Generic Name

Fluvoxamine

Mechanism

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that:
• Potently inhibits the serotonin transporter (SERT) in postsynaptic neurons, increasing extracellular serotonin levels.
• Has a higher affinity for SERT than many other SSRIs, leading to a robust serotonergic effect.
• Acts as a weak agonist at 5‑HT1A autoreceptors, which may contribute to its anxiolytic properties.
• Inhibits cytochrome P450 isoforms *CYP1A2* and *CYP2C19*, influencing drug‑drug interactions.

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Pharmacokinetics

• Absorption: Well absorbed orally; peak plasma concentrations reached within 1–4 h.
• Bioavailability: ~1.2% for oral dosing; food slightly reduces absorption.
• Metabolism: Primarily hepatic by *CYP1A2* and *CYP2C19*; minimal renal excretion.
• Half‑life: ~6–12 h (active metabolite N‑desmethyl‑fluvoxamine ~7 h).
• Protein Binding: ~85–90% (primarily to α‑1‑acid glycoprotein).
• Drug interactions: Strong inhibition of *CYP1A2* increases concentrations of drugs such as clozapine, theophylline, and certain beta‑blockers.

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Indications

• Obsessive‑Compulsive Disorder (OCD) – first‑line agent for moderate‑to‑severe cases.
• Panic Disorder – used when SSRIs are preferred or clomipramine is unsuitable.
• Social Anxiety Disorder – evidence supports benefit, although not FDA‑approved for this indication.
• Premenstrual Dysphoric Disorder – off‑label use as part of a comprehensive pharmacologic plan.

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Contraindications

• Contraindications:
• Hypersensitivity to fluvoxamine or any component.
• Concomitant use of MAO inhibitors (within 14 days).
• Warnings:
• Serotonin syndrome risk with monoamine‑modulating agents.
• QTc prolongation (elevated in patients on *CYP1A2* inhibitors).
• Drug‑induced hepatotoxicity – monitor liver enzymes in chronic therapy.
• Increased risk of bleeding when combined with NSAIDs or anticoagulants.

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Dosing

• Administer with or without food.
• Taper over 4–6 weeks to avoid withdrawal syndrome ("fluvoxamine discontinuation syndrome").

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Adverse Effects

Common:
• Nausea, dry mouth, insomnia, constipation
• Dizziness, weight gain (≥10 % baseline after 6–12 months)
• Sexual dysfunction (decreased libido, delayed orgasm)
• Tremor, hyperactivity in children and adolescents

Serious:
• Serotonin syndrome (hyperreflexia, clonus, agitation)
• QTc prolongation (monitor ECG in high‑risk comorbidities)
• Severe hyponatremia (particularly in elderly)
• Hepatotoxicity (elevated transaminases, cholestasis)
• Cerebral edema in children (rarely observed)

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Monitoring

• Baseline: CBC, CMP, pregnancy test (if applicable), ECG (QTc).
• During therapy:
• Serum electrolytes (Na⁺) in elderly or hyponatremia risk.
• Liver enzymes every 4–6 weeks for first 3 months, then every 6–12 months.
• ECG if >10 % QTc or concomitant QT‑prolonging drugs.
• Mental status: assess for serotonin syndrome and withdrawal symptoms.
• Special populations: Re‑evaluate doses in hepatic impairment or in use with CYP1A2 inhibitors.

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Clinical Pearls

• Titration Speed: Start low and go slow. Fluvoxamine’s metabolism may lead to unpredictable plasma levels; incremental increases allow early detection of serotonin syndrome.
• Drug–Drug Landscape: Because it’s a potent *CYP1A2* inhibitor, avoid prescribing it with drugs heavily metabolized by this enzyme (e.g., clozapine) without dose adjustments.
• Anxiety & Agitation: Initial doses can precipitate increased agitation; pre‑treat with benzodiazepines if needed.
• Pregnancy & Lactation: Category C; transplacental passage occurs, and it can be excreted into breast milk—careful risk–benefit assessment is required.
• Adherence Hack: Use the 100‑mg daily dose (50 mg BID × 2) as a convenient dosing format, especially for patients with forgetfulness.
• QTc Monitoring: Even though it’s not a classic QT‑prolonger, co‑administration with antipsychotics or high‑dose NSAIDs can pose risk—consult cardiology for baseline ECG.
• Re‑starting: In a patient who had an earlier trial, re‑initation at half the previous dose can reduce relapse of withdrawal symptoms.

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