Four Leading Antipsychotics Aren’t Safe or Effective in Older Adults


A 5-year study funded by the National Institute of Mental Health and conducted by U.C. San Diego School of Medicine, Stanford University and the University of Iowa, comparing the effects of Abilify, Zyprexa, Seroquel and Risperdal on 332 patients over the age of 40, finds that “While there were a few significant differences among the four drugs, the overall risk-benefit ratio for the AAPs in patients over age 40 was not favorable, irrespective of diagnosis and drug.” Results were released online yesterday by the Journal of Clinical Psychiatry.

Abstract →

Jin, Hua., Shih, P., Golshan, S., et al; Comparison of Longer-Term Safety and Effectiveness of 4 Atypical Antipsychotics in Patients Over Age 40: A Trial Using Equipoise-Stratified Randomization. Journal of Clinical Psychiatry. Online November 27, 2012

Of further interest:
Antipsychotic Drugs: 4 Commonly Used Meds Aren’t Effective Or Safe For Older Adults, New Study Finds (Huffington Post)
Four common antipsychotic drugs found to lack safety and effectiveness in older adults (Medical Express)
Four Commonly Used Antipsychotic Drugs Don’t Work (KPBS)
Off label atypical antipsychotic use lacks safety and effectiveness in patients over 40 (News Medical)
Long-Term Use of Some Antipsychotics Not Warranted in Older Adults: Study
(U.S. News)
Four Common Antipsychotic Drugs Found to Lack Safety and Effectiveness in Older Adults (Science Daily)
Study Questions Long-Term, Off-Label Use of Atypical Antipsychotics in Older Adults (Psychiatric News)

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Kermit Cole
Kermit Cole, MFT, founding editor of Mad in America, works in Santa Fe, New Mexico as a couples and family therapist. Inspired by Open Dialogue, he works as part of a team and consults with couples and families that have members identified as patients. His work in residential treatment — largely with severely traumatized and/or "psychotic" clients — led to an appreciation of the power and beauty of systemic philosophy and practice, as the alternative to the prevailing focus on individual pathology. A former film-maker, he has undergraduate and master's degrees in psychology from Harvard University, as well as an MFT degree from the Council for Relationships in Philadelphia. He is a doctoral candidate with the Taos Institute and the Free University of Brussels. You can reach him at [email protected].


  1. This is one of the most damning articles on this site. In one short page it says that one of the most promoted and relied on treatments of modern psychiatry is, on the whole, damaging and useless for those over 40.

    This would be extremely useful for anyone considering challenging psychiatry at a local or national level. It could be taken to meetings with regulators, politicians, healthcare trusts in the UK or individual psychiatrists when reviewing treatment options.

    I wonder if any similar experiments have been done for those under 40?

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  2. I agree. I will probably write a blog on this this week-end. From the paper:
    “The results of our study are sobering…there was no significant improvementi in BRPS total or psychosis subscale over a 6-month period.”
    Dilip Jeste is the President of the APA, I wonder if this paper will be highlighted in the APA newspaper.

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  3. Since this study was designed to compare the four atypicals to each other–there was no placebo group (“because of ethical considerations”)–I have a hard time understanding how the investigators reached a conclusion about efficacy. They say there was no “significant improvement in psychopathology” at follow up, but at baseline an unspecified number of patients were already on an atypical, if I understand the paper correctly.

    So supporters of the use of these drugs could claim that no improvement is to be expected, since the drug benefits were effected before baseline, and thereafter the drugs simply maintained the prior level of benefit.

    Can someone help me understand this better? Thanks. -Ken

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    • I think the most important aspect of the study is that whatever level of benefit there was could not offset the serious side effects. Movement disorders, lethargy and somnolence, metabolic disorders… These are things not worth an undramatic change in prognosis.

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      • Hi, Jeffrey. Thanks very much for your reply to my comment. Personally, I agree with you that the benefit (if any) does not outweigh the side effects, in many or perhaps all cases. It’s just that I’m not sure this study really provides a straightforward argument for that conclusion, as I’d hoped when I first saw the headline on this Web site.

        Advocates of these drugs might say that the outcomes would be even worse without the drugs, and the study really has nothing to say about that. The authors even cite a study that they claim shows that mortality is higher without the drugs.

        But it certainly is interesting that investigators seemed so shocked at the extent of the side effects, adverse events, and drug discontinuation. And it’s certainly a welcome admission that psychiatry might be overstating the benefits and understating the risks.

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        • I agree with what you have said there. While I certainly believe that the side effects have always outweighted any benefits in anyone I have known, psychaitrists continue to say otherwise.

          First and foremost many of them believe that psychosis is a fate worse than death, that it is a degenerative neurological condition that will simply continue to get worse, and that the drugs halt that progression and allow people to remain at the current level of functioning. It keeps them stable, is the bullshit they give.

          They also use that as the argument for needing to predict who will become psychotic, so that we can put them on the drugs early, so they never become unwell and the drugs can maintain the level of functioning they currently have!!!

          According to psychiatrists nothing in the world can ever be as bad as psychosis. While the side effects might be life threatening and horrible they will never be as bad as the underlying disease state.

          Well these are the arguments being made by Australian Psychiatrists. It is beyond me where the thinking comes from, but it is there. Maybe some antipsychotics could help them to get over it??????!!!!!!!!!!!!!!!!!!!!

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    • The average life expectancy of those on these drugs is now about 45. That would be the reason to study this group, to see if they really are benefiting them!!?? Since they kill most of them before this age, then I think that means the side effects were starting befor then!!! Metabolic issues do start immediately, they just take time to become lethal!!

      I love how it has become too unethical to have a placebo group!!!

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      • Yeah, for those who started the drugs usually in their 20’s, often non-compliant for most of the time until their mid 30’s when they find that they need to take the drugs to receive subsidized housing. Just think of how bad it’s going to be for the approximately one million kids on these drugs. Most of them wont live to be 30. Even those who get off the drugs will have brain damage, many will have movement and/or metabolic disorders. Most of them will have to live a life worse than death even if they escape the drugs at some point.

        And for what? Breaking tantrums, reducing agitation, putting them to sleep.

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  4. These are not really “older adults” but all over 40. In press about this study, Jeste is “damage controlling” – stating in dementia and off label we ought worry – but this is “aged > 40 years, having psychosis associated with schizophrenia, mood disorders” – i.e. the majority of the market. Keep that quiet. The real implication ought be shouted from the rooftops, all blogs etc. Best wishes to all on this forum, Rob Purssey

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