MedicalResearch.com Interview with:
Donald C. Goff, MD
Marvin Stern Professor
Vice Chair for Research
Department of Psychiatry
NYU Langone Medical Center
MedicalResearch.com: What is the background for this study?
Response: Since their introduction in the 1950’s antipsychotic drugs have been an integral part of the treatment of schizophrenia. However, over the past decade concerns have been raised about whether these drugs might negatively affect the long-term course of the illness—either by causing supersensitivity of dopamine receptors, which might make patients more prone to psychosis and relapse, or by direct toxic effects on the brain.
To address these concerns, we convened a panel of international experts to review the evidence supporting these concerns, including findings from clinical studies, brain imaging studies, post-mortem examination of the brains of people treated with these drugs, and studies in which these drugs were administered to animals.
MedicalResearch.com: What are the main findings?
Response: The main findings were the following:
- First, psychosis is a very serious condition, associated with self-injury, incarceration, disability and disruption of social relationships. The evidence is very strong that antipsychotics are effective for the acute treatment of psychosis and prevention of relapse, although they produce a wide range of side effects and some individuals with psychosis (approximately 10-20%) may recover without them.
- Evidence based on correlational studies (not randomized controlled studies) suggests that delays in the initiation of treatment are associated with poorer long-term course.
- There is evidence linking antipsychotics to brain volume loss in neuroimaging studies but it is not possible to tell whether the brain volume loss results from progression of the illness or from a toxic effect of drugs.
- Because of ethical concerns related to the withholding of effective treatment, no definitive clinical trial has randomly compared the long-term course of individuals assigned to medication versus placebo; based on the available evidence from clinical trials the panel of experts did not find compelling evidence of a negative long-term effect of antipsychotics, whereas the benefit is quite clear.
MedicalResearch.com: What should readers take away from your report?
Response: While it is not possible to predict outcomes in individual patients, overall, antipsychotic drugs are effective for the treatment of psychosis and the prevention of relapse. Failure to treat psychosis can result in serious negative outcomes, including violence and incarceration, whereas minimizing exposure to antipsychotics may reduce adverse effects of these drugs. Some patients might recover without antipsychotic treatment or may do well on a low dose, but since treatment delay and psychotic relapse have been associated with worse outcomes, there may be a risk to withholding or discontinuing treatment and dose reduction must be performed very carefully.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: More controlled antipsychotic treatment trials employing biomarkers are needed to understand the heterogeneity of antipsychotic effects—both positive and negative, so that we can personalize treatment based on predictive biomarkers.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Donald C. Goff, Peter Falkai, W. Wolfgang Fleischhacker, Ragy R. Girgis, Rene M. Kahn, Hiroyuki Uchida, Jingping Zhao, Jeffrey A. Lieberman. The Long-Term Effects of Antipsychotic Medication on Clinical Course in Schizophrenia. American Journal of Psychiatry, 2017; appi.ajp.2017.1 DOI: 10.1176/appi.ajp.2017.16091016
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