A faithful, structured lookup of Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76–83 — Table 3, with every footnote rendered inline so nothing is hidden.
📋 Source: Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76–83. doi:10.18773/austprescr.2016.039. Reproduced as a structured lookup of Table 3 with footnotes preserved. Half-lives from Table 1 of the same article. Serotonin syndrome reference: Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ 2014;348:g1626. Verified June 2026. This page is reference material for registered medical professionals. It is not prescribing advice; the cited article and current TGA Product Information are the authoritative sources for any prescribing decision.
Tier 2 — use clinical judgement. This is a structured presentation of published guidance, not a prescribing protocol. Every switch must be individualised for the patient, drug pharmacology, and current TGA Product Information. Refer to a psychiatrist where appropriate. Always consult the original article — the source is what you cite, not this page.
Serotonin syndrome is the central risk. Symptoms range from agitation, tremor, diaphoresis, shivering, mydriasis, hyperreflexia and diarrhoea, through to tachycardia, hyperthermia, hypertension, myoclonus, muscular rigidity, delirium — and in severe cases convulsions, organ failure, death. Prevention is by minimising overlap between potent serotonergic drugs (Buckley, Dawson, Isbister, BMJ 2014;348:g1626).
Select a current and new medication to see the recommended switching strategy and safety context.
Footnote key
* A washout of 2–5 half-lives (most often 2–5 days) between cessation and introduction of the new drug is the safest strategy. Cautious cross-taper may be used here if clinically appropriate and under close observation.
† Fluoxetine may still cause interactions 5–6 weeks after cessation (especially from higher doses) due to the long half-life of the parent drug and active metabolite norfluoxetine.
‡ Fluoxetine is likely to continue to elevate TCA concentrations for several weeks — risk of cardiotoxic plasma levels. Watch for drowsiness, tachycardia, postural hypotension.
§ Co-prescription of the two antidepressants in this combination is not recommended. A washout interval is required.
The four switching strategies (Table 2)
Strategy
Approach
Comment
Conservative
Taper first drug, washout of 5 half-lives, then start second drug at recommended dose
Lowest interaction risk. Discontinuation symptoms possible. Most appropriate for general practice.
Moderate
Taper first drug, 2–4 day washout, start second drug at low dose
Low interaction risk. Discontinuation symptoms possible. Also suitable for general practice.
Direct
Stop first drug; start second drug next day at therapeutic dose
Requires expertise. Substantial interaction risk. Only feasible in selected instances (e.g. between short-half-life SSRIs).
Cross-taper
Reduce first drug while introducing second drug at low dose simultaneously, then increase second drug as first is stopped
For high relapse-risk patients. Requires expertise. Drug interaction and combined adverse-effect risk. Only feasible in selected combinations.
Taper means gradual dose reduction with lowering by increments every few days, usually over ~4 weeks — modified by patient experience, drug, illness, and other factors. None of these strategies apply to irreversible MAOIs — see the picker output for MAOI-specific washout rules.
Approximate half-lives (Table 1)
These drive the washout intervals. Showing days unless noted.
Drug
Half-life (days)
Drug
Half-life (days)
citalopram
1.5
desvenlafaxine
0.4
escitalopram
1.5
duloxetine
0.5
paroxetine
1.0
venlafaxine
0.6 †
sertraline
1.1–1.3
mianserin
0.9–2.5
fluoxetine
4–16 *
mirtazapine
0.8–1.6 ‡
fluvoxamine
0.6
reboxetine
0.5
vortioxetine
2.4–2.8
amitriptyline
0.2–1.9
agomelatine
0.04–0.08
nortriptyline
0.8–2.3
clomipramine
0.6–2.5
dothiepin
2.1
moclobemide
~2 hours
phenelzine, tranylcypromine
activity persists 14–21 days §
* fluoxetine plus active metabolite norfluoxetine | † venlafaxine plus active metabolite desvenlafaxine | ‡ longer half-lives (up to 65 h) occasionally recorded | § irreversible MAOIs — biological activity persists 14–21 days after cessation
Withdrawal & relapse — practical notes
All antidepressants (possibly except agomelatine) can cause withdrawal syndromes if stopped or rapidly reduced after >6 weeks of use. This is not addiction — no tolerance, drug-seeking, or compulsive use.
Withdrawal usually starts within hours to days, with shorter half-lives the worst offenders. Venlafaxine is the most severe; paroxetine also troublesome; fluoxetine rarely causes withdrawal due to long half-life.
Distinguish from relapse — withdrawal symptoms are typically transient and physical; depressive relapse builds over days–weeks and includes cognitive and mood features. Relapse with suicidal ideation is a major risk of antidepressant discontinuation.
Usual taper: minimum 4 weeks, modified by patient experience. Some require months. A minority do better with rapid cessation; some need very gradual reduction in the final stages.
When to refer rather than DIY
Any switch to or from an irreversible MAOI (phenelzine, tranylcypromine).