Long-term Antipsychotics – making sense of the evidence

One of the strongest memories I have from the time when I was a medical student in the 1980s is of a young woman who was brought into a hospital in northern England. 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.

In my view antipsychotic drugs can be useful in suppressing psychotic symptoms, and sometimes, when 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 recently published long-term follow up data from the randomised controlled trial conducted in the Netherlands are so important. The original study 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. People in the group who had had the discontinuation strategy, however, were more than twice as likely to have recovered from a functional point of view. Recovery was defined as having no significant impairments in any area of social functioning as measured by the comprehensive Groningen Social Disability Schedule. Forty per cent of the discontinuation group had recovered at seven years, versus only 18% of the group allocated to maintenance treatment.

At seven year follow-up, 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 altogether, or were taking only low doses (less than 1mg per day of haloperidol or equivalent doses of other antipsychotics). As a group, people who had discontinued or were taking only minimal amounts of antipsychotics were more likely to show symptomatic and functional recovery (regardless of their randomised group) than people who remained on standard doses of antipsychotics (6).

The Dutch 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.

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.

This blog first appeared on the Mad in America website on 13th August 2013.

(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.

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19 thoughts on “Long-term Antipsychotics – making sense of the evidence

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  4. Dear Joanna, you have said that a conclusion you draw from this paper is that people should have an opportunity to see if they can manage without medication. But as the paper is specific to people experiencing a first episode of psychosis, does that mean the results, and your conclusions, cannot be generalised to patients who are not having a first episode, but who have recurring problems?
    Heidi

  5. Dear Joanna Moncrieff,

    Have just received your book the bitterest pill.

    Wondered if you have researched much on the use of rispiridone/dol on the autistic.

    It is a huge scandal. And I found out from net only last year Jansen got a conditional licence for use of it for anxiety in 18 + autistics, but conditional upon safety monitoring, so they did not accept the offer , says a lot about the safety of the drug.

    Since before 2000, it has been used off label for 8 year old autistics, but no one is told that there is no licence for it, when they receive it.

    My daughter is severely autistic now due to the abuse she has recieved in her enforced education, which has made her regress.

    At 8, she had a faecal impaction, which built up after a badly planed overnight respite, this built up in her stomach but she was not scanned, and cleared out by us for another year.

    Respirdone increases constipation, and as you are probably aware, 4 autistic patients being force feed respiridol died in 8 months in ST ANDREWS NHS Northampton last year..

    My daughter at 9, was put on respiridol, it was off label, and a trial, but we were not told. We were given a list of side effects, she was never physically examined this was all under CAMHS.

    The effect was terrible black rings under eyes, huge weight gain, breathlessness, crying all the time and wetting herself and inability to stop eating. We complained about the side effects, and were told they were not side effects of the drug as not on list.

    Thank goodness on a weekend away, someone stole our bags with the medicine in, and we did not get a new bottle, as our complaint lead to an immediate care supervisiion order being applied for by the LA

    The psychiatrist in the CAMHS team, who had prescribed this for her trial, now heads up a multimillion pound care pathway centre, where in 2012, they wanted to take Issy for a 12 week assessment, despite her tested IQ being over 100, and their requirement 50 or less.

    The CAMHS nurse NAS enforced school carers and social worker alleged that her repeating the abuse of her carers swearing in yorkshire accents, was evidence of her hearing voices and her repeating them in her PTSD state evidence of talking to them.

    I have also heard that this medicine actually causes the psychosis, which can then justify it.

    And, if you read the literature, all this CAMHS assessment, would result in, is a respiridol; patch for life. ‘Control without restraint’ is their marketing promotion.

    And these pathway centers, and the MCA 05 HAVE been set up by former government and implemented by present to use incapacity to create a huge market of adult autistics force fed antipsychotics.

    The autistic are now the new pharmacows, and the Mental Capacity Act has allowed forced medication of 18 year olds and over in iNDEPENDENT LIVING.

    Please read my fight to stop my daughter being tortured in secret as a pharmacow, she is 18 on wednesday, by googling finolamoss and reading my blog particularly posts on MCA.

    Thank you for your time but autistic use is now the main use and expansion for these harmful drugs and must be stopped but how with a policy geared to making profit from them in which so many have vested interests..

    • In terms of the cause of your daughter’s illness, no, I don’t agree with you. Genetics aside, there are much more terrible and traumatic things happening in the world right now that can trigger someone into acquiring auditory hallucinations. They are really people dying from war, hunger and disease in the world every single day, the minute I’m typing. Even if it is really caused by some bully’s negative remark, maybe someone is just too fagile for the world and in denial of the terrible things that are happening in the world. You mentioned CAMH right? Since you live in Canada, just be glad and thankful for all the peace and comfort around you already.

      • I’m afraid I do not understand your comment.

        My daughter was not experiencing auditory hallucinations.

        She was repeating abusive phrases, in a thick Yorkshire accent to her, said such as ‘you can’t live with your Mummy and Daddy’, and ‘stop mithering me woman’ etc in exactly the same voice, as this particular lady carer, who I knew.

        Her carers employers were being paid 177,000 per year, and were the National Autistic Society.

        It is beyond scandal, that autistics, are being used as cash cows by CAMHS, National Autistic Society, NHS and enforced supported living, and force fed, dangerous antipsychotic drugs, to make them more manageable, and, even verbal abuse itself, as with my daughter, is used to justify this.

        3 are, as I type, dying needlessly per day because of this. The last one I know of in Sheffield, a 20 year old autistic in a Sheffield adult treatment UNIT. Google my blog where you can read his beyond horrific abuse for which 4,000 per week was paid by googling finolamoss.

        I live in the UK, as far as I am aware, it is the only place in the world, the state routinely abuses the autistic in this way.

      • Right, autism, sorry. I got too excited because I personally know a few similar cases with similar circumstances where the young person experienced bullying which their parents suspect is the reason that triggered their illness, but these cases were all bi-polar or schizophenia related. I guess that was what I wanted to say to them rather than to you, and making a remark online was kind of my way of letting it out. Plus the author of the article did mention this patient she encountered during med school, who in fact, probably does have schizophenic hallucinations. I was interrupted a several of times during the writting process of my previous post, I would say that it is justifiable and forgivable to make a make a mistake here. Forgive me, and forgive my impulsive words and immature behaviour.

  6. Thanks Joanna, it is very nice to get your opinion, especially with all the references that I can dig further. Also, do you mind is I translate your article into Chinese to provide to some of the Chinese patients suffering from mental illness(like psychosis) and their family with information in terms of medication? I can also sent you a copy of it if you like.

      • Dear Joanna,
        I have sent over the translation to you a minute ago through the general comment/messages section of your blog. Please check to make sure that your computer software is able to receive and decode Chinese characters. If not, can you email me your email address so I can sent you a PDF of it? If you do not wish to share your email, please reply and I’ll upload it to a online site of somesort which the windows internet browser would be able to open and decode.
        Thank you

  7. Right, autism, sorry. I got too excited because I personally know a few similar cases with similar circumstances where the young person experienced bullying which their parents suspect is the reason that triggered their illness, but these cases were all bi-polar or schizophenia related. I guess that was what I wanted to say to them rather than to you, and making a remark online was kind of my way of letting it out. Plus the author of the article did mention this patient she encountered during med school, who in fact, probably does have schizophenic hallucinations. I was interrupted a several of times during the writting process of my previous post, I would say that it is justifiable and forgivable to make a make a mistake here. Forgive me, and forgive my impulsive words and immature behaviour.

    • Thanks for getting back. It is good of you.

      As you can imagine, I have too much already, to contend with.

      My main point was, that mental health services and all state services ie social, GP, etc follow their own agenda like a cabal, apparently regardless of the truth, which then even distort .

      They follows a process, and this system, does not allow dissent.

      And state abuse cannot even be mentioned, let alone investigated and stopped that is why so many autistic, learning disabled are dying.

      Best wishes,

      Finola

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