Habituation to antidepressants

Discussion on the Critical Psychiatry Network email list has firmed up my views about antidepressant withdrawal. As I point out on my Antidepressant Discontinuation Reactions webpage, there is confusion about the technical meanings of terms like drug dependence and drug addiction. Dependence and addiction in common parlance, though, tend to mean difficulty in managing without the drug. This is a psychological problem, and can also have a physical cause.

As I also say in a previous post, The National Institute for Health and Care Excellence (NICE) clearly states that antidepressants cause withdrawal symptoms even though they have not historically been classified as dependence-forming medicines. It sees dependence as characterised by tolerance and withdrawal symptoms. Addiction is said to include the additional characteristics of cravings, lack of control, overuse and continued use despite harm, associated with problematic behaviours.

People can become habituated to antidepressants. As I wrote in my OpenMind article :-

People may form attachments to their medications more because of what they mean to them than what they do. Psychiatric patients often stay on medications, maybe several at once, even though their actual benefit is questionable. Any change threatens an equilibrium related to a complex set of meanings that their medications have acquired.

Taking antidepressants can be an identity-altering experience (see previous post). No wonder people can have difficulties discontinuing them. People can be frightened about stopping antidepressants (see another previous post and yet another previous post).

Probably the first systematic review of antidepressant withdrawal was by Fava et al (2015) (see previous post). Personally, like Fava et al, I’ve always emphasised the vulnerability to relapse created by taking antidepressants (see another previous post). I’ve encouraged a focus on psychological aspects of prescribed drug dependence (see eg. my book chapter). Critical psychiatrists who believe in deprescribing often think the evidence for physical dependence is incontrovertible. But I do not agree.

There is little evidence that antidepressants cause increased tolerance, for example, in the same way as alcohol and opiates. Antidepressants are not primarily reinforcing like psychostimulants (see eg. previous post). I, therefore, think it is a mistake to say that antidepressants cause physical dependence. That’s not to diminish the power of psychological dependence, which they do cause.

Functional somatic symptoms caused by antidepressant withdrawal are of course common in medicine. It’s the nature of such symptoms that people find it difficult to appreciate they may not have a physical cause. Hence people who have experienced antidepressant withdrawal often disagree with me, sometimes vehemently. Nonetheless, the commonsense view is that people can become dependent on antidepressants for psychological reasons. This was a finding from the Defeat Depression campaign when it tried to educate the public that antidepressants are not addictive, when commonsense understanding is that they must be in the common parlance definition of addiction, as above, as the public already knew (see my BMJ letter).

As I note on my Antidepressant Discontinuation Reactions webpage, the strongest evidence in favour of physical dependence is neonatal withdrawal reactions. I note there, though, that data from spontaneous reporting is difficult to interpret. I haven’t updated that webpage for some time, but even so, neonatal reactions could be due to serotonin syndrome rather than withdrawal. It worries me about the dose of antidepressants that is getting through to neonates in utero. As far as I can see, the more recent studies of poor neonatal adaptation after antidepressant exposure in third trimester have not been able to distinguish that the cause is withdrawal rather than serotoninergic toxicity.

I’m old enough to remember the debate about whether withdrawal symptoms in benzodiazepines were merely due to habituation or physical dependence, led by someone like Malcolm Lader, who in the end came down on side of physical dependence, but he would never have denied psychological dependence. It is true that what led to the decline in the benzodiazepine market was the claim that benzodiazepines cause physical dependence, which I agree there is evidence for because of convulsions on withdrawal. Still, even with most physically dependence forming substance there is also psychological dependence and this must not be denied.

The problem with benzodiazepines is why the antidepressant market was so worried about also being labelled as causing physical dependence and went for admitting antidepressant discontinuation problems. Paxil/Seroxat makers, seen as being the worse for causing discontinuation, but I think probably unfairly because the fluoxetine people wanted to turn the focus away from themselves by pointing out the longer half-life, also had to admit that it caused addiction because of the common parlance use of the word (see Guardian article). The old common sense distinction between physical and psychological dependence got fudged by the syndromal approach of Edwards et al, even though there was strength in the syndromal approach with its seven elements (see Edwards & Gross (1976)).

Does anyone these days even know what I’m talking about when I say the syndromal approach to alcoholism and drug dependence? As I keep saying, psychological factors in antidepressant withdrawal cannot be denied. I’m just encouraging a sceptical attitude about physical withdrawal.