Thursday, October 08, 2020

Outcome-based prescribing

In her recent MIA blog post, Joanna Moncrieff concentrates on what psychiatric drugs actually do. She's right that it's commonly wrongly assumed they are correcting some sort of brain imbalance, which she calls the disease-centred model of drug action (see eg. previous post). 

She also mentions the harms caused by psychiatric drugs. For example, antipsychotic medication can cause brain shrinkage, although I think the clinical significance of this finding is unclear (see eg. previous post). Antidepressant discontinuation problems may have become better recognised since a formal complaint made to the Royal College of Psychiatrists two years ago (see eg. previous post). I actually think that believing the disease-centred model of antidepressant action is likely to increase the risk of discontinuation problems (see another previous post). 

Joanna defends what she calls a drug-centred rather than disease-centred model of drug action (see eg. another  blog post from her). As she also notes, psychiatrists may have an outcome-based understanding of drug action, without necessarily any apparent particular commitment to an explanation of the drug's action. I certainly don't believe in the disease-based model, but still prescribed psychotropic medication when I was working because the evidence, for what it is worth, is generally said to be that such medication is effective within NICE guidelines. It was difficult for me to refuse a request for medication within these parameters. This is despite my scepticism about the evidence (see eg. previous post) and recognition that any effect may be due to placebo (see eg. another previous post). I don't want to undermine people's belief in their medication, but not everyone is helped in the clinical trials and the difference between placebo and active medication in these trials is generally much smaller than most people realise. Because of psychological factors, I was very aware of the risk of discontinuation problems and often it seemed easier for patients maintained on medication to continue with it rather than stop (see eg. another previous post).

An advantage of the drug-centred model is that it makes us realise, as Jo says, "how little we really know about these drugs". Modern psychopharmacology started with the introduction of chlorpromazine in the 1950s. When testing drugs for treatment of protozoal infections and parasitic worms, chlorpromazine was noted to have strong anti-histamine properties. It was therefore investigated with allergic patients and reported to cause drowsiness. This 'drowsiness' effect was explored by Henri Laborit, a French surgeon, using chlorpromazine to potentiate anaesthesia with other agents by preventing surgical shock. He reported it induced 'detachment' in his patients, suggesting it produced an 'artificial hibernation' because of its hypothermic and hypnotic qualities. Jean Delay and Pierre Deniker, therefore, investigated the potential for the drug on its own at higher doses in calming manic patients. Their papers talked about chlorpromazine causing a 'chemical lobotomy' different from other sedatives. They coined the term 'neuroleptic syndrome' referring to a slowing down of motor activity, affective indifference and emotional neutrality. Trials of chlorpromazine undertaken by Heinz Lehmann in Montreal facilitated the new drug's introduction to North America. Extrapyramidal effects, such as parkinsonism, were difficult to differentiate from any anti-psychotic properties.

Imipramine, the first antidepressant, has a similar chemical structure to the phenothiazines, like chlorpromazine, but different psychoactive effects. Initial trials in schizophrenia failed but it was said to be spectacularly effective in vital depression (see previous post). As Jo says, the SSRI antidepressants seemed to be "relatively innocuous" compared to the tricyclic antidepressants, like imipramine. She speculates about how they might be "changing the brain in significant ways that we do not understand".

The trouble is that these are only speculations and psychological dependence could be a sufficient explanation of antidepressant discontinuation problems (see eg. previous post). I agree with Jo that we should concentrate on psychiatric harm (see eg. another previous post) and the way to do that is to be much clearer about the pharmacological effects of psychotropic medication. 

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