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Antidepressant Withdrawal and Rebound Phenomena.

BACKGROUND: Antidepressants are among the most commonly prescribed drugs worldwide. They are often discontinued, frequently without the knowledge of the prescribing physician. It is, therefore, important for physicians to be aware of the withdrawal and rebound phenomena that may arise, in order to prevent these phenomena, treat them when necessary, and counsel patients appropriately.

METHODS: This review is based on a comprehensive, structured literature search on antidepressant withdrawal phenomena that we carried out in the CENTRAL, PubMed (Medline), and Embase databases. We classified the relevant publications and reports by their methodological quality.

RESULTS: Out of a total of 2287 hits, there were 40 controlled trials, 38 cohort studies and retrospective analyses, and 271 case reports that met the inclusion criteria. Withdrawal manifestations are usually mild and self-limiting; common ones include dizziness, headache, sleep disturbances, and mood swings. More serious or pro- longed manifestations rarely arise. There is an increased risk with MAO inhibitors, tricyclic antidepressants, venlafaxine, and paroxetine; on the other hand, for agome- latine and fluoxetine, abrupt discontinuation seems to be unproblematic. There is also some evidence of rebound phenomena, i.e., of higher relapse rates or especially severe relapses of depression after the discontinuation of an anti- depressant.

CONCLUSION: A robust evidence base now indicates that there can be acute with- drawal phenomena when antidepressants are discontinued. Putative rebound phenomena have not been adequately studied to date. It is recommended that antidepressants should be tapered off over a period of more than four weeks.

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