclic Antidepressants: PARoxetine may enhance the serotonergic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider therapy modification

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Valbenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider therapy modification

Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy

Venlafaxine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). Venlafaxine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease serum concentrations of the active metabolite(s) of Venlafaxine. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Venlafaxine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Vortioxetine: Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may enhance the antiplatelet effect of Vortioxetine. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may enhance the serotonergic effect of Vortioxetine. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Vortioxetine. Management: Consider alternatives to this drug combination. If combined, reduce the vortioxetine dose by half and monitor for signs and symptoms of bleeding and serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, autonomic instability). Risk D: Consider therapy modification

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Zuclopenthixol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

Food Interactions

Peak concentration is increased, but bioavailability is not significantly altered by food. Management: Administer without regard to meals.

Reproductive Considerations

Paroxetine is approved for the treatment of generalized anxiety disorder, panic disorder, posttraumatic stress disorder, social anxiety disorder, unipolar major depressive disorder, and obsessive-compulsive disorder. If treatment for any of these indications is initiated for the first time in a patient planning to become pregnant, agents other than paroxetine are recommended (use of paroxetine is not preferred for use during pregnancy) (Larsen 2015; WFSBP [Bandelow 2012]).

Paroxetine is also approved for the treatment of premenstrual dysphoric disorder. For patients attempting to conceive, symptom-onset dosing may be beneficial to minimize potential fetal exposure (Ismaili 2016; Lanza di Scalea 2019).

Selective serotonin reuptake inhibitors (SSRIs) may be associated with male and female treatment-emergent sexual dysfunction (Coskuner 2018; WFSBP [Bauer 2013]). Decreased libido and orgasmic disturbances have been reported in females; abnormal ejaculation, decreased libido, and impotence have been reported in males with use. This may also be a manifestation of the psychiatric disorder. The actual risk associated with paroxetine is not known; however, the risk of treatment-emergent sexual dysfunction may be greater with paroxetine than other SSRIs. SSRI-related sexual dysfunction may resolve with dose reduction or discontinuation of the SSRI; in some cases, sexual dysfunction may persist once therapy is discontinued (Coskuner 2018; Jing 2016; Waldinger 2015).

Paroxetine is used off label for the treatment of premature ejaculation. Although data are limited, some studies have shown SSRIs may impair the motility of spermatozoa; therefore, use of other treatments may be preferred in males planning to father a child (Althof 2014; Siroosbakht 2019; Sylvester 2019).

Pregnancy Considerations

Paroxetine crosses the placenta (Hendrick 2003).

As a class, selective serotonin reuptake inhibitors (SSRIs) have been evaluated extensively in pregnant patients. Studies focusing on newborn outcomes following first trimester exposure often have inconsistent results due to differences in study design and confounders such as maternal disease and social factors (Anderson 2020; Biffi 2020; Fitton 2020; Reefhuis 2015; Womersley 2017). Adverse effects in the newborn following SSRI exposure late in the third trimester can include apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, respiratory distress, seizures, temperature instability, tremor, and vomiting. Prolonged hospitalization, respiratory support, or tube feedings may be required. Symptoms may be due to the toxicity of the SSRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn has been reported with SSRI exposure; although the absolute risk is small, monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). The long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are not known (CANMAT [MacQueen 2016]).

Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of paroxetine may be altered. The maternal CYP2D6 genotype also influences if paroxetine plasma concentrations increase or decrease during pregnancy (Hostetter 2000; Ververs 2009; Westin 2017). A case report describes symptoms of antidepressant discontinuation syndrome (night sweats, nightmares) in a patient during the first trimester of pregnancy, requiring a continued increase of her paroxetine dose as pregnancy progressed for resolution. The patient was found to be an extensive metabolizer of CYP2D6 (Javelot 2020). Close clinical monitoring as pregnancy progresses and therapeutic drug monitoring to detect patterns of changing plasma concentrations is recommended to assist dose adjustment when needed; CYP2D6 genotyping may also be considered (Schoretsanitis 2020).

If treatment is initiated for the first time during pregnancy, paroxetine is not recommended (CANMAT [MacQueen 2016]; Larsen 2015; WFSBP [Bauer 2013]). The American College of Obstetricians and Gynecologists also recommends that therapy with paroxetine be avoided during pregnancy, if possible, and that fetuses exposed in early pregnancy be assessed with a fetal echocardiography (ACOG 2008). If pregnancy occurs during paroxetine therapy, treatment should be changed, except in extraordinary circumstances (Larsen 2015). Untreated or inadequately treated psychiatric illness may lead to poor adherence with prenatal care and adverse pregnancy outcomes. Therapy with antidepressants during pregnancy should be individualized; treatment with antidepressant medication is recommended for pregnant patients with severe major depressive disorder (ACOG 2008; CANMAT [MacQueen 2016]). Patients treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued (68%) as compared to pregnant patients who continue taking antidepressant medications (26%) (Cohen 2006).

Menopausal vasomotor symptoms do not occur during pregnancy; therefore, the use of paroxetine for the treatment of menopausal vasomotor symptoms is contraindicated in pregnant patients.

Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Patients exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants. Pregnant patients 18 to 45 years of age or their health care providers may contact the registry to enroll; enrollment should be done as early in pregnancy as possible (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/).

Breastfeeding Considerations

Paroxetine is present in breast milk.

The relative infant dose (RID) of paroxetine has been calculated in review articles to be <3 % of the weight-adjusted maternal dose (Berle 2011; Orsolini 2015). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).

In 1 review, the RID of paroxetine was calculated using pooled data from 119 mother/infant pairs, providing an estimated daily infant dose via breast milk of 0.03 mg/day. The maternal dose and actual breast milk concentrations for the calculation were not provided (Berle 2011). A second review included information from 228 cases; maternal daily doses of paroxetine were 5 to 60 mg/day. The highest breast milk concentration of paroxetine presented was 776 ng/mL observed in 1 of 4 women following a maternal dose of 12.5 to 60 mg/day obtained after 0 to 18 weeks of treatment (Orsolini 2015). A study published since these reviews included 5 lactating women taking paroxetine 7 to 25 mg/day; the paroxetine breast milk concentrations and RID fell within the ranges presented in the earlier reviews. The highest calculated RID was 3.2% following a maternal dose of paroxetine 25 mg/day, providing a milk concentration of 32.9 ng/mL (Pogliani 2019). Milk and maternal plasma concentrations are linearly correlated (Misri 2000; Weissman 2004). Paroxetine was measurable in the serum of some breastfed infants (Orsolini 2015; Weissman 2004).

Constant crying, insomnia, lethargy, poor weight gain, and restlessness have been observed in breastfed infants exposed to some selective serotonin reuptake inhibitors (SSRIs), including paroxetine (Merlob 2004; Nordeng 2001; Uguz 2016; Weissman 2004); severe constipation was also observed in a case report (Uguz 2018). Infants exposed to an SSRI via breast milk should be monitored for irritability and changes in sleep, feeding patterns, and behavior as well as growth and development (ABM [Sriraman 2015]; Sachs 2013; Weissman 2004; WFSBP [Bauer 2013]).

Maternal use of an SSRI during pregnancy may cause delayed lactogenesis (Marshall 2010); however, the underlying maternal illness may also influence this outcome (Grzeskowiak 2018). Untreated severe or chronic depression in the postpartum period also has negative effects on the mother and the infant (Slomian 2019).

Psychotherapy or other nonmedication therapies are recommended for the initial treatment of mild depression in breastfeeding patients; antidepressant medication is recommended when psychotherapy is not an option or when symptoms are moderate to severe. If a specific SSRI was used effectively during pregnancy, it can be continued while breastfeeding if no contraindications exist (ABM [Sriraman 2015]). Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue paroxetine, considering the importance of treatment to the mother. When first initiating an antidepressant in a patient who is breastfeeding, paroxetine may be used; however, other agents should be considered if the patient requires long-term therapy and wishes to have another pregnancy (ABM [Sriraman 2015]; CANMAT [MacQueen 2016]; Larsen 2015).

Monitoring Parameters

Liver and renal function tests (baseline; as clinically indicated); serum sodium in at-risk populations (as clinically indicated); CBC (as clinically indicated); closely monitor patients for depression, clinical worsening, suicidality, psychosis, or unusual changes in behavior (eg, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures.

Mechanism of Action

Paroxetine is a selective serotonin reuptake inhibitor, chemically unrelated to tricyclic, tetracyclic, or other antidepressants; presumably, the inhibition of serotonin reuptake from brain synapse stimulated serotonin activity in the brain

Pharmacokinetics (Adult Data Unless Noted)

Onset of action:

Anxiety disorders (generalized anxiety, obsessive-compulsive, panic, and posttraumatic stress disorder): Initial effects may be observed within 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Issari 2016; Varigonda 2016; WFSBP [Bandelow 2023a]); some experts suggest up to 12 weeks of treatment may be necessary for response, particularly in patients with obsessive-compulsive disorder and posttraumatic stress disorder (BAP [Baldwin 2014]; Katzman 2014; WFSBP [Bandelow 2023a]; WFSBP [Bandelow 2023b]).

Body dysmorphic disorder: Initial effects may be observed within 2 weeks; some experts suggest up to 12 to 16 weeks of treatment may be necessary for response in some patients (Phillips 2008).

Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009; Taylor 2006).

Premenstrual dysphoric disorder: Initial effects may be observed within the first few days of treatment, with response at the first menstrual cycle of treatment (ISPMD [Nevatte 2013]).

Absorption: Completely absorbed following oral administration

Distribution: Vd: 8.7 L/kg (3 to 28 L/kg)

Protein binding: 93% to 95%

Metabolism: Extensively hepatic via CYP2D6 enzymes; primary metabolites are formed via oxidation and methylation of parent drug, with subsequent glucuronide/sulfate conjugation; nonlinear pharmacokinetics (via 2D6 saturation) may be seen with higher doses and longer duration of therapy. Metabolites exhibit ~2% potency of parent compound. Cmin concentrations are 70% to 80% greater in the elderly compared to nonelderly patients; clearance is also decreased.

Bioavailability: Immediate release tablet and oral suspension have equal bioavailability

Half-life elimination: Paxil: 21 hours; Paxil CR: 15 to 20 hours; Pexeva: 33.2 hours

Time to peak:

Capsules: Median: 6 hours (range: 3 to 8 hours)

Tablets, oral suspension: Immediate release: Mean: 5.2 to 8.1 hours

Tablets: Controlled release: 6 to 10 hours

Excretion: Urine (64%, 2% as unchanged drug); feces (36% primarily via bile, <1% as unchanged drug)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: AUC increased approximately 3.5 times with CrCl <30 mL/minute. AUC increased 2-fold with CrCl 30 to 60 mL/minute (Doyle 1989).

Hepatic function impairment: 2-fold increase in plasma concentrations and AUC after 14 days of daily administration in patients with alcohol-related cirrhosis (Dalhoff 1991).

Older adult: Minimum concentrations were 70% to 80% greater than in younger patients. Reduce initial dosage; no dosage adjustment is necessary with Brisdelle.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Paxitab | Seroxat;
  • (AR) Argentina: Ginstar | Meplar | Neurotrox | Olane xr | Paroxetina cevallos | Paroxetina lepret | Paroxetina Teva | Paxil | Psicoasten | Sicotral | Tiarix | Tioari | Xilanic;
  • (AT) Austria: Allenopar | Ennos | Paluxetil | Parocetan | Paroxat | Paroxetin +pharma | Paroxetin actavis | Paroxetin Alternova | Paroxetin arcana | Paroxetin easypharm | Paroxetin Genericon | Paroxetin interpharm | Paroxetin Merckle | Paroxetin pfizer | Paroxetin Ratiopharm | Paroxetin ratiopharm GmbH | Paroxetin Sandoz | Paroxetin-1a pharma gmbh | Seroxat;
  • (AU) Australia: Apo paroxetine | Aropax | Cm paroxetine | Extine | Genrx paroxetine | Oxetine | Paroxetine | Paroxetine Actavis | Paroxetine an | Paroxetine Generic Health | Paroxetine pfizer | Paroxetine sandoz | Paroxetine synthon | Paroxetine Winthrop | Paroxetine-Ga | Paxtine | Pharmacor Paroxetine | Pharmacor Paroxo | Roxet | Tw paroxetine;
  • (BD) Bangladesh: Melev | Oxat | Panirid | Parotin | Paroxet;
  • (BE) Belgium: Aropax | Paroxetin actavis | Paroxetine ab | Paroxetine bexal | Paroxetine eg | Paroxetine eurogenerics | Paroxetine merck-generics | Paroxetine pfizer | Paroxetine ratiopharm | Paroxetine sandoz | Paroxetine teva | Paroxetine topgen | Paroxiteva | Seroxat;
  • (BF) Burkina Faso: Deroxat;
  • (BG) Bulgaria: Depoxat | Parix | Paroxat | Paroxetine | Rexetin | Seroxat | Xetanor;
  • (BR) Brazil: Aropax | Arotin | Benepax | Cebrilin | Cloridrato de paroxetina | Moratus | Parox | Paroxiliv | Paxil | Paxil cr | Paxtrat | Pondera | Pondera xr | Pondix | Praxetina | Roxetin | Roxetin xr | Sertero | Zyparox;
  • (CH) Switzerland: Deroxat | Parexat | Paronex | Paroxetin - 1 A Pharma | Paroxetin actavis | Paroxetin mepha | Paroxetin spirig | Paroxetin Spirig HC | Paroxetin zentiva;
  • (CL) Chile: Arotex | Aroxat | Bectam | Deroxat | Pamax | Parodox | Seretran | Traviata;
  • (CN) China: Le you | Sai le te | Seroxat | Shu tan luo;
  • (CO) Colombia: Nath | Pacex | Paroxetina | Paxan | Seropax | Seroxat;
  • (CZ) Czech Republic: Apo parox | Arketis | Parolex | Paroxetin | Paroxetin +pharma | Paroxetin aurovitas | Paroxetin Orion | Paroxetin teva | Paroxinor | Remood | Seroxat;
  • (DE) Germany: Euplix | Oxet | Parolich | Parox | Paroxalon | Paroxat | Paroxedura | Paroxetin | Paroxetin 1a pharma | Paroxetin actavis | Paroxetin AL | Paroxetin aurobindo | Paroxetin Basics | Paroxetin Beta | Paroxetin CT | Paroxetin Heumann | Paroxetin Holsten | Paroxetin Hormosan | Paroxetin Isis | Paroxetin neuraxpharm | Paroxetin Ratiopharm | Paroxetin Real | Paroxetin Sandoz | Paroxetin Stada | Paroxetin teva | Seroxat | Tagonis;
  • (DK) Denmark: Paroxetin 1a farma | Paroxetin genthon | Paroxetin nm | Paroxetin pcd | Paroxetin Ratiopharm;
  • (DO) Dominican Republic: Europaroxet | Laparox | Meplar | Paroxet | Paroxetina | Paxil | Prexor | Traviata;
  • (EC) Ecuador: Paroten | Paroxetina | Paxil | Pondera | Seretran | Seretran CR | Xerenex;
  • (EE) Estonia: Arketis | Paroxat | Paroxetin hexal | Paroxetin nycomed | Paroxetine Orion | Rexetin | Seroxat;
  • (EG) Egypt: Depanx | Paroxedep cr | Paroxedur | Paroxetine | Paxetin | Seroxat | Xandol;
  • (ES) Spain: Arapaxel | Frosinor | Motivan | Paroxetina | Paroxetina almus | Paroxetina alter | Paroxetina angenerico | Paroxetina aphar | Paroxetina Apotex | Paroxetina Arafarma group | Paroxetina aurobindo | Paroxetina aurovitas | Paroxetina bayvit | Paroxetina bexal | Paroxetina bluepharma | Paroxetina cinfa | Paroxetina Combix | Paroxetina Curaxys | Paroxetina cuve | Paroxetina davur | Paroxetina Edigen | Paroxetina kern | Paroxetina Mabo | Paroxetina merck | Paroxetina mundogen | Paroxetina Normon | Paroxetina pensa | Paroxetina pharma combix | Paroxetina Pharmacia | Paroxetina pharmagenus | Paroxetina Qualigen | Paroxetina ranbaxy | Paroxetina rimafar | Paroxetina sandoz | Paroxetina stada | Paroxetina tarbis | Paroxetina Teva | Paroxetina vir | Paroxetina Winthrop | Seroxat | Xetin;
  • (ET) Ethiopia: Seroxat;
  • (FI) Finland: Optipar | Paroksetiini glaxo | Paroxetin actavis | Paroxetin Alpharma | Paroxetin avansor | Paroxetin Copyfarm | Paroxetin generics | Paroxetin Orion | Paroxetin pfizer | Paroxetin ratiopharma | Paroxetin Sandoz | Paroxetin Stada | Seroxat;
  • (FR) France: Deroxat | Divarius | Paroxetine Actavis | Paroxetine Alter | Paroxetine Arrow | Paroxetine cristers | Paroxetine eg | Paroxetine evolugen | Paroxetine g gam | Paroxetine irex | Paroxetine Isomed | Paroxetine merck | Paroxetine pfizer | Paroxetine phr lab | Paroxetine Qualimed | Paroxetine ratiopharm | Paroxetine RPG | Paroxetine sandoz | Paroxetine Zydus;
  • (GB) United Kingdom: Paroxetine | Paroxetine cox | Paroxetine kent | Paroxetine pfizer | Paroxetine sandoz | Seroxat;
  • (GR) Greece: Noprilex | Parolet | Parosat | Paroxetine | Paroxetine/mylan | Paroxetine/teva | Paroxia | Seroxat | Solben;
  • (HK) Hong Kong: Apo paroxetine | Parotin | Seroxat;
  • (HR) Croatia: Deprozel | Paluxon | Paroksetin PharmaS | Paroxin | Seroxat;
  • (HU) Hungary: Apodepi | Paretin | Parogen | Paroxat | Paroxetin pfizer | Paroxetin Ratiopharm | Rexetin | Seroxat | Xetanor;
  • (ID) Indonesia: Seroxat;
  • (IE) Ireland: Meloxat | Paroser | Parox | Paxt | Seroxat;
  • (IL) Israel: Paroxetine teva | Paxxet | Seroxat;
  • (IN) India: Anxifree p | Aroximat cr | Cnpaxet | Depaxil | Emoxet | Fordep | Nobix | Obsikon CR | Oxitine cr | Panex | Paradise XR | Pardep | Pari | Pari cr | Paro 40 | Paro cr | Parogen cr | Parolyst | Paronet cr | Parotin | Paroxee | Paroxet | Patinex | Patroxta | Paxgem xr | Paxidep-cr | Paxiford cr | Paxiniche cr | Paxinta cr | Paxit | Paxonil | Petin | Pexep | Pexep cr | Praxet CR | Praxo | Praxohenz cr | Pxn | Qxt | Raxit | Serotin | Xepar | Xet | Xet cr | Xl-paro | Xodep;
  • (IT) Italy: Daparox | Eutimil | Paroxetina | Paroxetina actavis | Paroxetina Almu | Paroxetina aurobindo | Paroxetina doc generici | Paroxetina eg | Paroxetina Ge | Paroxetina pensa | Paroxetina sandoz | Paroxetina zentiva | Sereupin | Seroxat;
  • (JO) Jordan: Paxitab | Seroxat | Unirox;
  • (JP) Japan: Paroxetine | Paroxetine aspen | Paroxetine dk | Paroxetine ffp | Paroxetine jg | Paroxetine Nissin | Paroxetine Towa | Paxil;
  • (KE) Kenya: Adco paroxetine | Pyrantin | Seroxat;
  • (KR) Korea, Republic of: A Xat | A xat cr | Paroctin | Parosenin | Parox | Parox cr | Paroxat cr | Paroxen | Paroxetine | Paroxil | Parozat | Paxerontine sr | Paxetil | Paxil | Paxil cr | Pharma paroxetine | Sandoz paroxetine | Seroksetin | Seroxart | Seroxat | Wi paroxetine | Yungjin paroxetine cr;
  • (KW) Kuwait: Paxitab | Seroxat;
  • (LB) Lebanon: Apo paroxetine | Parlotin | Paroxat | Paxera | Paxil | Paxitab | Pms-paroxetine | Seroxat | Unirox;
  • (LT) Lithuania: Arketis | Paroxetin hexal | Paroxetin Orion | Paroxetine Actavis | Paroxetine aurobindo | Seroxat;
  • (LU) Luxembourg: Aropax | Paroxetine apotex | Paroxetine eg | Paroxetine ratiopharm | Seroxat;
  • (LV) Latvia: Arketis | Paroxetin | Paroxetin actavis | Paroxetin aurobindo | Paroxetin nycomed | Paroxetin Orion | Rexetin | Seroxat;
  • (MA) Morocco: Deroxat | Divarius | Panekal | Paroxetine | Paroxetine win | Tre zen | Xerium;
  • (MX) Mexico: Andepa | Anziatina | Apo oxpar | Aropax | Aropax CR | Bioserox | Chipten | Collepax | Cronadyn | Daboxanil | Davol | Ixicrol | Lysande | Ocampina | Ontracel | Paroxetina | Paxil | Paxil cr | Riedilex | Tamcere | Umesalil | Xerenex | Xetroran;
  • (MY) Malaysia: Apo paroxetine | Seroxat;
  • (NG) Nigeria: Mizetin | Paroxetine sandoz | Seroxat;
  • (NL) Netherlands: Deroxat | Paroxetine | Paroxetine Actavis | Paroxetine Alpharma O.F. | Paroxetine cf | Paroxetine HCL | Paroxetine hcl-anhydraat A | Paroxetine merck | Paroxetine prolepha | Paroxetine sandoz | Seroxat;
  • (NO) Norway: Paroxat | Paroxetin | Paroxetin aristo | Paroxetin aurobindo | Paroxetin gea | Paroxetin GlaxoSmithKline | Paroxetin hexal | Paroxetin nycomed | Paroxetin pfizer | Paroxetin Sandoz | Seroxat;
  • (NZ) New Zealand: Apo paroxetine | Aropax | Loxamine | Paxtine;
  • (PE) Peru: Paroxet | Paroxetina | Paxil | Seroxat | Sindep | Xerenex;
  • (PH) Philippines: Seroxat | Xet;
  • (PK) Pakistan: Aeva | Auroprox | Brisdel | Depexil cr | Depin | Deroxat | Dexet plus | Exatine cr | Excite cr | Fyprox | Gerox | Gerox cr | Harmony | Hiprox | Impika | Impika cr | Invika CR | Jurox cr | Karox | Neoxetine | Ob parox | Obexil | Olixat cr | P ox | Panox cr | Paraice | Paraxyl | Paraxyl CR | Pari | Pari cr | Parinom | Parinom cr | Pariva | Pariz | Paromax | Paromax cr | Paronex | Paronex cr | Parotin | Parox Q | Paroxil | Paroxin | Paroxin cr | Paroxitol | Paroxiwel cr | Paroxywin cr | Parxet | Pax cr | Paxet | Paxetin | Perison cr | Peroxa | Peroxa cr | Peroxit | Pexeva | Pexot | Pexot cr | Pext cr | Pexta | Plasare | Praxlet | Praxlet cr | Prixteen | Prixteen cr | Progra | Proksitin | Pronitron | Quixet | Rapox | Raxil cr | Roxetine | Roxetine cr | Sadgon | Seroless | Seroxat | Zepid;
  • (PL) Poland: Parogen | Paroxetine aurobindo | Paroxetine aurovitas | Paroxinor | Paxtin | Rexetin | Seroxat;
  • (PR) Puerto Rico: Brisdelle | Paroxetine | Paroxetine extended release | Paroxetine HCL | Paxil | Pexeva;
  • (PT) Portugal: Denerval | Oxepar | Paroxetina | Paroxetina almus | Paroxetina aurobindo | Paroxetina aurovitas | Paroxetina generis | Paroxetina limeg | Paroxetina Pfizer | Paroxetina sandoz | Paroxetina tedec | Paroxetina Teva | Paxetil | Paxpar | Seroxat | Voltak | Zanoxina;
  • (PY) Paraguay: Aropax | Openlix | Paroxetina pasteur | Sicotropin | Tiarix;
  • (QA) Qatar: Paroxat | Paxitab | Seroxat | Seroxat CR | Unirox;
  • (RO) Romania: Als paroxetin | Arketis | Paroxetin teva | Rexetin | Seroxat;
  • (RU) Russian Federation: Actaparoxetine | Apo paroxetine | Paroxetine | Paxil | Plisil | Plisil n | Rexetin;
  • (SA) Saudi Arabia: Apo paroxetine | Axor | Pado | Paroxat | Paxitab | Pms-paroxetine | Seroxat;
  • (SE) Sweden: Arketis | Euplix | Paroxetin | Paroxetin actavis | Paroxetin Alpharma | Paroxetin Amneal | Paroxetin aurobindo | Paroxetin Copyfarm | Paroxetin ebb | Paroxetin Eql Pharma | Paroxetin gea | Paroxetin hexal | Paroxetin Mylan | Paroxetin Orion | Paroxetin Ratiopharm | Paroxetin Sandoz | Paroxetin teva | Paroxiflex | Paroxistad | Seroxat;
  • (SG) Singapore: Apo paroxetine | Seroxat;
  • (SI) Slovenia: Paluxon | Paroksetin Actavis | Plisil | Seroxat;
  • (SK) Slovakia: Arketis | Paretin | Parolex | Paroxetin | Paroxetin +pharma | Paroxetin Orion | Paroxetin teva | Remood | Seroxat;
  • (SY) Syrian Arab Republic: Depretin;
  • (TH) Thailand: Seroxat;
  • (TN) Tunisia: Deproxyl | Deroxat | Divarius | Parexat | Paroxine | Paxetin;
  • (TR) Turkey: Paroteva | Paxera | Paxil | Paxotin | Seroxat;
  • (TW) Taiwan: Apo paroxetine | Caremod | Eugine | Paroxe | Seroxat | Setine | Xet | Xetine-P;
  • (UA) Ukraine: Luxotil | Paroxin | Paxil | Rexetin;
  • (UY) Uruguay: Blifedan | Efil | Meplar | Parotina | Paroxet | Paxelle | Prexetin;
  • (VE) Venezuela, Bolivarian Republic of: Parexel | Parotin | Paroxetina | Paroxetina bluepharma | Paxil | Prismarox;
  • (VN) Viet Nam: Sumiko;
  • (ZA) South Africa: Adco paroxetine | Aropax | Deparoc | Hexal paroxetine | Lenio | Paroxetine Unicorn | Zydus Paroxetine;
  • (ZM) Zambia: Aropax | Pari cr;
  • (ZW) Zimbabwe: Aropax
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372 [PubMed 37139824]
  3. Ahmad S. Paroxetine-induced priapism. Arch Intern Med. 1995;155(6):645. [PubMed 7887764]
  4. Ahmed R, Eagleton C. Toxic epidermal necrolysis after paroxetine treatment. N Z Med J. 2008;121(1274):86-89. [PubMed 18535650]
  5. Alade SL, Brown RE, Paquet A. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  6. Althof SE, McMahon CG, Waldinger MD, et al. An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med. 2014;2(2):60-90. doi:10.1002/sm2.28 [PubMed 25356302]
  7. American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  8. American College of Obstetricians and Gynecologists (ACOG). ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020. doi:10.1097/AOG.0b013e31816fd910 [PubMed 18378767]
  9. American Psychiatric Association (APA). Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Published October 2010. Accessed June 8, 2020.
  10. American Psychological Association (APA). Clinical practice guideline for the treatment of depression across three age cohorts. https://www.apa.org/depression-guideline/guideline.pdf. Published February 16, 2019. Accessed April 21, 2021.
  11. Anderson KN, Lind JN, Simeone RM, et al. Maternal use of specific antidepressant medications during early pregnancy and the risk of selected birth defects. JAMA Psychiatry. 2020;77(12):1246-1255. doi:10.1001/jamapsychiatry.2020.2453 [PubMed 32777011]
  12. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. [PubMed 27060684]
  13. Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-1575. doi:10.4088/JCP.09r05786blu [PubMed 21190637]
  14. Andrews C, Pinner G. Postural hypotension induced by paroxetine. BMJ. 1998;316(7131):595. doi:10.1136/bmj.316.7131.595 [PubMed 9518913]
  15. Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI. Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109(6):811-819. doi:10.1038/ajg.2014.82 [PubMed 24777151]
  16. Azaz-Livshits T, Hershko A, Ben-Chetrit E. Paroxetine associated hepatotoxicity: a report of 3 cases and a review of the literature. Pharmacopsychiatry. 2002;35(3):112-115. doi:10.1055/s-2002-31515 [PubMed 12107856]
  17. Baldassano CF, Truman CJ, Nierenberg A, Ghaemi SN, Sachs GS. Akathisia: a review and case report following paroxetine treatment. Compr Psychiatry. 1996;37(2):122-124. doi:10.1016/s0010-440x(96)90572-6 [PubMed 8654061]
  18. Baldessarini RJ, Faedda GL, Offidani E, et al. Antidepressant-associated mood-switching and transition from unipolar major depression to bipolar disorder: a review. J Affect Disord. 2013;148(1):129-135. doi:10.1016/j.jad.2012.10.033 [PubMed 23219059]
  19. Baldwin D, Bobes J, Stein DJ, Scharwächter I, Faure M. Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group. Br J Psychiatry. 1999;175:120-126. [PubMed 10627793]
  20. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28(5):403-439. doi:10.1177/0269881114525674 [PubMed 24713617]
  21. Bandelow B, Allgulander C, Baldwin DS, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - version 3. Part I: anxiety disorders. World J Biol Psychiatry. 2023a;24(2):79-117. doi:10.1080/15622975.2022.2086295 [PubMed 35900161]
  22. Bandelow B, Allgulander C, Baldwin DS, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - version 3. Part II: OCD and PTSD. World J Biol Psychiatry. 2023b;24(2):118-134. doi:10.1080/15622975.2022.2086296 [PubMed 35900217]
  23. Bandelow B, Sher L, Bunevicius R, Hollander E, Kasper S, Zohar J; WFSBP Task Force on Mental Disorders in Primary Care; WFSBP Task Force on Anxiety Disorders, OCD and PTSD. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract. 2012;16(2):77-84. [PubMed 22540422]
  24. Bartlett D. Drug-induced serotonin syndrome. Crit Care Nurse. 2017;37(1):49-54. doi:10.4037/ccn2017169 [PubMed 28148614]
  25. Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Möller HJ; World Federation of Societies of Biological Psychiatry Task Force on Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013;14(5):334-385. [PubMed 23879318]
  26. Bauer M, Severus E, Köhler S, Whybrow PC, Angst J, Möller HJ; WFSBP Task Force on Treatment Guidelines for Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 2: maintenance treatment of major depressive disorder-update 2015. World J Biol Psychiatry. 2015;16(2):76-95. doi: 10.3109/15622975.2014.1001786. [PubMed 25677972]
  27. Bauer M, Whybrow PC, Anst J, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions. World J Biol Psychiatry. 2002;3(2):69-86. [PubMed 12479080]
  28. Benbow SJ, Gill G. Paroxetine and hepatotoxicity. BMJ. 1997;314(7091):1387. doi:10.1136/bmj.314.7091.1387a [PubMed 9161313]
  29. Berle JO, Spigset O. Antidepressant use during breastfeeding. Curr Womens Health Rev. 2011;7(1):28-34. [PubMed 22299006]
  30. Biffi A, Cantarutti A, Rea F, Locatelli A, Zanini R, Corrao G. Use of antidepressants during pregnancy and neonatal outcomes: an umbrella review of meta-analyses of observational studies. J Psychiatr Res. 2020;124:99-108. doi:10.1016/j.jpsychires.2020.02.023 [PubMed 32135392]
  31. Bismuth-Evenzal Y, Gonopolsky Y, Gurwitz D, Iancu I, Weizman A, Rehavi M. Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs. J Affect Disord. 2012;136(1-2):99-103. doi:10.1016/j.jad.2011.08.013 [PubMed 21893349]
  32. Bixby AL, VandenBerg A, Bostwick JR. Clinical management of bleeding risk with antidepressants. Ann Pharmacother. 2019;53(2):186-194. doi:10.1177/1060028018794005 [PubMed 30081645]
  33. Boisseau CL, Rasmussen SA. Unified protocol for the discontinuation of long-term serotonin reuptake inhibitors in obsessive compulsive disorder: Study protocol and methods. Contemp Clin Trials. 2018;65:157-163. [PubMed 29306047]
  34. Bonnot O, Warot D, Cohen D. Priapism associated with sertraline. J Am Acad Child Adolesc Psychiatry. 2007;46(7):790-791. doi:10.1097/chi.0b013e318067da56 [PubMed 17581442]
  35. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20. doi: 10.1056/NEJMra041867. Erratum in: N Engl J Med. 2007;356(23):2437. Erratum in: N Engl J Med. 2009;361(17):1714. [PubMed 15784664]
  36. Brisdelle (paroxetine) [prescribing information]. Roswell, GA: Sebela Pharmaceuticals Inc; August 2023.
  37. Brisdelle (paroxetine) [prescribing information]. Roswell, GA: Sebela Pharmaceuticals Inc; September 2021.
  38. Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA. The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom. 2016;85(5):270-288. doi:10.1159/000447034 [PubMed 27508501]
  39. Casper RF, Yonkers KA. Treatment of premenstrual syndrome and premenstrual dysphoric disorder. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 11, 2020.
  40. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm [PubMed 6423951]
  41. Chen HY, Lin CL, Lai SW, Kao CH. Association of selective serotonin reuptake inhibitor use and acute angle-closure glaucoma. J Clin Psychiatry. 2016;77(6):e692-e696. doi:10.4088/JCP.15m10038 [PubMed 27135704]
  42. Cheung AH, Zuckerbrot RA, Jensen PS, Laraque D, Stein REK; GLAD-PC Steering Group. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and ongoing management. Pediatrics. 2018;141(3):e20174082. doi:10.1542/peds.2017-4082 [PubMed 29483201]
  43. Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006;295(5):499-507. doi:10.1001/jama.295.5.499 [PubMed 16449615]
  44. Colakoglu O, Tankurt E, Unsal B, et al. Toxic hepatitis associated with paroxetine. Int J Clin Pract. 2005;59(7):861-862. doi:10.1111/j.1368-5031.2005.00572.x [PubMed 15963219]
  45. Coskuner ER, Culha MG, Ozkan B, Kaleagasi EO. Post-SSRI sexual dysfunction: preclinical to clinical. Is it fact or fiction? Sex Med Rev. 2018;6(2):217-223. doi:10.1016/j.sxmr.2017.11.004 [PubMed 29463440]
  46. Costagliola C, Parmeggiani F, Semeraro F, Sebastiani A. Selective serotonin reuptake inhibitors: a review of its effects on intraocular pressure. Curr Neuropharmacol. 2008;6(4):293-310. doi:10.2174/157015908787386104 [PubMed 19587851]
  47. Dall M, Schaffalitzky de Muckadell OB, Lassen AT, Hansen JM, Hallas J. An association between selective serotonin reuptake inhibitor use and serious upper gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2009;7(12):1314-1321. doi:10.1016/j.cgh.2009.08.019 [PubMed 19716436]
  48. Dalhoff K, Almdal TP, Bjerrum K, Keiding S, Mengel H, Lund J. Pharmacokinetics of paroxetine in patients with cirrhosis. Eur J Clin Pharmacol. 1991;41(4):351-354. doi:10.1007/BF00314966 [PubMed 1839532]
  49. De Picker L, Van Den Eede F, Dumont G, Moorkens G, Sabbe BG. Antidepressants and the risk of hyponatremia: a class-by-class review of literature. Psychosomatics. 2014;55(6):536-547. doi:10.1016/j.psym.2014.01.010 [PubMed 25262043]
  50. Deisenhammer EA, Trawöger R. Penile anesthesia associated with sertraline use. J Clin Psychiatry. 1999;60(12):869-870. doi:10.4088/jcp.v60n1218 [PubMed 10665639]
  51. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of paroxetine and paroxetine CR. Psychopharmacol Bull. 2003;37(suppl 1):S29-S41. [PubMed 14566199]
  52. Diler RS, Avci A. Selective serotonin reuptake inhibitor discontinuation syndrome in children: Six case reports. Current Therapeutic Research. 2002;63(3):188-197.
  53. Dopheide JA. Recognizing and treating depression in children and adolescents. Am J Health Syst Pharm. 2006;63(3):233-243. doi:10.2146/ajhp050264 [PubMed 16434782]
  54. Douros A, Ades M, Renoux C. Risk of intracranial hemorrhage associated with the use of antidepressants inhibiting serotonin reuptake: a systematic review. CNS Drugs. 2018;32(4):321-334. doi:10.1007/s40263-018-0507-7 [PubMed 29536379]
  55. Doyle GD, Laher M, Kelly JG, et al. The pharmacokinetics of paroxetine in renal impairment. Acta Psychiatr Scand Suppl. 1989;350:89-90. doi:10.1111/j.1600-0447.1989.tb07181.x [PubMed 2530798]
  56. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: Simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635-642. doi:10.1093/qjmed/hcg109 [PubMed 12925718]
  57. Eke T, Bates AK. Acute angle closure glaucoma associated with paroxetine. BMJ. 1997;314(7091):1387. doi:10.1136/bmj.314.7091.1387 [PubMed 9161312]
  58. Erie JC, Brue SM, Chamberlain AM, Hodge DO. Selective serotonin reuptake inhibitor use and increased risk of cataract surgery: a population-based, case-control study. Am J Ophthalmol. 2014;158(1):192-197.e1. doi:10.1016/j.ajo.2014.03.006 [PubMed 24631758]
  59. Etminan M, Mikelberg FS, Brophy JM. Selective serotonin reuptake inhibitors and the risk of cataracts: a nested case-control study. Ophthalmology. 2010;117(6):1251-1255. doi:10.1016/j.ophtha.2009.11.042 [PubMed 20207418]
  60. Evrensel A, Önen Ünsalver B, Akyol A, Ceylan ME. A case of galactorrhea during paroxetine treatment. Int J Psychiatry Med. 2016;51(3):302-305. doi:10.1177/0091217416651257 [PubMed 27284122]
  61. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  62. Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: a systematic review. Psychother Psychosom. 2015;84(2):72-81. doi:10.1159/000370338 [PubMed 25721705]
  63. Fenske JN, Petersen K. Obsessive-compulsive disorder: diagnosis and management. Am Fam Physician. 2015;92(10):896-903. [PubMed 26554283]
  64. Fenske JN, Schwenk TL. Obsessive compulsive disorder: diagnosis and management. Am Fam Physician. 2009;80(3):239-245. [PubMed 19621834]
  65. Fitton CA, Steiner MFC, Aucott L, et al. In utero exposure to antidepressant medication and neonatal and child outcomes: a systematic review. Acta Psychiatr Scand. 2020;141(1):21-33. doi:10.1111/acps.13120 [PubMed 31648376]
  66. Friedman RA, Leon AC. Expanding the black box - depression, antidepressants, and the risk of suicide. N Engl J Med. 2007;356(23):2343-2346. doi:10.1056/NEJMp078015 [PubMed 17485726]
  67. Gandhi S, Shariff SZ, Al-Jaishi A, et al. Second-generation antidepressants and hyponatremia risk: a population-based cohort study of older adults. Am J Kidney Dis. 2017;69(1):87-96. doi:10.1053/j.ajkd.2016.08.020 [PubMed 27773479]
  68. Geller DA, Wagner KD, Emslie G, et al. Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: A randomized, multicenter, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2004;43(11):1387-1396. [PubMed 15502598]
  69. Gill N, Bayes A, Parker G. A review of antidepressant-associated hypomania in those diagnosed with unipolar depression-risk factors, conceptual models, and management. Curr Psychiatry Rep. 2020;22(4):20. doi:10.1007/s11920-020-01143-6 [PubMed 32215771]
  70. González E, Minguez L, Sanguino RM. Galactorrhea after paroxetine treatment. Pharmacopsychiatry. 2000;33(3):118. doi:10.1055/s-2000-7979 [PubMed 10855465]
  71. Goodman NF, Cobin RH, Ginzburg SB, Katz IA, Wood DE; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause: executive summary of recommendations. Endocr Pract. 2011;17(6):949-954. [PubMed 22193145]
  72. Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM. Antidepressant-induced sexual dysfunction. Ann Pharmacother. 2002;36(10):1577-1589. doi:10.1345/aph.1A195 [PubMed 12243609]
  73. Grzeskowiak LE, Leggett C, Costi L, Roberts CT, Amir LH. Impact of serotonin reuptake inhibitor use on breast milk supply in mothers of preterm infants: a retrospective cohort study. Br J Clin Pharmacol. 2018;84(6):1373-1379. doi:10.1111/bcp.13575 [PubMed 29522259]
  74. Haddad PM. Antidepressant discontinuation syndromes. Drug Saf. 2001;24(3):183-197. [PubMed 11347722]
  75. Halperin D, Reber G. Influence of antidepressants on hemostasis. Dialogues Clin Neurosci. 2007;9(1):47-59. [PubMed 17506225]
  76. Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry. 2006;63(3):332-339. doi:10.1001/archpsyc.63.3.332 [PubMed 16520440]
  77. Hathaway EE, Walkup JT, Strawn JR. Antidepressant treatment duration in pediatric depressive and anxiety disorders: How long is long enough? Curr Probl Pediatr Adolesc Health Care. 2018;48(2):31-39. [PubMed 29337001]
  78. Heller HM, Ravelli ACJ, Bruning AHL, et al. Increased postpartum haemorrhage, the possible relation with serotonergic and other psychopharmacological drugs: a matched cohort study. BMC Pregnancy Childbirth. 2017;17(1):166. doi:10.1186/s12884-017-1334-4 [PubMed 28577352]
  79. Hendrick V, Stowe ZN, Altshuler LL, et al. Placental passage of antidepressant medications. Am J Psychiatry. 2003;160(5):993-996. [PubMed 12727706]
  80. Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2012;11:CD004851. doi:10.1002/14651858.CD004851.pub3 [PubMed 23152227]
  81. Hirsch M, Birnbaum RJ. Discontinuing antidepressant medications in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 29, 2021a.
  82. Hirsch M, Birnbaum RJ. Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 17, 2022.
  83. Hirsch M, Birnbaum RJ. Switching antidepressant medications in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 9, 2021b.
  84. Hostetter A, Stowe ZN, Strader JR Jr, et al. Dose of selective serotonin uptake inhibitors across pregnancy: Clinical implications. Depress Anxiety. 2000;11(2):51-57. [PubMed 10812529]
  85. Hudd TR, Blake CS, Rimola-Dejesus Y, Nguyen TT, Zaiken K. A case report of serotonin syndrome in a patient on selective serotonin reuptake inhibitor (SSRI) monotherapy. J Pharm Pract. 2020;33(2):206-212. doi:10.1177/0897190019841742 [PubMed 31030620]
  86. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  87. Ismaili E, Walsh S, O'Brien PMS, et al. Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder. Arch Womens Ment Health. 2016;19(6):953-958. doi:10.1007/s00737-016-0631-7 [PubMed 27378473]
  88. Issari Y, Jakubovski E, Bartley CA, Pittenger C, Bloch MH. Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder: a meta-analysis. J Clin Psychiatry. 2016;77(5):e605-e611. doi:10.4088/JCP.14r09758 [PubMed 27249090]
  89. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  90. Jacob S, Spinler SA. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother. 2006;40(9):1618-1622. doi:10.1345/aph.1G293 [PubMed 16896026]
  91. Javelot H, Fichter A, Meyer G, Michel B, Hingray C. A case of paroxetine-induced antidepressant discontinuation syndrome related to pregnancy: time to redefine the syndrome? Psychiatry Res. 2020;291:113259. doi:10.1016/j.psychres.2020.113259 [PubMed 32619827]
  92. Jha MK, Rush AJ, Trivedi MH. When discontinuing SSRI antidepressants is a challenge: management tips. Am J Psychiatry. 2018;175(12):1176-1184. doi:10.1176/appi.ajp.2018.18060692 [PubMed 30501420]
  93. Jing E, Straw-Wilson K. Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and potential solutions: a narrative literature review. Ment Health Clin. 2016;6(4):191-196. doi:10.9740/mhc.2016.07.191 [PubMed 29955469]
  94. Katzman MA, Bleau P, Blier P, et al; Canadian Anxiety Guidelines Initiative Group. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(suppl 1):S1. doi:10.1186/1471-244X-14-S1-S1 [PubMed 25081580]
  95. Keller MB, Ryan ND, Strober M, et al. Efficacy of paroxetine in the treatment of adolescent major depression: A randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2001;40(7):762-772.
  96. Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry. 2003;160(4):790-792. doi:10.1176/appi.ajp.160.4.790 [PubMed 12668373]
  97. Khanassov V, Hu J, Reeves D, van Marwijk H. Selective serotonin reuptake inhibitor and selective serotonin and norepinephrine reuptake inhibitor use and risk of fractures in adults: a systematic review and meta-analysis. Int J Geriatr Psychiatry. 2018;33(12):1688-1708. doi:10.1002/gps.4974 [PubMed 30247774]
  98. Khera M, Cunningham GR. Treatment of male sexual dysfunction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 11, 2020.
  99. Kirkham J, Seitz D. Evidence of ocular side effects of SSRIs and new warnings. Evid Based Ment Health. 2017;20(1):27. doi:10.1136/eb-2016-102528 [PubMed 27993931]
  100. Kirwan JF, Subak-Sharpe I, Teimory M. Bilateral acute angle closure glaucoma after administration of paroxetine. Br J Ophthalmol. 1997;81(3):252. doi:10.1136/bjo.81.3.252 [PubMed 9135392]
  101. Koo JR, Yoon JY, Joo MH, et al. Treatment of depression and effect of antidepression treatment on nutritional status in chronic hemodialysis patients. Am J Med Sci. 2005;329(1):1-5. doi:10.1097/00000441-200501000-00001 [PubMed 15654172]
  102. Kopp R, Kunitz O, Baumert JH, Rossaint R. A patient with nodal tachycardia after general anesthesia during medication with a selective serotonin reuptake inhibitor [in German]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2001;36(3):184-187. doi:10.1055/s-2001-11822 [PubMed 11324355]
  103. Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164(7)(suppl):S5-S53. [PubMed 17849776]
  104. Labos C, Dasgupta K, Nedjar H, Turecki G, Rahme E. Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ. 2011;183(16):1835-1843. doi:10.1503/cmaj.100912 [PubMed 21948719]
  105. Lai H, Tolat R. Paroxetine-related tremor. Geriatrics. 2005;60(7):18-20. [PubMed 16026177]
  106. Lake MB, Birmaher B, Wassick S, Mathos K, Yelovich AK. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol. 2000;10(1):35-38. doi:10.1089/cap.2000.10.35 [PubMed 10755580]
  107. Lanza di Scalea T, Pearlstein T. Premenstrual dysphoric disorder. Med Clin North Am. 2019;103(4):613-628. doi:10.1016/j.mcna.2019.02.007 [PubMed 31078196]
  108. Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28. [PubMed 26344706]
  109. Lee YK, Shin JS, Kim Y, et al. Antidepressants-related cardiovascular adverse events using the adverse event reporting system. Psychiatry Res. 2018;268:441-446. doi:10.1016/j.psychres.2018.07.044 [PubMed 30130711]
  110. Leerssen ECM, Tak RO, Breur JMPJ. Severe transient neonatal long QT syndrome due to maternal paroxetine usage: a case report. Cardiol Young. 2019;29(10):1300-1301. doi:10.1017/S1047951119001938 [PubMed 31475669]
  111. Leon AC. The revised warning for antidepressants and suicidality: unveiling the black box of statistical analyses. Am J Psychiatry. 2007;164(12):1786-1789. doi:10.1176/appi.ajp.2007.07050775 [PubMed 18056231]
  112. Lewis CF, DeQuardo JR, DuBose C, Tandon R. Acute angle-closure glaucoma and paroxetine. J Clin Psychiatry. 1997;58(3):123-124. doi:10.4088/jcp.v58n0307b [PubMed 9108816]
  113. Liebowitz MR, Stein MB, Tancer M, Carpenter D, Oakes R, Pitts CD. A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treatment of generalized social anxiety disorder. J Clin Psychiatry. 2002;63(1):66-74. [PubMed 11838629]
  114. Liu BA, Mittmann N, Knowles SR, Shear NH. Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports. CMAJ. 1996;155(5):519-527. [PubMed 8804257]
  115. Liu Q, Gao H, Huang Y, et al. Comparison of fluoxetine with other selective serotonin reuptake inhibitors in the treatment of premature ejaculation: a systematic review and meta-analysis. Andrologia. 2022;54(8):e14500. doi:10.1111/and.14500 [PubMed 35760074]
  116. Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2008;27(1):31-40. doi:10.1111/j.1365-2036.2007.03541.x [PubMed 17919277]
  117. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  118. Maia JM, Guedes F, Aragão I, Cardoso T. Eosinophilic pneumonia presenting as life-threatening ARDS. BMJ Case Rep. 2015;2015:bcr2014207379. doi:10.1136/bcr-2014-207379 [PubMed 26150613]
  119. MacQueen GM, Frey BN, Ismail Z, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 6. special populations: youth, women, and the elderly. Can J Psychiatry. 2016;61(9):588-603. doi:10.1177/0706743716659276 [PubMed 27486149]
  120. Mameli C, Tadini G, Cattaneo D, Cerini C, Zuccotti GV. Acute generalized exanthematous pustulosis induced by paroxetine in an adolescent girl. Acta Derm Venereol. 2013;93(6):733-734. doi:10.2340/00015555-1559 [PubMed 23450307]
  121. Mancini C, Ameringen MV. Paroxetine in social phobia. J Clin Psychiatry. 1996;57(11):519-522. [PubMed 8968300]
  122. Mannesse CK, Jansen PA, Van Marum RJ, et al. Characteristics, prevalence, risk factors, and underlying mechanism of hyponatremia in elderly patients treated with antidepressants: a cross-sectional study. Maturitas. 2013;76(4):357-363. doi:10.1016/j.maturitas.2013.08.010 [PubMed 24094459]
  123. Margolese HC, Chouinard G, Beauclair L, Rubino M. Cutaneous vasculitis induced by paroxetine. Am J Psychiatry. 2001;158(3):497. doi:10.1176/appi.ajp.158.3.497 [PubMed 11230000]
  124. Marshall AM, Nommsen-Rivers LA, Hernandez LL, et al. Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution. J Clin Endocrinol Metab. 2010;95(2):837-846. [PubMed 19965920]
  125. Marshall RD, Lewis-Fernandez R, Blanco C, et al. A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults. Depress Anxiety. 2007;24(2):77-84. doi: 10.1002/da.20176. [PubMed 16892419]
  126. Martin A, Young C, Leckman JF, Mukonoweshuro C, Rosenheck R, Leslie D. Age effects on antidepressant-induced manic conversion. Arch Pediatr Adolesc Med. 2004;158(8):773-780. doi:10.1001/archpedi.158.8.773 [PubMed 15289250]
  127. Masarwa R, Bar-Oz B, Gorelik E, Reif S, Perlman A, Matok I. Prenatal exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors and risk for persistent pulmonary hypertension of the newborn: a systematic review, meta-analysis, and network meta-analysis. Am J Obstet Gynecol. 2019;220(1):57.e1-57.e13. doi:10.1016/j.ajog.2018.08.030 [PubMed 30170040]
  128. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore). 2000;79(4):201-209. doi:10.1097/00005792-200007000-00001 [PubMed 10941349]
  129. Mera MT, Pérez BV, Fernández RO, Iglesias JF. Hypersensitivity to paroxetine. Allergol Immunopathol (Madr). 2006;34(3):125-126. doi:10.1016/s0301-0546(06)73527-3 [PubMed 16858890]
  130. Merlob P, Stahl B, Sulkes J. Paroxetine during breast-feeding: infant weight gain and maternal adherence to counsel. Eur J Pediatrm. 2004;163(3):135-139. [PubMed 14745552]
  131. Misri S, Corral M, Wardrop AA, Kendrick K. Quetiapine augmentation in lactation: a series of case reports. J Clin Psychopharmacol. 2006;26(5):508-511. [PubMed 16974194]
  132. Misri S, Kim J, Riggs KW, Kostaras X. Paroxetine levels in postpartum depressed women, breast milk, and infant serum. J Clin Psychiatry. 2000;61(11):828-832. [PubMed 11105735]
  133. Mithani H, Hurwitz TA. Paroxetine-induced angioedema and tongue swelling. J Clin Psychiatry. 1996;57(10):486. [PubMed 8909336]
  134. Montejo AL, Prieto N, de Alarcón R, Casado-Espada N, de la Iglesia J, Montejo L. Management strategies for antidepressant-related sexual dysfunction: a clinical approach. J Clin Med. 2019;8(10):1640. doi:10.3390/jcm8101640 [PubMed 31591339]
  135. Montejo-González AL, Llorca G, Izquierdo JA, et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997;23(3):176-194. doi:10.1080/00926239708403923 [PubMed 9292833]
  136. Moore TJ, Glenmullen J, Furberg CD. Prescription drugs associated with reports of violence towards others. PLoS One. 2010;5(12):e15337. doi:10.1371/journal.pone.0015337 [PubMed 21179515]
  137. Morrison J, Remick RA, Leung M, Wrixon KJ, Bebb RA. Galactorrhea induced by paroxetine. Can J Psychiatry. 2001;46(1):88-89. [PubMed 11221498]
  138. Movig KL, Janssen MW, de Waal Malefijt J, Kabel PJ, Leufkens HG, Egberts AC. Relationship of serotonergic antidepressants and need for blood transfusion in orthopedic surgical patients. Arch Intern Med. 2003;163(19):2354-2358. doi:10.1001/archinte.163.19.2354 [PubMed 14581256]
  139. Mullen S. Major depressive disorder in children and adolescents. Ment Health Clin. 2018;8(6):275-283. doi:10.9740/mhc.2018.11.275 [PubMed 30397569]
  140. Mullish BH, Kabir MS, Thursz MR, Dhar A. Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation. Aliment Pharmacol Ther. 2014;40(8):880-892. doi:10.1111/apt.12925 [PubMed 25175904]
  141. Nagler EV, Webster AC, Vanholder R, Zoccali C. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2012;27(10):3736-3745. doi:10.1093/ndt/gfs295 [PubMed 22859791]
  142. Näslund J, Hieronymus F, Emilsson JF, Lisinski A, Nilsson S, Eriksson E. Incidence of early anxiety aggravation in trials of selective serotonin reuptake inhibitors in depression. Acta Psychiatr Scand. 2017;136(4):343-351. doi:10.1111/acps.12784 [PubMed 28859218]
  143. National Collaborating Centre for Mental Health (NCCMH). Depression: The Treatment and Management of Depression in Adults (Updated Edition). National Institute for Health & Clinical Excellence (NICE). 2010. [PubMed 22132433]
  144. National Institute for Health and Care Excellence (NICE). Obsessive-compulsive disorder and body dysmorphic disorder: treatment. https://www.nice.org.uk/guidance/cg31. Published November 2005. Accessed June 19, 2019.
  145. Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc. 2011;59(4):577-585. doi:10.1111/j.1532-5415.2011.03355.x [PubMed 21453380]
  146. Nevatte T, O'Brien PM, Bäckström T, et al; Consensus Group of the International Society for Premenstrual Disorders. ISPMD consensus on the management of premenstrual disorders. Arch Womens Ment Health. 2013;16(4):279-291. doi:10.1007/s00737-013-0346-y [PubMed 23624686]
  147. Ng QX, Venkatanarayanan N, Ho CYX, Sim WS, Lim DY, Yeo WS. Selective serotonin reuptake inhibitors and persistent pulmonary hypertension of the newborn: an update meta-analysis. J Womens Health (Larchmt). 2019;28(3):331-338. doi:10.1089/jwh.2018.7319 [PubMed 30407100]
  148. Nielsen AG, Pedersen RS, Noehr-Jensen L, Damkier P, Brosen K. Two separate dose-dependent effects of paroxetine: mydriasis and inhibition of tramadol's O-demethylation via CYP2D6. Eur J Clin Pharmacol. 2010;66(7):655-660. doi:10.1007/s00228-010-0803-8 [PubMed 20354688]
  149. Nishida T, Wada M, Wada M, Ito H, Narabayashi M, Onishi H. Activation syndrome caused by paroxetine in a cancer patient. Palliat Support Care. 2008;6(2):183-185. doi:10.1017/S1478951508000278 [PubMed 18501054]
  150. Nordeng H, Bergsholm YK, Bøhler E, Spigset O. The transfer of selective serotonin reuptake inhibitors to human milk. Tidsskr Nor Laegeforen. 2001;121(2):199-203. [PubMed 11475200]
  151. Ogle NR, Akkerman SR. Guidance for the discontinuation or switching of antidepressant therapies in adults. J Pharm Pract. 2013;26(4):389-396. doi: 10.1177/0897190012467210. [PubMed 23459282]
  152. Ono S, Suzuki Y, Someya T. Prolongation of idiopathic thrombocytopenic purpura associated with paroxetine administration. Gen Hosp Psychiatry. 2013;35(2). doi:10.1016/j.genhosppsych.2012.06.008 [PubMed 22832136]
  153. Opatrny L, Delaney JA, Suissa S. Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: a new look. Br J Clin Pharmacol. 2008;66(1):76-81. doi:10.1111/j.1365-2125.2008.03154.x [PubMed 18460039]
  154. Orsolini L, Bellantuono C. Serotonin reuptake inhibitors and breastfeeding: a systematic review. Hum Psychopharmacol. 2015;30(1):4-20. doi:10.1002/hup.2451 [PubMed 25572308]
  155. Papakostas GI, Perlis RH, Scalia MJ, Petersen TJ, Fava M. A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder. J Clin Psychopharmacol. 2006;26(1):56-60. doi:10.1097/01.jcp.0000195042.62724.76 [PubMed 16415707]
  156. Patel R, Reiss P, Shetty H, et al. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study. BMJ Open. 2015;5(12):e008341. doi:10.1136/bmjopen-2015-008341 [PubMed 26667012]
  157. Paxil (paroxetine) [prescribing information]. Weston, FL: Apotex Corp; September 2021.
  158. Paxil (paroxetine) [prescribing information]. Weston, FL: Apotex Corp; August 2023.
  159. Paxil CR (paroxetine) [prescribing information]. Weston, FL: Apotex Corp; September 2021.
  160. Paxil CR (paroxetine) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; September 2022.
  161. Pexeva (paroxetine) [prescribing information]. Miami, FL: Noven Therapeutics; July 2014.
  162. Pexeva (paroxetine mesylate) [prescribing information]. Roswell, GA: Sebela Pharmaceutical Inc; December 2020.
  163. Pexeva (paroxetine mesylate) [prescribing information]. Roswell, GA: Sebela Pharmaceutical Inc; August 2023.
  164. Phillips KA. Body dysmorphic disorder: Choosing treatment and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 19, 2019.
  165. Phillips KA, Hollander E. Treating body dysmorphic disorder with medication: evidence, misconceptions, and a suggested approach. Body Image. 2008;5(1):13-27. doi:10.1016/j.bodyim.2007.12.003 [PubMed 18325859]
  166. Pogliani L, Baldelli S, Cattaneo D, et al. Selective serotonin reuptake inhibitors' passage into human milk of lactating women. J Matern Fetal Neonatal Med. 2019;32(18):3020-3025. doi:10.1080/14767058.2018.1455180 [PubMed 29557689]
  167. Pollack MH, Zaninelli R, Goddard A, et al. Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial [published correction appears in J Clin Psychiatry. 2001;62(8):658]. J Clin Psychiatry. 2001;62(5):350-357. [PubMed 11411817]
  168. Posternak MA, Zimmerman M. Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry. 2005;66(2):148-158. doi:10.4088/jcp.v66n0201 [PubMed 15704999]
  169. Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. AACAP. J Am Acad Child Adolesc Psychiatry. 2012;51(1):98-113. doi:10.1016/j.jaac.2011.09.019 [PubMed 22176943]
  170. Rabenda V, Nicolet D, Beaudart C, Bruyère O, Reginster JY. Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporosis International. 2013;24(1):121-137. [PubMed 22638709]
  171. Rand EH. Priapism in a patient taking sertraline. J Clin Psychiatry. 1998;59(10):538. doi:10.4088/jcp.v59n1007e [PubMed 9818637]
  172. Reefhuis J, Devine O, Friedman JM, Louik C, Honein MA; National Birth Defects Prevention Study. Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. BMJ. 2015;351:h3190. doi:10.1136/bmj.h3190 [PubMed 26156519]
  173. Reeves RR, Ladner ME. Antidepressant-induced suicidality: an update. CNS Neurosci Ther. 2010;16(4):227-234. doi:10.1111/j.1755-5949.2010.00160.x [PubMed 20553304]
  174. Refer to manufacturer's labeling.
  175. Richards JB, Papaioannou A, Adachi JD, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188-194. doi:10.1001/archinte.167.2.188 [PubMed 17242321]
  176. Rizzoli R, Cooper C, Reginster JY, et al. Antidepressant medications and osteoporosis. Bone. 2012;51(3):606-613. [PubMed 22659406]
  177. Rodríguez-Pazos L, Gómez-Bernal S, Montero I, Rodríguez-Granados M, Toribio J. Erythema multiforme photoinduced by paroxetine and herpes simplex virus. Photodermatol Photoimmunol Photomed. 2011;27(4):219-221. doi:10.1111/j.1600-0781.2011.00600.x [PubMed 21729172]
  178. Rosenberg DR, Stewart CM, Fitzgerald KD, et al. Paroxetine open-label treatment of pediatric outpatients with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 1999;38(9):1180-1185. [PubMed 10504818]
  179. Rottach KG, Schaner BM, Kirch MH, et al. Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr Res. 2008;43(1):70-75. doi:10.1016/j.jpsychires.2008.02.006 [PubMed 18468624]
  180. Sachs HC; Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796-e809. [PubMed 23979084]
  181. Safer DJ, Zito JM. Treatment-emergent adverse events from selective serotonin reuptake inhibitors by age group: children versus adolescents. J Child Adolesc Psychopharmacol. 2006;16(1-2):159-169. doi:10.1089/cap.2006.16.159 [PubMed 16553536]
  182. Sanz-Fuentenebro FJ, Huidobro A, Tejadas-Rivas A. Restless legs syndrome and paroxetine. Acta Psychiatr Scand. 1996;94(6):482-484. doi:10.1111/j.1600-0447.1996.tb09896.x [PubMed 9021005]
  183. Schatzberg AF, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry. 2006;67(Suppl 4):27-30. [PubMed 16683860]
  184. Schoretsanitis G, Spigset O, Stingl JC, Deligiannidis KM, Paulzen M, Westin AA. The impact of pregnancy on the pharmacokinetics of antidepressants: a systematic critical review and meta-analysis. Expert Opin Drug Metab Toxicol. 2020;16(5):431-440. doi:10.1080/17425255.2020.1750598 [PubMed 32238008]
  185. Sharma T, Guski LS, Freund N, Gøtzsche PC. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ. 2016;352:i65. doi:10.1136/bmj.i65 [PubMed 26819231]
  186. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  187. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313. [PubMed 7746084]
  188. Shelton RC. Steps following attainment of remission: discontinuation of antidepressant therapy. Prim Care Companion J Clin Psychiatry. 2001;3(4):168-174. [PubMed 15014601]
  189. Shindel AW, Althof SE, Carrier S, et al. Disorders of ejaculation: an AUA/SMSNA guideline. J Urol. 2022;207(3):504-512. doi:10.1097/JU.0000000000002392 [PubMed 34961344]
  190. Siris SG, Braga RJ. Anxiety in schizophrenia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 19, 2019.
  191. Siroosbakht S, Rezakhaniha S, Rezakhaniha B. Which of available selective serotonin reuptake inhibitors (SSRIs) is more effective in treatment of premature ejaculation? A randomized clinical trial. Int Braz J Urol. 2019;45(6):1209-1215. doi:10.1590/S1677-5538.IBJU.2019.0121 [PubMed 31808410]
  192. Slaton RM, Champion MN, Palmore KB. A review of paroxetine for the treatment of vasomotor symptoms. J Pharm Pract. 2015;28(3):266-274. doi: 10.1177/0897190014544785. [PubMed 25107421]
  193. Slomian J, Honvo G, Emonts P, Reginster JY, Bruyère O. Consequences of maternal postpartum depression: a systematic review of maternal and infant outcomes. Womens Health (Lond). 2019;15:1745506519844044. doi:10.1177/1745506519844044 [PubMed 31035856]
  194. Smith MM, Smith BB, Lahr BD, et al. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are not associated with bleeding or transfusion in cardiac surgical patients. Anesth Analg. 2018;126(6):1859-1866. doi:10.1213/ANE.0000000000002668 [PubMed 29210786]
  195. Sobieraj DM, Baker WL, Martinez BK, et al. Adverse Effects of Pharmacologic Treatments of Major Depression in Older Adults. Rockville (MD): Agency for Healthcare Research and Quality (US); 2019. doi:10.23970/AHRQEPCCER215 [PubMed 30964616]
  196. Sriraman NK, Melvin K, Meltzer-Brody S. ABM clinical protocol #18: use of antidepressants in breastfeeding mothers. Breastfeed Med. 2015;10(6):290-299. [PubMed 26204124]
  197. Stahl SM. Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. J Affect Disord. 1998;51(3):215-235. doi:10.1016/s0165-0327(98)00221-3 [PubMed 10333979]
  198. Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003;289(21):2827-2834. doi: 10.1001/jama.289.21.2827. [PubMed 12783913]
  199. Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005;23(28):6919-6930. doi: 10.1200/JCO.2005.10.081. [PubMed 16192581]
  200. Stein MB. Management of posttraumatic stress disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 17, 2022b.
  201. Stein MB. Pharmacotherapy for social anxiety disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 17, 2022a.
  202. Stein MB, Goin MK, Pollack MH, et al; American Psychiatric Association (APA). Practice guideline for the treatment of patients with panic disorder. 2nd ed. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/panicdisorder.pdf. Published January 2009. Accessed June 19, 2019.
  203. Stein MB, Liebowitz MR, Lydiard RB, Pitts CD, Bushnell W, Gergel I. Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial. JAMA. 1998;280(8):708-713. [PubMed 9728642]
  204. Stevens DL. Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome. Ann Pharmacother. 2008;42(9):1290-1297. doi: 10.1345/aph.1L066. [PubMed 18628446]
  205. Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf. 2008;7(5):587-596. doi:10.1517/14740338.7.5.587 [PubMed 18759711]
  206. Sylvester C, Menke M, Gopalan P. Selective serotonin reuptake inhibitors and fertility: considerations for couples trying to conceive. Harv Rev Psychiatry. 2019;27(2):108-118. doi:10.1097/HRP.0000000000000204 [PubMed 30676405]
  207. Szegedi A, Jansen WT, van Willigenburg AP, van der Meulen E, Stassen HH, Thase ME. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009;70(3):344-353. doi:10.4088/jcp.07m03780 [PubMed 19254516]
  208. Taniguchi G, Miyajima M, Watanabe M, et al. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: a report of three cases. Epilepsy Behav Case Rep. 2014;3:8-11. doi:10.1016/j.ebcr.2014.10.003 [PubMed 25737963]
  209. Tanii H, Ichihashi K, Inoue K, Fujita K, Okazaki Y. Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(6):1176-1178. doi:10.1016/j.pnpbp.2006.04.006 [PubMed 16720068]
  210. Targownik LE, Bolton JM, Metge CJ, Leung S, Sareen J. Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol. 2009;104(6):1475-1482. doi:10.1038/ajg.2009.128 [PubMed 19491861]
  211. Taylor MJ, Freemantle N, Geddes JR, Bhagwagar Z. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry. 2006;63(11):1217-23. doi:10.1001/archpsyc.63.11.1217 [PubMed 17088502]
  212. Thibaut F, De La Barra F, Gordon H, Cosyns P, Bradford JM; WFSBP Task Force on Sexual Disorders. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of paraphilias. World J Biol Psychiatry. 2010;11(4):604-655. doi: 10.3109/15622971003671628. [PubMed 20459370]
  213. Tomlin AM, Reith DM, Woods DJ, et al. A pharmacoepidemiology database system for monitoring risk due to the use of medicines by New Zealand primary care patients. Drug Saf. 2017;40(12):1259-1277. doi:10.1007/s40264-017-0579-1 [PubMed 28766108]
  214. Tondo L, Vázquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Acta Psychiatr Scand. 2010;121(6):404-414. doi:10.1111/j.1600-0447.2009.01514.x [PubMed 19958306]
  215. Uguz F. Better tolerance of citalopram in a breastfed infant who could not tolerate sertraline and paroxetine. Breastfeed Med. 2018;13(1):89-90. doi:10.1089/bfm.2017.0168 [PubMed 29185803]
  216. Uguz F. Rapid weight gain associated with edema after use of paroxetine and venlafaxine: 2 case reports. Clin Neuropharmacol. 2014;37(1):34-35. doi:10.1097/WNF.0000000000000012 [PubMed 24434531]
  217. Uguz F, Arpaci N. Short-term safety of paroxetine and sertraline in breastfed infants: a retrospective cohort study from a university hospital. Breastfeed Med. 2016;11:487-489. [PubMed 27575664]
  218. Uguz F, Sonmez EÖ. Neuroleptic malignant syndrome following combination of sertraline and paroxetine: a case report. Gen Hosp Psychiatry. 2013;35(3):327.e7-327.e8. doi:10.1016/j.genhosppsych.2012.11.004 [PubMed 23312145]
  219. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 11, 2023.
  220. Varigonda AL, Jakubovski E, Bloch MH. Systematic review and meta-analysis: early treatment responses of selective serotonin reuptake inhibitors and clomipramine in pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2016;55(10):851-859.e2. doi:10.1016/j.jaac.2016.07.768 [PubMed 27663940]
  221. Velez LI, Shepherd G, Roth BA, Benitez FL. Serotonin syndrome with elevated paroxetine concentrations. Ann Pharmacother. 2004;38(2):269-272. doi:10.1345/aph.1D352 [PubMed 14742765]
  222. Verma R, Balhara YP, Deshpande SN. Angular cheilitis after paroxetine treatment. J Clin Psychopharmacol. 2012;32(1):150-151. doi:10.1097/JCP.0b013e31823f878a [PubMed 22217958]
  223. Ververs FF, Voorbij HA, Zwarts P, et al. Effect of cytochrome P450 2D6 genotype on maternal paroxetine plasma concentrations during pregnancy. Clin Pharmacokinet. 2009;48(10):677-683. doi: 10.2165/11318050-000000000-00000. [PubMed 19743889]
  224. Votolato NA, Stern S, Caputo RM. Serotonergic antidepressants and urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2000;11(6):386-388. doi:10.1007/s001920070009 [PubMed 11147747]
  225. Wadhwa R, Kumar M, Talegaonkar S, Vohora D. Serotonin reuptake inhibitors and bone health: a review of clinical studies and plausible mechanisms. Osteoporos Sarcopenia. 2017;3(2):75-81. doi:10.1016/j.afos.2017.05.002 [PubMed 30775508]
  226. Wagner KD, Berard R, Stein MB, et al. A multicenter, randomized, double-blind, placebo-controlled trial of paroxetine in children and adolescents with social anxiety disorder. Arch Gen Psychiatry. 2004;61(11):1153-1162. doi:10.1001/archpsyc.61.11.1153 [PubMed 15520363]
  227. Wakeno M, Okugawa G, Takekita Y, et al. Delirium associated with paroxetine in an elderly depressive patient: a case report. Pharmacopsychiatry. 2007;40(5):199-200. doi:10.1055/s-2007-985882 [PubMed 17874351]
  228. Waldinger MD. Psychiatric disorders and sexual dysfunction. Handb Clin Neurol. 2015;130:469-489. doi:10.1016/B978-0-444-63247-0.00027-4 [PubMed 26003261]
  229. Waldinger MD, Hengeveld MW, Zwinderman AH. Ejaculation-retarding properties of paroxetine in patients with primary premature ejaculation: a double-blind, randomized, dose-response study. Br J Urol. 1997;79(4):592-595. [PubMed 9126089]
  230. Waldinger MD, Zwinderman AH, Olivier B. Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone. J Clin Psychopharmacol. 2001;21(3):293-297. [PubMed 11386492]
  231. Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B. Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis. Int J Impot Res. 2004;16(4):369-381. doi:10.1038/sj.ijir.3901172 [PubMed 14961051]
  232. Walter HJ, Bukstein OG, Abright AR, et al. Clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2020;59(10):1107-1124. doi:10.1016/j.jaac.2020.05.005 [PubMed 32439401]
  233. Warden SJ, Fuchs RK. Do selective serotonin reuptake inhibitors (SSRIs) cause fractures? Curr Osteoporos Rep. 2016;14(5):211-218. doi:10.1007/s11914-016-0322-3 [PubMed 27495351]
  234. Warner, CH, Bobo W, Warner C, et al. Antidepressant discontinuation syndrome. Am Fam Physician. 2006;74:449-456. [PubMed 16913164]
  235. Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161(6):1066-1078. doi:10.1176/appi.ajp.161.6.1066 [PubMed 15169695]
  236. Welsh JP, Cusack CA, Ko C. Urticarial vasculitis secondary to paroxetine. J Drugs Dermatol. 2006;5(10):1012-1014. [PubMed 17373154]
  237. Wenzel-Seifert K, Wittmann M, Haen E. QTc prolongation by psychotropic drugs and the risk of torsade de pointes. Dtsch Arztebl Int. 2011;108(41):687-693. doi:10.3238/arztebl.2011.0687 [PubMed 22114630]
  238. Westin AA, Brekke M, Molden E, Skogvoll E, Spigset O. Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: changes in drug disposition. PLoS One. 2017;12(7):e0181082. doi:10.1371/journal.pone.0181082 [PubMed 28708853]
  239. Williams AJ, Lai Z, Knight S, Kamali M, Assari S, McInnis MG. Risk factors associated with antidepressant exposure and history of antidepressant-induced mania in bipolar disorder. J Clin Psychiatry. 2018;79(3):17m11765. doi:10.4088/JCP.17m11765 [PubMed 29873955]
  240. Womersley K, Ripullone K, Agius M. What are the risks associated with different selective serotonin re-uptake inhibitors (SSRIs) to treat depression and anxiety in pregnancy? An evaluation of current evidence. Psychiatr Danub. 2017;29(suppl 3):629-644. [PubMed 28953843]
  241. Yasui-Furukori N, Sato Y, Kato H, Kaneko S. Paroxetine-associated hypereosinophilia may clinically resemble a panic attack. Clin Neuropharmacol. 2012;35(1):47-48. doi:10.1097/WNF.0b013e31823da9a8 [PubMed 22240860]
  242. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009;114(3):703-713. doi: 10.1097/AOG.0b013e3181ba0632 [PubMed 19701065]
  243. Zhang D, Cheng Y, Wu K, Ma Q, Jiang J, Yan Z. Paroxetine in the treatment of premature ejaculation: a systematic review and meta-analysis. BMC Urol. 2019;19(1):2. doi:10.1186/s12894-018-0431-7 [PubMed 30606186]
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