Introduction
Lexapro (escitalopram) is a selective serotonin reuptake inhibitor (SSRI) antidepressant approved by the FDA in 2002. It is the active S-enantiomer of citalopram and is widely prescribed for the treatment of major depressive disorder and anxiety disorders. Lexapro is considered one of the most selective SSRIs available, with well-established efficacy and tolerability.
Mechanism of Action
Escitalopram exerts its therapeutic effects through potent inhibition of serotonin reuptake at the presynaptic neuronal membrane. It binds with high affinity to the human serotonin transporter (SERT), preventing serotonin reuptake into presynaptic neurons. This action increases synaptic concentrations of serotonin in the central nervous system, enhancing serotonergic neurotransmission. Escitalopram has minimal affinity for adrenergic, dopaminergic, histaminergic, and muscarinic receptors, contributing to its favorable side effect profile.
Indications
- Major Depressive Disorder (MDD) in adults and adolescents aged 12-17 years
- Generalized Anxiety Disorder (GAD) in adults
- Off-label uses include: panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder
Dosage and Administration
Adults:- MDD and GAD: Initial dose 10 mg once daily
- May increase to 20 mg daily after minimum of 1 week
- Maximum recommended dose: 20 mg/day
- Recommended dose: 10 mg daily
- Severe hepatic impairment: Maximum 10 mg daily
- Mild to moderate impairment: No dosage adjustment needed
- Severe renal impairment: Use with caution
- Oral administration with or without food
- Tablets should be swallowed whole with water
- Liquid formulation available (5 mg/5 mL)
Pharmacokinetics
Absorption: Well absorbed after oral administration with peak plasma concentrations occurring approximately 5 hours post-dose. Bioavailability is approximately 80%. Distribution: Mean volume of distribution is 12 L/kg. Plasma protein binding is approximately 56%. Metabolism: Primarily metabolized in the liver by cytochrome P450 enzymes CYP2C19, CYP3A4, and CYP2D6 to demethylated and didemethylated metabolites. The S-demethylated metabolite (S-desmethylcitalopram) has weak SSRI activity. Elimination: Terminal half-life is approximately 27-32 hours. Primarily excreted as metabolites in urine (80%) and feces (20%).Contraindications
- Hypersensitivity to escitalopram or any component of the formulation
- Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI therapy
- Concurrent use with pimozide
- Patients taking linezolid or intravenous methylene blue
Warnings and Precautions
Suicidal Thoughts and Behaviors: Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Monitor closely for clinical worsening and emergence of suicidal behaviors. Serotonin Syndrome: Risk particularly with concomitant use of other serotonergic drugs. Symptoms may include mental status changes, autonomic instability, neuromuscular symptoms, and gastrointestinal symptoms. QT Prolongation: Dose-dependent QT interval prolongation. Avoid use in patients with congenital long QT syndrome, and consider ECG monitoring in patients with conditions that predispose to arrhythmias. Discontinuation Syndrome: Abrupt discontinuation may lead to dizziness, sensory disturbances, agitation, anxiety, and other symptoms. Taper dose gradually when discontinuing treatment. Bleeding Risk: SSRI use may increase risk of bleeding events, particularly when used with NSAIDs, aspirin, or other drugs that affect coagulation. Hyponatremia: SSRI use can cause syndrome of inappropriate antidiuretic hormone secretion (SIADH), particularly in elderly patients. Activation of Mania/Hypomania: May occur in patients with bipolar disorder. Screen patients for bipolar disorder before initiating treatment.Drug Interactions
MAOIs: Contraindicated due to risk of serotonin syndrome Serotonergic drugs: Increased risk of serotonin syndrome with tramadol, triptans, other SSRIs/SNRIs, tricyclic antidepressants CYP2C19 inhibitors: Fluoxetine, fluvoxamine, omeprazole may increase escitalopram levels Drugs that prolong QT interval: Avoid concomitant use with other QT-prolonging drugs NSAIDs/aspirin: Increased risk of bleeding Warfarin: May increase anticoagulant effect; monitor INR closely Cimetidine: May increase escitalopram levelsAdverse Effects
Common (≥5%):- Nausea (15%)
- Insomnia (9%)
- Ejaculation disorder (9%)
- Fatigue (5%)
- Somnolence (6%)
- Increased sweating (5%)
- Suicidal thoughts and behaviors
- Serotonin syndrome
- QT prolongation and torsades de pointes
- Seizures
- Angle-closure glaucoma
- Hyponatremia
- Abnormal bleeding
- Withdrawal symptoms upon discontinuation
Monitoring Parameters
- Mental status for depression, suicidal ideation, and emergence of anxiety/agitation
- Signs and symptoms of serotonin syndrome
- Electrolytes (particularly sodium in elderly patients)
- Bleeding signs and symptoms
- ECG monitoring in patients at risk for QT prolongation
- Liver function tests in patients with hepatic impairment
- Therapeutic response and side effects at regular intervals
Patient Education
- Take medication at the same time each day
- Do not stop abruptly; consult provider for tapering instructions
- May take several weeks to achieve full therapeutic effect
- Report any worsening depression, suicidal thoughts, or unusual changes in behavior
- Avoid alcohol during treatment
- Inform all healthcare providers about Lexapro use before starting new medications
- Use caution when driving or operating machinery until effects are known
- Report any symptoms of serotonin syndrome (agitation, hallucinations, fever, sweating)
- Notify provider if pregnant, planning pregnancy, or breastfeeding
References
1. FDA Prescribing Information: Lexapro (escitalopram) tablets. Revised 2021. 2. Sánchez 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. 3. Kennedy SH, Andersen HF, Lam RW. Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J Psychiatry Neurosci. 2006;31(2):122-131. 4. 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;19(4):234-240. 5. Trivedi MH, Cutler AJ, Richards C, et al. A randomized controlled trial of the efficacy and safety of twice-daily versus once-daily escitalopram in major depressive disorder. J Clin Psychiatry. 2013;74(12):1244-1251. 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. 2010.