By DUNCAN DOUBLE

Mainstream psychiatry has minimised the significance of antidepressant withdrawal, as I first pointed out in a BMJ letter in 1997. My complaint then was that the Defeat Depression Campaign, launched in January 1992 by the Royal College of Psychiatrists in association with the Royal College of General Practitioners, advocated educating patients and doctors that discontinuing antidepressant treatment is not a problem.

As I explained in my book chapter, what caused so much consternation to the Defeat Depression Campaign was that 78% of people in a door-to-door survey of public opinion thought that antidepressants are addictive. I suggested in the BMJ letter that the general public actually understood this issue better than the Royal Colleges of Psychiatrists and General Practitioners. It’s common sense to believe that discontinuing taking medication that is thought to improve mood may be difficult.

The British National Formulary (BNF), which doctors use for reference about medication, has given a warning since 1990 that symptoms may occur if an antidepressant is stopped suddenly after regular administration for 8 weeks or more. In fact, case reports of discontinuation reactions have appeared since antidepressants were first introduced. The Drugs and Therapeutic Bulletin (DTB), which publishes independent, practical, patient-orientated, evidence-based content on medicines for healthcare professionals, recommended in 1999 that if maintenance antidepressant treatment is discontinued that both the doctor and patient need to be alert to the risk of discontinuation effects and the re-emergence of depressive symptoms, which can occur on cessation of any antidepressant. It made clear that antidepressants should not be stopped abruptly, nor treatment courses interrupted, unless there is a good clinical reason, for example a serious adverse effect or patient request.

A new class of antidepressants called serotonin specific reuptake inhibitors (SSRIs) was introduced onto the UK market in 1987. Withdrawal symptoms were only acknowledged by the drug companies after SSRIs had been in widespread clinical use for several years. A consensus meeting of experts, sponsored by Eli Lilly, the manufacturers of fluoxetine, or Prozac™, as it is known by its trade name, was held in Phoenix, Arizona, at the end of 1996. This led to an editorial in the British Medical Journal in 1998 acknowledging that antidepressant  discontinuation problems existed (Haddad et al, 1998). It suggested, though, that they were both preventable and simple to treat. The same authors only two years later acknowledged that discontinuation symptoms are common (Young & Haddad, 2000).

The National Institute for Health and Clinical Excellence, which evaluates treatments for NHS use, therefore, stated in its 2004 depression guideline the opposite of what was recommended by the Defeat Depression campaign: ie. that all patients prescribed antidepressants should be informed that discontinuation/withdrawal symptoms may occur on stopping, missing doses or, occasionally, on reducing the dose of the drug. It qualified this, though, by saying that symptoms are usually mild and self-limiting but can occasionally be severe, particularly if the drug is stopped abruptly.

More recently in its 2022 guidance on ‘Medicines associated with dependence or withdrawal symptoms: Safe prescribing and withdrawal management for adults’, NICE clearly states that antidepressants cause withdrawal symptoms even though they have not historically been classified as dependence-forming medicines. In its updated 2022 depression guideline, it now says that withdrawal symptoms can be mild and usually go away within 1 to 2 weeks; can sometimes be more difficult, with symptoms lasting longer (in some cases several weeks, and occasionally several months); and can sometimes be severe, particularly if the antidepressant medication is stopped suddenly. At least the guideline now acknowledges that withdrawal symptoms are not as usually mild and self-limiting as the previous version of the guideline stated.

This amendment was made after a complaint was made to the Royal College of Psychiatrists, which I signed (see eg. previous post). Although the complaint was initially wrongly dismissed, the College did eventually accept there should be greater recognition of the potential in some people for severe and long-lasting withdrawal symptoms on and after stopping antidepressants and called for NICE to update its guideline on antidepressant withdrawal (see eg. another previous post).

I still worry, though, that the full importance of antidepressant withdrawal has, after all these years, not been understood by mainstream psychiatry (see previous post). There is in fact limited scientific evidence on this topic and recommendations are too driven by personal opinions or experiences rather than evidence as such (see another previous post). There are also methodological problems with antidepressant discontinuation studies, not least that blinding strategies are often insufficient to properly address placebo and nocebo aspects. What is commonly overlooked is that antidepressant withdrawal symptoms even occur in blinded antidepressant arms when antidepressants are continued.

This finding has been confirmed in a new systematic review based on short-term industry studies (see Psychology Today article). One in three people were found to have at least one withdrawal symptom in the antidepressant withdrawal arm, but one in six people were still found to have withdrawal symptoms in the control arm even though antidepressants were continued.

The problem with the new systematic review is that it minimises the frequency of antidepressant withdrawal, suggesting they occur in only 15% of people. But withdrawal symptoms may occur during and despite slow tapering and may persist for a long time (see eg. previous post). Even with the help of CBT to prevent relapse after withdrawal, only 36% of patients succeeded in discontinuing antidepressants over 16 months in a failed trial that found no difference between CBT and controls. Only 28% did not have a recurrence.

Patients are actually, generally, very reluctant to take part in antidepressant discontinuation trials (see previous post). Fear of recurrence, relapse, or disturbing current mental equilibrium is common and prior failed attempts to discontinue antidepressants reinforce these expectations. People have also commonly been taken in by the myth of chemical imbalance in the brain as the cause of depression (see eg. another previous post) and are, therefore understandably, fearful and uncertain about stopping antidepressants, as the thought is their chemical imbalance could return. This fear overpowers the concern and uncertainty about continuing antidepressants. It’s understandable if people think it’s better to be safe than sorry by continuing antidepressants (see eg. yet another previous post).

So, even though we may have gone from the situation of antidepressant withdrawal symptoms being denied, as in the Defeat Depression campaign, to one in which they are accepted but the significance minimised (see eg. previous post), there is still insufficient understanding of the nature of antidepressant withdrawal. The situation has not really changed from what I wrote in an Openmind article nearly 25 years ago:-