Fluvoxamine - Drug Monograph

Introduction

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) primarily used for the treatment of obsessive-compulsive disorder (OCD) and major depressive disorder. It was the first SSRI approved by the FDA specifically for OCD and remains an important therapeutic option in psychiatric practice. Unlike some other SSRIs, fluvoxamine has additional applications in anxiety disorders and off-label uses that continue to be explored in clinical research.

Mechanism of Action

Fluvoxamine exerts its therapeutic effects through potent and selective inhibition of serotonin (5-hydroxytryptamine, 5-HT) reuptake in the presynaptic neuron. By blocking the serotonin transporter (SERT), fluvoxamine increases synaptic concentrations of serotonin in the central nervous system, enhancing serotonergic neurotransmission. This mechanism is shared with other SSRIs, though fluvoxamine has particularly strong sigma-1 receptor agonist activity, which may contribute to its efficacy in anxiety and obsessive-compulsive symptoms. The drug has minimal affinity for adrenergic, cholinergic, histaminergic, and dopaminergic receptors.

Indications

• Obsessive-compulsive disorder (OCD) in adults and children aged 8-17 years
• Major depressive disorder (MDD) in adults

• Social anxiety disorder
• Panic disorder
• Post-traumatic stress disorder
• Premenstrual dysphoric disorder
• Bulimia nervosa

Dosage and Administration

• OCD: Initial dose 50 mg once daily at bedtime, increase by 50 mg every 4-7 days to target dose of 100-300 mg/day
• Depression: Initial dose 50 mg once daily, may increase to maximum 300 mg/day
• Maximum recommended dose: 300 mg/day

• Start with lower initial doses (25 mg daily)
• Titrate more slowly with careful monitoring

• Use caution and consider dose reduction
• Monitor closely for adverse effects

• Administer with food to minimize gastrointestinal upset
• Bedtime administration may reduce daytime sedation
• Available as immediate-release tablets (25, 50, 100 mg)

Pharmacokinetics

Contraindications

• Hypersensitivity to fluvoxamine or any component of the formulation
• Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy
• Concomitant use with thioridazine, pimozide, or other drugs that prolong QT interval
• Uncontrolled narrow-angle glaucoma

Warnings and Precautions

• Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults

• Serotonin syndrome risk, especially with other serotonergic drugs
• Activation of mania/hypomania in bipolar disorder
• Discontinuation syndrome with abrupt cessation
• Increased bleeding risk (especially with anticoagulants/antiplatelets)
• QT interval prolongation at high doses
• Hyponatremia (SIADH) particularly in elderly patients
• Seizure threshold reduction

Drug Interactions

• MAOIs: Risk of serotonin syndrome (contraindicated)
• Thioridazine, pimozide: Increased QT prolongation risk
• Warfarin: Increased anticoagulant effect
• Theophylline: Increased levels (5-fold increase)
• Clozapine: Elevated levels requiring dose reduction
• Benzodiazepines: Increased sedation
• Triptans: Increased serotonin syndrome risk

• Strong CYP1A2 inhibitor (affects: theophylline, clozapine, caffeine)
• Moderate CYP2C19/3A4 inhibitor
• CYP2D6 inhibitor (affects: TCAs, beta-blockers, antipsychotics)

Adverse Effects

• Nausea (40%)
• Somnolence (22%)
• Headache (18%)
• Insomnia (14%)
• Asthenia (12%)

• Dizziness, nervousness
• Constipation, diarrhea
• Anorexia, dry mouth
• Sweating, tremor
• Sexual dysfunction

• Serotonin syndrome
• Suicidal ideation
• Seizures
• Mania/hypomania
• Bleeding events
• SIADH

Monitoring Parameters

• Comprehensive metabolic panel (including sodium)
• CBC with platelets
• ECG (if cardiac risk factors or high-dose therapy)
• Suicide risk assessment
• Pregnancy test if applicable

• Therapeutic response and side effects at each visit
• Serum sodium (especially in elderly)
• Bleeding signs/symptoms
• Mood changes, activation symptoms
• Weight changes
• Sexual function assessment

• Periodic reassessment of continued need
• Bone density in long-term users (emerging evidence)

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Therapeutic effects may take 4-8 weeks to become apparent
• Common side effects often diminish with continued use
• Report any worsening depression, suicidal thoughts, or unusual behaviors
• Avoid alcohol during treatment
• Use caution when driving or operating machinery until effects are known
• Inform all healthcare providers about fluvoxamine use
• Use reliable contraception; discuss pregnancy plans with provider
• Report signs of serotonin syndrome (agitation, hallucinations, fever, tachycardia)
• Monitor for bleeding tendencies and report unusual bruising

References

1. FDA Prescribing Information: Fluvoxamine Tablets (2023) 2. Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2021. 3. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 14th ed. McGraw-Hill; 2023. 4. Baldwin DS et al. Efficacy of drug treatments for obsessive-compulsive disorder. Lancet Psychiatry. 2021;8(9):779-791. 5. Wagner G et al. Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med. 2021;384:2257-2266. 6. Micromedex Solutions. Fluvoxamine Drug Monograph. Truven Health Analytics; 2023. 7. Lexicomp Online. Fluvoxamine: Drug Information. Wolters Kluwer; 2023.