Write a short note on antidepressants — classes, mechanism, adverse effects and serotonin syndrome.

Classes & Mechanism

Principles of Use

• Latency of action: mood improves only after 2–4 weeks; sleep and appetite improve earlier. Patients must be told this, otherwise they stop the drug prematurely.
• Adequate trial: full therapeutic dose for at least 4–6 weeks before declaring failure.
• Duration: continue for 6–9 months after remission of a first episode; 2 years or longer for recurrent depression.
• Stopping: taper gradually — abrupt cessation causes a discontinuation syndrome (dizziness, "electric shock" sensations, flu-like symptoms, insomnia), worst with paroxetine and venlafaxine (short half-lives) and least with fluoxetine.

Choosing an Agent

• SSRIs are first-line because of their safety in overdose and tolerability.
• Mirtazapine suits depression with insomnia and weight loss.
• Bupropion avoids sexual dysfunction and aids smoking cessation but lowers the seizure threshold.
• Amitriptyline is useful where neuropathic pain coexists.
• TCAs are dangerous in overdose — cardiotoxic with QRS widening and arrhythmia — an important consideration in a suicidal patient.

Adverse Effects

• SSRI: nausea, headache, insomnia or sedation, sexual dysfunction (the commonest cause of non-adherence), hyponatraemia due to SIADH (especially in the elderly), increased bleeding risk with NSAIDs or antiplatelets, and QT prolongation with citalopram.
• TCA: anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), postural hypotension, sedation, weight gain, cardiac conduction delay.
• MAOI: hypertensive crisis with tyramine-containing foods (cheese, red wine, pickled and fermented foods) — the "cheese reaction"; multiple drug interactions.
• All antidepressants: may precipitate mania in bipolar disorder — always screen for a past manic episode before prescribing. Regulatory warnings note a small increase in suicidal ideation in those under 25 during early treatment, requiring close initial follow-up.

Serotonin Syndrome

A potentially fatal reaction to serotonergic excess, typically when two serotonergic drugs are combined — SSRI with tramadol, linezolid, triptans, MAOI, St John's wort or ondansetron.

Clinical triad:

• Neuromuscular excitability — clonus (inducible and ocular), hyperreflexia, tremor, rigidity; lower limbs affected more than upper.
• Autonomic instability — hyperthermia, tachycardia, sweating, mydriasis, diarrhoea.
• Altered mental state — agitation, confusion, restlessness.

Onset is rapid — within 24 hours of the offending dose.

Management: stop all serotonergic agents, supportive care with intravenous fluids, benzodiazepines for agitation and rigidity, active cooling, and cyproheptadine (a 5-HT2A antagonist) in severe cases. Most cases resolve within 24 hours of withdrawal.