Vilazodone

Vilazodone is an antidepressant that combines serotonin reuptake inhibition with partial agonism of the 5-HT1A receptor. It is used for major depression, mainly in the United States and a few other regions, and must be taken with food for adequate absorption. Diarrhoea and nausea are its leading adverse effects.

Classification. SSRI with 5-HT1A partial agonist activity.

Mechanism. Potently inhibits the serotonin transporter and partially agonises 5-HT1A receptors. The added clinical value of 5-HT1A activity is unproven.

Pharmacokinetics. Bioavailability about 72% with food and about 50% when fasting, so it must be taken with a meal. Metabolised by CYP3A4, with minor CYP2C19 and CYP2D6 contributions. Half-life about 25 hours.

Oral; no loading dose.

Major depression, adults.

• Start 10 mg once daily for 7 days, then 20 mg once daily for 7 days, then 40 mg once daily.
• Maintenance 20 to 40 mg daily. Maximum 40 mg daily.
• Duration: at least 6 months after remission.

Dose limits. Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin): maximum 20 mg daily. Strong CYP3A4 inducers (carbamazepine, rifampicin): may need up to double the dose, to a maximum of 80 mg, and reduce when the inducer stops. Severe liver impairment: not studied; caution.

Contraindications. MAOI use now or within 14 days of stopping it, linezolid, intravenous methylene blue, hypersensitivity.

Serious adverse effects. Boxed-warning-level risk of suicidal thinking and behaviour in under 25 years. Serotonin syndrome, hyponatraemia, bleeding, mania or hypomania, seizures, angle-closure glaucoma.

Common adverse effects. Diarrhoea, nausea, vomiting, insomnia, dizziness, abnormal dreams, dry mouth, sexual dysfunction (less frequent than with several SSRIs).

Interactions. Strong CYP3A4 inhibitors raise levels. Carbamazepine and rifampicin lower levels. Bleeding risk rises with NSAIDs, aspirin and anticoagulants. Serotonin syndrome risk rises with tramadol, triptans, lithium and linezolid.

Common prescribing errors. Giving on an empty stomach; starting at 40 mg; not reducing the dose with ketoconazole or ritonavir.

Special groups.

• Pregnancy: limited data; use only if benefit outweighs risk.
• Breastfeeding: limited data; avoid unless benefit is clear.
• Children: not advised in under 18 years.
• Older adults: no adjustment, but check sodium and bleeding risk.
• Kidney impairment: no adjustment.
• Liver impairment: no adjustment for mild to moderate; caution in severe impairment.

Formulations. Tablets 10 mg, 20 mg and 40 mg. Take once daily with food. Availability is limited outside a few regions.

Baseline. Mood history including past mania, suicide risk, sodium in older adults, bleeding risk, medicines list for CYP3A4 inhibitors and inducers.

Monitoring. Review within 1 to 2 weeks and after each dose change for suicidality and tolerability. 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. If there is no improvement after 4 to 6 weeks at an adequate dose, increase the dose or switch.

Stopping. Taper over at least 2 to 4 weeks, reducing the dose in steps of 10 mg.

Referral and escalation. Refer to psychiatry for suicidal intent, psychosis, mania or failure of two adequate courses. Suspected serotonin syndrome needs emergency care.