Relapse in Antipsychotic Drug Trials is Poorly Defined

There is a lack of consensus in the definition of ‘relapse’ across randomized controlled trials of antipsychotic maintenance treatment for schizophrenia and psychosis.


A new review of the literature, published in Schizophrenia Research, investigates how ‘relapse’ is defined in trials of antipsychotic maintenance treatment. The results of the analysis indicate that the definition of ‘relapse’ in trials of antipsychotic maintenance treatment varies to a considerable degree. This raises concern, as the primary aim of long-term antipsychotic treatment for schizophrenia spectrum disorders is relapse prevention. Therefore, further research must be conducted to determine how to define relapse more consistently, in a reliable and clinically significant manner.

“Among the 82 trial reports, there were a total of 54 different primary definitions of relapse,” write the researchers, led by critical psychiatrist Joanna Moncrieff.

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Trials of antipsychotic medication suggest that there are lower rates of relapse with continuous antipsychotic maintenance treatment as opposed to intermittent treatment or discontinuation of antipsychotic medication. However, reviews of the literature indicate that the definitions of what constitutes a relapse vary across studies. As a result, there is a lack of clarity as to what relapse is across the field of psychiatry, raising the question – how can the claim be made that these medications contribute to lower rates of something that thus far, has been unable to be clearly articulated?

Further, as these medications have been demonstrated elsewhere in the research to have potentially dangerous and permanent side effects, it is imperative that the necessity of their use be based in strong, empirical evidence which the current study calls into question.

In an attempt to examine and describe the definitions of relapse utilized in randomized controlled trials (RCTs) of long-term antipsychotic treatment for individuals struggling with schizophrenia or psychosis, the researchers analyzed studies found in the literature. They examined 82 trials in total, including studies that addressed comparisons between antipsychotic maintenance treatment and placebo, intermittent antipsychotic treatment, and/or medically guided reduction or discontinuation. Further, studies were only included if they addressed outcomes such as relapse, or related areas such as hospitalization, deterioration, and treatment failure.

Of the 82 trials they included, the authors found that there were 54 different definitions of relapse amongst these studies. The researchers compared and contrasted trials occurring before, and after 1990, and found that the definitions of relapse became more complex and detailed as time progressed. In addition, none of the trials that they examined discriminated between individuals who had experienced complete remission of symptoms, versus individuals who were experiencing ongoing psychotic symptoms, which contributes to the murkiness of understanding as to what constitutes a relapse.

Moreover, criteria for relapse that is based on rating scales was demonstrated to differ substantially across trials. Although 23 studies employed the Positive and Negative Syndrome Scale (PANSS), which assesses positive and negative symptoms of schizophrenia, to define relapse, 18 varying sets of PANSS-based criteria were used across the trials. Levels of change varied as well, ranging from a 10 point increase in PANNS total, to a 30 point increase, with scores varying from mild to severe.

Along similar lines, more recent trials typically used the Clinical Global Impressions (CGI) Severity (-S) or Improvement (-I) to describe relapse. However, only 3 of these trials required any change on these scales, which measure patient outcomes, to be categorized as a relapse. Additionally, there was a lack of consensus on what severity level indicates a relapse. The researchers write, “. . . thresholds varied between CGI-S of 3 (mildly ill) to CGI-S of 6 (severely ill) and CGI-I of 6 (much worse).” The researchers also noted a lack of inclusion of behavioral functioning or other clear, noticeable signs of relapse – only four studies included hospitalization or necessary or imminent hospitalization as part of the criteria for relapse.

Furthermore, the researchers’ ratings of the reliability and clinical relevance of the definitions of relapse across the trials reviewed indicates that more reliable, and clinically relevant definitions of relapse are badly needed. Only 37 trials, or 41.5% of the studies were rated by researchers as reliably defining relapse, and only 7 of the studies were rated to describe relapse in clinically relevant terms. The researchers write, “Only six trials showed both good reliability and clinical relevance of the primary definitions of relapse, and four of these used hospitalizations as the sole relapse criterion.”

The researchers found inconsistencies in the frequency of the use of assessment procedures, like routinely administrating the scales addressed above, across the trials. Thirty-seven of the trials regularly assessed for relapse throughout the study. However, the researchers discovered that none of the studies addressed the issue of how to complete measures that require client cooperation, like the PANNS, with individuals who may be experiencing symptoms of psychosis that prevent or make challenging their full participation and collaboration.

Consistent with the variation described throughout their research, the authors found that what constituted a relapse according to the assessments conducted varied across studies. The trials were demonstrated to most frequently use psychosis item scores and clinical judgment as criteria to define relapse, although other studies included criteria such as hospitalization and suicidal or aggressive behavior.

The findings of this review indicate that further research needs to be conducted to develop a more reliable and clinically relevant description of relapse of schizophrenia and psychosis. The authors offer suggestions for future research, such as clarifying what constitutes a clinically significant change in rating scales, as to how to begin to address the lack of reliable and clinically relevant definitions of relapse.

They also suggest using clinical case notes as a way to avoid the issue of attempting to use measurements with clients experiencing florid psychosis, which could allow for a more consistent understanding of what criteria constitute a relapse. It is vital that clear definitions of relapse related to psychosis be identified, as this could prevent the use of unnecessary antipsychotic maintenance treatment, which has been shown elsewhere to be harmful and lacking in research evidence.



Moncrieff, J., Crellin, N. E., Long, M. A., Cooper, R. E., & Stockmann, T. (in press, 2019). Definitions of relapse in trials comparing antipsychotic maintenance with discontinuation or reduction for schizophrenia spectrum disorders: A systematic review. Schizophrenia Research. (Link)


    • Exactly Julie. Giving them because they know it causes weight gain is not a good enough excuse for all the destruction it caused me. I will NEVER trust a psych again. There was NEVER any healing, only muted cries in anguish, undetected by them.

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    • Those of us who were not psychotic, but given the antipsychotics, got to learn the hard way that the antipsychotics make people psychotic. Despite the fact that all our doctors, including all the psychiatrists, are taught in med school that both the antidepressants and antipsychotics can make people psychotic, via anticholinergic toxidrome poisoning. But apparently most the doctors have forgotten this? Oh, that’s because this medically known way to make people psychotic is conveniently – for the “mental health” workers – missing from the DSM billing code “bible.”

      Those of us who were not psychotic, but given the antipsychotics, also got to learn that withdrawal from the antipsychotics also makes a person psychotic, via a drug withdrawal induced super sensitivity manic psychosis. But most the doctors misdiagnose this as a “relapse.”

      Learning about this seemingly intentional and systemic harm, by the psychiatrists and other doctors, does help me understand why Jesus supposedly said, during my drug withdrawal induced super sensitivity manic psychosis, “all the doctors are going to hell.” I found a doctor with a brain in his head, thankfully, but I do have concern for the souls of the many doctors who’ve bought into the psychiatrists’ “bullshit.” Doctors who won’t stop their mass psychiatric drugging of Western civilization, even after the author of the psychiatrists’ “bible,” confessed that it is all “bullshit.”

      And especially since, the psychiatric drugs are killing millions and millions of people.

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  1. I read that
    “Scientists have developed a way to detect schizophrenia – by testing human hairs.
    Japanese researchers said levels of the enzyme MPST was linked to people having the severe mental illness, symptoms of which can include hallucinations, delusions and disorganised thinking. They looked at MPST levels in post mortem brain samples from patients who had schizophrenia and compared them to unaffected people. The levels correlated with the severity of symptoms. Blah blah blah and if you havent figured out the problem with this research yet, take a pill.
    But then this
    “Drug treatments focus on two brain chemicals- dopamine and serotonin. But the study suggests there may be scope for designing a drug that would work on hydrogen sulphide levels in the brain.”
    Is it any wonder the “chemical imbalance” myth continues with newspapers publishing this stuff? Why not at least mention that the “drug treatments that focus on dopamine and serotonin” don’t actually work? Instead they feed right back into the myth. Giving the impression that there are chemical treatments available to balance the dopamine and serotonin, but that they are trying to ‘tweak’ the current treatments. Another oft quoted lie told in these fine establishments of ‘healing’.
    Mind you, this particular article was a couple of pages on from a call for our Treasurer to become involved in the cost of mental illness to our community. Reinforcing the popular myths and lending weight to those nodding their heads that ‘something needs to be done about these nut jobs running around the streets creating havoc’. It won’t be long before the posters telling how much these folk are costing your honest to goodness taxpayer and how we have treatments for these greedy eaters available via our Volutary Assisted Dying legislation that was rushed through Parliament and seems to contain a loophole that doesn’t provide human rights for these ‘patients’.
    I mean 80 percent of the community wanted it right? Yes, they also want the death penalty but I don’t see that being given an express ticket through both Houses with a level of negligence hardly seen before.
    Debate has consisted of discussions between politicians and doctors, with the newspapers unable to even identify any other stakeholders with an interest in the Bill. Talk about silenced. Makes one wonder why we bother with Royal Commissions into the abuse in Aged Care. Oh wait, nooooo they wouldn’t would they?

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  2. I was offered antipsychotic medication once 20 years ago. When I heard the word “antipsychotic” (which I had never heard before, I was traumatized because I thought I must be psychotic, even though I had no clue what that meant. I told him I did not want such a drug. He replied that it would curb my hyperawareness and ‘intrusive thoughts’. I still did not want to try them. He kept pestering me, telling me I could just take a tiny dose, like 10 mg. I still declined and went home to research and learned about ‘psychosis’. I watched a neighbour in my area, a gentle gentle man, become completely lobotomized by drugs, it is the saddest thing I have ever had to witness. Why knife surgery lobotomies were replaced with chemical lobotomies and goes under the radar is beyond me. Why such a dark, very sick power exists to control vulnerable people, yet nothing can be done about it, is beyond me. I still remember that shrink from 20 years ago, how he could not make eye contact in that open human way, and I now understand why. I was a lot more put together than he was and he knew it. I’m sure he in his staunchly held belief system figured I was the one who needed help, OR, perhaps he had a moment of where he felt his ego being challenged and had to pick himself up again. Psychiatrists rarely give up their careers, they have to keep that lie alive. I believe this hurts those shrinks who know the truth and yet others simply believe, although I can’t believe that anyone would believe the bullcrap out of their bible. A sad desperate dark lot they are, all of them. I often wonder what it must be like to live within such a mind. I would MUCH rather I think live in mine, at least I’ve only hurt a few with my words and actions. At least I was given a brain to be cognizant of my words and deeds.

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  3. As a child I knew my aunt was ‘sick’, we were told she was sick and sent away. This was over 50 years ago in a third world country. I saw my mom, her sister arguing as I grew up, my aunt storming out, and my mom seeing my aunt as sick. When we moved to Canada, (my aunt was already in Canada) the angry aunt would make appearances, most often my mom argued with her. Even I as a child, something felt wrong about the situation. I never knew exactly what I was feeling. I have no clue how many ECT treatments my aunt endured, no clue how many drugs. However I know it must have been many and large doses of who knows what. I was a mother already, and my mom and aunt were still arguing, mostly my mom getting angry about aunt’s visions and beliefs. I proceeded to ask about my aunts early years, and my mom made a mention of my aunt having been severely in love at 16, and my grandfather put an end to the love. My aunt became angrier and angrier. Things started to make sense to me. Even though we were a family that was not a community, no kinship encouraged, my aunt made a point of wanting me to come to her one room rental in a rooming house. It was always neat and tidy, she cooked her own food. And after my daughter was born, she had used what tiny money she had and bought a high quality outfit for my baby. My aunt was/used to be highly intelligent. On one of my rare visits, I asked her if she ever got depressed, she answered “no”. I thought to myself, that is because they tried to fry your brain. She was fine around me and I always sensed that she trusted me. She died on her own, in her little space, she was in her early 80’s. I refuse to this day to see her as sick. I feel deep inside that her reaction to her environment caused her symptoms. And that is what they were, symptoms of coping. Not an ‘illness’ to be drugged. I have no answers, although complete assimilation, a safe place, for an extended period is probably one of the answers. The answers do not lie in pretentious caring or listening. It goes to show that children often do not see ‘illness’, or colors of skin, often children get confused by information fed to them, yet many kids go on to believing in mental illness, even to the point of doubting themselves, purely because that is the information fed to them.

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