In an analysis for the British Journal of Psychiatry, experts in the UK question the evidence for the common practice of prescribing antipsychotics long-term after a single episode of psychosis. They suggest that psychiatrists consider the severe side effects and slowly reduce patients to the lowest dose that prevents the return of distressing symptoms.
“Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure.”
While it has become common practice for those with a diagnosis of schizophrenia to remain on antipsychotics long-term, prophylactic use, meant to prevent the reemergence of symptoms, has come under increased scrutiny of late. This paper addresses five issues with this practice in particular: the effects of the drugs on physical health, on brain structure, the efficacy (or lack of evidence for efficacy) for long-term use, antipsychotic-induced dopamine receptor sensitivity, and ‘treatment-resistant schizophrenia’ (TRS).
Physical health
Due to the substantial adverse effects of antipsychotic drugs on overall physical health, the researchers suggest that psychiatrists attempt, whenever possible, to prescribe drugs with lower risks for weight gain and to make efforts to facilitate exercise and healthy diet with patients. Beyond these recommendations, however, psychiatrists are compelled to consider reducing “the use, or at least the dosage, of long-term antipsychotics.”
Brain structure
Citing both human and animal studies, the researchers detail how first and second-generation antipsychotics have been linked to decreased cortical volume, impaired memory, gray matter changes, and cognitive and functional decline. The methodology of these previous studies make it difficult to separate the effects of the drugs from the changes associated with the diagnoses and the researchers conclude that they are unsure about what can be done about the drugs’ effects on brain structure.
Efficacy of long-term use
The researchers write that “long-term ‘maintenance’ treatment with antipsychotics is based on hope rather than evidence.” Going further, they cite studies (including Harrow and Wunderink) that show that a significant percentage of patients with psychosis can successfully withdraw from antipsychotic medication “without detriment in the long-term.”
Dopamine receptor supersensitivity
Drawing on animal studies, the researchers argue that antipsychotics can induce changes the d2/d3 dopamine receptors leading to diminished effectiveness of the drugs over the long term. This raises the possibility, the researchers argue, that “antipsychotic medication may make some schizophrenic patients more vulnerable to future relapse than would be the case in the natural course of the illness.” The assumption of withdrawal or rebound psychosis confounds previous studies of long-term use, as they often compared the outcomes of patients maintained on the drugs to those who were withdrawn.
“There is an urgent need for neurochemical imaging studies addressing the question of dopamine supersensitivity in patients. We also need further RCTs to examine the risk of relapse after dose reduction and/or discontinuation of D2 blockers, as well as of partial D2 agonists, in order to establish guidelines on when and how antipsychotics can be safely reduced over time.”
‘Treatment-resistant schizophrenia’
Patients diagnosed with TRS may have a supersensitivity to upregulation of d2 receptors, the researchers argue, and they call for studies that attempt to determine whether continuing TRS patients on non-clozapine antipsychotics “has some partial benefit or just produces side-effects.”
In their conclusion, the researchers ask, “What is the wise psychiatrist to do faced with the concerns we have reviewed?” They suggest the following:
“He or she will treat acute psychosis with the minimum necessary dose of antipsychotics, employing weight sparing antipsychotics wherever possible; dopamine partial agonists have this property and may also be less likely to induce dopamine supersensitivity. Following recovery, the psychiatrist should work with each patient to decrease the dose to the lowest level compatible with freedom from troublesome psychotic symptoms; in a minority of patients, this level will be zero.”
They emphasize that such an approach can only be accomplished if there is greater access to and reliance on non-pharmacologic treatments, like psychotherapy. They call on psychiatrists to begin a campaign to make sure that their patients have access to alternative treatments.
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Murray, R.M., Quattrone, D., Natesan, S., van Os, J., Nordentoft, M., Howes, O., Di Forti, M. and Taylor, D., 2016. Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?. The British Journal of Psychiatry, 209(5), pp.361-365.(Abstract)
Long term antipsychotic use is in the spotlight now. Hopefully science can revolve and move forward on this critical issue.
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My response to selected parts of this article:
Quote: “In an analysis for the British Journal of Psychiatry, experts in the UK question the evidence for the common practice of prescribing antipsychotics long-term after a single episode of psychosis. They suggest that psychiatrists consider the severe side effects and slowly reduce patients to the lowest dose that prevents the return of distressing symptoms.”
I agree with this, except to say that voices, delusions, hallucinations, and withdrawal are not “symptoms” of any illness, but are primarily understandable responses to loneliness, stress, trauma, neglect, poverty, etc, and to the terror/rage/confusion generated by these experiences. One cannot discuss these issues very realistically, in my opinion, as long as people’s lived experiences are being overwritten with the meaningless word “symptoms.”
Courageously (for a psychiatric journal), the researchers says,
“The researchers write that “long-term ‘maintenance’ treatment with antipsychotics is based on hope rather than evidence. Going further, they cite studies (including Harrow and Wunderink) that show that a significant percentage of patients with psychosis can successfully withdraw from antipsychotic medication “without detriment in the long-term.” ”
Based on hope rather than evidence, indeed. An interesting later section proceeded:
Quote: “the researchers ask, “What is the wise psychiatrist to do faced with the concerns we have reviewed?” They suggest the following:
“He or she will treat acute psychosis with the minimum necessary dose of antipsychotics, employing weight sparing antipsychotics wherever possible; dopamine partial agonists have this property and may also be less likely to induce dopamine supersensitivity. Following recovery, the psychiatrist should work with each patient to decrease the dose to the lowest level compatible with freedom from troublesome psychotic symptoms; in a minority of patients, this level will be zero.”
Firstly, the wise psychiatrist would understand that there is no valid biogenetic illness entity called schizophrenia, and that alternations in brain chemistry and epigenetics due to adverse experiences are reversible, as well as that one cannot predict what proportion of a vaguely-labeled group of people will or will not need tranquilizers for what length of time in what circumstances.
Secondly, the assumption that drugs are necessary as a front-line treatment is a mistake. The researchers should have stated that it is often possible to help acutely psychotic people with no drugs at all, but using instead an intensive psychotherapeutic approach, as did the Open Dialogue researchers and psychiatrist-psychologists such as Boyer, Volkan, Karon, Rosenfeld, etc. Then again, such an honest statement could not be published in today’s psychiatric journals.
The researchers make the assumption that most “patients” – not that the people involved have any clearly delineated disease that doctors are treating – will need to stay on some low level of drugging indefinitely. This is also mistaken, as outcomes in poor countries such as India (in the WHO) and in intensive interventions such as Open Dialogue (in Finland) have shown that most psychotic people can get better and not use or get off drugs long-term.
The article finally notes:
Quote: “They emphasize that such an approach (using less drugs) can only be accomplished if there is greater access to and reliance on non-pharmacologic treatments, like psychotherapy. They call on psychiatrists to begin a campaign to make sure that their patients have access to alternative treatments.”
Yep. Sounds like they should go to: http://www.isps.org
In my view they could have also noted that seeing a psychiatrist is not necessary to effectively intervene with psychotic states. Non-medical therapists can do curative transformative work without the necessity for psychiatrists nor drugging for many, perhaps most cases. In poorer countries the support of family and community can be enough.
Lastly, here is the list of conflicts of interest for the authors of this article, which included Jim Van Os, who (surprisingly to me) apparently has his fingers in the cookie jar of Big Pharma:
R.M.M. and J.v.O. have received honoraria from Bristol-Myers Squibb, Janssen, Lilly, Roche, Servier and Lundbeck for lectures, and M.D.F. has received honoraria from Janssen and Lundbeck. O.H. has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, Bristol-Myers Squibb, Eli Lilly, Heptares, Janssen, Lundbeck, Leyden Delta, Otsuka, Servier, Sunovion, Rand and Roche.
With a list of conflicts of interest that long, you have to be impressed they would speak as honestly as they did.
Hi Justin – hope you will pay attention to the medical language in reviewing this article, and try to gradually shift to more human-sounding words. Still, nice report.
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Hi Matt,
Great commentary as usual.
I think If “Psychiatrists” were able to get people better, then we might expect they would be doing this.
My Disability between 1980 and 1984 was caused by the Psychiatric drugs I was consuming (Fluphenazine Depot) and I recovered in 1984 as a result of stopping these drugs.
http://insights.ovid.com/clinical-psychopharmacology/jcps/1983/08/000/suicide-associated-akathisia-depot-fluphenazine/6/00004714
The death rate on these drugs in Ireland is high:-
http://ps.psychiatryonline.org/doi/abs/10.1176/ps.49.10.1361-b
My Psychiatrist and his Research University were promoting these drugs on behalf of the manufacturer – and my Disability, Suicidal Reaction and Recovery were suppressed on the Records.
There is such a thing as Supersensitivity Withdrawal Syndrome (High Anxiety) and this is covered along with other useful information in Robert Whitakers Affidavit.
http://www.mindfreedom.org/kb/mental-health-system/whitaker-affidavit/view
I found Psychotherapy suitable for “Normal Anxiety” also worked for “High Anxiety”. But without effective psychotherapy I’m sure I wouldn’t have recovered.
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Good comments. I found the article and it brings together threads of evidence which is seldom presented together. There’s some tension in the paper still – perhaps because it is difficult to get a paper with these views published if it is too blunt. Or perhaps because of other interests. In the conclusion, for example, it says:
“Many psychiatrists rely largely on antipsychotics, not because they dismiss the value of, for example, cognitive–behavioural therapy or vocational training, but rather because financial constraints limit the availability of such interventions.”
I think it is very simplistic to blame the over-reliance on antipsychotics on financial constraints because there are so many different interests involved in how it came to be. They point to: “The Abandoned Illness. Rethink, 2012” as a reference – but it is an 80+ page report so it’s not very specific. Robin Murray is coauthor of both this paper and the 2012 report.
Perhaps the authors are right – that it is financial constraints that have driven the use of antipsychotics. But I fear there are stronger interests at play, some of which have to do with power and hierarchy within mental health services. So although the paper is good news in that it brings the critique of AP use forward it is strangely lacking (or naive) in addressing the underlying incentives driving the prominence of using AP to handle psychosis.
The question is if things can be changed without properly addressing the causes of the problem…
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Hi Jonathan
“…..perhaps because it is difficult to get a paper with these views published if it is too blunt…..”
“….But I fear there are stronger interests at play, some of which have to do with power and hierarchy within mental health services…”
For the most part its the treatment thats causing the long term problems.
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Matt I agree that when going through a psychotic experience there are other people to see first before a psychiatrist. Cbt is a safer first line treatment for psychosis.
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Justiin,
This seems to be a publication of fundamental significance in addressing and challenging the catastrophic, brain, endocrine, metabolic, cardiovascular and other iatrogenic, multi systems injuries and deaths, caused by the extended, enforced or coerced use of these non-specific and extremely toxic drugs.
Is there any means by which M.I.A. can make the full text available please?
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Long term?
How much time does it take from when my hand releases them, until they hit the toilet bowl water?
Nomadic
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Does the brain volume loss is irreversible after long term use of Antipsychotics?
Or does Brain Volume will return to baseline after a period of discontinuing the drug?
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Sorry, ronen- you likely don’t get the volume back, but you do improve the efficiency of what is left, once you’ve cleared the neuroleptic.
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@bcharris
Can you bring me the source of the study
that support your response please?
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I’m actually just making educated guesses. I do know that hardware stuff doesn’t seem to return, and, although I thought it might bother you, you’d probably have some results on a nutrient program (I do have decades of Journals of Orthomolecular Medicine, where the subject is covered in a general fashion, and I’ve also read AR Luria). I suspect the mineral manganese might be helpful for you if you got the involuntary movements, but you’ll have to see some kind of practitioner about that- comes from the work of a Richard Kunin in the 1908’s Journals.
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I fully recovered from Tardive Dyskinesia.
But i also, tremendously changed my diet, to a starch based diet,
Without salt, sugar or refined carbs , oil and caffeine and other highly processed food.
And i also stopped watching tv.
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Well, that is a good start. Still there are still two crucial parts missing. Minimum level of antipsychotics that one can use is not a natural value nor a constant, but depends on earlier medication and a threat that user encounters from psychiatrist and family and society.
Another one is that some level of psychotic symptoms is a necessity to withdrawal and to force a change in environment. Idea of psychosis as a sickness makes understanding the reality hard. Behavior considered as psychosis has a part that is related to learning of nervose system (like visions and irrational thinking and katatonia and anxiety) and a part that is related to a current threat and a necessity to force a change in environment (like paranoia and aggressive behavior).
Without giving an ability to learn and enabling forcing the environment the threat that the environment imposes stays causing a necessity to learn excessively therefore making the cure impossible. As stays the disability due the lack of skills that are often lost because of the medication.
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