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 <12 years of age.
Note: Some experts suggest lower starting doses of 5 mg/day and lower titration increments of 5 mg in patients sensitive to adverse effects, particularly in patients with anxiety who are generally more sensitive to overstimulation effects (eg, anxiety, insomnia) with antidepressants (Ref).
Binge eating disorder (off-label use): Based on limited data: Oral: Initial: 10 mg once daily; may increase 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): Based on limited data: Oral: Initial: 10 mg once daily; may increase 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 in BDD is 12 to 16 weeks, including maximum tolerated doses for at least 3 to 4 of those weeks (Ref).
Bulimia nervosa (alternative agent) (off-label use): Based on limited data; recommendations based on expert opinion: Oral: Initial: 10 mg once daily; may increase 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: 10 mg once daily; dose may be increased after ≥1 week based on response and tolerability to a maximum of 20 mg once daily.
Major depressive disorder (unipolar): Oral: Initial: 10 mg once 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; 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).
Premature ejaculation (off-label use): Based on limited data; recommendations based on expert opinion: Oral: Initial: 10 mg once daily; may increase 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: Based on limited data; recommendations based on expert opinion: 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).
Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). Reasons for a slower taper (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).
Switching antidepressants:Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, 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).
10 mg once daily (level of hepatic dysfunction not specified). Some experts recommend initial doses of 5 mg/day for 2 weeks in patients with mild and moderate impairment (Child-Pugh A or B) (Ref).
(For additional information see "Escitalopram: Pediatric drug information")
Generalized anxiety disorder including social anxiety disorder and obsessive compulsive disorder (OCD): Limited data available:
Note: In pediatric patients, selective serotonin reuptake inhibitor (SSRI) therapy is considered first-line pharmacologic treatment for moderate to severe anxiety disorders in combination with cognitive behavioral therapy (CBT); a preferred SSRI has not been defined; therapeutic selection should be based on pharmacokinetic and pharmacodynamic data, patient tolerability, cost, and unique risks/precautions with specific agents (eg, QT prolongation) (Ref). In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary it should be used in combination with CBT and an SSRI should be used first line; a preferred agent has not been identified; a meta-analysis of pediatric OCD trials suggested escitalopram is more effective than other SSRIs (fluvoxamine, paroxetine, sertraline) and clomipramine (Ref).
Children and Adolescents 10 to 17 years: Oral: Initial: 5 mg once daily for 2 to 7 days, then 10 mg/day for 7 days; may then increase at weekly intervals by 5 mg/day if needed, based on clinical response and tolerability; maximum dose: 20 mg/day. Dosing based on prospective, placebo-controlled, and open-label trials (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.
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 ≥12 years and Adolescents: Oral:
Mild to moderate impairment: No dosage adjustment needed.
Severe impairment: CrCl <20 mL/minute: Use with caution.
Children ≥12 years and Adolescents: Depression: Oral: Maximum daily dose: 10 mg/day (level of hepatic dysfunction not defined).
Major depressive disorder (unipolar); generalized anxiety disorder: Oral: 10 mg once daily; lower initial doses of 5 mg once daily have been suggested for depression (Ref).
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
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)
Tablet, Oral:
Lexapro: 5 mg
Lexapro: 10 mg, 20 mg [scored]
Generic: 5 mg, 10 mg, 20 mg
Yes
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
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021365s038,021323s053lbl.pdf#page=21, must be dispensed with this medication.
Oral: Administer once daily (morning or evening), with or without food.
Oral: Administer once daily (morning or evening); may be administered with or without food.
Major depressive disorder (unipolar): Acute and maintenance treatment of unipolar major depressive disorder (MDD)
Generalized anxiety disorder: Acute treatment of generalized anxiety disorder (GAD)
Binge eating disorder; Body dysmorphic disorder; Bulimia nervosa; Obsessive-compulsive disorder; Panic disorder; Posttraumatic stress disorder; Premature ejaculation; Premenstrual dysphoric disorder; Vasomotor symptoms associated with menopause
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 2019]).
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]
Antidepressants (when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients with unipolar major depressive disorder (MDD) have been reported, as many cases of bipolar disorder present in episodes of MDD (Ref).
Mechanism: Non-dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref).
Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy, but not thereafter (up to 4.6 years) (Ref). 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)
• Female sex (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 GI bleeding (UGIB), intracranial hemorrhage, postpartum hemorrhage, 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. SSRIs may also increase gastric acidity, which can increase the risk of GI bleeding (Ref).
Onset: Varied; bleeding risk is likely delayed for several weeks until SSRI-induced platelet serotonin depletion becomes clinically significant (Ref), although the onset of bleeding may be more unpredictable if patients are taking concomitant antiplatelets, anticoagulants, or nonsteroidal anti-inflammatory drugs (NSAIDs). For UGIB, some studies have found risk to be the highest in the first 28 to 30 days (Ref), whereas another study reported a median time of onset of 25 weeks (Ref).
Risk factors:
• Concomitant use of anticoagulants and/or antiplatelets (Ref)
• Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor) (Ref)
• Concomitant use of NSAIDs increases the risk for UGIB (Ref)
Limited data from observational studies involving mostly older adults (≥50 years of age) suggest selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of bone fractures (Ref).
Mechanism: Time-related; mechanism not fully elucidated; postulated to be through a direct effect by SSRIs on bone metabolism via interaction with 5-HT and osteoblast, osteocyte, and/or osteoclast activity (Ref). 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).
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 is reversible with discontinuation of therapy (Ref).
Mechanism: May cause SIADH via release of antidiuretic hormone (ADH) (Ref) or may cause nephrogenic SIADH by increasing the sensitivity of the kidney to ADH (Ref).
Onset: Intermediate; usually develops within the first few weeks of treatment (Ref)
Risk factors:
• Older age (Ref)
• Females (Ref)
• Concomitant use of diuretics (Ref)
• Low body weight (Ref)
• Lower baseline serum sodium concentration (Ref)
• Volume depletion (Ref)
• History of hyponatremia (potential risk factor) (Ref)
• Symptoms of psychosis (potential risk factor) (Ref)
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, changes in vision, swelling, and redness, which can rapidly lead to permanent blindness if not treated (Ref). In addition, SSRIs may be associated with an increased risk of cataract development (Ref).
Mechanism: AACG: Unclear; hypothesized SSRIs may increase the intraocular pressure via serotonergic effects on ciliary body muscle activation and pupil dilation (Ref).
Risk factors:
For AACG:
• Females (Ref)
• ≥50 years of age (slight increase) (Ref)
• Hyperopia (slight increase) (Ref)
• Personal or family history of AACG (Ref)
• Inuit or Asian descent (Ref)
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 dysfunction 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).
Mechanism: Increases in serotonin may affect other hormones and neurotransmitters involved in sexual function; in particular, testosterone's effect on sexual arousal and dopamine's role in achieving orgasm (Ref).
Risk factors:
• Depression (sexual dysfunction is commonly associated with depression; SSRI-associated sexual dysfunction may be difficult to differentiate in treated patients) (Ref)
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 gradual dosage reduction) of an antidepressant treatment that has lasted >3 weeks, particularly a drug with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref) .
• Prior history of antidepressant withdrawal symptoms (Ref)
• High dose (Ref)
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 [Safer 2006]), 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 pain (2%), constipation (3% to 6%), decreased appetite (3%), dyspepsia (2% to 6%), flatulence (2%), toothache (2%), vomiting (3%; literature suggests incidence is higher in adolescents compared to adults, and is two- to threefold higher in children compared to adolescents [Safer 2006]), xerostomia (4% to 9%)
Genitourinary: Impotence (3%) (table 3), urinary tract infection (children ≥2%)
|
Drug (Escitalopram) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Escitalopram) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
3% |
<1% |
Males |
10 to 20 mg/day |
Major depressive disorder |
225 |
188 |
Nervous system: Abnormal dreams (3%), anorgasmia (2% to 6%), dizziness (4% to 7%), fatigue (2% to 8%), lethargy (3%), paresthesia (2%), yawning (2%)
Neuromuscular & skeletal: Back pain (children ≥2%), neck pain (≤3%), shoulder pain (≤3%)
Respiratory: Flu-like symptoms (5%), nasal congestion (children ≥2%), 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: Irritability, 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, cardiac failure, cerebrovascular accident (Douros 2018), deep vein thrombosis, edema, flushing, hypertensive crisis, hypotension, orthostatic hypotension, phlebitis, prolonged QT interval on ECG (Funk 2013), pulmonary embolism, syncope, tachycardia, thrombosis, torsades de pointes, ventricular arrhythmia, ventricular tachycardia
Dermatologic: Alopecia, dermatitis, ecchymoses, erythema multiforme, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Diabetes mellitus, heavy menstrual bleeding, hypercholesterolemia, hyperglycemia, hyperprolactinemia, hypoglycemia, hypokalemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranges from <1% to as high as 32% [Jacob 2006; Rawal 2017]), SIADH (Raj 2018)
Gastrointestinal: Dysphagia, gastroesophageal reflux disease, gastrointestinal hemorrhage (Kumar 2009), pancreatitis
Genitourinary: Dysuria, erectile dysfunction, orgasm disturbance, priapism (rare: <1%) (Budak 2019), sexual disorder (common: ≥10%) (Roy 2019), spontaneous abortion, urinary retention
Hematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, hemolytic anemia, hypoprothrombinemia, immune thrombocytopenia, increased INR, leukopenia, rectal hemorrhage, thrombocytopenia
Hepatic: Hepatic failure, hepatic necrosis, hepatitis, increased liver enzymes, increased serum bilirubin
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Abnormal gait, aggressive behavior, agitated depression, agitation, akathisia, amnesia, anxiety, apathy, ataxia, choreoathetosis, delirium, delusion, depersonalization, dystonia, extrapyramidal reaction, hallucination, hyperactive behavior (agitation, hyperactivation, hyperkinesis, restlessness occurring in children at a two- to threefold higher incidence compared to adolescents; it is more prevalent in adolescents compared to adults) (Safer 2006), hypoesthesia, hypomania (rare: <1%) (Sharma 2009b), mania (rare: <1%) (Prapotnik 2004), myasthenia, myoclonus, neuroleptic malignant syndrome (Stevens 2008), nightmares, panic, paranoid ideation, parkinsonism, psychosis, restless leg syndrome, seizure, serotonin syndrome (rare: <1%) (Huska 2007; Sanyal 2010), suicidal ideation (Madsen 2019), suicidal tendencies, tardive dyskinesia, vertigo, withdrawal syndrome (De Berardis 2014; Fava 2015)
Neuromuscular & skeletal: Bone fracture (fragility) (Khanassov 2018), dyskinesia, rhabdomyolysis, tremor
Ophthalmic: Acute angle-closure glaucoma (rare: <1%) (AlQuorain 2016; Zelefsky 2006), diplopia, mydriasis, nystagmus disorder, subconjunctival hemorrhage (Sharma 2009a), visual disturbance
Renal: Acute renal failure
Respiratory: Dyspnea, epistaxis (rare: <1%) (Lake 2000)
Hypersensitivity to escitalopram, citalopram, or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either escitalopram or the MAO inhibitor); initiation of escitalopram in a patient receiving linezolid or intravenous methylene blue; concurrent use of pimozide
Canadian labeling: Additional contraindications (not in US labeling): Known QT-interval prolongation or congenital long QT syndrome
Disease-related concerns:
• Cardiovascular disease: Patients with a recent history of MI or unstable heart disease were excluded from clinical trials; use with caution.
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and half-life and plasma concentrations are increased; dosage adjustment may be required. 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 adjustment may be required.
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).
Substrate of CYP2C19 (major), 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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider therapy modification
Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy
Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Brexanolone: Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination
BuPROPion: May enhance the adverse/toxic effect of Escitalopram. Risk C: Monitor therapy
BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Escitalopram. Risk C: Monitor therapy
Citalopram: May enhance the antiplatelet effect of Escitalopram. Escitalopram may enhance the QTc-prolonging effect of Citalopram. Escitalopram may enhance the serotonergic effect of Citalopram. This could result in serotonin syndrome. Risk X: Avoid combination
CloZAPine: May enhance the QTc-prolonging effect of Escitalopram. CloZAPine may enhance the serotonergic effect of Escitalopram. This could result in serotonin syndrome. 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 therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May increase the serum concentration of Escitalopram. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Escitalopram. Risk C: Monitor therapy
Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Dabrafenib: May enhance the QTc-prolonging effect 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 therapy
Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
DULoxetine: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of DULoxetine. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of DULoxetine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Esomeprazole: May increase the serum concentration of Escitalopram. Risk C: Monitor therapy
Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Fexinidazole: May enhance the QTc-prolonging effect of Escitalopram. Fexinidazole may increase the 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 therapy
Fluconazole: Escitalopram may enhance the QTc-prolonging effect of Fluconazole. Fluconazole may increase the serum concentration of Escitalopram. Risk C: Monitor therapy
Fluorouracil Products: May enhance the QTc-prolonging effect 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 therapy
Gilteritinib: Escitalopram may enhance the QTc-prolonging effect of Gilteritinib. Gilteritinib may diminish the therapeutic effect of Escitalopram. 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
Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Haloperidol may enhance the serotonergic effect 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 therapy
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Hydroxychloroquine: Escitalopram may enhance the hypoglycemic effect of Hydroxychloroquine. Hydroxychloroquine may enhance the QTc-prolonging effect of Escitalopram. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy
Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Levomethadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lofexidine: May enhance the QTc-prolonging effect of Escitalopram. Escitalopram may enhance the QTc-prolonging effect 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 therapy
Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the serotonergic effect 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 therapy
MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Mivacurium: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Nefazodone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Omeprazole: May increase the serum concentration of Escitalopram. Risk C: Monitor therapy
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may enhance the serotonergic effect 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 therapy
Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy
Pentamidine (Systemic): May enhance the QTc-prolonging effect 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 therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect 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 enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Escitalopram may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antipsychotics (Moderate Risk) may enhance the serotonergic effect 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 therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect 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 therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect 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 therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Escitalopram may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect 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 therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Escitalopram may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor therapy
Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Rasagiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid combination
Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Safinamide: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of other Selective Serotonin Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of other Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Selegiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Risk X: Avoid combination
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
TraMADol: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. 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 therapy
Tricyclic Antidepressants: May enhance the serotonergic effect of Escitalopram. Escitalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voriconazole: Escitalopram may enhance the QTc-prolonging effect of Voriconazole. Voriconazole may increase the serum concentration of Escitalopram. Risk C: Monitor therapy
Vortioxetine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Vortioxetine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Escitalopram is approved for the treatment of unipolar major depressive disorder. If treatment for major depressive disorder is initiated for the first time in a patient planning to become pregnant, escitalopram is not one of the preferred selective serotonin reuptake inhibitors (SSRIs) (Larsen 2015).
Escitalopram is also used off label for the treatment of premenstrual dysphoric disorder. For patients attempting to conceive, symptom onset dosing may be beneficial to minimize potential fetal exposure (Ismaili 2016; Lanza di Scalea 2019).
SSRIs may be associated with male and female treatment-emergent sexual dysfunction (Coskuner 2018; WFSBP [Bauer 2013]). Decreased libido and anorgasmia have been reported in females; ejaculation disorder, decreased libido, and impotence have been reported in males with escitalopram use. This may also be a manifestation of the psychiatric disorder. The actual risk associated with escitalopram is not known. SSRI-related sexual dysfunction may resolve with dose reduction or discontinuation of the SSRI; in some cases, sexual dysfunction may persist once therapy is discontinued (Coskuner 2018; Jing 2016; Waldinger 2015).
Amenorrhea followed by a false positive urine pregnancy test was reported in a patient treated with escitalopram for premenstrual dysphoric disorder and panic disorder. After ~4 months of escitalopram treatment, she missed a period and took a home pregnancy test, which was positive. A serum pregnancy test was negative. Escitalopram was discontinued and menses resumed 2 weeks later (Selvaraj 2017).
Escitalopram and desmethylcitalopram cross the placenta and are distributed into the amniotic fluid (Loughhead 2006; Rampono 2009; Sit 2011).
As a class, selective serotonin reuptake inhibitors (SSRIs) have been evaluated extensively in pregnant patients. Studies focusing on newborn outcomes following first trimester exposure often have inconsistent results due to differences in study design and confounders such as maternal disease and social factors (Anderson 2020; Biffi 2020; Fitton 2020; Reefhuis 2015; Womersley 2017). Adverse effects in the newborn following SSRI exposure late in the third trimester can include apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, respiratory distress, seizures, temperature instability, tremor, and vomiting. Prolonged hospitalization, respiratory support, or tube feedings may be required. Symptoms may be due to the toxicity of the SSRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn has been reported with SSRI exposure; although the absolute risk is small, monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). The long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are not known (CANMAT [MacQueen 2016]).
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of 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).
If treatment for major depressive disorder is initiated for the first time during pregnancy, escitalopram can be considered (CANMAT [MacQueen 2016]); however, if pregnancy occurs during treatment, escitalopram can be continued (Larsen 2015). Untreated or inadequately treated psychiatric illness may lead to poor adherence with prenatal care and adverse pregnancy outcomes. Therapy with antidepressants during pregnancy should be individualized; treatment with antidepressant medication is recommended for pregnant patients with severe major depressive disorder (ACOG 2008; CANMAT [MacQueen 2016]). Patients treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued (68%) as compared to pregnant patients who continue taking antidepressant medications (26%) (Cohen 2006).
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Patients exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants. Pregnant patients 18 to 45 years of age or their health care providers may contact the registry to enroll; enrollment should be done as early in pregnancy as possible (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/).
Escitalopram and its desmethylcitalopram (DCT) metabolite are present in breast milk.
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). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).
In one review, the RID of escitalopram was calculated using pooled data from 12 mother/infant pairs providing an estimated daily infant dose via breast milk of 0.04 mg/day. 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). 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 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).
Agitation, poor feeding, poor weight gain, restlessness, and excessive sedation have been reported in infants exposed to escitalopram via breast milk. Infants exposed to a selective serotonin reuptake inhibitor (SSRI) via breast milk should be monitored for irritability and changes in sleep, feeding patterns, and behavior, as well as growth and development (ABM [Sriraman 2015]; Sachs 2013; Weissman 2004; WFSBP [Bauer 2013]).
Maternal use of an SSRI during pregnancy may cause delayed lactogenesis (Marshall 2010); however, the underlying maternal illness may also influence this outcome (Grzeskowiak 2018). Untreated severe or chronic depression in the postpartum period also has negative effects on the mother (Slomian 2019).
Psychotherapy or other nonmedication therapies are recommended for the initial treatment of mild depression in breastfeeding patients; antidepressant medication is recommended when psychotherapy is not an option or symptoms are moderate to severe. If a specific SSRI was used effectively during pregnancy, it can be continued while breastfeeding if no contraindications exist (ABM [Sriraman 2015]). 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. When first initiating an antidepressant in a breastfeeding patient, agents other than escitalopram are preferred. Patients successfully treated with escitalopram during pregnancy may continue use while breastfeeding if there are no other contraindications (ABM [Sriraman 2015]; Larsen 2015).
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); signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures.
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 2012]); 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 2012]).
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%.
Solution (Escitalopram Oxalate Oral)
5 mg/5 mL (per mL): $0.79 - $0.96
Tablets (Escitalopram Oxalate Oral)
5 mg (per each): $4.14 - $4.51
10 mg (per each): $4.33 - $4.72
20 mg (per each): $4.51 - $4.92
Tablets (Lexapro Oral)
5 mg (per each): $15.24
10 mg (per each): $15.94
20 mg (per each): $16.63
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