Fluvoxamine

Fluvoxamine is an SSRI used mainly for obsessive-compulsive disorder and, in some regions, depression and social anxiety disorder. Its clinical weight lies in its interactions: it strongly inhibits CYP1A2 and CYP2C19, which raises levels of theophylline, caffeine, clozapine, olanzapine, warfarin and tizanidine.

Classification. SSRI, 2-aminoethyl oxime ether structure.

Mechanism. Inhibits the presynaptic serotonin transporter and is also a sigma-1 receptor agonist. Response in obsessive-compulsive disorder may take 8 to 12 weeks.

Pharmacokinetics. Well absorbed and unaffected by food. Extensive hepatic metabolism to inactive metabolites. Half-life about 15 hours. Smoking induces CYP1A2 and lowers levels.

All regimens are oral with no loading dose.

Obsessive-compulsive disorder, adults (first-line SSRI choice).

• Start 50 mg once daily at bedtime.
• Titration: increase by 50 mg every 4 to 7 days to the usual range of 100 to 300 mg daily.
• Maximum 300 mg daily. Give doses over 100 mg in two divided doses, with the larger dose at bedtime.
• Duration: continue for at least 12 months after response, and longer if relapse follows a reduction.

Major depression, adults (licensed in some regions). Start 100 mg daily in the evening; usual 100 to 200 mg daily; maximum 300 mg daily, with doses over 150 mg divided.

Children aged 8 years and over with obsessive-compulsive disorder. Start 25 mg at bedtime; increase by 25 mg every 4 to 7 days. Maximum 200 mg daily aged 8 to 11 years and 300 mg daily in adolescents.

Contraindications. MAOI use now or within 14 days of stopping it, tizanidine, ramelteon, pimozide, thioridazine, agomelatine, alosetron, linezolid, hypersensitivity.

Serious adverse effects. Boxed-warning-level risk of suicidal thinking and behaviour in under 25 years. Serotonin syndrome, hyponatraemia, bleeding, mania, seizures, QT prolongation (uncommon), angle-closure glaucoma, hepatic dysfunction.

Common adverse effects. Nausea, vomiting, somnolence, insomnia, asthenia, headache, constipation, sexual dysfunction.

Interactions. Theophylline levels can rise up to threefold: reduce the theophylline dose to one third and monitor levels. Clozapine and olanzapine levels rise, so start low and monitor. Warfarin effect rises, so check INR. Caffeine clearance falls. Levels of tricyclic antidepressants, methadone, ropinirole, propranolol and some benzodiazepines (diazepam, alprazolam) rise. Cigarette smoking lowers fluvoxamine levels. Serotonin syndrome risk rises with tramadol, triptans and linezolid.

Common prescribing errors. Adding fluvoxamine to clozapine or theophylline without dose reduction; stopping smoking or starting it while on clozapine without level checks; combining with tizanidine.

Special groups.

• Pregnancy: limited data; use only if benefit outweighs risk, with the usual neonatal adaptation counselling.
• Breastfeeding: low infant levels; acceptable with monitoring.
• Children: licensed from 8 years for obsessive-compulsive disorder only.
• Older adults: levels rise; start 25 mg and titrate slowly.
• Kidney impairment: no formal adjustment; start low and titrate slowly.
• Liver impairment: start low, titrate slowly and monitor liver tests.

Formulations. Tablets 50 mg and 100 mg; some regions also supply 25 mg. Swallow with water, with or without food.

Baseline. Mood history including past mania, suicide risk, medicines list for CYP1A2 and CYP2C19 substrates, smoking status, liver tests if liver disease.

Monitoring. Review within 1 to 2 weeks and after each dose change for suicidality and activation. 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. Measure drug levels of theophylline, clozapine and warfarin INR when starting or stopping fluvoxamine.

Stopping. Taper over at least 4 weeks, as discontinuation symptoms are common with its short half-life.

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