Friday, September 25, 2020

Information about antidepressant withdrawal

I expressed concern about the position statement on antidepressants and depression produced by the Royal College of Psychiatrists (RCPsych) last year (see previous post). The College has now produced an online resource on stopping antidepressants. Even though the document has a disclaimer, I’m not convinced the information for patients is as good as it should be.

For a start, the licensed indications for the various antidepressants on the market do not only include depressive illness, anxiety disorder or obsessive-compulsive disorder. Licences have been granted for other indications that RCPsych does not mention eg. bulimia nervosa.

I think it would have been helpful if the document made clearer that continuation treatment of antidepressants is only really recommended if the medication helps. Some people with depression are not helped within six weeks and there is unlikely to be much point in persisting with the same treatment beyond this period. A change of antidepressant is often tried, and even though no antidepressant has been found to be any better than any other, this change may seem to help. But not everyone benefits from antidepressants, even in the clinical trials.

I can’t find any mention in the document of what I think is probably the most important advice about withdrawal symptoms (which is included in the NICE depression guideline). This is that people should be warned of the risk of discontinuation/withdrawal problems when they first start medication. I commonly used to make a comment like “try not to get too dependent on your medication”. I’ve no evidence that this sort of advice necessarily helps, but I think it stands to reason that it might. People can get psychologically dependent on all sorts of things. Starting antidepressants when one might be feeling desperate and unwell, hoping that the medication may help with such negative feelings, is almost inevitably likely to create a psychological dependence, perhaps particularly if the medication seems to help. When I was working, I always found that patients generally understood what I was saying about the risk of psychological dependence (see previous post).

I’m not quite sure what the evidence is for the position taken in the document that the severity of risk of withdrawal symptoms varies with different antidepressants. For example, as I mention on my ‘Antidepressant discontinuation reactions‘ webpage, fluoxetine was reported to be less likely to cause discontinuation problems, maybe because of its longer half-life, but there was conflict of interest in this work, as it could have had marketing implications for fluoxetine. Perhaps more significantly, no mention is made of the similarity of antidepressant withdrawal with the symptoms of benzodiazepine withdrawal.

Although the document says that the cause of antidepressant discontinuation problems is poorly understand, it does seem to very much favour the idea of re-regulation of receptors. But I’m not sure what the evidence is for this speculation (see eg. previous post). It also uses this speculation to support the argument for tapering. but if this is the explanation for the cause of withdrawal symptoms, then why, for example, is it generally easier to withdraw from antidepressants if they have been prescribed for a shorter period of time? I’m not saying that tapering is not important, which it usually is, but some people do seem to be able to stop suddenly, and the need for tapering also fits with my hypothesis of psychological dependence.

I’m also unclear what the evidence is when the document states that only one third to one half of people experience withdrawal symptoms. For example, in a failed trial of CBT to prevent relapse when withdrawing antidepressants, only 36% of patients succeeded in discontinuing antidepressants over 16 months (see previous post).

Although the document says, “Withdrawal symptoms normally start soon after your medication is reduced or stopped”, I’m not sure if the authors believe in delayed withdrawal problems. Late onset can occur (see previous post).

It is a common misunderstanding that antidepressants take weeks to work (see previous post). Where this comes from is that it generally takes 4-6 weeks for a statistically significant difference between active and placebo treatment to be detected in clinical trials. But this is an artefact of the way in which statistical significance is measured. Larger size clinical trials will detect a statistical difference earlier than trials with smaller numbers of subjects. Actually, the largest improvement per unit time produced by antidepressants occurs within the first 2 weeks of treatment.

There’s no mention in the document about making sure that people close to you are supporting you if you are withdrawing from medication. I think it’s much more difficult to withdraw from antidepressants if your relatives, for example, do not agree that you should be stopping.

I wonder whether it should have been made clearer in the document that gradual tapering does not completely eliminate the risk of withdrawal symptoms. Moreover, taking antidepressants also seems to increase the vulnerability to relapse, as well as cause withdrawal symptoms. That’s why continuation treatment was proposed in the first place.

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