Introduction
Escitalopram is a selective serotonin reuptake inhibitor (SSRI) widely prescribed for the treatment of major depressive disorder and anxiety disorders. As the S-enantiomer of citalopram, it represents a refined molecular formulation with improved selectivity and potentially enhanced therapeutic profile. First approved by the FDA in 2002, escitalopram has become one of the most commonly prescribed antidepressants worldwide due to its favorable efficacy and tolerability profile.
Mechanism of Action
Escitalopram exerts its therapeutic effects through potent and selective inhibition of serotonin reuptake at the presynaptic neuronal membrane. The drug binds with high affinity to the serotonin transporter (SERT), blocking serotonin reuptake and increasing synaptic concentrations of serotonin in the central nervous system. This enhanced serotonergic activity is believed to underlie its antidepressant and anxiolytic effects. Unlike racemic citalopram, escitalopram demonstrates approximately 30-fold greater potency for serotonin reuptake inhibition with minimal affinity for other neurotransmitter systems, resulting in reduced side effects associated with non-selective receptor binding.
Indications
- FDA-approved:
- Major depressive disorder (MDD) in adults and adolescents aged 12-17 years - Generalized anxiety disorder (GAD) in adults - Panic disorder with or without agoraphobia
- Off-label uses (supported by clinical evidence):
- Social anxiety disorder - Obsessive-compulsive disorder - Post-traumatic stress disorder - Premenstrual dysphoric disorder - Vasomotor symptoms of menopause
Dosage and Administration
Standard dosing:- Depression and generalized anxiety: Initial dose 10 mg once daily, may increase to 20 mg daily after minimum 1 week
- Panic disorder: Initial dose 5 mg daily, increase to 10 mg daily after 1 week
- Oral administration with or without food
- Tablets should be swallowed whole with water
- Morning administration recommended to minimize potential sleep disturbances
- Hepatic impairment: Maximum dose 10 mg daily
- Renal impairment: Caution advised in severe impairment; no specific dosage adjustment
- Elderly: Consider lower starting dose (5 mg daily)
- CYP2C19 poor metabolizers: Maximum dose 10 mg daily
Pharmacokinetics
Absorption: Well absorbed orally with absolute bioavailability of approximately 80%. Peak plasma concentrations reached within 3-5 hours post-administration. Food does not significantly affect absorption. Distribution: Extensive tissue distribution with apparent volume of distribution of 12-26 L/kg. Plasma protein binding is approximately 56%, primarily to albumin and α1-acid glycoprotein. Metabolism: Primarily metabolized in the liver via cytochrome P450 enzymes, mainly CYP2C19 and to a lesser extent CYP3A4 and CYP2D6. Demethylation and deamination are the primary metabolic pathways. Elimination: Terminal elimination half-life of approximately 27-32 hours. Steady-state concentrations achieved within approximately one week. Excretion is primarily hepatic with metabolites eliminated in urine (50%) and feces (46%). Less than 10% excreted unchanged in urine.Contraindications
- Hypersensitivity to escitalopram, citalopram, or any component of the formulation
- Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation
- Concurrent use with pimozide
- Known congenital long QT syndrome
Warnings and Precautions
Boxed Warning:- Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults (ages 18-24) during initial treatment periods
- Serotonin syndrome: Risk increased with concomitant serotonergic drugs
- QT interval prolongation: Dose-dependent effect; monitor ECG in patients with cardiac disease
- Bleeding risk: SSRI use associated with increased risk of bleeding, especially gastrointestinal
- Activation of mania/hypomania: Screen for bipolar disorder before initiation
- Discontinuation syndrome: Taper gradually when discontinuing treatment
- Hyponatremia: Monitor sodium levels, particularly in elderly patients
- Angle-closure glaucoma: Cases reported with SSRI use
Drug Interactions
Major interactions:- MAOIs: Risk of serotonin syndrome (contraindicated)
- Other serotonergic agents: Increased risk of serotonin syndrome (tramadol, triptans, linezolid)
- Drugs that prolong QT interval: Additive effects (antiarrhythmics, antipsychotics)
- NSAIDs/aspirin: Increased bleeding risk
- CYP2C19 inhibitors: Increased escitalopram levels (omeprazole, fluvoxamine)
- Warfarin: Altered anticoagulant effect; monitor INR
- CYP3A4 inhibitors: Possible increased escitalopram levels
- Lithium: Enhanced serotonergic effects
- Tryptophan: Serotonin syndrome risk
Adverse Effects
Common (≥5%):- Nausea (15-25%)
- Headache (15-20%)
- Fatigue (5-10%)
- Insomnia (5-10%)
- Ejaculation disorder (5-10%)
- Somnolence (5-10%)
- Dry mouth (5-10%)
- Diarrhea
- Constipation
- Dizziness
- Increased sweating
- Decreased libido
- Anorgasmia
- Serotonin syndrome
- QT prolongation
- Suicidal ideation
- Seizures
- Hyponatremia
- Manic episodes
- Bleeding events
Monitoring Parameters
Baseline assessment:- Comprehensive psychiatric evaluation
- Cardiac history and ECG if risk factors present
- Renal and hepatic function tests
- Sodium levels in elderly patients
- Pregnancy test if indicated
- Therapeutic response and side effects at 2-4 week intervals
- Suicide risk assessment, especially during initial weeks
- Blood pressure and heart rate periodically
- ECG monitoring in patients with cardiac risk factors
- Serum sodium in elderly patients and those on diuretics
- Weight changes in pediatric patients
- Bleeding signs in patients on anticoagulants
- Manic symptoms in patients with bipolar risk
- Sexual dysfunction with long-term use
Patient Education
Key points to discuss:- Therapeutic effects may take 2-4 weeks to become apparent
- Do not discontinue abruptly due to risk of withdrawal symptoms
- Take medication at same time each day
- Report any worsening depression or suicidal thoughts immediately
- Avoid alcohol during treatment
- Inform all healthcare providers about escitalopram use
- Use effective contraception during treatment
- Be aware of potential drowsiness; use caution when driving or operating machinery
- Report any unusual bleeding or bruising
- Monitor for signs of serotonin syndrome (agitation, hallucinations, fever)
- Inform provider of all other medications, including over-the-counter products
- Notify provider if pregnancy occurs or is planned
- Maintain regular follow-up appointments
- Combine medication with recommended psychotherapy
- Practice good sleep hygiene
- Maintain healthy diet and exercise routine
References
1. FDA Prescribing Information: Lexapro (escitalopram oxalate) 2. Sánchez C, et al. The pharmacology of citalopram enantiomers: the antagonistic effect of R-citalopram on the escitalopram-induced increase in extracellular 5-HT. J Psychopharmacol. 2014;28(1):3-8 3. Cipriani A, 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 4. Davidson JR, et al. A psychopharmacological treatment algorithm for generalised anxiety disorder (GAD). J Psychopharmacol. 2010;24(1):3-26 5. Howland RH. A critical review of the cardiac safety of escitalopram. Expert Opin Drug Saf. 2015;14(11):1-10 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. 2010 7. National Institute for Health and Care Excellence (NICE). Depression in adults: recognition and management. Clinical guideline [CG90]. 2009 8. Spina E, et al. Clinically relevant drug interactions with newer antidepressants. CNS Drugs. 2016;30(1):1-15
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.