Antipsychotic Dose Reduction Linked To Long-term Improvements In First-Episode Schizophrenia Patients

Rob Wipond
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Careful reductions in dosage levels of antipsychotic medications over time improved long-term rates of recovery and functional remission in patients diagnosed with a first-episode psychosis, according to a study led by Lex Wunderink reported in a Supplement of European Psychiatry.

The summary of the study was included in the Supplement as one of the Abstracts of the 23rd European Congress of Psychiatry, which occurred in March of this year. It was a 7-year follow-up by Wunderink and other researchers at the Dutch University Medical Center Groningen on a previous 18-month trial comparing 108 people who’d experienced a first episode of psychosis and were either on maintenance treatment (MT) with antipsychotics or were put into a dose-reduction/discontinuation (DR) program.

The 7-year follow-up involved 103 patients. At 40% compared to 18%, patients in the dose-reduction/discontinuation group showed twice the recovery-rate of maintenance-treatment patients, wrote the authors. “Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR.” Relapse rates were initially higher in the dose-reduction/discontinuation group, but after 3 years were nearly the same for both groups.

Dose reduction or discontinuation of antipsychotics during early stages of remitted first-episode psychosis “significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment,” concluded the authors.

MIA Editors note: Though some of the figures seem slightly different, some MIA readers have pointed out that this appears to be a re-presentation of a study previously published by Wunderink et al in JAMA Psychiatry and reported on by MIA in 2013.

Wunderink, L., R. Nieboer, F. Nienhuis, S. Sytema, and D. Wiersma. “Long Term Recovery Rates in Schizophrenia After Early Antipsychotic Dose Reduction.” European Psychiatry 30 (n.d.): 67. Accessed June 21, 2015. doi:10.1016/S0924-9338(15)30056-0. (Abstract)

12 COMMENTS

  1. This is heartening news, I hope it is another step towards a more cautious and judicious use of antipsychotic drugs.

    I think the difficulty is having a culture where reducing dosage of antipsychotic drugs is acceptable. Such a culture can be achieved through the framework of using approaches such as Soteria houses, Open Dialogue and other non-drug ways of supporting a person in psychosis. The important aspect for better outcomes seems to be lesser use, specifically, of antipsychotic drugs. It is very important to support professionals to feel ok about using less antipsychotic drugs for shorter periods.

  3. I think it’s good news anyway. But
    maybe to avoid another ‘break’ the underlying situation might need to be looked at. I don’t (necessarily) mean the external circumstances – I mean what goes on inside in someone’s head that makes them susceptible to immobilisation. Once that side of things is covered then ‘psychosis’ might never occur again.

    • I think properly addressing a person’s real life concerns, and actually looking at the known ADRs and withdrawal effects of drugs they are currently on and recently withdrawn from. Rather than just claiming all the person’s real life concerns to be psychosis, while ignoring the fact that synthetic opioids given under other names can and do cause odd thoughts and antidepressants have long term withdrawal effects (or other drug ADRs, especially pot, I’m told), would greatly decrease so called ‘bipolar’ and ‘schizophrenia’ rates.

      I’m quite certain today’s ‘mindless’ bio-psychiatric approach of ignoring all real life aspects of the patient’s life, defaming as many patients as possible as ‘psychotic,’ and then creating the ‘schizophrenia’ symptoms in people with the neuroleptic drugs – either via neuroleptic induced deficit syndrome or the central symptoms of neuroleptic induced anticholinergic intoxication syndrome (or anticholinergic toxidrome), is the etiology of most, if not all, ‘bipolar’ / ‘schizophrenia’ in our society today.

  4. A major problem with psychiatric treatment of psychosis (as well as most other conditions) is that in general the psychiatric institutions focus more on symptom reduction than on functioning and well-being. It is more “cost-efficient” from their point of view to heavily medicate someone so the person will not need to use system resources. Whether the person feels well or can function becomes irrelevant. There was a patient who was in medical school who had been diagnosed as bipolar. When he appeared to be having a manic episode, his behaviour was a concern to his supervisors, and he was in danger of having to discontinue his education. However his symptoms were able to be calmed down enough with the short-term, occasional use of just 50 mg of chlorpromazine. He continued to function well, was never on other medication, and would need this medication for about a month, once a year. After a few years he didn’t appear to have any further episodes. I have another patient who was on high doses of anti-psychotics and had multiple hospitalizations, yet had heard voices that never went away. She’s been on almost no medication for over twenty years now, is happy and functions well, though does have her, mostly friendly voices. I know when she is having a harder time when her voices turn less friendly, and I then spend more time with her, but have not resorted to medication changes. Functioning and happiness should always take precedence over symptom extinguishing.

    • I’ve got a friend that does the same with 50 mg of largactil (probably with his doctors understanding). The medication is prescribed regularly but he only takes it as he feels he benefits from it, and this works.

      I’ve got another friend and he’s prescribed everything, but the only thing that works for him is talking to another person with similar life experience about how he feels.

  6. Thank you for this interesting study saying: “The 7-year follow-up involved 103 patients. At 40% compared to 18%, patients in the dose-reduction/discontinuation group showed twice the recovery-rate of maintenance-treatment patients, wrote the authors”.

    Are there other studies replicating these results?

    Is it possible to give a rough guess on the long-term effect of antipsychotics on recovery?

    Antipsychotic medications are viewed as cornerstones for both the short-term and long-term treatment of schizophrenia. The evidence for symptom reduction will be critically reviewed. Are there benefits in terms of recovery?
    Leucht et al has 2009 found (How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials) the effect NNT(Number Need to Treat)=6 for short time treatment (1). However this was looking at 50% or more reduction of symptoms on the Positive and Negative Syndrome Scale (PANSS).
    Leucht et al 2012 looks at maintenance treatment with antipsychotic drugs. Between 7 to 12 month are covered. The results published are better but conclude that it is necessary to “clarify the long-term morbidity”.
    Bola et al. Cochrane.org 2011 (5) found just 5 studies with real placebo, i. e. RCT (Randomized controlled trial). One of them Rappaport et al 1978 found that umedicated patients managed better, e. g. readmission into hospital. NNH turned out to be 2.9 (NNH= number need to harm).
    The Council of Evidence-based Psychiatry exists to communicate evidence of the potentially harmful effects of psychiatric drugs to the people (3).
    Nancy Sohler et al. gives 2016 this summary: «For many years, this (…)clinicians’ belief in the need for long-term use of antipsychotic medications strong (Lehmann, 1966) that it has been impossible to design a sound observational study to address the question of efficacy or harm … (O)ur study also could not conclusively evaluate whether long-term antipsychotic medication treatment results in better outcomes on average. We believe the pervasive acceptance of this treatment modality has hindered rigorous scientific inquiry that is necessary to ensure evidence-based psychiatric care is being offered.»
    So I understand there are nearly no RCT controlled studies (avoiding «cold turkey» problems) answering my question on recovery.
    Real world outcomes and results

    However is it possible to use other studies to evaluate effects based on other studies and real world results?
    WHO Cross-Cultural Studies, 1970s/1980s found (Jablensky, A. 1992, Hopper, K. 2000): 16% of patients in the developing countries were regularly maintained on antipsychotics, versus 61% of the patients in rich countries. 63.7% of the patients in the poor countries were doing fairly well at the end of two years. In contrast, only 36.9% of the patients in the seven developed countries were doing fairly well at the end of two years. In the developing countries, 53% of schizophrenia patients were “never psychotic” anymore, and 73% were employed. In the rich countries, only 37 percent of the patients had good outcomes, and 59 percent had become chronically ill.
    Naturalistic studies of e. g. Harrow, M. & Jobe, T.H. (2012), Harrow et al 2014 (11), Wunderink (4,7) and Wils et al 2017 show that patients do better without long-time antipsychotic medication. Harrow, M. & Jobe, T.H. (2017) concludes in “A 20-Year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia”:
    “Negative evidence on the long-term efficacy of antipsychotics have emerged from our own longitudinal studies and the longitudinal studies of Wunderink, of Moilanen, Jääskeläinena and colleagues using data from the Northern Finland Birth Cohort Study, by data from the Danish OPUS trials the study of Lincoln and Jung in Germany, and the studies of Bland in Canada,” (Bland R. C. and Orn H. (1978): 14-year outcome in early schizophrenia; Acta. Psychiatrica Scandinavica 58,327-338) the authors write. “These longitudinal studies have not shown positive effects for patients with schizophrenia prescribed antipsychotic for prolonged periods. In addition to the results indicating the rarity of periods of complete recovery for patients with schizophrenia prescribed antipsychotics for prolonged intervals, our research has indicated a significantly higher rate of periods of recovery for patients with schizophrenia who have gone off antipsychotics for prolonged intervals.”
    Jaakko Seikkula et al 2010 (Journal Psychosis Volume 3, 2011 – Issue 3) has reported on long-term outcome of first-episode psychotic patients treated with Open Dialogue Therapy in Western Lapland approx. 80% recovery (6). “Showing the benefit of using not much medication supported by psychosocial care.” 19% were on disability allowance or sick leave with 17% ongoing neuroleptics. Sveberg (2001) reported 62% on disability allowance or sick leave following standard care and 75% ongoing neuroleptics (11). Disability allowance or sick leave goes up more then 40%.
    The effect of cognitive therapy (8) and psychotherapy (9) is documented.
    Bjornestad, Jone et al. 2017 reported “Antipsychotic treatment: experiences of fully recovered service users”: “(b)etween 8,1 and 20% of service users with FEP achieve clinical recovery (Jaaskelainen et al., 2013)” under the profession’s current protocols.
    Approx. 60% or so of first-episode patients may recover without the use of antipsychotics (Whitaker 2017).
    In order to maintain the narrative of antipsychotis beeing “effective” schizophrenia is falsely declared chronic i. e. drug dependence is preferred over recovery.
    Now I know this guess is not exact science, but does it seem that approx. 40% of patients subject to regular medication (e. g. in Norway “National guideline for diagnosis, treatment and follow-up of individuals with psychotic disorders”) loose long-term recovery compared to non-medicated patients?
    Would this be a fair guess of the long-term effect of antipsycotics on recovery?
    Alternatives to medication

    Morrison et al. 2012 (8) concludes «A response rate analysis found that 35% and 50% of participants achieved at least a 50% reduction in PANSS total scores by end of (cognitive) therapy and follow-up respectively» i. e. NNT=2 for «follow-up» with cognitive therapy. Antipsychotic drugs perform NNT=6 according to Leucht et al. 2009. This shows Klingbergs conclusion (9): “In conclusion, psychosis psychotherapy does not have an evidence problem but an implementation problem.”
    Choice

    Patients have a right to know in advance to decide with informed consent the benefit of actual symptom reduction in the beginning at the price of long-term reduction of recovery. Where there is a risk there has to be a choice.
    I would appreciate your answer based on your knowledge of studies. Thank you in advance.

    Answer no. 1: «Hi Walter, I am afraid I am going to disappoint you, which is unfortunate given the time and effort you put into your comment.»
    Follow-up: Jim Gottstein: Schizophrenia Drugs Reduce Recovery Rates from 80% to 5% (Comparison Open dialogue/Harrow results)

    References:
    1)Leucht S, Arbter D, Engel RR et al. How effective are second-generation antipsychotic drugs?
    A meta-analysis of placebo-controlled trials. Mol Psychiatry 2009; 14: 429–447
    http://www.nature.com/mp/journal/v14/n4/full/4002136a.html
    2)Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM.2012 May 16;(5):CD008016. doi: 10.1002/14651858.CD008016.pub2.
    Maintenance treatment with antipsychotic drugs for schizophrenia.
    https://www.ncbi.nlm.nih.gov/pubmed/22592725
    3)Council of Evidence-based Psychiatry
    http://cepuk.org/unrecognised-facts/long-lasting-negative-effects/
    4)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 StrategyLong-term Follow-up of a 2-Year Randomized Clinical Trial.
    JAMA Psychiatry. 2013;70(9):913-920. doi:10.1001/jamapsychiatry.2013.19
    http://jamanetwork.com/journals/jamapsychiatry/fullarticle/1707650
    5)Bola JR, Kao D, Soydan H, Adams CE. Antipsychotic medication for early episode schizophrenia. 15 June 2011. http://www.cochrane.org/CD006374/SCHIZ_antipsychotic-medication-early-episode-schizophrenia
    6)Robert Whitaker. Harrow + Wunderink + Open Dialogue = An Evidence-based Mandate for A New Standard of Care:
    https://www.madinamerica.com/2013/07/harrow-wunkerlink-open-dialogue-an-evidence-based-mandate-for-a-new-standard-of-care/
    7)Dr. Lex Wunderink, MD, PHD of the University of Gronigen (Netherlands) speaks about his findings for long-terms use of antipsychotic drugs at the 2015 Yale Symposium: New Data and New Hopes Call for New Practices in Clinical Psychiatry. https://www.youtube.com/watch?v=RKeBjLG-ueY
    8)Morrison AP, Hutton P, Wardle M et al. Psychological Medicine. Volume 42, Issue 5 May 2012, pp. 1049-1056. Cognitive therapy for people with a schizophrenia spectrum diagnosis not taking antipsychotic medication: an exploratory trial. Psychol Med 2012; 42: 1049 – 56
    https://www.ncbi.nlm.nih.gov/pubmed/21914252?dopt=Abstract
    9)Klingberg S, Wittorf A. Evidence­based psychotherapy for schizophrenic psychosis. Nervenarzt 2012; 83: 907-918.
    https://www.ncbi.nlm.nih.gov/labs/articles/22733380/
    10)Harrow M, Jobe TH, Faull RN. Psychol Med. 2014 Oct;44(14):3007-16. doi: 10.1017/S0033291714000610. Epub 2014 Mar 24.
    Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. https://www.ncbi.nlm.nih.gov/pubmed/25066792
    11)Scientific Symposium. Pharmaceuticals – risks and alternatives. The 15th of October 2016 in Gothenburg, Sweden. Jaakko Seikkula, Professor of Psychotherapy, Clinical Psychologist, Finland. Naturalistic study designs for developing the system to reduced medication
    12)Open letter to the Directorate of Health, Knowledge Centre, Public Health, Medicines Agency, Patient Safety Program, Norment, Experience Expertise 12. February 2017:
    Knowledge- and research-based liquidation of current harmful psychiatric medication in favour of evidence-based practice to promote recovery http://home.broadpark.no/~wkeim/files/open_letter_knowledge.html