Makindo Medical Notes

💊 Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) used for depression, anxiety, and related disorders. It has a higher incidence of withdrawal symptoms than other SSRIs, so abrupt discontinuation should be avoided. Taper gradually over weeks to reduce the risk of dizziness, agitation, or sensory disturbances ("electric shock" sensations).

📘 About

• Always check the BNF entry here for current dosing, contraindications, and interactions.
• Effective for major depressive disorder, panic disorder, OCD, PTSD, and social anxiety disorder.
• Short half-life (~21 h) contributes to higher withdrawal risk compared with fluoxetine or sertraline.

⚙️ Mode of Action

• Inhibits presynaptic serotonin (5-HT) reuptake transporter → increases synaptic serotonin availability.
• Minimal noradrenergic or dopaminergic activity; mild antimuscarinic effect relative to other SSRIs.
• Gradual adaptive receptor changes mediate antidepressant effect after 2–4 weeks.

💊 Indications & Dose

• Major depression, OCD, PTSD, panic disorder, social anxiety disorder.
• Start at 20 mg PO once daily (morning); may increase by 10 mg increments up to 50–60 mg/day as tolerated.
• Adjust dose in hepatic or severe renal impairment.

🔄 Interactions

• MAOIs: Contraindicated — risk of serotonin syndrome (separate by ≥14 days).
• Other serotonergic drugs: (e.g. triptans, tramadol, linezolid) → additive serotonin toxicity risk.
• Warfarin, NSAIDs, aspirin: ↑ bleeding risk due to platelet inhibition.
• See BNF for a full list.

⚠️ Cautions

• Monitor closely in early treatment — risk of increased suicidal ideation, particularly in young adults.
• Use with caution in cardiac disease, hepatic impairment, epilepsy, or hyponatraemia.
• May cause or worsen sexual dysfunction; discuss proactively with patients.

🚫 Contraindications

• Concurrent use with MAOIs or linezolid.
• Uncontrolled epilepsy or severe hepatic impairment (relative).
• Hypersensitivity to paroxetine or excipients.

💥 Adverse Effects

• Common: Nausea, dry mouth, insomnia, somnolence, sexual dysfunction, sweating.
• Hyponatraemia (SIADH), especially in elderly or diuretic users.
• Antimuscarinic effects: Constipation, blurred vision, mild tachycardia.
• Extrapyramidal symptoms may occur (rare).
• Withdrawal effects: dizziness, “brain zaps”, irritability, vivid dreams.

🧠 Teaching Note

Paroxetine’s short half-life explains its higher withdrawal risk — it should always be tapered gradually over several weeks. When selecting an SSRI, consider pharmacokinetic and tolerability differences: fluoxetine suits patients with poor adherence (long half-life), whereas paroxetine may cause more sedation and discontinuation symptoms.

📚 References

• BNF: Paroxetine
• NICE NG222: Depression in adults (2024)
• NICE CKS: Anxiety disorders

🕓 Revisions

• 2025-10 — Expanded and annotated by Dr O’Kane (Makindo edition).