Version July 2025
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. Escitalopram is not approved for use in pediatric patients <7 years of age.
Dosage guidance:
Dosing: Some experts suggest lower starting doses of 5 mg/day and lower titration increments of 5 mg, particularly in patients with anxiety who are sensitive to antidepressant-associated overstimulation effects (eg, anxiety, insomnia) (Ref).
Binge eating disorder (off-label use): Oral: Initial: 10 mg once daily; may increase daily dose based on response and tolerability in 10 mg increments at intervals ≥1 week up to 30 mg/day (Ref).
Body dysmorphic disorder (off-label use): Oral: Initial: 10 mg once daily; may increase daily dose gradually based upon response and tolerability in increments of 10 mg at intervals of every 2 to 3 weeks to 30 mg/day by week 6 to 10 (Ref). Some experts suggest usual doses of 40 mg/day and that in some patients for optimal response doses up to 60 mg/day may be necessary; however, ECGs are recommended at every 10 mg dosing increment above 30 mg/day (eg, at 40 mg/day, 50 mg/day, 60 mg/day) and then as clinically indicated (Ref). Note: An adequate trial for assessment of effect is 12 to 16 weeks, including a dose of 30 mg for at least 4 of those weeks, if needed and tolerated (Ref).
Bulimia nervosa (alternative agent) (off-label use): Oral: Initial: 10 mg once daily; may increase daily dose based on response and tolerability in increments of 10 mg at intervals ≥1 week. Maximum dose: 30 mg/day (Ref).
Generalized anxiety disorder: Oral: Initial: 5 to 10 mg once daily; may gradually increase dose based on response and tolerability in 5 to 10 mg increments at intervals ≥1 week to a maximum of 20 mg once daily (Ref). Doses may be increased every 3 to 4 days if warranted in inpatient settings. Some experts recommend maintaining the initial therapeutic dose for 4 to 6 weeks to assess for efficacy before increasing further (Ref).
Major depressive disorder (unipolar): Oral: Initial: 10 mg once daily; daily dose may be increased in 10 mg increments after ≥1 week based on response and tolerability up to a maximum dose of 20 mg once daily (according to the manufacturer's labeling); however, doses up to 30 mg/day are used in practice and may provide further benefit (Ref).
Obsessive-compulsive disorder (OCD) (off-label use): Oral: Initial: 10 mg once daily; daily dose may be increased in 10 mg increments at intervals ≥1 week up to 40 mg once daily (Ref). Higher doses up to ~60 mg/day have been evaluated in open-label trials and may be considered in refractory patients; however, adverse effects may be increased (Ref). Note: An adequate trial for assessment of effect in OCD is considered to be ≥6 weeks at maximum tolerated dose (Ref).
Panic disorder (off-label use): Oral: Initial: 5 mg once daily for 3 to 7 days, then increase dose to 10 mg once daily (Ref). May further increase daily dose at intervals ≥1 week to 20 mg once daily based on response and tolerability; mean dose in a clinical trial was ~10 mg once daily (Ref). Some experts maintain dose at 10 mg for 4 weeks before considering further dose increases. May require 6 weeks at maximally tolerated dose for adequate treatment trial (Ref).
Posttraumatic stress disorder (off-label use): Oral: Initial: 10 mg once daily; may gradually increase daily dose (4-week intervals used in some trials) based on response and tolerability up to 40 mg once daily (Ref). Some experts suggest dose titrations of 5 to 10 mg increments every 1 to 4 weeks (Ref).
Premature ejaculation (off-label use): Oral: Initial: 10 mg once daily; may increase daily dose based on response and tolerability at intervals of ~3 to 4 weeks up to 20 mg once daily (Ref).
Premenstrual dysphoric disorder (off-label use):
Continuous daily dosing regimen: Oral: Initial: 5 to 10 mg once daily; over the first month, may increase dose based on response and tolerability to 20 mg once daily (Ref).
Intermittent regimens:
Luteal phase dosing regimen: Oral: 5 to 10 mg once daily during the luteal phase of menstrual cycle (beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase dose to 20 mg once daily during the luteal phase (Ref).
Symptom-onset dosing regimen: Oral: 5 to 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 to 20 mg once daily (Ref).
Social anxiety disorder (off-label use): Oral: Initial: 5 to 10 mg once daily; may increase up to 20 mg once daily after ≥4 weeks based on response and tolerability (Ref).
Vasomotor symptoms associated with menopause (alternative agent) (off-label use):
Note: Nonhormonal alternative for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy (Ref).
Oral: Initial: 10 mg once daily, increase daily dose to 20 mg once daily after 4 weeks if symptoms not adequately controlled (Ref).
Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). For brief treatment (eg, 2 to 3 weeks), may taper over 1 to 2 weeks; <2 weeks of treatment generally does not warrant tapering (Ref). Reasons for a slower taper (eg, over 4 weeks) include 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 a monoamine oxidase inhibitor (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, and 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 escitalopram.
Allow 14 days to elapse between discontinuing escitalopram 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.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: No escitalopram-specific pharmacokinetic evaluations have been conducted. The following recommendation are inferred from citalopram pharmacokinetic information (Ref).
Altered kidney function:
CrCl ≥20 mL/minute: No dosage adjustment necessary.
CrCl <20 mL/minute: Initial: 5 mg once daily; gradually titrate based on tolerability and response with close monitoring for adverse effects (eg, QT prolongation) (Ref).
Hemodialysis, intermittent (thrice weekly): Neither citalopram nor its active metabolite, desmethylcitalopram, are significantly dialyzed (1% (Ref)):
Note: An increase in sudden cardiac death in hemodialysis patients prescribed selective serotonin reuptake inhibitors (SSRIs) with higher QT-prolonging potential (citalopram, escitalopram) compared to SSRIs with lower QT-prolonging potential was observed in a retrospective cohort study (Ref). Therefore, use of an SSRI with a lower QT-prolonging potential may be preferred.
Initial: 5 mg once daily; gradually titrate based on tolerability and response with close monitoring for adverse effects (eg, QT prolongation) (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound, large Vd) (Ref):
Note: An increase in sudden cardiac death in hemodialysis patients prescribed SSRIs with higher QT-prolonging potential (citalopram, escitalopram) compared to SSRIs with lower QT-prolonging potential was observed in a retrospective cohort study (Ref). A similar risk has not been observed in patients on peritoneal dialysis (has not been studied), but use of an SSRI with a lower QT-prolonging potential may be preferred.
Initial: 5 mg once daily; gradually titrate based on tolerability and response with close monitoring for adverse effects (eg, QT prolongation) (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Escitalopram's AUC increased 69% in patients with Child-Turcotte-Pugh class B liver impairment in a single-dose pharmacokinetic trial with no serious adverse events reported (Ref). Accumulation in cirrhosis can be expected with repeat dosing; dosing recommendations are based on the known escitalopram pharmacokinetics, tolerability, toxicology, and dosage form availability (Ref).
Liver impairment prior to treatment initiation:
Child-Turcotte-Pugh class A to C: Oral: Initial: 5 mg once daily; may increase daily dose gradually based on response and tolerability in increments of 5 to 10 mg at intervals of ≥2 weeks (Ref), not to exceed the usual indication-specific maximum recommended dose.
Liver impairment developing in patient already receiving escitalopram:
Chronic disease progression (eg, outpatient):
Baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (eg, maintain current dose) if tolerating; if suspecting intolerance, then reduce dose; not to exceed the usual indication-specific maximum recommended dose (Ref).
Acute worsening of liver function (eg, requiring hospitalization):
Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (eg, maintain current dose) if tolerating; if suspecting intolerance, then reduce dose; not to exceed the usual indication-specific maximum recommended dose (Ref).
Generalized anxiety disorder; major depressive disorder (unipolar): Oral: 10 mg once daily; lower initial doses of 5 mg once daily have been suggested for depression (Ref).
Vasomotor symptoms associated with menopause (alternative agent) (off-label use): Oral: Lower initial doses of 5 mg once daily for titration have been suggested (Ref).
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
(For additional information see "Escitalopram: Pediatric drug information")
Generalized anxiety disorder, social anxiety disorder (SAD): Limited data available for SAD:
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 (eg, QT prolongation) (Ref).
Children ≥7 years and Adolescents <18 years: Oral: Initial: 10 mg once daily; may then increase after 2 weeks by 5 or 10 mg/day if needed, based on clinical response and tolerability; maximum dose: 20 mg/day (Ref).
Major depressive disorder: Note: In the management of depression in children and adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, a selective serotonin reuptake inhibitor (SSRI) should be used first line; escitalopram is an alternative SSRI option for patients for whom fluoxetine is not an option (Ref).
Children ≥12 years and Adolescents: Oral: Initial: 10 mg once daily; may be increased to 20 mg/day after at least 3 weeks if needed; maximum daily dose: 20 mg/day.
Discontinuation of therapy: Consider planning antidepressant discontinuation for lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to antidepressant discontinuation (Ref). Upon discontinuation of antidepressant 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 limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (Ref).
Switching antidepressants: Evidence for ideal selective serotonin reuptake inhibitor (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. 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 monoamine 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.
Children ≥7 years and Adolescents: Oral:
Mild to moderate impairment: No dosage adjustment needed.
Severe impairment: CrCl <20 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Children ≥7 years and Adolescents: Oral: Maximum daily dose: 10 mg/day (level of hepatic dysfunction not defined).
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). In addition, treatment-emergent mania or hypomania has been described in patients receiving antidepressants, including selective serotonin reuptake inhibitors, for the treatment of obsessive-compulsive disorder (OCD) without a history of bipolar disorder (with or without comorbid 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). In a systematic review of patients with OCD who experienced switching, the manic/hypomanic episodes were more common within 12 weeks of antidepressant treatment initiation; however, episodes occurred up to 9 months in these patients (Ref). In case reports involving escitalopram, treatment-emergent mania typically emerged in the first few months of treatment initiation and subsequent upward titration (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)
• Females (Ref)
Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematomas, petechiae, purpuric disease, and epistaxis to cerebrovascular accident, upper gastrointestinal hemorrhage, intracranial hemorrhage, postpartum hemorrhage (exposure during late gestation), and perioperative bleeding, although conflicting evidence also exists (Ref).
Mechanism: Possibly via inhibition of serotonin-mediated platelet activation (inhibition of the serotonin reuptake transporter) and subsequent platelet dysfunction. Escitalopram is considered to display moderate affinity for the serotonin reuptake receptor (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 upper GI bleeding, 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 upper GI bleeding (Ref)
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). In addition, several trials and subsequent meta-analyses have found an increased risk of bone fracture with the use of SSRIs in stroke survivors (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). An increased tendency to fall may also contribute to the increased risk of fractures associated with SSRIs (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). Conversely, the increased risk of bone fracture in stroke survivors who received an SSRI (fluoxetine) was no longer statistically significant at 12 months post-stroke (Ref).
Risk factors:
• Long-term use may be a risk factor (Ref)
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 may be 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 with an SSRI (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)
Selective serotonin reuptake inhibitors (SSRIs) are associated with acute angle-closure glaucoma (AACG) in case reports and a case-control study. AACG may cause symptoms including eye pain, visual disturbance, 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)
Dose-dependent prolonged QT interval on ECG has been reported with use (Ref), including postmarketing reports of torsades de pointes (TdP); however, data are inconsistent on its effect on the QTc interval and its clinical significance (Ref). One meta-analysis observed an increase in the QTc by an average of 7.3 ms (Ref), while another study found an increase of only 3.5 ms (Ref). Of note, citalopram is associated with a greater effect on QTc prolongation (mean QTc increase 7.8 ms [10 to 20 mg citalopram] and 10.3 ms [20 to 40 mg citalopram]) compared to escitalopram, the S-enantiomer of citalopram (Ref).
Mechanism: Dose-related; escitalopram is believed to cause QTc prolongation via direct blockade of rapid potassium delayed rectifier current (IKr), the delayed potassium rectifier current, encoded by the human ether-à-go-go-related gene (hERG) (Ref).
Risk factors:
Drug-induced QT prolongation/TdP (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with a reduced ejection fraction) (Ref)
• History of drug-induced TdP (Ref)
• Genetic defects of cardiac ion channels (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypokalemia, hypocalcemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Coadministration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QT prolonging medications (Ref)
• Substance use (Ref)
Serotonin syndrome has been reported and typically occurs with coadministration of multiple serotonergic drugs but can occur following a single serotonergic agent at therapeutic doses (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, monoamine oxidase inhibitors [MAOIs]). Of note, concomitant use of some serotonergic agents, such as MAOIs, are contraindicated.
Selective serotonin reuptake inhibitors (SSRIs) are commonly associated with sexual disorder in both men and women. The following adverse reactions have been associated with SSRI use: Ejaculatory disorder (primarily ejaculatory delay), orgasm disturbance, erectile dysfunction, decreased libido (Ref). Priapism and decreased penile sensation have also been reported with SSRIs (Ref). The impact on sexual health may be lessened with drug holidays; in an open-label trial, patients taking an SSRI (other than fluoxetine) who were instructed to not take their medication on the weekends (n=63) reported improved erection, ejaculation, satisfaction, and overall sexual health without significant worsening in their mental health status (Ref).
Mechanism: Dose-related (Ref); 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)
Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years of age) in short-term studies. In adults >24 years of age, 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, 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, mania) have been reported, primarily following abrupt discontinuation. 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 dose taper) or tapering the antidepressant too quickly (Ref).
• Drugs with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)
• Higher doses (Ref)
• Longer duration of treatment (eg, ≥4 weeks) (Ref)
• Prior history of antidepressant withdrawal symptoms (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Diarrhea (6% to 14%), nausea (15% to 18%)
Genitourinary: Ejaculatory disorder (9% to 14%) (table 1)
|
Drug (Escitalopram) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Escitalopram) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
14% |
2% |
Males |
10 to 20 mg/day |
Generalized anxiety disorder |
182 |
195 |
|
9% |
<1% |
Males |
10 to 20 mg/day |
Major depressive disorder |
225 |
188 |
Nervous system: Drowsiness (4% to 13%; literature suggests incidence is lower in children and adolescents compared to adults (Ref)), headache (24%), insomnia (7% to 14%)
1% to 10%:
Dermatologic: Diaphoresis (3% to 8%)
Endocrine & metabolic: Decreased libido (3% to 7%) (table 2), menstrual disease (2%)
|
Drug (Escitalopram) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Escitalopram) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
7% |
2% |
Adults |
10 to 20 mg/day |
Generalized anxiety disorder |
429 |
427 |
|
3% |
1% |
Adults |
10 to 20 mg/day |
Major depressive disorder |
715 |
592 |
Gastrointestinal: Abdominal distress (children, adolescents: 3%), abdominal pain (2%), constipation (3% to 6%), decreased appetite (3%), dyspepsia (2% to 6%), flatulence (2%), vomiting (3%; literature suggests incidence is higher in adolescents compared to adults, and is two- to threefold higher in children compared to adolescents (Ref)), xerostomia (4% to 9%)
Genitourinary: Anorgasmia (2% to 6%), erectile dysfunction (3%) (table 3), urinary tract infection (children, adolescents: ≥2%)
|
Drug (Escitalopram) |
Placebo |
Population |
Dose |
Number of Patients (Escitalopram) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
3% |
<1% |
Males |
10 to 20 mg/day |
225 |
188 |
Nervous system: Abnormal dreams (3%), dizziness (3% to 7%), fatigue (2% to 8%), irritability (≤2%), lethargy (3%), outbursts of anger (children, adolescents: 2%), paresthesia (2%), yawning (2%)
Neuromuscular & skeletal: Back pain (children, adolescents: ≥2%), neck pain (≤3%), shoulder pain (≤3%)
Respiratory: Flu-like symptoms (5%), nasal congestion (children, adolescents: ≥2%), nasopharyngitis (children, adolescents: 3%), rhinitis (5%), sinusitis (3%)
<1%:
Cardiovascular: Chest pain, hypertension, palpitations
Dermatologic: Skin rash
Endocrine & metabolic: Hot flash, weight gain
Gastrointestinal: Abdominal cramps, gastroenteritis, heartburn, increased appetite
Genitourinary: Dysmenorrhea, urinary frequency
Hypersensitivity: Hypersensitivity reaction
Nervous system: Lack of concentration, migraine
Neuromuscular & skeletal: Arthralgia, jaw tightness, limb pain, myalgia
Ophthalmic: Blurred vision
Otic: Tinnitus
Respiratory: Bronchitis, cough, paranasal sinus congestion, sinus headache
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Acute myocardial infarction, atrial fibrillation, bradycardia, deep vein thrombosis, edema, flushing, heart failure, hypertensive crisis, hypotension, orthostatic hypotension, phlebitis, prolonged QT interval on ECG (Ref), pulmonary embolism, syncope, tachycardia, thrombosis, torsades de pointes (Ref), ventricular arrhythmia, ventricular tachycardia
Dermatologic: Alopecia (Ref), dermatitis, ecchymoses, erythema multiforme, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Diabetes mellitus, galactorrhea not associated with childbirth (Ref), heavy menstrual bleeding, hypercholesterolemia, hyperglycemia, hyperprolactinemia, hypoglycemia, hypokalemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranges from <1% to as high as 32% (Ref)), SIADH (Ref)
Gastrointestinal: Dysphagia, gastroesophageal reflux disease, gastrointestinal hemorrhage (Ref), pancreatitis, rectal hemorrhage
Genitourinary: Abnormal orgasm, abnormal uterine bleeding (postmenopausal) (Ref), dysuria, mastalgia (Ref), priapism (Ref), sexual disorder (Ref), spontaneous abortion, urinary retention
Hematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, hemolytic anemia, hypoprothrombinemia, immune thrombocytopenia, increased INR, leukopenia, thrombocytopenia
Hepatic: Hepatic failure, hepatic necrosis, hepatitis (including cholestatic hepatitis) (Ref), increased liver enzymes, increased serum bilirubin
Hypersensitivity: Anaphylaxis, angioedema (Ref), drug reaction with eosinophilia and systemic symptoms
Nervous system: Abnormal gait, aggressive behavior, agitated depression, akathisia (Ref), amnesia, anosmia (including hyposmia), apathy, asthenia, ataxia, cerebrovascular accident (Ref), choreoathetosis, delirium, delusion, depersonalization, extrapyramidal reaction, falling, hallucination, hyperactive behavior (including agitation, hyperkinetic muscle activity, and restlessness occurring in children at a two- to threefold higher incidence compared to adolescents; it is more prevalent in adolescents compared to adults) (Ref), hypoesthesia, hypomania (Ref), malaise, mania (Ref), myasthenia, myoclonus, nervousness, neuroleptic malignant syndrome (Ref), nightmares, panic, paranoid ideation, parkinsonism, psychosis, restless leg syndrome, seizure, serotonin syndrome (Ref), suicidal ideation (Ref), suicidal tendencies, tremor, vertigo, withdrawal syndrome (Ref)
Neuromuscular & skeletal: Bone fracture (fragility) (Ref), dyskinesia, dystonia, rhabdomyolysis, tardive dyskinesia (Ref)
Ophthalmic: Acute angle-closure glaucoma (Ref), diplopia, mydriasis, nystagmus disorder, subconjunctival hemorrhage (Ref), visual disturbance
Renal: Acute kidney injury
Respiratory: Dyspnea, epistaxis (Ref)
Hypersensitivity to escitalopram, citalopram, or any component of the formulation; use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either escitalopram or the MAOI); initiation of escitalopram in a patient receiving IV methylene blue; concurrent use of pimozide.
Note: Although escitalopram is contraindicated per the manufacturer labeling when used in combination with linezolid, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore these agents can be administered concomitantly when necessary. Monitor patients on this combination; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006).
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): Known QT-interval prolongation or congenital long QT syndrome
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. Small pharmacokinetic studies showed alterations in citalopram exposure with wide interpatient variability especially early post-surgery (eg, <30 days) (Garin 2023; Marzinke 2015; Schoretsanitis 2023). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• Cardiovascular disease: Patients with a recent history of MI or unstable heart disease were excluded from clinical trials; use with caution.
• Liver impairment: Use with caution in patients with liver impairment; clearance is decreased and half-life and plasma concentrations are increased. However, selective serotonin reuptake inhibitors such as escitalopram are considered the safest antidepressants to use in chronic liver disease because of their relative lack of side effects and high therapeutic index (Mauri 2014; Mullish 2014).
• Metabolic disease: Use with caution; limited data in patients with altered metabolism.
• Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustment may be required.
• Seizure disorders: Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.
Special populations:
• CYP2C19 poor metabolizers: Escitalopram systemic exposure may be increased in CYP2C19 poor metabolizers.
• Older adult: Bioavailability and half-life are increased by 50% in older adult patients.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral:
Generic: 5 mg/5 mL (10 mL [DSC], 240 mL); 10 mg/10 mL (10 mL)
Tablet, Oral:
Lexapro: 5 mg
Lexapro: 10 mg, 20 mg [scored]
Generic: 5 mg, 10 mg, 20 mg
Yes
Solution (Escitalopram Oxalate Oral)
5 mg/5 mL (per mL): $0.79 - $2.25
Tablets (Escitalopram Oxalate Oral)
5 mg (per each): $0.12 - $4.51
10 mg (per each): $0.14 - $4.72
20 mg (per each): $0.17 - $4.92
Tablets (Lexapro Oral)
5 mg (per each): $17.65
10 mg (per each): $18.45
20 mg (per each): $19.25
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Cipralex: 10 mg, 20 mg
Generic: 10 mg, 15 mg, 20 mg
Tablet Disintegrating, Oral:
Generic: 10 mg, 20 mg
Oral: Administer once daily (morning or evening), with or without food.
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN; Lucas E. Orth, PharmD, BCPPS; Russel J. Roberts, PharmD, BCCCP, FCCM.
Oral solution (commercially available):
Gastric (eg, NG, G-tube ) or post-pyloric (eg, J-tube) tubes: Dilute dose with at least an equivalent volume of purified water prior to administering to reduce osmolality and viscosity; some experts recommend diluting in a volume of purified water that is 3 times the escitalopram solution volume (eg, 10 mL escitalopram solution diluted in 30 mL purified water); draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: One undiluted formulation has been reported to have an osmolality of ~6,000 mOsm/kg (Ref); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition (EN) during escitalopram administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, at least 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, at least 15 mL) and restart EN (Ref).
Oral tablet:
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Crush tablet(s) into a fine powder and disperse in ≥10 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated escitalopram tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are dispersed sufficiently with an adequate amount of purified water prior to administration (Ref).
General guidance: Hold EN during escitalopram administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart EN (Ref).
No te: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN; Lucas E. Orth, PharmD, BCPPS; Russel J. Roberts, PharmD, BCCCP, FCCM.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Oral: Administer once daily (morning or evening); may be administered with or without food.
Oral solution (commercially available): Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Dilute dose with at least an equivalent volume of purified water prior to administering to reduce osmolality and viscosity; some experts recommend diluting in a volume of purified water that is 3 times the escitalopram solution volume (eg, 10 mL escitalopram solution diluted in 30 mL purified water); draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: One undiluted formulation has been reported to have an osmolality of ~6,000 mOsm/kg (Ref); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during escitalopram administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Tablet:
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Crush tablet(s) into a fine powder and disperse in ≥10 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some tablets may be film-coated; administration of film-coated escitalopram tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are sufficiently dispersed prior to administration (Ref).
General guidance: Hold enteral nutrition during escitalopram administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Lexapro: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021323s057,021365s040lbl.pdf
Generalized anxiety disorder: Acute treatment of generalized anxiety disorder in adults and pediatric patients ≥7 years of age.
Major depressive disorder (unipolar): Acute and maintenance treatment of unipolar major depressive disorder in adults and pediatric patients ≥12 years of age.
Binge eating disorder; Body dysmorphic disorder; Bulimia nervosa; Obsessive-compulsive disorder; Panic disorder; Posttraumatic stress disorder; Premature ejaculation; Premenstrual dysphoric disorder; Social anxiety disorder; Vasomotor symptoms associated with menopause
Escitalopram may be confused with citalopram, enalapril
Lexapro may be confused with Loxitane [DSC]
Beers Criteria: Selective Serotonin Reuptake Inhibitors (SSRIs) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).
Escitalopram is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with a history of recurrent falls due to an increased risk of falls. In addition, some disease states of concern include QTc prolongation, hyponatremia, and recent or current significant bleeding (O’Mahony 2023).
Zavesca: Brand name for escitalopram [in multiple international markets; ISMP April 21, 2010], but also brand name for miglustat [Canada, US, and multiple international markets]
Substrate of CYP2C19 (Major with inhibitors), CYP2C19 (Minor with inducers), CYP2D6 (Minor), CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (Weak);
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitor may increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. 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 increase serotonergic effects 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
Alosetron: May increase serotonergic effects 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
Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor
Amphetamines: May increase serotonergic effects 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). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor
Anagrelide: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Anticoagulants (Miscellaneous Agents): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor
Antiemetics (5HT3 Antagonists): May increase serotonergic effects 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
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Antipsychotic Agents: Serotonergic Agents (High Risk) may increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Aspirin: Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Aspirin. Risk C: Monitor
Brexanolone: Selective Serotonin Reuptake Inhibitor may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. Risk X: Avoid
BuPROPion: May increase adverse/toxic effects of Escitalopram. Risk C: Monitor
BusPIRone: May increase serotonergic effects 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
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Cimetidine: May increase serum concentration of Escitalopram. Risk C: Monitor
Citalopram: Escitalopram may increase QTc-prolonging effects of Citalopram. Escitalopram may increase serotonergic effects of Citalopram. This could result in serotonin syndrome. Citalopram may increase antiplatelet effects of Escitalopram. Risk X: Avoid
CloZAPine: May increase serotonergic effects of Escitalopram. This could result in serotonin syndrome. CloZAPine may increase QTc-prolonging effects of Escitalopram. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, serotonin syndrome, and neuroleptic malignant syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
Cyclobenzaprine: May increase serotonergic effects 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
CYP2C19 Inhibitors (Moderate): May increase serum concentration of Escitalopram. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Escitalopram. Risk C: Monitor
Cyproheptadine: May decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Dabrafenib: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Dapoxetine: May increase serotonergic effects 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
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Dexmethylphenidate-Methylphenidate: May increase serotonergic effects 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
Dextromethorphan: May increase serotonergic effects 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
Direct Oral Anticoagulants (DOACs): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Domperidone: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
DULoxetine: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of DULoxetine. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of DULoxetine. 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
Eletriptan: May increase serotonergic effects 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
Encorafenib: May increase QTc-prolonging effects of Escitalopram. Encorafenib may decrease serum concentration of Escitalopram. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and reduced citalopram concentrations and efficacy when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Epinephrine (Racemic): Selective Serotonin Reuptake Inhibitor may increase adverse/toxic effects of Epinephrine (Racemic). Risk X: Avoid
Ergot Derivatives: May increase serotonergic effects 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
Esomeprazole: May increase serum concentration of Escitalopram. Risk C: Monitor
Fenfluramine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Fexinidazole: May increase QTc-prolonging effects of Escitalopram. Fexinidazole may increase serum concentration of Escitalopram. Management: Monitor for increased escitalopram toxicities (including increased QTc prolongation and serotonin syndrome) if combined with fexinidazole. Consider limiting the escitalopram dose to 10 mg daily when these agents are combined. Risk C: Monitor
Fluconazole: Escitalopram may increase QTc-prolonging effects of Fluconazole. Fluconazole may increase serum concentration of Escitalopram. Risk C: Monitor
Fluorouracil Products: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Fondaparinux: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Gepirone: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Gepirone may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Risk C: Monitor
Gilteritinib: May decrease therapeutic effects of Escitalopram. Escitalopram may increase QTc-prolonging effects of Gilteritinib. Management: Avoid use of this combination if possible. If use is necessary, monitor for reduced response to escitalopram and for QTc prolongation and arrhythmias. Patients with other risk factors may be at greater risk for these serious toxicities. Risk D: Consider Therapy Modification
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Haloperidol. Haloperidol may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor
Heparin: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparin. Risk C: Monitor
Heparins (Low Molecular Weight): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Hydroxychloroquine: May increase QTc-prolonging effects of Escitalopram. Escitalopram may increase hypoglycemic effects of Hydroxychloroquine. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Ioflupane I 123: Coadministration of Selective Serotonin Reuptake Inhibitor and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Lasmiditan: May increase serotonergic effects 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
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid
Levomethadone: May increase serotonergic effects 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
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Linezolid: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Lofexidine: May increase QTc-prolonging effects of Escitalopram. Escitalopram may increase QTc-prolonging effects of Lofexidine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Metaxalone: May increase serotonergic effects 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
Methylene Blue: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid
Metoclopramide: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring 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
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Mivacurium: Selective Serotonin Reuptake Inhibitor may increase serum concentration of Mivacurium. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid
Nefazodone: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. 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
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. 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 increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omeprazole: May increase serum concentration of Escitalopram. Risk C: Monitor
Ondansetron: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation or serotonin syndrome may be at even higher risk. Risk C: Monitor
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May increase serotonergic effects 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
Opioid Agonists (metabolized by CYP3A4): May increase serotonergic effects 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
Opioid Agonists: May increase serotonergic effects 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
Opipramol: May increase serotonergic effects 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
Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects 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
OxyCODONE: May increase serotonergic effects 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
Pentamidine (Systemic): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor
QT-prolonging Agents (Highest Risk): May increase QTc-prolonging effects of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider Therapy Modification
QT-prolonging Antidepressants (Moderate Risk): Escitalopram may increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Escitalopram may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Risk C: Monitor
QT-prolonging Antipsychotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antipsychotics (Moderate Risk) may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Escitalopram may increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor
QT-prolonging Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Escitalopram may increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor
Ramosetron: May increase serotonergic effects 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
Rasagiline: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid
Safinamide: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Selective Serotonin Reuptake Inhibitor: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. 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
Selegiline: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Selegiline. This could result in serotonin syndrome. Risk X: Avoid
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Serotonergic Agents (High Risk, Miscellaneous): May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. 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
Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects 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
Serotonergic Opioids (High Risk): May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. 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
Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects 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
Serotonin/Norepinephrine Reuptake Inhibitor: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Serotonin/Norepinephrine Reuptake Inhibitor. 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
Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease 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
Syrian Rue: May increase serotonergic effects 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
Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitor may increase hyponatremic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Thyroid Products: Selective Serotonin Reuptake Inhibitor may decrease therapeutic effects of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor
Tilidine: May increase serotonergic effects 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
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
TraMADol: May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and seizures when these agents are combined. Risk C: Monitor
Tricyclic Antidepressants: May increase serotonergic effects of Escitalopram. Escitalopram may increase 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 C: Monitor
Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor
Venlafaxine: Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Venlafaxine. Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Venlafaxine. 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
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Voriconazole: Escitalopram may increase QTc-prolonging effects of Voriconazole. Voriconazole may increase serum concentration of Escitalopram. Risk C: Monitor
Vortioxetine: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Vortioxetine may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. 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
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ziprasidone: May increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Ziprasidone. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider Therapy Modification
Evaluate pregnancy status prior to initiating treatment in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of antidepressant response (ACOG 2023; WFSBP [Dodd 2018]). When treating depression, anxiety, obsessive-compulsive disorder, or post-traumatic stress disorder, selective serotonin reuptake inhibitors (SSRIs) are preferred for use prior to conception in patients who are treatment naive or who do not have a history of effective treatment. Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]).
Escitalopram is also used off label for the treatment of premenstrual dysphoric disorder. Symptom-onset dosing, which is initiated on the day of symptom onset and continued until after the start of menses, may be beneficial in patients attempting to conceive (Freeman 2005; Lanza di Scalea 2019).
Menstrual disorders have been reported following use of escitalopram. SSRI use may cause hyperprolactinemia and, rarely, changes in thyroid function, both of which can be associated with menstrual irregularities. Depression is also associated with menstrual changes. (Padda 2021).
Some studies suggest SSRIs may impair semen parameters, including the motility of spermatozoa; use of other treatments may be preferred in male patients planning a pregnancy (ISSM [Althof 2014]; Sylvester 2019). SSRIs are associated with an increased risk of sexual dysfunction (Tarchi 2023). Escitalopram may delay ejaculation and is used off label for the treatment of premature ejaculation (ISSM [Althof 2014]; Sathianathen 2021).
Escitalopram and desmethylcitalopram cross the placenta and are distributed into the amniotic fluid (Schoretsanitis 2021).
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. Overall, an increased risk of major congenital malformations has not been observed when considering differences in study design and confounders (ACOG 2023; Anderson 2020; BAP [McAllister-Williams 2017]; Biffi 2020; Fitton 2020; Gao 2018; Lebin 2022). Adverse effects in the newborn following SSRI exposure in the third trimester include neonatal adaptation syndrome and persistent pulmonary hypertension of the newborn (PPHN). Neonatal adaptation syndrome can occur shortly after birth and typically resolves within 2 weeks. Mechanisms of neonatal adaptation syndrome are not well understood but may be due to either SSRI toxicity or withdrawal. Reducing the dose or discontinuing the SSRI prior to delivery to reduce the risk of neonatal adaptation syndrome is not recommended (ACOG 2023). Symptoms 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.
PPHN is a rare complication of SSRI use during pregnancy with symptoms of respiratory distress within the first hours of life and an increased risk of neonatal mortality (ACOG 2023). Monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). Data related to the long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are limited (CANMAT [MacQueen 2016]; Lebin 2022).
SSRIs may increase the risk of bleeding. Exposure late in pregnancy is associated with less than a 2-fold increase in postpartum hemorrhage. The clinical significance of this is uncertain (BAP [McAllister-Williams 2017]; Lebin 2022).
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of escitalopram may be altered, possibly due to CYP2C19 inhibition. However, changes are not likely to have clinical implications. Close clinical monitoring as pregnancy progresses is recommended to assist dose adjustment when needed (Schoretsanitis 2020).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated or undertreated depression is associated with preterm birth, low birth weight (LBW), preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Anxiety disorders during pregnancy are associated with LBW, preterm birth, and adverse behavioral outcomes in the offspring. Discontinuing effective medications during pregnancy increases the risk of symptom relapse. Management should be made as part of a shared decision-making process (ACOG 2023). Patients effectively treated for depression, anxiety, obsessive-compulsive disorder or post-traumatic stress disorder pre-pregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; ; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023).
SSRIs are preferred for use in pregnant patients who are treatment naive or who do not have a history of effective treatment with another medication. Escitalopram is a preferred option for pregnant patients with no prior medication history (ACOG 2023). SSRI dosing should be initiated with half the lowest recommended dose and titrated gradually over 4 to 10 days. Dose adjustments may be required as pregnancy progresses to keep symptoms in remission (ACOG 2023).
When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Monthly monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023). Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Pregnant patients 45 years of age and younger with a history of psychiatric illness are encouraged to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants).
Escitalopram and its desmethylcitalopram (DCT) metabolite are present in breast milk.
Multiple reports summarize data related to the presence of escitalopram in breast milk (Berle 2011; Orsolini 2015; Schoretsanitis 2021):
• The relative infant dose (RID) of escitalopram has been calculated in review articles to be 3% to 6% of the weight adjusted maternal dose (Berle 2011; Orsolini 2015); RIDs up to 10.5% have also been located (Delaney 2018).
• A review article used pooled data from 12 mother/infant pairs to calculate the estimated daily infant dose of escitalopram via breast milk to be 0.04 mg/day providing a relative infant dose (RID) of 3% to 6%. The maternal dose and actual breast milk concentrations for the calculation were not provided (Berle 2011).
• A second review included information from 37 cases; maternal daily doses of escitalopram were 5 to 20 mg/day. The highest breast milk concentrations of escitalopram presented were 27 to 99 ng/mL from a study of 8 women 3 to 32 weeks postpartum, providing a RID of 5.3%; the DCT metabolite was also present in breast milk (Orsolini 2015).
• A study published since these reviews reports breast milk concentrations that are almost double following a maternal dose of escitalopram 30 mg/day. At this maternal dose, the peak escitalopram breast milk concentration was 202.2 ng/mL and the RID of escitalopram is 10.5%, providing an estimated daily infant dose via breast milk of 0.03 mg/kg/day. Metabolite concentrations were not evaluated (Delaney 2018).
• Escitalopram and DCT were measured as part of a study to validate a method of detecting antidepressants in breast milk. One lactating patient taking escitalopram 20 mg/day provided one breast milk sample 12 hours after the last dose at 1 week postpartum. Maternal plasma concentrations were 94 ng/mL (escitalopram) and 12 ng/mL (DCT). Escitalopram concentrations were 173 ng/mL in foremilk and 195 ng/mL in hindmilk. ECT concentrations were 21 ng/mL and 24 ng/mL in the foremilk and hindmilk, respectively. Authors of the study calculated the RID to be 9% (Weisskopf 2017).
• Although maternal genotype was not evaluated in these studies, a pharmacokinetic modeling study has demonstrated mothers who are poor metabolizers of CYP2C19 would have greater breast milk concentrations of escitalopram. The model predicts a median escitalopram RID of 5.7% in breastfed infants of mothers who are poor metabolizers compared to 3% for other phenotypes, following a maternal dose of escitalopram 5 to 20 mg/day (RID range 0.8% to 11.3% inclusive of all phenotypes) (Weisskopf 2020).
• 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 (Anderson 2021).
In one study, mean peak milk concentrations of escitalopram occurred ~5.5 hours after the maternal dose; the mean peak concentration of DCT was reported at ~4.8 hours (Rampono 2006). However, avoiding breastfeeding during the expected peak concentrations will generally not decrease infant exposure significantly for antidepressants with long half-lives (Berle 2011).
Adverse events following exposure to escitalopram and other selective serotonin reuptake inhibitors (SSRIs) via breast milk have been reported in some infants (Lanza di Scalea 2009; Orsolini 2015). Product labeling notes agitation, excessive sedation, restlessness, poor feeding, and poor weight gain have been noted in infants exposed to escitalopram via breast milk. 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]; BAP [McAllister-Williams 2017]; Weissman 2004).
Maternal use of an SSRI during pregnancy may delay lactogenesis (Marshall 2010); however, the underlying maternal illness and various other factors may also influence this outcome. Patients who wish to breastfeed during treatment with an SSRI may need additional assistance to initiate and maintain breastfeeding (Anderson 2021).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Patients effectively treated for depression, anxiety, obsessive-compulsive disorder, or post-traumatic stress disorder during pregnancy may continue their medication postpartum unless contraindications to breastfeeding exist. The presence and concentration of the drug in breast milk, efficacy of maternal treatment, and infant age should be considered when initiating a medication for the first-time postpartum. When first initiating an antidepressant in a patient who is treatment naive and breastfeeding, an SSRI other than escitalopram may be preferred (ABM [Sriraman 2015]; BAP [McAllister-Williams 2017]). Breastfeeding may be continued in patients treated with an SSRI during pregnancy (ABM [Sriraman 2015]; ACOG 2023). Treatment should not be withheld or discontinued based only on breastfeeding status (ACOG 2023).
ECG (in patients at increased risk for QT-prolonging effects); electrolytes (potassium and magnesium concentrations at baseline and as clinically indicated); liver and renal function tests (baseline; as clinically indicated); serum sodium in at-risk populations (as clinically indicated); CBC (as clinically indicated); screen all patients for any personal or family history of bipolar disorder, hypomania, or mania (prior to initiating therapy); 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).
Escitalopram is the S-enantiomer of the racemic derivative citalopram, which selectively inhibits the reuptake of serotonin with little to no effect on norepinephrine or dopamine reuptake. It has no or very low affinity for 5-HT1-7, alpha- and beta-adrenergic, D1-5, H1-3, M1-5, and benzodiazepine receptors. Escitalopram does not bind to or has low affinity for Na+, K+, Cl-, and Ca++ ion channels.
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]).
Distribution: Vd: ~20 L/kg (Søgaard 2005)
Protein binding: ~56% to plasma proteins
Metabolism: Hepatic via CYP2C19 and 3A4 to S-desmethylcitalopram (S-DCT); S-DCT is metabolized to S-didesmethylcitalopram (S-DDCT) via CYP2D6; in vitro data suggest metabolites do not contribute significantly to the antidepressant effects of escitalopram
Bioavailability: 80%; tablets and oral solution are bioequivalent
Half-life elimination: Mean: Adolescents: 19 hours; Adults: ~27 to 32 hours (increased ~50% in the elderly and doubled in patients with hepatic impairment)
Time to peak: Escitalopram: Adolescents: 2.9 hours; Adults: ~5 hours
Excretion: Urine (8% as unchanged drug; S-DCT 10%)
Altered kidney function: No data available for escitalopram. Citalopram clearance decreased by 17% in mild to moderate impairment. Limited information is available in patients with severe impairment (Joffe 1998; Spigset 2000).
Hepatic function impairment: Patients with mild and moderate hepatic impairment had a 51% and 69% increase in AUC, respectively. Additionally, the clearance/F of those with moderate impairment was 16 L/hour compared to a 25 L/hour clearance in healthy patients (Areberg 2006).
Older adult: AUC and half-life increased ~50%.
