Drug Monograph
Escitalopram (Lexapro)
escitalopram oxalate — S-enantiomer of citalopram
Pharmacokinetic Profile
Half-Life
27–33 h
Metabolism
CYP2C19, CYP2D6, CYP3A4
Protein Binding
56% (low)
Tmax
~3–5 h
Volume of Distribution
~1,100 L (~12–20 L/kg)
Clinical Information
Drug Class
SSRI
Available Doses
Tablets: 5, 10, 20 mg; Oral solution: 1 mg/mL
Route
Oral
Renal Adjustment
Mild–moderate: none; Severe: caution
Hepatic Adjustment
Recommended max 10 mg/day
Pregnancy
Third trimester: neonatal withdrawal risk; PPHN risk
Lactation
Present in breast milk
Schedule
Rx only; Not a controlled substance
Generic Available
Yes
Black Box Warning
Suicidal thoughts & behaviors in youth/young adults
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Major depressive disorder (MDD) | Adults and paediatric patients ≥12 years | Monotherapy (acute and maintenance) | FDA Approved |
| Generalised anxiety disorder (GAD) | Adults and paediatric patients ≥7 years | Monotherapy (acute treatment) | FDA Approved |
Escitalopram is the pharmacologically active S-enantiomer of the racemic SSRI citalopram, offering enhanced serotonin transporter selectivity. It is one of the most commonly prescribed antidepressants globally and has been identified in large network meta-analyses as among the most effective and best-tolerated first-line treatments for major depression. The 2024 PI update expanded the GAD paediatric indication to include children aged 7 years and older.
Off-Label Uses
Panic disorder, social anxiety disorder, OCD, PTSD, PMDD: Commonly prescribed off-label with moderate-quality evidence for each. Vasomotor symptoms (menopause): Evidence quality: Moderate. Premature ejaculation: Evidence quality: Low–Moderate.
Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| MDD — adults | 10 mg/day | 10 mg/day | 20 mg/day | Once daily, morning or evening, with or without food. May increase after ≥1 week. Fixed-dose trials showed no greater benefit of 20 mg over 10 mg. 10 mg is both the starting and recommended dose for most patients. |
| MDD — paediatric (≥12 yr) | 10 mg/day | 10 mg/day | 20 mg/day | May increase after ≥3 weeks if clinically needed. Longer titration interval in adolescents vs adults. |
| GAD — adults | 10 mg/day | 10 mg/day | 20 mg/day | May increase after ≥1 week. |
| GAD — paediatric (≥7 yr) | 10 mg/day | 10 mg/day | 20 mg/day | May increase after ≥2 weeks. Recently approved for ages 7+; safety and efficacy not established below 7 years for GAD. |
| Elderly patients (≥65 yr) | 10 mg/day recommended | 10 mg/day | Half-life increased ~50% in elderly; Cmax unchanged. Higher sensitivity possible. | |
| Hepatic impairment | 10 mg/day recommended | 10 mg/day | Reduced clearance of racemic citalopram in hepatic impairment. | |
| Severe renal impairment (CrCl <20) | Not determined; use with caution | No adjustment for mild–moderate impairment. Unchanged drug is a minor elimination route. | ||
Clinical Pearl: 10 mg Is Often Sufficient
Unlike many SSRIs that require uptitration, escitalopram 10 mg/day is both the starting and the recommended therapeutic dose for most patients. A fixed-dose trial failed to demonstrate a greater benefit of 20 mg over 10 mg for MDD, though some individual patients may benefit from the higher dose. Adverse reactions at 20 mg are approximately double those at 10 mg in several categories (insomnia, diarrhoea, dry mouth, somnolence). This makes escitalopram one of the simplest SSRIs to initiate.
Pharmacology
Mechanism of Action
Escitalopram is the therapeutically active S-enantiomer of the racemic drug citalopram and is the most selective of the SSRIs for the serotonin transporter (SERT). It inhibits the reuptake of serotonin into the presynaptic neuron, increasing serotonin availability in the synaptic cleft. Unlike citalopram, the R-enantiomer does not contribute to SERT inhibition and may even partially antagonise the binding of the S-enantiomer, which is one rationale for developing escitalopram as a single-enantiomer product. Escitalopram has negligible affinity for other monoamine transporters and receptor systems, contributing to its favourable tolerability profile among SSRIs.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Tmax ~3–5 h; food does not affect absorption; dose-proportional and linear PK over 10–30 mg/day range; high oral bioavailability | Can be taken with or without food at any time of day; predictable pharmacokinetics across the dosing range |
| Distribution | Vd ~1,100 L (~12–20 L/kg); protein binding 56% (low); crosses blood-brain barrier | Low protein binding (vs 98% for sertraline) means protein displacement interactions are unlikely; wide tissue distribution |
| Metabolism | Hepatic via CYP2C19 (primary), CYP2D6, CYP3A4; principal metabolite: S-desmethylcitalopram (S-DCT, ~1/3 parent level, weak SERT inhibitor); S-DDCT typically below quantifiable levels; escitalopram is a weak CYP2D6 inhibitor | CYP2C19 is the main metabolising enzyme — CYP2C19 poor metabolisers may have elevated escitalopram levels. Weak CYP2D6 inhibition can raise levels of some substrates (desipramine AUC increased ~100% at 20 mg/day) |
| Elimination | t½ 27–33 h; steady state in 7–10 days; accumulation ratio ~2.2–2.5x; renal excretion of unchanged drug is minor; elderly: t½ increased ~50%, Cmax unchanged | Once-daily dosing appropriate; ~1 week to steady state informs minimum interval between dose changes; lower doses in elderly due to increased exposure |
Side Effects
≥5%Very Common — MDD Trials (N=715 vs 592 Placebo)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 15% (vs 7% placebo) | Most common AE; usually self-limiting within 1–2 weeks. Taking with food may help |
| Insomnia | 9% (vs 4% placebo) | Consider morning dosing; dose-dependent (14% at 20 mg vs 7% at 10 mg) |
| Ejaculation disorder (males) | 9% (vs <1% placebo) | Primarily ejaculatory delay; underreported. Inquire proactively |
| Somnolence | 6% (vs 2% placebo) | Dose-dependent (9% at 20 mg). Evening dosing may help if daytime sedation occurs |
| Dry mouth | 6% (vs 5% placebo) | Mild; small difference from placebo |
| Dizziness | 5% (vs 3% placebo) | Usually mild and transient |
| Sweating increased | 5% (vs 2% placebo) | Dose-dependent (8% at 20 mg) |
| Fatigue | 5% (vs 2% placebo) | Differentiate from depression-related fatigue |
| Diarrhoea | 8% (vs 5% placebo) | Dose-dependent (14% at 20 mg vs 6% at 10 mg) |
2–5%Common (MDD Trials)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Decreased appetite | 3% (vs 1% placebo) | Monitor weight, especially in paediatric patients |
| Decreased libido | 3% (vs 1% placebo) | Class effect; inquire proactively |
| Constipation | 3% (vs 1% placebo) | Dose-dependent (6% at 20 mg) |
| Impotence (males) | 3% (vs <1% placebo) | Address alongside ejaculatory dysfunction |
| Indigestion | 3% (vs 1% placebo) | Dose-dependent (6% at 20 mg) |
| Anorgasmia (females) | 2% (vs <1% placebo) | Underreported |
SeriousSerious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Suicidal thoughts/behaviours | 14 per 1,000 (<18 yr); 5 per 1,000 (18–24 yr) vs placebo | First weeks or dose changes | Close monitoring; involve family/caregivers. FDA Boxed Warning |
| Serotonin syndrome | Rare | Hours to days after serotonergic initiation/increase | Discontinue all serotonergic agents; supportive care; cyproheptadine for severe cases |
| QTc prolongation / TdP | Rare (post-marketing; dose-related) | Variable | ECG in at-risk patients; avoid QTc-prolonging co-medications; note: citalopram has a stronger QTc signal than escitalopram |
| Hyponatraemia (SIADH) | Uncommon (higher risk in elderly) | First weeks | Check sodium if confusion/weakness/falls; discontinue if symptomatic. Cases with Na <110 mmol/L reported |
| Activation of mania/hypomania | 0.1% in MDD trials (1/715) | First weeks | Screen for bipolar disorder before prescribing; discontinue if mania develops |
| Seizures | Rare | Variable | Use with caution in seizure disorders; discontinue if seizures occur |
| Angle-closure glaucoma | Rare | Variable | Avoid in untreated anatomically narrow angles |
DiscontinuationDiscontinuation Rates
MDD Adults
6% vs 2% placebo
Key: 10 mg discontinuation rate (4%) was similar to placebo (3%); 20 mg rate was 10%. Top reasons: nausea (2%), ejaculation disorder (2% of males)
GAD Adults
8% vs 4% placebo
Top reasons: Nausea (2%), insomnia (1%), fatigue (1%)
Dose-Dependent Adverse Reactions
In fixed-dose MDD trials, the overall AE incidence at 10 mg (66%) was similar to placebo (61%), while the 20 mg group showed a notably higher rate (86%). Specific AEs approximately doubling from 10 mg to 20 mg include: insomnia (7% to 14%), diarrhoea (6% to 14%), dry mouth (4% to 9%), somnolence (4% to 9%), sweating (3% to 8%), constipation (3% to 6%), and indigestion (2% to 6%). This supports starting at 10 mg and reserving 20 mg for non-responders.
Drug Interactions
Escitalopram is metabolised primarily by CYP2C19, with contributions from CYP2D6 and CYP3A4. It is a weak inhibitor of CYP2D6. Its low protein binding (56%) and negligible effects on most CYP isoforms and P-glycoprotein make it one of the SSRIs with the lowest drug interaction potential. The most critical interactions involve MAOIs (contraindicated), pimozide (contraindicated), and other serotonergic agents.
MajorMAOIs
MechanismDual serotonin reuptake inhibition and metabolism blockade
EffectPotentially fatal serotonin syndrome
ManagementContraindicated. Minimum 14-day washout in either direction
FDA PI — ContraindicationMajorPimozide
MechanismPotential for increased pimozide levels and additive QTc prolongation
EffectRisk of QTc prolongation and ventricular arrhythmias
ManagementContraindicated
FDA PI — ContraindicationMajorOther serotonergic agents
MechanismAdditive serotonergic activity
EffectIncreased serotonin syndrome risk
ManagementAvoid concomitant SSRIs/SNRIs/tryptophan; monitor with triptans, lithium, tramadol, fentanyl, buspirone, St. John’s Wort
FDA PIModerateCYP2D6 substrates (desipramine, metoprolol)
MechanismEscitalopram weakly inhibits CYP2D6
EffectDesipramine AUC increased ~100%, Cmax ~40% at escitalopram 20 mg; metoprolol AUC +82%, Cmax +50%
ManagementMonitor for substrate toxicity; may need dose reduction of CYP2D6 substrate
FDA PI / Published dataModerateCYP2C19 inhibitors (omeprazole, cimetidine)
MechanismInhibition of escitalopram’s primary metabolising enzyme
EffectOmeprazole increased escitalopram exposure by ~51%; cimetidine by ~72%
ManagementGenerally not considered clinically significant, but monitor for AEs at higher exposures
FDA PIModerateNSAIDs / Anticoagulants / Antiplatelets
MechanismSSRI-mediated platelet serotonin depletion + pharmacodynamic interaction
EffectIncreased GI and other bleeding risk
ManagementMonitor for bleeding; monitor INR with warfarin
FDA PIMonitoring
- Suicidality / Clinical WorseningWeekly × 4 wk, biweekly × 4 wk, then monthly
RoutineFDA Boxed Warning. Monitor closely in patients <25, during first months, and at dose changes. Engage caregivers. - Symptom ResponseBaseline, then q2–4 wk
RoutineUse PHQ-9 (depression) or GAD-7 (anxiety). Allow 4–6 weeks at adequate dose before assessing response. - Sexual FunctionBaseline, then at follow-up
RoutineInquire proactively. PI specifically advises pre-treatment assessment and ongoing monitoring. Underreporting is common. - Serum SodiumIf at-risk or symptomatic
Trigger-basedHyponatraemia (SIADH) more likely in elderly and those on diuretics. Check if confusion, weakness, or falls develop. - Bipolar ScreeningBefore initiation
RoutineScreen for personal/family history of bipolar disorder, mania, hypomania before starting. - Weight / Growth (Paediatric)Baseline, then q3 months
RoutineDecreased appetite and weight changes observed with SSRIs. Monitor height and weight in children and adolescents.
Contraindications & Cautions
Absolute Contraindications
- Concomitant MAOI use or within 14 days of stopping MAOIs (including linezolid and IV methylene blue).
- Concomitant pimozide.
- Known hypersensitivity to escitalopram or citalopram or any inactive ingredient.
Relative Contraindications (Specialist Input Recommended)
- Unscreened or known bipolar disorder: Screen before prescribing.
- Untreated anatomically narrow angles: SSRI-induced mydriasis may trigger angle-closure glaucoma.
- CYP2C19 poor metabolisers: May accumulate escitalopram — consider lower starting dose or therapeutic drug monitoring.
Use with Caution
- Pregnancy: Third trimester SSRI exposure associated with neonatal withdrawal and PPHN risk. No adequate controlled studies in pregnant women. Weigh risk-benefit.
- Seizure disorders: Not systematically evaluated; use with caution.
- Elderly (≥65): t½ increased ~50%; recommended max 10 mg/day; higher SIADH/hyponatraemia risk.
- Severe renal impairment (CrCl <20): Appropriate dose not determined; use with caution.
- Concomitant anticoagulants/NSAIDs: Increased bleeding risk.
FDA Boxed Warning
Suicidal Thoughts and Behaviours in Paediatric and Young Adult Patients
Antidepressants increased the risk of suicidal thoughts and behaviours in patients <18 years (14 additional per 1,000) and 18–24 years (5 additional per 1,000). In adults 25–64, there was a reduction (1 fewer per 1,000), and in those ≥65, a further reduction (6 fewer per 1,000). Monitor all patients closely, especially during initiation and dose changes. Escitalopram is not approved for use in patients <7 years of age.
Patient Counselling
Purpose of Therapy
Escitalopram works by increasing serotonin levels in the brain to help improve mood and reduce anxiety. Most patients find that 10 mg daily is sufficient. Improvement typically begins within 1–4 weeks, with full benefits often taking 4–6 weeks. Treatment should be continued even after feeling better, as stopping prematurely increases relapse risk.
How to Take
Take once daily, morning or evening, with or without food. Swallow tablets whole; scored tablets can be halved if needed for a 5 mg dose.
Mood Changes & Suicidal Thoughts
Tell patientIn some people, especially under 25, antidepressants may initially cause new or worsening thoughts of self-harm. This risk is highest in the first weeks. Have a trusted person check in regularly.
Call prescriberImmediately if you experience worsening depression, anxiety, agitation, panic, irritability, or thoughts of harming yourself.
Nausea & GI Symptoms
Tell patientNausea is the most common side effect and usually improves within the first 1–2 weeks. Taking escitalopram with food can help.
Call prescriberIf nausea is severe, persistent beyond 2 weeks, or causing inability to eat or drink.
Sexual Side Effects
Tell patientSome patients experience changes in sexual desire, performance, or satisfaction. This is a known class effect. If it affects your quality of life, discuss management options rather than stopping medication abruptly.
Call prescriberIf sexual side effects are significantly impacting your well-being or relationship.
Stopping Treatment
Tell patientDo not stop escitalopram suddenly. Abrupt discontinuation can cause dizziness, irritability, electric-shock sensations, nausea, and sleep problems. Always taper gradually under medical guidance.
Call prescriberIf you experience distressing symptoms when reducing or stopping your dose.
Serotonin Syndrome
Tell patientInform all healthcare providers that you take escitalopram. Combining it with certain medications (migraine drugs, pain medications like tramadol, supplements like St. John’s Wort) can cause a dangerous reaction.
Call prescriberSeek emergency care for agitation, confusion, rapid heartbeat, high fever, muscle stiffness/twitching, or loss of coordination.
Sources
Regulatory (PI / SmPC)
- AbbVie Inc. LEXAPRO (escitalopram) tablets and oral solution: US Prescribing Information. NDA 021323. Revised 10/2023. FDA LabelPrimary source for all dosing, pharmacokinetic, safety, and indication data in this monograph.
Key Clinical Trials
- Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357–1366. doi:10.1016/S0140-6736(17)32802-7Landmark NMA identifying escitalopram as among the most effective and acceptable first-line antidepressants for MDD.
- Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry. 2002;63(4):331–336. doi:10.4088/JCP.v63n0410Fixed-dose trial comparing 10 mg and 20 mg escitalopram to placebo; demonstrated efficacy of both doses with no additional benefit at 20 mg over 10 mg.
- Davidson JR, Bose A, Korotzer A, Zheng H. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo-controlled, flexible-dose study. Depress Anxiety. 2004;21(3):100–108. doi:10.1002/da.20069Pivotal RCT demonstrating escitalopram efficacy for GAD, supporting FDA approval for this indication.
- Wagner KD, Jonas J, Findling RL, Ventura D, Saikali K. A double-blind, randomized, placebo-controlled trial of escitalopram in the treatment of pediatric depression. J Am Acad Child Adolesc Psychiatry. 2006;45(3):280–288. doi:10.1097/01.chi.0000192250.38400.9eKey paediatric MDD trial supporting FDA approval of escitalopram in adolescents aged 12–17.
Guidelines
- National Institute for Health and Care Excellence (NICE). Depression in adults: treatment and management. NICE guideline [NG222]. June 2022. NICE NG222UK guideline recommending SSRIs including escitalopram as first-line pharmacotherapy for moderate-to-severe depression.
- National Institute for Health and Care Excellence (NICE). Generalised anxiety disorder and panic disorder in adults: management. NICE guideline [CG113]. Updated June 2020. NICE CG113UK guideline recommending SSRIs as first-line pharmacotherapy for GAD; sertraline cited as preferred but escitalopram widely used.
Mechanistic / Basic Science
- Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and sertraline: are they all alike? Int Clin Psychopharmacol. 2014;29(4):185–196. doi:10.1097/YIC.0000000000000023Comparative review of SSRI pharmacology; discusses escitalopram’s superior SERT selectivity and the R-enantiomer hypothesis.
- Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001;50(5):345–350. doi:10.1016/S0006-3223(01)01145-3Key study demonstrating escitalopram’s high SERT selectivity compared to other SSRIs.
Pharmacokinetics / Special Populations
- Rao N. The clinical pharmacokinetics of escitalopram. Clin Pharmacokinet. 2007;46(4):281–290. doi:10.2165/00003088-200746040-00002Comprehensive PK review covering absorption, distribution, metabolism, elimination, and special populations for escitalopram.
- Sogaard B, Mengel H, Rao N, Larsen F. The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects. J Clin Pharmacol. 2005;45(12):1400–1406. doi:10.1177/0091270005280860Definitive PK study establishing IV and oral pharmacokinetic parameters (Vd 1100 L, CL 31 L/h, t½ 27–33 h, high bioavailability).
- Malling D, Poulsen MN, Sogaard B. The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram. Br J Clin Pharmacol. 2005;60(3):287–290. doi:10.1111/j.1365-2125.2005.02423.xDrug interaction study showing cimetidine and omeprazole increase escitalopram exposure by 72% and 51% respectively, considered not clinically significant.