Escitalopram

Escitalopram is the S-enantiomer of citalopram and the most selective SSRI for the serotonin transporter. It is used for depression, generalised anxiety disorder, social anxiety disorder, panic disorder and obsessive-compulsive disorder, with few interactions and a dose-dependent effect on the QT interval.

Classification. SSRI; 10 mg of escitalopram is roughly equal to 20 mg of citalopram.

Mechanism. Binds the primary site of the serotonin transporter and, through an allosteric site, may prolong its own binding. Response builds over 2 to 4 weeks.

Pharmacokinetics. Bioavailability about 80%, unaffected by food. Metabolised by CYP2C19, CYP3A4 and CYP2D6 to weakly active metabolites. Half-life 27 to 32 hours. Exposure is higher in CYP2C19 poor metabolisers, who are less frequent in people of African ancestry than in East Asian populations.

All regimens are oral with no loading dose.

Major depression, adults (first-line).

• Start 10 mg once daily.
• Titration: after at least 1 week, increase to 20 mg if response is inadequate.
• Maintenance 10 to 20 mg daily. Maximum 20 mg daily.
• Duration: at least 6 months after remission; 2 years or more for recurrent illness.

Generalised anxiety disorder and social anxiety disorder. Start 10 mg daily; increase to 20 mg after at least 1 week if needed. Maximum 20 mg daily.

Panic disorder. 5 mg daily for the first week, then 10 mg daily; may increase to a maximum of 20 mg daily.

Obsessive-compulsive disorder. Start 10 mg daily; usual 10 to 20 mg daily. Maximum 20 mg daily.

Adolescents aged 12 to 17 years with depression. 10 mg daily, increased after at least 3 weeks to a maximum of 20 mg daily.

Dose limits. Adults over 65 years: start 5 mg, usual maximum 10 mg daily. Liver impairment: 5 mg for the first 2 weeks, then up to 10 mg daily. CYP2C19 poor metabolisers: maximum 10 mg daily.

Contraindications. MAOI use now or within 14 days of stopping it, pimozide, linezolid, congenital long QT syndrome, known QT prolongation, use with other QT-prolonging drugs, hypersensitivity.

Serious adverse effects. Boxed-warning-level risk of suicidal thinking and behaviour in under 25 years. Dose-dependent QT prolongation and torsades de pointes, particularly with hypokalaemia, hypomagnesaemia, bradycardia or heart failure. Serotonin syndrome, hyponatraemia, bleeding, mania, seizures, angle-closure glaucoma.

Common adverse effects. Nausea, headache, insomnia or somnolence, sweating, sexual dysfunction, diarrhoea.

Interactions. QT-prolonging drugs (for example haloperidol, ondansetron, macrolides, quinolones, antimalarials such as quinine and artemether-lumefantrine, and amisulpride) are avoided. Omeprazole, esomeprazole, cimetidine and fluvoxamine raise levels, so cap the dose at 10 mg. Bleeding risk rises with NSAIDs and anticoagulants. Serotonin syndrome risk rises with tramadol, triptans and linezolid.

Common prescribing errors. Using 20 mg in older adults; combining with QT-prolonging drugs without an ECG; leaving electrolyte disturbance uncorrected.

Special groups.

• Pregnancy: use only if benefit outweighs risk; small risks of neonatal adaptation symptoms and persistent pulmonary hypertension of the newborn with late exposure.
• Breastfeeding: moderate transfer; monitor the infant for sedation and poor feeding.
• Children: licensed from 12 years for depression in many regions.
• Older adults: maximum 10 mg daily; check sodium.
• Kidney impairment: no adjustment for mild to moderate; caution when creatinine clearance is under 30 mL/min.
• Liver impairment: maximum 10 mg daily.

Formulations. Tablets 5 mg, 10 mg and 20 mg; oral drops in some regions. Give once daily with or without food.

Baseline. Mood history including past mania, suicide risk, sodium, potassium and magnesium where QT risk exists, ECG if cardiac disease, bradycardia, syncope or QT-prolonging co-medication. Avoid or use cautiously if baseline QTc is over 450 ms in men or 470 ms in women.

Monitoring. Review within 1 to 2 weeks and after each dose change for suicidality and activation. Repeat the ECG after dose increases in high-risk patients and stop if QTc stays over 500 ms. Check sodium 2 to 4 weeks after starting in high-risk patients; review the need for the drug if sodium falls under 130 mmol/L and stop it if under 125 mmol/L or if symptomatic.

Stopping. Taper over at least 4 weeks.

Referral and escalation. Refer to psychiatry for suicidal intent, psychosis, mania, or failure of two adequate courses. Syncope, palpitations or QTc over 500 ms needs same-day cardiac assessment.