When Switching Antipsychotics, No Difference Between Immediate and Gradual Discontinuation

Review study compares outcomes of gradual vs. immediate antipsychotic discontinuation when switching from one drug to another

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A recently published systematic review and meta-analysis in the journal Schizophrenia Bulletin finds no significant differences in adverse events between immediate and gradual discontinuation of an antipsychotic when switching from one antipsychotic to another. This outcome contradicts previous research suggesting gradual tapering as a safer method.

The researchers write, “previous reviews of antipsychotic switching strategies recommend gradual antipsychotic discontinuation as a safer method in general; such endorsement is based on empirical evidence but not on actual data from clinical trials.”

“withdrawal” by john.squires, Flickr

Immediate discontinuation of antipsychotics has been associated with numerous risks including dopamine supersensitivity syndromes, rebound syndromes related to cholinergic, histaminergic, and serotonergic activity, and the emergence/exacerbation of symptoms. Gradual discontinuation also comes with some negative consequences including increased risk of side effects that may be additive or synergistic when used in a crossover approach.

While this review provides some insight on discontinuation, the participants did not remain off antipsychotics, therefore it provides only a short window demonstrating the effects of discontinuation. A previous study which reported on the long-term outcomes of discontinuation found that of the 51% of participants who discontinued all antipsychotic medication, 35.3% had no relapse and showed a reduction in symptoms. Moreover, successful discontinuation was predicted by better social integration, higher quality of life, more years of education, and a better prognosis at baseline.

Further, a new trial (RADAR) has been announced which will randomize participants to receive maintenance antipsychotic treatment or to participate in the antipsychotic reduction group. The main outcome of interest will be social functioning along with relapse, side effects, employment, and costs. At the time of writing, no updates have yet been published on the RADAR trial.

The authors of the current study explain that clinicians are more likely to use abrupt switching strategies even though gradual antipsychotic discontinuation is recommended as a safer method. The present systematic review and meta-analysis analyzed 9 randomized control trials (RCTs) that compare immediate vs gradual antipsychotic discontinuation in patients diagnosed with schizophrenia.

Nine studies including a total of 1416 patients (n= 714 immediate discontinuation and n= 702 gradual discontinuation) were included. Study duration ranged from 3 to 12 weeks. The participants in the study were on risperidone, olanzapine, or haloperidol at the beginning of the studies and were transitioned on to another antipsychotic (risperidone, olanzapine, ziprasidone, aripiprazole, iloperidone, or clozapine) at the conclusion of the studies. The tapering was completed over 1 (n=3), 2 (n= 4), 3 (n=2), and 4 (n=1) weeks. The studies also varied in their strategies for starting back up on the new antipsychotic, with some using immediate initiation (n=8), and others using gradual or wait-and-gradual approaches.

The results of the analysis show no significant differences between the immediate and gradual groups when comparing the number of patients who discontinued, psychopathology, extrapyramidal symptoms, and the number of patients who experienced any Treatment-Emergent Adverse Events (TEAEs; akathisia, anxiety, diarrhea, headache, insomnia, nausea, and somnolence). However, the immediate group tended to have a less favorable outcome on insomnia.

More specifically, when switching to olanzapine significant differences were found on insomnia in favor of gradual discontinuation. When participants were switched to ziprasidone there were significant differences on extrapyramidal symptom scores on the Simpson-Angus Scale (SAS) in favor of gradual discontinuation.

Conversely, there were significant differences on somnolence in favor of immediate discontinuation. Lastly, while not statistically significant, the extrapyramidal symptom scores on the Abnormal Involuntary Movement Scale (AIMS) favored gradual discontinuation. Overall, while there was a tendency toward better outcomes with gradual discontinuation, but the differences were mostly not significant between the two strategies.

After examining the nine RCTs included in this study, no significant difference was found between antipsychotic discontinuation strategies on clinical outcomes. The authors draw attention to the fact that the findings are at odds with numerous reviews of antipsychotic switching strategies that recommend gradual discontinuation.

The significant and well-known evidence of the negative side effects that accompany AP drugs, combined with the lack of significant findings in this review, draws attention to the importance of and the upcoming results of the RADAR study.

 

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Takeuchi, H., Kantor, N., Uchida, H., Suzuki, T., & Remington, G. (2017). Immediate vs gradual discontinuation in antipsychotic switching: a systematic review and meta-analysis. Schizophrenia bulletin, 43(4), 862-871. (Link)

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Bernalyn Ruiz
Bernalyn Ruiz
MIA Research News Team: Bernalyn Ruiz-Yu is a Postdoctoral Fellow in the Department of Psychiatry and Biobehavioral Sciences at the University of California, Los Angeles. She completed her Ph.D. in Counseling Psychology from the University of Massachusetts Boston. Dr. Ruiz-Yu has diverse clinical expertise working with individuals, families, children, and groups with a special focus on youth at risk for psychosis. Her research focuses on adolescent serious mental illness, psychosis, stigma, and the use of sport and physical activity in our mental health treatments.

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27 COMMENTS

    • Where’s the scientific method? It strikes me this is a whole lot of comparing apples to oranges, without the “scientists” even knowing what an apple or an orange is.

      The antipsychotics/neuroleptics can create what appears to be the negative symptoms of “schizophrenia” to the DSM believing “mental health professionals,” via what is actually neuroleptic induced deficit syndrome.

      https://en.wikipedia.org/wiki/Neuroleptic-Induced_Deficit_Syndrome

      And the antipsychotics/neuroleptics can also create what appears to be the positive symptoms of “schizophrenia” to the DSM believing “mental health professionals,” via what is actually anticholinergic toxidrome.

      https://en.wikipedia.org/wiki/Toxidrome

      But neither of these psychiatric drug induced illnesses is listed in the DSM, so they are always misdiagnosed by the mind numbingly ignorant psychiatrists.

      And we know between 80-90% of those being drugged with the antipsychotics are child abuse victims given, “the prevalence of childhood trauma exposure within borderline personality disorder patients has been evidenced to be as high as 92% (Yen et al., 2002). Within individuals diagnosed with psychotic or affective disorders, it reaches 82% (Larsson et al., 2012)

      Thus the primary actual function of today’s psychiatric industry is covering up rape of children for the satanic globalist pedophile “elite,” and today’s “mental health professionals” are their satanic money worshipping only minion today.

      So the psychiatric and psychological industries don’t actually want to wean these child abuse victims off the drugs anyway, they want to continue to do satanic tests on them for profit.

      Where’s the science? “Lying evil pigs. Karmas coming soon piggies.” God is not stupid, and He will not be mocked.

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      • Click on the link to get these details. It’s all there.

        It was a meta-analysis, BTW, not an original study.

        I’m not sure why people find this conclusion so threatening. I would think it’s good news for people getting of these drugs.

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        • But I don’t think that their conclusions are correct. When I see someone jerked off one neuroleptic and put on another the person usually gets totally out of control, which the psychiatrists interpret as the person getting worse. No, they’re not getting worse, they are responding to being quickly removed from one drug and placed on another. One of our units has has resident psychiatrists and you can always tell when we get a new batch of them on the unit because people get out of control due to the switching of the drugs that these residents like to fiddle with. No one has ever told them that the Geneva Convention forbids experimenting on human beings without their permission.

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  3. Thanks for posting this Bernalyn. This study is interesting but concerning too. The effects of stopping an antipsychotic or antidepressant in some people can manifest weeks or months after cessation of the drug and can be very different to the immediate withdrawal effects. If this study did only follow participants for a short time then the picture is incomplete. What we need are longer term studies that compare the outcomes of patients that have withdrawn and stayed off the drugs for a significant period. As you point out, hopefully the RADAR study will help the evidence base for withdrawal.

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      • No, it’s not what they found but you’d only know that if you read the article. They did not find that there was no difference between withdrawing rapidly or gradually in those withdrawing completely. They found that there was no difference – statistically, over the entire class of drugs – when switching from one drug to another. And even then, if you read deeper into the study, you’ll see that with some of the neuroleptics, they found no difference and with others they found significant differences. Only when it is averaged over the entire class of available neuroleptics, and only when transitioning from one drug to another in a short term trial, did they find no difference. It’s an irresponsible misleading headline.

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        • I didn’t infer anything about complete withdrawal from this item or the headline. If you did, if was an inference of your own creation. The post clearly refers to switching medications. There was no need to read the actual article to establish that (although I did read it before commenting).

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          • The original title (“Study Reports No Difference Between Immediate and Gradual Discontinuation of Antipsychotics”) said nothing about the study participants switching to another drug. It did imply that the study found it safe to quit “anti-psychotics” cold-turkey.

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  5. Like quitting smoking, I support cold turkey quitting , though I do not think it is easy at all.
    The longer on the drug the more damage is occurring to the brain. A person usually heals from injury, electroshock included.
    “The main outcome of interest will be social functioning along with relapse, side effects, employment, and costs”
    Regarding employment, F U ! What does a SMI person want with employment? I will work for those that tortured and jailed me unjustly? You got to be kidding me.
    You going to remove the SMI status from my medical files? Give me years of my life back that were lost to your worship of magical molecules? F U.

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  6. They never use the scientific method. They’ve created their own. It’s called the Scientific Method of Psychiatry and Psychology and the problem is that nothing can be proven wrong. I have a sneaking suspicion that this is funded by the industry itself. They will gain a lot in revenue in inpatient enrollment by following this study. I think one of the posters here at MIA have figured out if they can arrest a homeless person and get them involuntarily committed, we’re looking at basically about a million dollars that are billable for that one unfortunate customer.

    They completely ignore how the week wash out period have proved that these drugs look like they have a 30% efficacy. What a joke! And they forget one part of the scientific method, repeat-ability before anything is implemented.

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  7. I’m really not sure how much stock can be put into a study of such a short nature when the goal was to transition to another drug, not to withdraw completely. In other words, this study doesn’t seem applicable in any way to withdrawal, but may have application to those merely changing drugs. Since it’s not applicable to withdrawal, I’m not sure why it’s front page news on MIA. I also agree that the headline is misleading. Given the percentage of people who only read the headline and don’t read articles, I think this was not the best reporting job that could have been done on this study, as the takeaway from reading only the headline is essentially “Cold Turkey Withdrawal From Antipsychotics Perfectly Fine”. I’m not one to generally criticize the editors, but this could have been better presented.

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  8. I don’t quite know what to make of this. On the one hand, it kind of makes sense, intuitively. Neuroleptics are highly toxic. The faster a person can drop a highly toxic drug, the better. On the other hand, there’s lots of other data, plus personal experiences, that contradict this latest “development” in the land of Mental Health, Inc.

    My personal opinion–cearly, as a “mental patient,” I won’t find many people who will listen, except perhaps here on MIA–is that there’s tremendous heterogeneity here. If a person is living comfortably, safely, not being oppressed and abused, etc., and they’re also physically more or less healthy and they have some psychosocial support, stuff to do, perhaps some spiritual beliefs+practices, then I could easily see how suddeen discontinuation of a neuroleptic might be a viable option.

    On the other hand, if a personal has been drugged for years upon years, they’re stressed, they have physical problems, they live in isolation, oppression, and poverty (clearly, these factors are interrelated), then suddenly stopping the tranquilizer/neuroleptic might prove to be a hellish experience.

    I think its worth noting that psychiatrists often go out of their way to break people/”patients,” to make us/them more “manageable.” It happened to me, at a young age. Truth be told, I didn’t so much “recover” as I was transformed by a so-called “spiritual awakening” (don’t let the “Christians” on the TV fool you; Jesus loves the least of these, “mental patients” included).

    Once a psychiatrist has broken a person, the torment usually gets worse. I know this from personal experience. Many (most? all?) of them find destroying human beings quite amusing, actually. Maybe that’s why they settle for a field that pays less than other branches of medicine?

    In my own life, I’ve found that once one is healed, transformed, etc., from being broken by Mental Health, Inc., then it becomes much, much easier to get on with things. Of course, the absolute last thing the people of Mental Health, Inc. want, or really what much of society wants, either, is for a broken “mental patient” to be healed and transformed.

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    • If by “breaking” you mean taming in the sense of wild horses, then I’d completely, wholeheartedly agree. I think this is what my old psychiatrist’s aim was when she deliberately withdrew me from Lamictal over a three week period and then, when in a hellish withdrawal I begged her to represcribe, she made me “admit” to needing medications to function. I’m here to say her attempt to break me was unsuccessful.

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  10. I am an MIA author myself.

    I believe in the gradual discontinuation of drugs, but I do not believe in taking years to do it. I believe that one drug should be discontinued at at time — the most powerful one — but that each drug can be discontinued in a matter of a few months.

    Schizophrenia is a whole other topic, and the “rebound syndrome” is something that I do not believe exists. Rebound is not a result of drugs.

    Think of it this way. God knew exactly what human beings were a few thousand years ago. Religious — which is to say, schizophrenic — experience has been with us that whole time. Jesus and Mary, if they were with us now, would be subjected to a whole range of drug and neuro treatments.j

    There is no such thing as rebound. What there is is a re-emergence of the experience of God, which is nothing at all like what is described as “schizo” in the DSM. It is simply the re-emergence of the God experience — which is, yes, very painful and very difficult and very, very hard to get through. But there is no drug rebound. There is simply the re-emergence of the spiritual experience. And that is very different.

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  11. I would like only to add this: I do not believe in “rebound”, but I do believe that when you come off the drugs, in the physical universe that God created, that you do, once again, enter his universe. There is no “rebound.” What there is is a kind of re-entry into God’s world, and that He created it this way on purpose. I am not trying to discredit any “science” of the brain. I am simply trying to emphasize the power of the world that God made.

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