Antipsychotics: No Evidence of Long-term Harm

Megan Brooks

May 08, 2017

There is very little evidence to support claims of a negative long-term effect of antipsychotic medication on the clinical course of schizophrenia, an expert panel has concluded.

"Psychosis is really quite serious, distressing, disabling, and potentially dangerous," lead author Donald C. Goff, MD, of NYU Langone Medical Center in New York City, told Medscape Medical News.

"There is no question that antipsychotics are highly effective in the short term. And the conclusion of this expert group is that the evidence suggesting a negative long-term effect of initial or maintenance antipsychotic treatment is not compelling," said Dr Goff.

The study was published online May 5 in the American Journal of Psychiatry.

Brain Volume Loss Due to Drugs or Disease?

Recently, the "widely accepted" recommendation that all patients with new-onset schizophrenia receive acute and maintenance antipsychotic treatment has been challenged out of concern that the medication might adversely affect long-term outcomes, the researchers note.

Evidence cited for these concerns includes the association of antipsychotic treatment with brain volume reduction and with dopamine receptor sensitization, which might make patients more vulnerable to relapse or progression of psychosis, the researchers note.

"Unfortunately, these concerns have led a lot of patients and their family members to decide not to take antipsychotics," Dr Goff told Medscape Medical News.

To help inform "difficult decisions" regarding antipsychotic treatment, an international panel of experts in antipsychotic pharmacology, neuroimaging, and neuropathology came together to review the preclinical and clinical evidence supporting potential adverse effects of antipsychotics on long-term outcomes.

"The purpose of the paper was to review in a very balanced and fair way all of the data to try to guide clinicians and families," said Dr Goff.

The panel found little evidence of a negative long-term effect of initial or maintenance antipsychotic treatment on schizophrenia outcomes, compared with withholding treatment.

The evidence from randomized controlled trials "strongly support" the efficacy of antipsychotics for the acute treatment of psychosis and prevention of relapse, and correlational evidence suggests that early intervention and reduced duration of untreated psychosis might improve longer-term outcomes, the panel concluded.

"The conclusion of this expert group was that there is pretty strong evidence that delayed treatment or untreated psychosis may in fact worsen the long-term course of the illness. That is, psychosis itself may be toxic," said Dr Goff.

The panel also noted that on the basis of available clinical imaging studies, it is not possible to say whether brain volume loss observed during the course of illness is due to antipsychotic medication or to the underlying illness.

Dr Goff noted that evidence from naturalistic studies suggests there may be "a small group of patients – maybe 10% to 20% – who don't require long-term treatment with these drugs, but we need more research to be able to identify those people."

Helpful, Effective

Commenting on the findings for Medscape Medical News, Juan Gallego, MD, service chief, Psychotic Disorders Program, Weill Cornell Medicine and New York-Presbyterian Hospital, said the mainstream thought is that antipsychotics are very helpful and efficacious.

"We need to use them. This is a good paper to support the mainstream clinical view that antipsychotics are needed, required, and we cannot treat schizophrenia without them."

Dr Gallego said it is "very common that some patients refuse antipsychotics for various reasons. But in the vast majority of cases, it's more harmful not to be on an antipsychotic when indicated."

The study had no commercial funding. Dr Goff has received research support from Avanir Pharmaceuticals. A complete list of author disclosures is included in the original article.

Am J Psychiatry. Published online May 4, 2017. Abstract


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