Benefits of Maintenance Antipsychotics Outweigh Risks, International Panel Concludes

Antipsychotics have been considered the best option for treating patients with schizophrenia for decades; however, more recent studies have raised questions about whether long-term treatment with the medications might adversely affect the course of the disease.

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While conducting placebo-controlled trials in medication-naïve patients with schizophrenia would be unethical, analysis of preclinical and clinical studies suggesting potential adverse effects of antipsychotics could aid clinicians and patients in decisions about these medications.

In a review article published in AJP in Advance in May, Donald Goff, M.D., the Marvin Stern Professor of Psychiatry at New York University Langone Medical Center, and colleagues described how their evaluation of adverse clinical outcomes arising from antipsychotic use in patients with schizophrenia led them to conclude the benefits of acute and maintenance antipsychotics outweigh the risks when treating patients with schizophrenia.

“There is no question that psychosis is disruptive and frightening,” Goff told Psychiatric News. “And there is no question that antipsychotic drugs are generally effective in treating psychosis and preventing relapse.” Nevertheless, he noted there have been concerns that the medications might make patients more vulnerable to relapse and illness progression.

Goff was part of an expert panel of leaders in antipsychotic pharmacology, pathology, and neuroimaging who recently reviewed clinical and preclinical evidence (including journal articles, books, and more) reporting adverse effects of antipsychotics on long-term outcomes. They then compared these findings with the existing evidence related to antipsychotic efficacy and relapse prevention.

As the analyzed the data, they asked four main questions:

• Does acute treatment with antipsychotics worsen long-term outcomes in patients with schizophrenia?

• Does maintenance treatment with antipsychotics worsen long-term outcomes in patients with schizophrenia?

• What evidence is there to suggest that antipsychotics are neurotoxic?

• What evidence is there to suggest that antipsychotics can sensitize dopamine receptors?

Overall, the panel consensus was that there was no compelling clinical evidence that initial or maintenance antipsychotic treatment worsens the course of illness in patients. Further, there was no compelling evidence that antipsychotics directly contribute to outcomes such as loss of brain volume, cognitive deficits, or relapse of psychosis.

Although the panel acknowledged that there are data to suggest long-term antipsychotic use is associated with these changes, they noted that this evidence is from animal studies or indirect observations from clinical trials. Teasing apart the source of adverse outcomes is complicated by the fact that research suggests psychosis itself can be toxic to the brain.

The panel acknowledged that while not all patients with psychosis require long-term medication (between 10 percent to 20 percent of patients can recover from a psychosis episode spontaneously and stay remitted for extended periods without medication), there is currently no way to identify the patients who might benefit from discontinuing antipsychotics.

While the benefits of antipsychotics are well established, these medications still carry many risks, Goff said. Such risks include metabolic problems or sexual dysfunction that can affect patient quality of life. The panel noted that such side effects should be taken into consideration when deciding how long a patient should be on medication.

“Our hope is that we do not expose people to these drugs who do not need them, and do not withhold these drugs from people who do,” Goff said. For patients receiving maintenance antipsychotic therapy, it’s important to ensure they receive the lowest possible effective dose, he added.

In addition to Goff, the panel consisted of Peter Falkai, M.D., Ph.D., of the Ludwig-Maximilians-University of Munich; W. Wolfgang Fleischhacker, M.D., of Medical University Innsbruck in Austria; Rene Kahn, M.D., Ph.D., of the Icahn School of Medicine at Mount Sinai in New York; Hiroyuki Uchida, M.D., Ph.D., of Keio University School of Medicine in Tokyo; Jingping Zhao, M.D., Ph.D., of the Second Xiangya Hospital of Central South University in Changsha, China; and Ragy Girgis, M.D., and Jeffrey Lieberman, M.D., of New York Presbyterian Hospital-Columbia University Medical Center. ■