Escitalopram
1. Drug Name
Generic Name: Escitalopram
Brand Names: Lexapro, Cipralex, Seroplex, Escitalopram Oxalate.
2. Drug Classification
Class: Antidepressant
Subclass: Selective Serotonin Reuptake Inhibitor (SSRI)
3. Mechanism of Action
Escitalopram is a selective serotonin reuptake inhibitor (SSRI) that works by increasing the concentration of serotonin (5-hydroxytryptamine) in the brain. It does this by inhibiting the reuptake of serotonin into the presynaptic neuron, thereby increasing serotonin levels in the synaptic cleft.
Escitalopram is the S-enantiomer of citalopram, and it has a more potent and selective action on serotonin reuptake compared to its racemic counterpart.
Receptor Interaction: Unlike older antidepressants, escitalopram has minimal affinity for other receptors such as dopamine, norepinephrine, or histamine receptors, which accounts for its relatively favorable side effect profile.
4. Pharmacokinetics
Absorption:
Escitalopram is well absorbed after oral administration, with a bioavailability of approximately 80%.
Food does not significantly affect its absorption, and it can be taken with or without food.
Distribution:
Volume of Distribution (Vd): Approximately 12 L/kg, indicating good distribution into body tissues, including the brain.
Protein Binding: Escitalopram is about 56% protein-bound, primarily to albumin.
Metabolism:
Escitalopram is metabolized in the liver primarily by CYP2C19 and CYP3A4 enzymes.
The S-enantiomer is metabolized to inactive metabolites, but these have minimal pharmacological activity.
Excretion:
Half-life (t½): The elimination half-life is approximately 27 to 32 hours, which supports once-daily dosing.
Excretion: Escitalopram is excreted predominantly in the urine (mainly as metabolites), with a smaller amount excreted unchanged.
Special Considerations:
Dose adjustment may be necessary for patients with hepatic impairment or severe renal dysfunction.
5. Indications
Primary Indications:
Major Depressive Disorder (MDD): Escitalopram is commonly prescribed for the treatment of depression in adults and adolescents (12–17 years).
Generalized Anxiety Disorder (GAD): It is approved for the treatment of generalized anxiety disorder.
Off-label Uses:
Panic Disorder: Escitalopram is sometimes used off-label to treat panic attacks and panic disorder.
Obsessive-Compulsive Disorder (OCD): It is occasionally prescribed for OCD, although fluoxetine is typically preferred.
Post-Traumatic Stress Disorder (PTSD): Some clinicians use escitalopram off-label for PTSD, though SSRIs like sertraline are commonly favored.
Special Populations:
In children and adolescents, escitalopram may be prescribed for depression and anxiety, but only under close monitoring due to increased suicide risk in younger individuals.
6. Dosage and Administration
Adult Dosing:
Major Depressive Disorder: Start with 10 mg once daily, which may be increased to 20 mg/day after one week if necessary. The maximum dose is 20 mg/day.
Generalized Anxiety Disorder: Start with 10 mg once daily, with a potential increase to 20 mg/day.
Panic Disorder: Start with 5 mg daily and increase gradually to 10–20 mg daily.
Pediatric Dosing:
For adolescents (12–17 years) with MDD, the usual starting dose is 10 mg/day, with a maximum dose of 20 mg/day.
For GAD, the usual starting dose is 10 mg/day, with a maximum of 20 mg/day.
Route of Administration: Oral (tablet or oral solution).
Dosing Adjustments:
Hepatic Impairment: Lower doses should be used in patients with liver impairment (usually half of the usual adult dose).
Renal Impairment: Adjustments are generally not required unless there is significant renal dysfunction.
Escitalopram should be used with caution in elderly patients, starting at the lower end of the dosing range.
7. Contraindications
Absolute Contraindications:
Known hypersensitivity to escitalopram or any of its components.
Concomitant use with monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping an MAOI, due to the risk of serotonin syndrome.
Pimozide (an antipsychotic) due to the risk of QT prolongation and arrhythmias.
Relative Contraindications:
History of seizures, as escitalopram may lower the seizure threshold.
Caution is advised in patients with bipolar disorder due to the potential for inducing mania.
8. Warnings and Precautions
Black Box Warning:
Suicidality: Antidepressants, including escitalopram, carry a black box warning for increased risk of suicidality in children, adolescents, and young adults, particularly during the initial treatment phase.
Other Warnings:
Serotonin Syndrome: This rare but life-threatening condition can occur when escitalopram is combined with other drugs that increase serotonin levels (e.g., MAOIs, triptans, linezolid).
QT Prolongation: Escitalopram may cause QT prolongation, especially in higher doses or in patients with pre-existing cardiac conditions.
Hyponatremia: SSRI use can lead to low sodium levels (especially in elderly patients), which should be monitored.
Bleeding Risk: SSRIs, including escitalopram, may increase the risk of bleeding, particularly when taken with anticoagulants, NSAIDs, or antiplatelet agents.
9. Adverse Effects
Common Adverse Effects:
Gastrointestinal: Nausea, diarrhea, dry mouth, constipation.
Central Nervous System: Headache, insomnia, dizziness, sexual dysfunction (e.g., decreased libido, erectile dysfunction).
Less Common but Clinically Significant:
Serotonin Syndrome: Symptoms include agitation, hyperreflexia, fever, tremor, muscle rigidity, and autonomic instability.
QT prolongation: Can increase the risk of arrhythmias and Torsades de Pointes.
Hyponatremia: Particularly in elderly patients, escitalopram may cause a decrease in serum sodium levels.
Rare/Serious:
Seizures: Though rare, escitalopram may lower the seizure threshold.
Suicidal Thoughts: Increased risk in young adults during the initial treatment phase.
10. Drug Interactions
Major Drug Interactions:
MAOIs (e.g., phenelzine, tranylcypromine): Serious and potentially fatal interactions due to serotonin syndrome.
Other serotonergic drugs (e.g., triptans, linezolid, tramadol): Increase the risk of serotonin syndrome.
CYP2C19 inhibitors (e.g., omeprazole, fluconazole) can increase escitalopram levels.
CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) may also elevate escitalopram levels.
Food-Drug Interactions: No significant food-drug interactions.
Lab Test Interactions:
Prothrombin time and INR may be altered when escitalopram is combined with warfarin or other anticoagulants, increasing the risk of bleeding.
11. Clinical Pharmacology
Escitalopram’s clinical efficacy is primarily related to its ability to increase serotonin levels in the synaptic cleft. By inhibiting the serotonin reuptake transporter (SERT), escitalopram enhances serotonin signaling in the brain, which is believed to be central to its antidepressant and anxiolytic effects.
It does not significantly interact with other neurotransmitters such as norepinephrine or dopamine, which contributes to its relatively favorable side-effect profile compared to other antidepressants.
12. Special Populations
Pregnancy: Category C (US FDA). Escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates exposed to SSRIs late in pregnancy may experience serotonin withdrawal or persistent pulmonary hypertension.
Lactation: Escitalopram is excreted in breast milk. Use with caution, and monitor the infant for any adverse effects, including sedation or weight changes.
Pediatrics: Approved for use in adolescents (12–17 years) with MDD and GAD. Close monitoring for suicidality is required.
Geriatrics: Elderly patients are more susceptible to side effects, especially hyponatremia and sedation. Starting with a lower dose (5 mg/day) is recommended.
Renal and Hepatic Dysfunction: In patients with significant liver impairment, dose reduction may be required, and caution should be exercised in renal dysfunction.
13. Therapeutic Uses
Major Depressive Disorder (MDD): First-line treatment.
Generalized Anxiety Disorder (GAD): First-line treatment.
Off-label Uses: Panic disorder, OCD, and PTSD.
Clinical studies demonstrate the efficacy of escitalopram in MDD and GAD, with some trials also supporting its use in OCD and panic disorder.
14. Monitoring and Follow-Up
Before Treatment: Baseline weight, blood pressure, ECG (for QT prolongation), renal and liver function tests, and CBC in elderly or those with bleeding risks.
During Treatment: Regular monitoring of serum sodium levels, weight, lipid profile, and blood glucose (especially in long-term therapy).
Therapeutic Levels: No routine blood level monitoring is needed, but efficacy should guide dosing adjustments.
15. Overdose Management
Symptoms of Overdose: Severe sedation, drowsiness, nausea, vomiting, seizures, serotonin syndrome.
Treatment Protocol:
Activated charcoal within 1 hour of ingestion.
Symptomatic treatment including IV fluids, respiratory support, and cardiovascular monitoring.
Antidote: No specific antidote for escitalopram overdose.
16. Patient Counseling Information
Key Points:
Take escitalopram exactly as prescribed, once daily.
It may take 1-4 weeks for the full therapeutic effects to be felt.
Avoid alcohol and other central nervous system depressants while taking escitalopram.
Signs for Immediate Medical Attention:
Any signs of serotonin syndrome (fever, confusion, tremors).
Symptoms of suicidality, such as worsening depression or thoughts of harming oneself.