Two-Thirds of Schizophrenia Patients Do Not Remit on Antipsychotics

A new analysis of antipsychotic treatment of schizophrenia has found that two-thirds of patients do not experience symptom remission.

Peter Simons
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A new analysis of antipsychotic treatment of schizophrenia (published in Schizophrenia Bulletin) has found that two-thirds of patients treated this way do not experience symptom remission. Additionally, one in five did not experience any improvement at all. The research was led by Myrto Samara, Adriani Nikolakopoulou, Georgia Salanti, and Stefan Leucht, working through the Institute of Social and Preventive Medicine (ISPM) at the University of Bern, Switzerland.

The authors note that treatment guidelines, textbooks, and other resources on psychiatry generally make vague statements that somewhere between 10% and 60% of patients do not benefit from antipsychotic medications or experience only a “partial” improvement. These resources also generally fail to cite references for their numbers.

Samara and the other researchers write that “The treatment guidelines from the American Psychiatric Association mention that ‘about 10%–30% of patients have little or no response to antipsychotic medications, and up to an additional 30% of patients have partial responses to treatment,’ but the authors fail to provide any reference.” However, that does equate to about 60% of patients who do not sufficiently improve when taking antipsychotics, which matches the new data.

Photo Credit: “Masked,” by Andi Jetaime (Flickr)

The researchers analyzed the data from 16 randomized controlled trials (RCTs), considered the gold standard of evidence for clinical studies. This included 6,221 participants with a diagnosis of schizophrenia who were assigned to take one antipsychotic medication from the following list: amisulpride, flupenthixol, haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone. Their progress was assessed over 4-6 weeks, depending on the study.

Samara and colleagues reported finding that “The overall percentage of no symptomatic remission was 66.9%”—meaning that only about a third of people with schizophrenia experienced full improvement on antipsychotic medications. 19.8% of the patients in the study did not experience any improvement at all after taking antipsychotic drugs.

The researchers also report data using numerous cut-off points, because different definitions of “symptom remission” and “improvement” exist in the clinical literature. Notably, if a more stringent definition was used (requiring at least a 75% reduction in symptom severity), only about 13% of participants improved.

According to Samara and the other researchers, those who were diagnosed with schizophrenia at a younger age and those whose symptoms were less severe were less likely to improve. Additionally, certain antipsychotics appeared to have higher rates of response. However, the researchers caution that because their study was not designed to test which antipsychotics were more efficacious, these results cannot be interpreted.

 

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Samara, M. T.,  Nikolakopoulou, A., Salanti, G., & Leucht, S. (2018). How many patients with schizophrenia do not respond to antipsychotic drugs in the short term? An analysis based on individual patient data from randomized controlled trials. Schizophrenia Bulletin. doi:10.1093/schbul/sby095 (Link)

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Peter Simons
MIA-UMB News Team: Peter Simons comes from a background in the humanities where he studied English, philosophy, and art. Now working on his PhD in Counseling Psychology, his recent research has focused on conflicts of interest in the psychopharmaceutical research literature, the use of antipsychotic medications in the treatment of depression, and the general philosophical and sociopolitical implications of psychiatric taxonomy in diagnosis and treatment.

14 COMMENTS

  1. An interesting study, but it should be emphasized some points:

    “We used individual patient data from 16 randomized controlled trials (RCTs) that compared the efficacy of olanzapine or amisulpride with other antipsychotics or placebo for the treatment of patients with acute exacerbation of schizophrenia. Treatment efficacy was measured using the PANSS scale in 8 studies and the BPRS scale in the other 8 studies. The 16 RCTs were sponsored by the pharmaceutical industry and have already been published. 10–25 All trials were randomized, and all, but one open-label, 19 were double-blind. One study included only first-episode patients 21 and one study patients with predominant negative symptoms. 25 Important characteristics of the included studies are presented in the supplementary eTable 1.

    As our research question was how many patients do not respond to antipsychotic medication after adequate time of treatment, we defined a period of 4–6 weeks (preferably 6) as follow-up time to assess response 26 and we excluded patients who received placebo or an antipsychotic drug at an ineffective dose, ie, outside the target dose ranges according to the International Consensus of Antipsychotic Dosing published by Gardner et al. 27 Six thousand two hundred twenty-one patients who received amisulpride (N = 1092), flupenthixol (N = 62), haloperidol (N = 1421), olanzapine (N = 2604), quetiapine (N = 175), risperidone (N = 596), and ziprasidone (N = 271) were included in the analysis. The mean age of the included patients was 37.2 years (CI: 36.9–37.5), the mean duration of illness was 13.6 years (CI: 13.4–3.9), and most of them were males (65.8%, N = 4093).”

    Only one study focused on the first-episode patients and the mean duration of illness was 13.6 years, so it is likely that the majority of patients have been on neuroleptics for a long time. Thus, the “acute exacerbation of schizophrenia” could actually be a psychosis of hypersensitivity, or a psychosis of withdrawal. No comments are made in the study on this possibility.

    The possibility that the exacerbation of psychotic symptoms is caused by psychosis of hypersensitivity is to the advantage of neuroleptics, because the re-increase of the dose will naturally attenuate the syndrome of withdrawal.

    Placebo patients were excluded from the study, but this is not a bad thing given that people on placebo are often not a real placebo group, but more likely a brutal withdrawal group.

    • This is interesting because I think these are reputable researchers.

      They say “For symptomatic remission, we used the definition proposed by Andreasen without employing the time criterion.” and this is a common assumption and for short 6-12 week trials – there is no other option really. But the time criterion of 6 months where symptom reduction of 50% or is achieved is there for good reason, since psychotic symptoms are episodic. To be honest, to only achieve 33% with that level of improvement over 4-6 weeks is rather dissapointing – you can be sure that the proportion that would stay in good shape for 6 months (true remission) would be much, much less.

      The other thing, as you point out, is the mean duration of “illness” of 13.6 years. What are we measuring here? Not people developing psychosis and getting better through antipsychotic drugs. There is no way this cohort would not be on antipsychotics anyway. I think what we are measuring is when they change the antipsychotic to the test drug. So, as you say, you have the efffects of chronic use, possible withdrawal etc. I find it hard to glean anything new here, since the effect sizes of many antipyschotics are rather small anyhow. But it is good that the question is being asked.

  2. Other relevant elements:

    “In the last 36 months, Stefan Leucht has received honoraria for lectures from EliLilly, Lundbeck (Institute), Pfizer, Janssen, BMS, Johnson and Johnson, Otsuka, Roche, SanofiAventis, ICON, Abbvie, AOP Orphan, Servier; for consulting/advisory boards from Roche, Janssen, Lundbeck, EliLilly, Otsuka, TEVA; for the prep- aration of educational material and publications from Lundbeck Institute and Roche. The other authors have no conflict of interest to declare.”

    And all the analyzed studies come from the pharmaceutical industry.

  3. It shouldn’t be surprising to anyone that torture doesn’t work. What it does convey, though, is the mindset of those that inflict it. Psychiatrists in general are not surprised by the inefficacy of their treatment, It’s not their goal to heal, in their mind there is no cure. Two strikes and your out. That’s the definition of schizophrenia.

  4. Could it be possible that “two thirds of schizophrenia patients do not remit on antipsychositics,” at least in part, because the antipsychotics can create the positive symptoms of “schizophrenia,” via anticholinergic toxidrome? And the antipsychotics can create the negative symptoms of “schizophrenia,” via neuroleptic induced deficit syndrome.

    Perhaps, if the psychiatrists would stop force drugging people with antipsychotics, a drug class medically known to create both the negative and positive symptoms of schizophrenia, the patients would do much better?

  5. Perhaps because I came to medicine from science, I thought of symptoms as a guide to the origin of the suffering, not as something to drug or shock away. The same holds for physical symptoms; they help find the physical pathology, if any.
    With psychosis or other deep seated pathology, we often found that the trauma began in infancy, and that healing required attempting to supply the missing nurturing.