Tapering of SSRI treatment to mitigate withdrawal symptoms

In their Personal View, published in The Lancet Psychiatry, Mark Horowitz and David Taylor¹ propose that SSRI treatment should be tapered hyperbolically and slowly, much in the same way as benzodiazepines are usually withdrawn after a period of prolonged use. The paper is valuable because it provides the informed clinician with new insight into the potential neurobiology of SSRI discontinuation. The tapering regimen proposed by the authors merits further study and might prove useful in certain clinical circumstances, such as that of a patient who has been stable on a short-acting SSRI for more than a year and who considers elective drug discontinuation. At the same time, it seems to us that certain important caveats in relation to the so-called SSRI withdrawal syndrome should be plainly enunciated.

First, the placebo effect appears to contribute, to a considerable extent, to the antidepressant response, in particular in mild and moderate depression.² Therefore, a similar nocebo effect, associated with the expectation of reacting poorly to SSRI discontinuation, should also exist. This mechanism will, no doubt, be reinforced by the recently growing interest, in the lay media, in antidepressant withdrawal effects.

Second, genuine withdrawal symptoms have to be distinguished from symptoms of the underlying disease (eg, relapse and recurrence of depression). Matters are complicated further by the fact that SSRIs are frequently prescribed to patients with presentations that extend beyond or are distinct from pure major depression.³ Against this background, imaginative, yet rigorous clinical research is urgently required. Clearly, the currently available evidence base supporting the claim of long-term SSRI withdrawal syndromes lasting for months, or even years, is dubious at best. For example, the survey by the All Party Parliamentary Group for Prescribed Drug Dependence,⁴ referenced repeatedly throughout the manuscript,¹ represents an exclusively online survey of individuals self-identifying as experiencing withdrawal from psychoactive drugs, especially antidepressants and benzodiazepines.

Third, many clinical situations can arise (especially in liaison psychiatry) where abrupt SSRI discontinuation might be the preferred course (eg, because of side effects or drug interactions, or in pregnancy or before surgery). In addition, most antidepressants are prescribed in primary care,⁵ where sophisticated drug-tapering regimes might be impractical, if not impossible, to deliver.