Citalopram

Citalopram is a racemic SSRI used for depression, panic disorder and, in some regions, obsessive-compulsive disorder. Its dose ceiling is set by dose-dependent QT prolongation, and it has few pharmacokinetic interactions apart from CYP2C19 inhibitors.

Classification. SSRI, racemic mixture of S-citalopram (active as escitalopram) and R-citalopram.

Mechanism. Inhibits the presynaptic serotonin transporter. Response builds over 2 to 4 weeks.

Pharmacokinetics. Bioavailability about 80%, unaffected by food. Metabolised by CYP2C19, CYP3A4 and CYP2D6 to weakly active demethylated metabolites. Half-life about 35 hours; exposure rises in older adults, liver impairment and CYP2C19 poor metabolisers.

All regimens are oral with no loading dose.

Major depression, adults (first-line).

• Start 20 mg once daily.
• Titration: increase by 10 to 20 mg after at least 1 week if needed.
• Maintenance 20 to 40 mg daily. Maximum 40 mg daily; do not exceed.
• Duration: at least 6 months after remission; 2 years or more for recurrent illness.

Panic disorder. 10 mg daily for 1 week, then 20 mg daily; may increase to a maximum of 40 mg daily.

Obsessive-compulsive disorder (licensed in some regions). Start 20 mg daily; usual 20 to 40 mg daily. Maximum 40 mg daily.

Dose limits. Adults over 65 years (over 60 years in some regions): start 10 mg, maximum 20 mg daily. Liver impairment: maximum 20 mg daily. CYP2C19 poor metabolisers, or use with cimetidine, omeprazole, esomeprazole or fluvoxamine: maximum 20 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. Uncorrected hypokalaemia or hypomagnesaemia and recent myocardial infarction or decompensated heart failure are further reasons to avoid it.

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

Common adverse effects. Nausea, dry mouth, sweating, somnolence or insomnia, tremor, sexual dysfunction, diarrhoea.

Interactions. QT-prolonging drugs (for example haloperidol, ondansetron, macrolides, quinolones, quinine and artemether-lumefantrine) are avoided. Cimetidine, omeprazole, esomeprazole and fluvoxamine raise levels. Bleeding risk rises with NSAIDs and anticoagulants. Serotonin syndrome risk rises with tramadol, triptans and linezolid.

Common prescribing errors. Prescribing 40 mg in older adults or with CYP2C19 inhibitors; ignoring QT-prolonging co-medication; not correcting electrolytes.

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: higher infant levels than with sertraline or paroxetine; monitor the infant for sedation and poor feeding.
• Children: not advised in under 18 years.
• Older adults: maximum 20 mg daily; check sodium.
• Kidney impairment: no adjustment for mild to moderate; caution in severe impairment.
• Liver impairment: start 10 mg, maximum 20 mg daily.

Formulations. Tablets 10 mg, 20 mg and 40 mg; oral drops in some regions, in which 8 mg equals 10 mg of tablet. Give once daily with or without food.

Baseline. Mood history including past mania, suicide risk, sodium, potassium and magnesium, 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.