Paroxetine

# Paroxetine ## Overview Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with the most potent inhibition of serotonin reuptake among SSRIs. It has a short half-life (~21 hours) and is associated with significant withdrawal syndrome upon abrupt discontinuation. ## Primary Indications - Major depressive disorder (MDD) - Obsessive-compulsive disorder (OCD) - Panic disorder (with or without agoraphobia) - Social anxiety disorder (social phobia) - Generalized anxiety disorder (GAD) - Post-traumatic stress disorder (PTSD) - Premenstrual dysphoric disorder (PMDD) ## Adult Dosing - **MDD**: Start 20 mg once daily (usually morning). Range 20–50 mg/day. Max 50 mg/day. - **OCD**: Start 20 mg once daily. Range 20–60 mg/day. Max 60 mg/day. - **Panic disorder**: Start 10 mg once daily (to minimize initial anxiety). Titrate by 10 mg/week. Range 20–60 mg/day. Max 60 mg/day. - **Social anxiety/GAD**: Start 20 mg once daily. Range 20–50 mg/day. Max 50 mg/day. - **PTSD**: Start 20 mg once daily. Range 20–50 mg/day. Max 50 mg/day. - **PMDD**: 10–30 mg once daily (intermittent or continuous dosing; exact protocol varies). ## Pediatric Dosing - **Not FDA-approved for MDD in children/adolescents** (increased risk of suicidal ideation). - **OCD (ages 8–17)**: Start 10 mg once daily. Titrate by 10 mg/week. Range 20–40 mg/day. Max 50 mg/day (lower weight: max 40 mg/day). - Use in pediatric patients requires careful risk-benefit assessment and close monitoring. ## Dose Adjustments - **Elderly/debilitated**: Start 10 mg once daily. Max 40 mg/day. - **Renal impairment** (CrCl <30 mL/min): Start 10 mg once daily. Max 40 mg/day. - **Hepatic impairment** (severe): Start 10 mg once daily. Max 40 mg/day. - **Tapering**: Reduce by 10 mg/day every 1–2 weeks to avoid withdrawal. Do not abruptly stop. ## Contraindications - Concomitant use with MAOIs (including linezolid, methylene blue) – risk of serotonin syndrome. Allow 14-day washout between. - Concomitant use with pimozide or thioridazine. - Known hypersensitivity to paroxetine. - Pregnancy (especially first trimester) – associated with cardiac malformations; use only if benefit outweighs risk. ## Adverse Effects - **Common**: Nausea, somnolence, insomnia, dry mouth, constipation, dizziness, sexual dysfunction (delayed ejaculation, anorgasmia, decreased libido), weight gain. - **Serious**: Serotonin syndrome (agitation, hyperthermia, clonus, hyperreflexia), suicidal ideation (especially in young adults <25), hyponatremia (SIADH), QT prolongation (rare), bleeding risk (especially with NSAIDs/anticoagulants), withdrawal syndrome. ## Key Drug Interactions - **MAOIs**: Risk of serotonin syndrome – contraindicated. - **Serotonergic drugs** (e.g., other SSRIs, SNRIs, triptans, tramadol, St. John’s wort): Increased serotonin syndrome risk. - **NSAIDs/anticoagulants**: Increased bleeding risk (GI). - **CYP2D6 substrates** (e.g., tamoxifen, atomoxetine, risperidone): Paroxetine inhibits CYP2D6 – may increase levels of these drugs. - **Cimetidine**: May increase paroxetine levels. - **Alcohol**: Enhanced CNS depression. ## Monitoring - Baseline: Assess for bipolar disorder risk (screen for mania), suicidal ideation, bleeding risk. - Follow-up: Monitor for clinical response, adverse effects (especially sexual dysfunction, weight gain), suicidal ideation (weekly for first 4 weeks in young adults), serum sodium (if elderly or at risk for hyponatremia). - Periodic: Liver function tests (if hepatic impairment), ECG (if QT risk factors). ## Clinical Pearls - Paroxetine is the most anticholinergic SSRI – avoid in elderly due to sedation, falls, and cognitive impairment. - Withdrawal syndrome is more common and severe than with other SSRIs – always taper slowly. - Higher risk of sexual dysfunction compared to other SSRIs. - Use with caution in pregnancy – consider alternative SSRIs (e.g., sertraline, fluoxetine) if possible. - For panic disorder, start at 10 mg to avoid initial anxiety exacerbation. - Paroxetine is not recommended for use in children/adolescents for depression due to lack of efficacy and increased suicidal risk. --- **Disclaimer:** This information is for educational purposes only and does not replace professional clinical judgment. Always verify current prescribing information from the manufacturer’s label and local guidelines before initiating or adjusting therapy.