Antipsychotics for Depression: Added Risk for Little Benefit


A review of research on antipsychotic medications as an adjunctive treatment for depression published this week in PLoS Medicine finds that the widespread practice produces either no benefit or a very small to moderate benefit on quality of life, while also being linked to adverse events such as akathisia, sedation, metabolic effects and weight gain. The authors urge that although clinicians may observe very small to moderate improvement of symptoms, “the lack of benefit with regards to quality of life or functional impairment, and the abundant evidence of potential treatment-related harm” suggest caution.

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Spielmans, G., Berman, M., Linardatos, E., et al; Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes. PLoS Medicine 10(3): e1001403. Online March 12, 2013

Of Further Interest:
Use of adjunctive antipsychotic medications in depression (Medical Xpress)
Antipsychotic Meds Not So Helpful for Depression? (WebMD)
Adding antipsychotic meds to depression treatment offers risks, little benefit, Metro State study finds (MinnPost)

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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. Adding an antipsychotic to an antidepressant is just another flim flam approach of the drug companies to make more money off their toxic, poison drugs. They will tell you that the anipsychotic “jumpstarts” the antidepressant and makes it work quicker and better! This is nothing more than a very large pile of bull manure. The sad thing is that medical and psychiatric doctors are doing prescribing the two together!

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  2. Dopamine is a feel good neurotransmitter.
    Antipsychotics (neuroleptics) are dopamine antagonists.

    So, it would seem as no surprise that blocking dopamine reception would not help with depression. In fact it would induce *more* depression.

    Is there anyone left in psychiatry with a 3-digit I.Q.?!


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  3. This survey finds a modest improvement in the experimental group
    (anti-depressants plus neuroleptics, and/or other drugs with which I am not familiar) as reflected in clinician-assessed decrease of depressive symptoms. This however was in contrast to no improvement in overall well being and abundance of harmful effects such as akathisia, weight-gain, abnormal metabolic lab results. It does not mention sexual impotence although the authors know it is effect of SSRIs. One reason for disparity is that the studies were not blinded since they used inert placebo rather than active placebos. Thus both subjects and clinicians knew who was getting “medication.” This also accounted for lack of improvement in quality of life which was judged by subjects not by clinicians whom we know have clear pro-drug bias.
    I don’t know enough about methodology to answer my question: Why were subjects not much worse?? Both SSRIs and neuroleptics cause akathisia. Akathisia is so unpleasant that it is highly correlated with suicide–I’m saying this based on other studies and books I’ve read. The subjects in these experiments were exposed to double jeopardy from both drugs. Furthermore both cause tardive dyskinesia and other similar neurological symptoms. This also causes suicidality. Many patients have been driven to suicide by akathisia which is not just “restlessness” but an extremely unpleasant “chalk on a blackboard” type of inner restlessness.SSRIs cause extreme akathisia sometimes. People have jumped off bridges to end this inner dis–ease that was driving them crazy. Almost every person I know who was placed on neuroleptics found them unpleasant. Thus I would expect their quality of life to be far worse than those treated with placebo. Why isn’t it?

    The only explanation I have is that studies that showed these effects were not published. And that in these studies surveyed HERE patients who showed these effects often leading to suicidality dropped out of the experiment and thus were not included in data.

    My theory is that the combination of these drugs—SSRIs and neuroleptics– would have a highly detrimental psychological effects–as well as physical–on patients. It should lead to great exacerbation of depressive symptoms and great increase in suicidality. Neither of the latter showed up.

    Anyone have any comments on my thesis and any explanation why an worsening of depression is not reported in this study? Obviously the authors of this study were more skeptical than most shrinks about the value of psychotropic drugs.
    Seth Farber, Ph.D.

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