Antidepressant medication in late-life depression

General principle. Antidepressants are just as effective in older people as in younger adults; tolerability, not efficacy, dictates the choice. "Start low, go slow — but go all the way": the commonest error is an inadequate dose for an inadequate duration. Response begins at 4 weeks and takes 6–12 weeks for full effect, longer than in younger patients.

SSRIs — first-line. Sertraline (fewest interactions, safest after myocardial infarction) and escitalopram are the drugs of choice. Adverse effects: hyponatraemia and SIADH (check sodium in mEq/L at baseline and at 2 weeks), GI upset, falls and fracture, upper gastrointestinal bleeding, especially with NSAIDs or aspirin, sexual dysfunction, and QTc prolongation with citalopram and escitalopram (maximum citalopram 20 mg/day above 60 years). Avoid paroxetine — anticholinergic, short half-life, marked discontinuation symptoms. Avoid fluoxetine — very long half-life and CYP inhibition.

SNRIs — second-line. Venlafaxine (dose-dependent hypertension, prominent discontinuation symptoms) and duloxetine (useful when neuropathic pain or stress incontinence coexists; avoid in significant hepatic or renal impairment). Venlafaxine was as effective as nortriptyline in a randomised trial in elderly depressed inpatients.

Other useful agents. Mirtazapine — noradrenergic and specific serotonergic; the drug of choice where insomnia, anorexia and weight loss coexist; causes sedation and weight gain, rarely agranulocytosis. Bupropion — activating, no sexual dysfunction, but lowers the seizure threshold. Vortioxetine — possible pro-cognitive benefit. Trazodone — low dose for insomnia; causes orthostatic hypotension.

Agents to avoid or use with caution. TCAs — as effective as SSRIs but with far greater risk: anticholinergic effects (delirium, urinary retention, constipation, glaucoma), orthostatic hypotension and falls, cardiac conduction delay, and lethality in overdose. If used, nortriptyline is preferred, with a baseline ECG. MAOIs — tyramine and pressor-amine hypertensive crisis, and fatal serotonin syndrome if combined with an SSRI or pethidine. The Beers Criteria list TCAs and paroxetine as potentially inappropriate in older adults.

Augmentation, duration and stopping. For non-response to an SSRI — switch, or add lithium; after TCA failure, lithium augmentation is probably the best option; ECT for treatment resistance. Continue at the remission dose for ≥1 year after a first recurrence and consider lifelong maintenance after a second or subsequent recurrence. Never stop abruptly — taper over weeks to avoid a discontinuation syndrome of dizziness, flu-like symptoms, electric-shock sensations and insomnia.

Antidepressant discontinuation (2023–2025). A 2024 Lancet Psychiatry systematic review and meta-analysis quantified discontinuation symptoms — commonest with paroxetine and venlafaxine, least with fluoxetine — and the Maudsley Deprescribing Guidelines (2024) established hyperbolic tapering (progressively smaller absolute dose reductions, guided by receptor occupancy rather than fixed steps) as the recommended method. This matters especially in older adults, in whom withdrawal symptoms are easily mistaken for relapse.