Antidepressant Guide — Choice & Switching

Choosing, switching & stopping antidepressants

Field: Mental HealthCode: MH-05BUpdated: June 2026Reference: RANZCP 2020 / AMH / Maudsley

20+ antidepressants are available — choose by patient profile, not a flowchart. Cross-reference with the severity-based stepped-care framework in MH-05. Always taper to stop; never stop abruptly, even after a short course.

Choosing by patient profile

By clinical scenario.

Most adults (default): escitalopram — commonly favoured for a tolerability/efficacy balance.

Pregnancy / breastfeeding: sertraline — most evidence for safety and the lowest relative infant dose via milk.

Cardiovascular disease or elderly/frail: sertraline or escitalopram — start low, watch for hyponatraemia & falls.

Insomnia, weight loss wanted, or sexual side-effects a concern: mirtazapine or agomelatine.

Chronic pain comorbid: duloxetine or venlafaxine (SNRI) — dual mood and pain benefit.

Adolescent (<18) or OCD: fluoxetine — the only PBS-listed SSRI for adolescent depression, often needs a higher dose/longer trial for OCD.

Treatment-resistant: venlafaxine plus augmentation (lithium or aripiprazole) — psychiatry input.

Typical starting doses. Starting and target doses vary by agent and indication — confirm current dosing and titration in the Australian Medicines Handbook (AMH) or eTG, and PBS-listed strengths at pbs.gov.au.

Switching strategies

Direct switch: stop drug 1, start drug 2 next day at usual dose; suits same-class, short half-life agents.
Cross-taper (most common): taper drug 1 over 1–2 weeks while titrating drug 2 up; suits switching classes.
Washout: stop, wait roughly 5 half-lives, then start; required before/after an MAOI (commonly ~2 weeks, longer after fluoxetine) to avoid serotonin syndrome.

Key interactions to avoid

MAOI + SSRI/SNRI — serotonin syndrome risk; needs a washout period.
Tramadol or pethidine + antidepressant — serotonin syndrome risk; consider alternative analgesia.
Warfarin + SSRI — increased INR/bleeding risk; monitor INR after starting or stopping.
NSAIDs + SSRI — increased GI bleeding risk; consider PPI cover.
Citalopram/escitalopram + other QT-prolonging drugs — check ECG if combining multiple agents.

Stopping — tapering approach. Withdrawal symptoms are common (not "addiction") and can start within 24–72 hours of stopping abruptly. A standard taper (reduce 25–50% every 2–4 weeks) suits many shorter courses; a slower, hyperbolic taper with smaller reductions at lower doses suits long-term use or a prior history of withdrawal symptoms — see the Maudsley deprescribing guidance or the AMH switching/stopping tool for drug-specific detail.

Safety

MAOI combinations need a washout (commonly ~2 weeks; longer after fluoxetine) — confirm before switching.
Never stop abruptly — taper, even after a short course.
Sertraline/escitalopram are commonly preferred in pregnancy, breastfeeding, and frail/elderly patients.
Generic brands are bioequivalent — a brand switch is not the same as a drug switch.

Red flags / refer

Treatment-resistant after two adequately dosed trials — consider augmentation or psychiatry referral.
Suspected serotonin syndrome — same-day medical assessment.
Complex polypharmacy or multiple QT-prolonging agents — pharmacist or specialist review.
Diagnostic uncertainty about bipolar features before starting an antidepressant.

MH-05B v1.0 · Reviewed Jun 2026 · Review Jun 2027

For health-professional use. Choice, switching & stopping adapted from RANZCP 2020, the AMH, and Maudsley deprescribing guidance. Severity-based stepped care — see MH-05. Confirm exact doses and PBS listings at the AMH and pbs.gov.au.