Why is it so difficult to stop psychiatric drug treatment?: It may be nothing to do with the original problem

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Summary

In this paper, I argue that the problems that occur after discontinuation or reduction of long-term psychiatric drug treatment may be caused by the process of drug withdrawal itself, rather than representing the course of the underlying illness. Adverse effects induced by discontinuation of psychiatric medication include: (1) a somatic discontinuation syndrome that includes psychological symptoms which may be mistaken for relapse, (2) a rapid onset psychotic reaction after withdrawal of both conventional neuroleptic drugs and some atypicals, notably clozapine (sometimes referred to as supersensitivity psychosis), (3) a psychological reaction to withdrawal, which may be mistaken for relapse or may itself precipitate relapse, (4) a genuine relapse of the underlying condition precipitated by the process of withdrawal. The implications of these effects include the possibility that much of the research on maintenance treatment is flawed and that the recurrent nature of psychiatric conditions may sometimes be iatrogenic. If withdrawal induced adverse effects could be effectively managed, the success of drug discontinuation might be much greater than usually assumed and might outweigh the disadvantages of continued treatment.

Introduction

Although long-term drug treatment is recommended for most patients with schizophrenia, bipolar disorder, recurrent depression and many other psychiatric conditions, there are many reasons to stop or reduce this medication. Firstly, patients may request to do so. Secondly, doses may be excessive. Evidence concerning neuroleptics, for example, suggests that patients often receive doses that exceed the maximally effective range [1]. Thirdly, it has long been believed that some patients with psychosis do not need long-term drug treatment, especially those with good prognostic features [2], and some authors have suggested that most patients do not benefit from such treatment [3]. Elsewhere I have suggested that antidepressants do not have specific effects on depression that warrant their short or long-term use [4], [5].

My clinical experience suggests that even small reductions in drug treatments are frequently problematic. This is usually attributed to the re-emergence of the underlying disorder in the absence of treatment and used to justify the need for recommencing or increasing drugs. However, there is a considerable body of research that suggests that there are intrinsic problems related to the process of withdrawal from long-term psychotropic drug treatment.

Section snippets

Hypothesis

This paper suggests that the problems that occur after withdrawal of psychiatric drugs may often be related to the process of withdrawal of that medication, rather than the natural course of the underlying condition. If this is the case, then the recurrent nature of psychiatric disorders may be partially attributable to the iatrogenic effects of psychiatric drugs. In addition, it calls for re-interpretation of the trial evidence that forms the basis of recommendations for long-term treatment in

Somatic discontinuation syndromes (also known as withdrawal or rebound reactions)

These syndromes refer to physiological and psychological manifestations of the biological effects caused by the withdrawal of a regularly administered drug. These syndromes have been conceptualised as a result of the biological adaptations to continued drug exposure, which become suddenly unopposed when drugs are withdrawn. It is now recognised that discontinuation or withdrawal syndromes occur with many classes of drugs, not just drugs of abuse, including antidepressants [6], [7] and

Mechanisms of withdrawal related disorders

Two possible mechanisms for withdrawal related disorders are suggested by the preceding evidence.

Implications for maintenance treatment

Since all the adverse effects outlined above may be mistaken for re-emergence of underlying illness, evidence on the value of maintenance drug treatment in psychiatry needs to be re-evaluated. Maintenance studies involve a group of people who have been taking medication for some time. Such people are then randomised either to continue medication or to have it withdrawn and replaced by placebo, usually quite rapidly. Hence, the placebo group are in reality a “medication withdrawal” group and are

Implications for management of drug discontinuation

Research shows that a proportion of people even with severe psychotic disorders (somewhere between 20% and 40% [26], [36]) can stop long-term drug treatment without difficulty. If withdrawal related morbidity could be managed effectively, then the outcome of drug discontinuation might be more successful. For psychotic episodes brought on by drug withdrawal some combination of short-term drug therapy, psychological therapy and social support might be necessary. For other problems, including the

Acknowledgements

I thank Professor Ross Baldessarini and Dr. Philip Thomas for helpful comments on the contents of this paper.

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