Little evidence exists to suggest that antipsychotic medications have a negative impact on patient outcomes or the brain, either in the short-term or with long-term maintenance therapy. The finding comes from a study by an international group of experts that was published in The American Journal of Psychiatry.

“Anyone who doubts this conclusion [that the benefits of antipsychotics greatly outweigh side effects] should talk with people whose symptoms have been relieved by treatment and literally given back their lives,” said Jeffrey Lieberman, MD, Director of the New York State Psychiatric Institute and lead author of the study. 

The panel included experts from Germany, the U.S., Japan, Australia and China, and they specifically reviewed the use of antipsychotics in treating schizophrenia. The widely accepted use of these treatments for new-onset schizophrenia cases has been disputed recently, with some studies citing two possible adverse effects 1) antipsychotic-induced dopamine D2 receptor sensitization and 2) brain volume loss witnessed in neuroimaging studies in animal models.

The systemic meta-analysis of 38 placebo-controlled trials of second-generation antipsychotics found that the treatments had a moderate effect size of 0.51 and response rate of 41% compared with 24% with placebo. This therapeutic effect is comparable to much of the treatments in other – non-psychiatric – fields of medicine. 

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A total of nine studies were identified and assessed that compared antipsychotic treatment vs. no pharmacotherapy in medication-naïve first-episode psychosis patients. Of these, three studies (Odegard, O. et al Am J Psychiatry. 1964; Peterson, DB. Arch Gen Psyhiatry. 1964; McWalter, HS et al. Am J Psychiatry. 1961) focused on hospitalization rates, finding that initial antipsychotic treatment was tied to increased rates of discharge and reduced rates of hospitalization. Additionally, a further three studies (Huber G et al. Schizophr Bull. 1980; Astrup C. 1966; Pritchard M. Br J Psychiatry. 1967) that focused on measuring functional outcomes, found that the group initially treated with antipsychotics had higher rates of remission and lower rates of deterioration. The remaining three studies investigated first-episode patients randomly assigned to a medication compared with no medication. Results demonstrated that those who were originally assigned to an antipsychotic alone or in combination, or to ECT, had less hospitalizations and showed superior functioning over the following three years.

The authors note that no contemporary randomized placebo-controlled study has examined long-term outcomes of withholding antipsychotic treatment. However one quasi-experimental study (Melle I et al. Arch Gen Psycchiatry. 2008) did find a reduction in the gap between onset of psychotic symptoms and treatment with antipsychotics resulted in improved long-term outcomes. 

“While a minority of patients who recover from an initial psychotic episode may maintain their remission without antipsychotic treatment, there is currently no clinical biomarker to identify them, and it is a very small number of patients who may fall into this subgroup,” said Dr. Lieberman.

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