This blog is based on material from Joanna Moncrieff’s new book on antipsychotics, out in September entitled “The Bitterest Pills: the troubling story of antipsychotic drugs” (publisher Palgrave Macmillan).

One of my strongest memories from being a medical student was of a young woman who was brought into a hospital in northern England in the 1980s. Confused and frightened, she poured out a profusion of fragmented ideas about having a gadget implanted in her body and feeling that she was being watched and manipulated by vague but malignant forces. She was started on an antipsychotic drug, and as the dose was gradually increased she became increasingly quiet, subdued, emotionless, expressionless and physically sluggish. To me she seemed empty and lifeless compared to what she had been before, although admittedly less distressed. The consensus was she was ‘better’.

Instances like this, combined with the crowds of patients who shuffled about the back wards of the old asylums, soon convinced me that antipsychotic drugs are rightly thought of as a chemical straight jacket, as Thomas Szasz and others have described them. They produce an artificial state of neurological restriction, which affects both the body and the mind. The lower doses that are often used nowadays mean the drug-induced effects are more subtle than they once were, but they occur nonetheless.

On the other hand, severe mental disturbance can be prolonged and disabling. Looking at hospital records from before the days of modern drugs, some people never came out of it, and spent their lives in a state of extreme confusion and degradation, unable to perform the most basic functions, or to communicate with anyone around them. I have occasionally seen people today who have been in this sort of state for many years, some of whom had had little or no drug treatment.

There are times when the use of antipsychotic drugs seems to produce just enough suppression that people can put aside their psychotic preoccupations and re-establish a connection with the outside world. The emotion-numbing effects of the drugs are particularly salient here. Pierre Deniker, one of the French psychiatrists who first used chlorpromazine back in the 1950s, described how people on antipsychotics just lose interest in their delusions.(1)

In the 1950s, when the drugs we now call ‘antipsychotics’ first came along, psychiatrists recognised that they were toxic substances that happened to have the ability to suppress thoughts and emotions without simply putting people to sleep in the way the old sedatives did. The mental restriction the drugs produced was noted to be part of a general state of physical and mental inhibition that at extremes resembled Parkinson’s disease. Early psychiatrists didn’t doubt that this state of neurological suppression was potentially damaging to the brain(1), as Peter Breggin has subsequently and repeatedly pointed out, to little avail. Mainstream psychiatry was uncomfortable with the notion that its principle treatment worked by being a neurological toxin, however. The drugs were soon transformed in official sources into a sophisticated, treatment that targeted an underlying chemical imbalance or other abnormality, even though there was, and still is, no convincing evidence that this is the case.

When you understand antipsychotic drugs in the earlier way, it is obvious that receiving treatment for years and years might have harmful consequences. Yet this is what rapidly became the norm for people diagnosed with a serious mental condition from the time the drugs were introduced in the 1950s. It remains the norm today. Current guidelines insist that ‘long-term treatment is indicated for all patients with schizophrenia’.(2) The new belief that antipsychotics are targeted treatments that rectify an underlying abnormality helped to erase the memory of their disabling effects, and to convince the psychiatric community that long-term treatment was necessary and benign.

Now I believe that antipsychotic drugs can be useful in suppressing psychotic symptoms, and that in some cases, where people are beset by these symptoms on a continual basis, life on long-term drug treatment, even with all its drawbacks, might be preferable to life without it. But most people who experience a psychotic breakdown recover. In this situation, antipsychotics are recommended not on the basis that they provide relief from severe symptoms, but because they are said to reduce the risk of relapse.

There are two problems here. First, the studies that provide evidence that antipsychotic treatment reduces relapse are flawed in a number of ways. They do not consist of a comparison between people who are started on long-term treatment and those who are not, but of a comparison between people who are withdrawn from long-term antipsychotics, usually abruptly, and those who continue to take them. Hence these studies are likely to be influenced by the fact that people who stop drug treatment, especially after being on it for some time, are likely to experience withdrawal-related effects, which we know include agitation, insomnia and occasional psychotic symptoms (sometimes known as supersensitivity psychosis). The difference in relapse rates is almost certainly exaggerated in these studies, therefore, especially since relapse is often defined only in terms of a modest deterioration in general condition or symptoms. Moreover the studies rarely last beyond six months, and in fact studies that last longer than a year show an evening up of relapse rates between people on maintenance treatment and those whose antipsychotics are discontinued.(3)

The other fundamental problem with these studies is that they provide little data on anything other than relapse. After people have had a relapse they are not followed up any further, and attempts to assess how people are actually functioning have rarely been made. Coupled with the loose definition of relapse employed in most studies, this means that people might be worse off on continuous drug treatment overall than they would have been without it, even if they did experience a ‘relapse’. Since the data has not been collected, we just don’t know.

Some other evidence seems to indicate that this might be the case, however, such as Martin Harrow’s long-term cohort study, which shows that people who take antipsychotics for long periods have lower rates of recovery than those who do not.(4) This has been ignored because psychiatry has become so fixated on randomised controlled trials. Even if the trials don’t tell you what you need to know, if they are out there, then they should dictate practice. Those who wished to defend long-term antipsychotic treatment could point to the fact that the people in Harrow’s study who did not take antipsychotics were likely to have had milder conditions to start with. Since it was not a randomised trial, comparing drug treated and non-drug treated people was not comparing like with like.

This is why the results of the long-term follow up of the randomised controlled trial conducted in the Netherlands are so important. This study, which Bob Whitaker has described in detail in his recent blog, involved randomising people who had recovered from a first episode of psychosis to routine ‘maintenance’ treatment with antipsychotics, or to have their antipsychotics reduced in a flexible manner, and discontinued if possible. After the first follow-up at 18 months, twice as many people had experienced a relapse in the discontinuation group as in the maintenance group, although only 20% of the discontinuation group had actually stopped antipsychotics at this point.(5)

Seven years later, however, there was no difference in relapse rates, and levels of psychotic symptoms were similar in both groups, but people in the group who had had the discontinuation strategy were more than twice as likely to have recovered from a functional point of view. By this time 42% of the group who had originally had the antipsychotic discontinuation programme, and 24% of those who were allocated to maintenance treatment had discontinued antipsychotics, or were taking only low doses (less than 1mg per day of haloperidol or equivalent doses of other antipsychotics). They were more likely to show symptomatic and functional recovery than people who remained on standard doses of antipsychotics.(6)

This study provides tentative confirmation that long-term antipsychotic use impairs people’s ability to function, and this is exactly what we should expect from drugs that inhibit mental processes and nervous activity. The study also shows that if you reduce people’s antipsychotics in a gradual and supported manner, people are better off in the long-term. Some will manage to stop their antipsychotics completely and do well, and overall people will not suffer higher levels of symptoms or relapses than if they had stayed on their original level of medication.

As Bob Whitaker and others on this site have stressed, this study should fundamentally change the way antipsychotics are used. These are not innocuous drugs, and people should be given the opportunity to see if they can manage without them, both during an acute psychotic episode and after recovery from one. If psychiatrists had not forgotten the lessons of the past, and if they had been prepared to acknowledge what they saw the drugs doing with their own eyes, this would have come about long ago.

Joanna Moncrieff’s new book on the history of antipsychotics is out in September entitled “The Bitterest Pills: the Troubling Story of Antipsychotic Drugs” published by Palgrave Macmillan.

References:

(1) Deniker P. Experimental neurological syndromes and the new drug therapies in psychiatry. Compr Psychiatry 1960 Apr;1:92-102.

(2) Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 2013 Feb;14(1):2-44.

(3) Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012 Jun 2;379(9831):2063-71.

(4) Harrow M, Jobe TH, Faull RN. Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychol Med 2012 Feb 17;1-11.

(5) Wunderink L, Nienhuis FJ, Sytema S, Slooff CJ, Knegtering R, Wiersma D. Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry 2007 May;68(5):654-61.

(6) Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy: Long-term Follow-up of a 2-Year Randomized Clinical Trial. JAMA Psychiatry 2013 Jul 3.