Benefits of Antipsychotics Appear to Outweigh Risks, Experts Conclude

Despite recent concerns that long-term antipsychotic use adversely affects health outcomes—possibly by desensitizing dopamine receptors or through direct neurotoxic effects—a review article in AJP in Advance has concluded that the benefits of antipsychotics for the acute treatment of psychosis and the prevention of relapse largely outweigh the risks. Additionally, because delays in the treatment of psychosis and relapse have been associated with poorer outcomes, the review noted there may be risk associated with withholding or discontinuing medication.

“Patients and their families should be made aware of the strong evidence supporting antipsychotic efficacy and of the side effects that vary between drugs,” wrote an international panel of experts in antipsychotic pharmacology, neuroimaging, and neuropathology led by Donald Goff, M.D. “Additional research is needed to help quantify the risk-benefit ratio associated with continuation compared with discontinuation of antipsychotic treatment and to identify predictive biomarkers in order to facilitate shared decision making and a personalized medicine approach.”

Based on a review of available clinical and preclinical evidence of antipsychotic benefits and risks, the panel drew several conclusions:

• The efficacy of antipsychotics for the initial treatment of psychosis and maintenance treatment for the prevention of relapse is well established. Evidence from controlled clinical trials that initial antipsychotic treatment worsens the long-term course of the illness “is not compelling,” the authors wrote.
• A subgroup of patients, which may be as large as 20%, may maintain remission or partial remission for extended periods off medication. The use of low doses or of medication discontinuation may have long-term benefits for some patients, but there are currently no biomarkers that can help identify this subset of patients.
• Evidence linking a reduction in brain volume to antipsychotic treatment is “potentially confounded by the underlying illness and by uncertainty whether higher antipsychotic dosing is a response to, or a contributor to, progressive brain volume loss.”
• Despite evidence from animal models that antipsychotics can produce D2 receptor sensitization and D1 receptor desensitization, “clinical studies have not provided compelling evidence that treatment with antipsychotics worsens the course of illness, increases risk of relapse, or causes cognitive deficits.”

“Although not covered in this review, medical morbidity and mortality associated with antipsychotic use is highly relevant to decisions about long-term treatment,” the authors added. “Many antipsychotics increase risk for metabolic syndrome and thus the risk of heart disease, diabetes, and stroke, which are among the common causes of premature mortality in schizophrenia.”

For related information, see the Psychiatric News article “Does Aggressive Treatment of Psychosis Mean Sustained Use of Antipsychotics?”

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