Antidepressant Drugs: Classification, Pharmacology and Safe Clinical Use

Fluoxetine

Mechanism and dose

• SSRI; start 20 mg once daily, commonly 20–60 mg/day. Long half-life reduces withdrawal but prolongs interactions.

Indications

• Depression, OCD, panic disorder and selected eating-disorder pathways.

Common side effects

• Nausea/diarrhoea: serotonergic GI stimulation.
• Insomnia/activation: consider morning dosing and review anxiety.
• Sexual dysfunction: ask specifically; it is often not volunteered.

Serious effects, cautions and interactions

• Serotonin syndrome: clonus, hyperreflexia, fever, sweating and agitation require urgent assessment.
• Hyponatraemia/bleeding: increased risk in frail adults and with NSAIDs/anticoagulants.
• Do not combine with MAOIs; CYP2D6 inhibition affects several medicines. Long washout is needed when switching.

Monitoring and counselling

• Review mood, suicidal thoughts, sleep, sexual function and interactions early; do not stop without a plan.

Sertraline

Mechanism and dose

• SSRI; start 25–50 mg once daily, usual range 50–200 mg/day.

Indications

• Depression, anxiety disorders, OCD, panic disorder and PTSD where locally indicated.

Common side effects

• Diarrhoea/nausea: commonly early and dose-related.
• Sexual dysfunction: libido, orgasm and erection effects need review.
• Sleep change/tremor: distinguish from anxiety or relapse.

Serious effects, cautions and interactions

• Serotonin syndrome, hyponatraemia and bleeding: key class emergencies/risks.
• MAOIs/linezolid are unsafe combinations; NSAIDs, aspirin and anticoagulants increase bleeding risk.

Monitoring and counselling

• Review benefit, activation, suicidality, sodium/bleeding risk and withdrawal before any taper.

Venlafaxine and duloxetine

Mechanism and dose

• SNRIs increase serotonin and noradrenaline. Venlafaxine: 37.5–75 mg/day to start, commonly 75–225 mg/day. Duloxetine: 30 mg daily then commonly 60 mg daily.

Indications

• Depression/anxiety; duloxetine also has selected neuropathic and chronic-pain uses.

Common side effects

• Nausea, sweating and sexual dysfunction: serotonergic effects.
• Insomnia/activation and raised BP: noradrenergic effects, particularly with higher venlafaxine doses.

Serious effects, cautions and interactions

• Severe discontinuation syndrome: dizziness, electric-shock sensations, anxiety and flu-like symptoms after abrupt venlafaxine cessation.
• Hypertension/serotonin syndrome: monitor BP and combinations.
• Duloxetine needs caution in liver disease, heavy alcohol use and severe renal impairment.

Monitoring and counselling

• Monitor BP/pulse, pain/function, mood and withdrawal; taper slowly.

Amitriptyline and clomipramine

Mechanism and dose

• TCAs block monoamine reuptake plus muscarinic, histamine, alpha and cardiac sodium channels. Amitriptyline pain starts at 10–25 mg at night; depression doses need gradual specialist titration. Clomipramine commonly begins 25 mg/day for OCD/depression pathways.

Common side effects

• Dry mouth, constipation, blurred vision and retention: antimuscarinic block.
• Sleepiness/weight gain: histamine block.
• Postural hypotension: alpha-blockade causes falls.

Serious effects, cautions and interactions

• Cardiotoxic overdose: seizures, QRS widening and ventricular arrhythmia can be fatal.
• Delirium, ileus and angle closure: anticholinergic emergencies.
• Avoid casual use with MAOIs/SSRIs, QT drugs or in high overdose risk, conduction disease, glaucoma, BPH or severe constipation.

Monitoring and counselling

• Consider ECG when risk is present; dispense limited quantities where overdose risk matters. Suspected overdose needs urgent ECG/ABC care.

Mirtazapine

Mechanism and dose

• Alpha₂ antagonist with serotonergic and H₁ effects; start 15 mg at night, commonly 15–45 mg nightly.

Indications

• Depression when insomnia, poor appetite or weight loss is prominent.

Common side effects

• Sleepiness: histamine blockade can be useful or disabling.
• Increased appetite/weight gain: requires active monitoring.
• Dry mouth/constipation: may occur.

Serious effects, cautions and interactions

• Neutropenia: fever/sore throat/infection needs urgent FBC evaluation.
• Do not combine with MAOIs; alcohol, opioids and benzodiazepines add sedation.

Monitoring and counselling

• Monitor weight, daytime sedation, mood and infection symptoms; report mania or self-harm thoughts urgently.

Bupropion, trazodone and MAOIs

Mechanism and dose

• Bupropion: noradrenaline–dopamine reuptake inhibitor; XL often 150 mg each morning then 300 mg/day.
• Trazodone: serotonergic antidepressant with sedating H₁/alpha effects; often 50–100 mg at night initially.
• MAOIs: irreversible monoamine-oxidase inhibitors for specialist treatment-resistant depression; doses and washouts must follow exact protocol.

Critical safety

• Bupropion seizure: contraindicated in seizure disorder and anorexia/bulimia; avoid with abrupt alcohol/sedative withdrawal.
• Trazodone priapism: painful prolonged erection is an emergency; also causes orthostasis/falls.
• MAOI hypertensive crisis/serotonin syndrome: tyramine, sympathomimetics, SSRIs/SNRIs/TCAs, tramadol and linezolid can be dangerous.

Monitoring and counselling

• For bupropion review sleep, anxiety, alcohol, seizures and eating disorder; for trazodone warn about sedation/slow standing; MAOI patients need written food and drug-interaction instructions.