Benefits of Weight Loss for Those With Severe Mental Illness

Can new weight loss drugs help obese individuals taking antipsychotics?

Reviewed by Michelle Quirk

Key points

• People with severe mental disorders are often obese.
• Certain antipsychotics have metabolic side effects that contribute to weight gain.
• New weight loss medications may help decrease morbidity and mortality in obese persons with mental illness.

This post was written by Eugene Rubin, MD, Ph.D., and Charles Zorumski, MD.

Many individuals suffering from psychiatric disorders, especially severe mental illnesses, are substantially overweight. Furthermore, some antipsychotic medications are associated with weight gain, and this contributes to obesity. The shortened life expectancy of people with serious mental illness may partially result from obesity-associated disorders such as diabetes and heart disease. Smoking also contributes to premature aging and death in these individuals.

Metformin is a medication that can decrease the risk of developing diabetes and help individuals lose weight. However, the effectiveness of this drug is variable, and weight loss may only be in the range of 3 to 5 percent of body weight.

Over the last several years, a class of drugs known as glucagon-like peptide 1 (GLP-1) receptor agonists has dramatically influenced the treatment of type 2 diabetes and, more recently, obesity. Semaglutide is one such drug. These drugs work by stimulating the receptors for GLP-1, which “decreases glucagon secretion and stimulates insulin secretion in a glucose-dependent manner, delays gastric emptying, and lowers food intake by promoting satiety.”

Can these drugs benefit overweight individuals with severe mental illness? As pointed out by Sri Mahavir Agarwal and Margaret Hahn in a recent JAMA Psychiatry viewpoint article, previous clinical studies of these groundbreaking drugs have largely excluded people with severe mental illnesses. Semaglutide is currently being studied in several ongoing trials involving people with severe mental illness, but results are not yet available.

In an earlier article, Agarwal, Hahn, and colleagues reported results of a preliminary study using semaglutide to treat 12 individuals with severe mental illness who were taking antipsychotics and had maximized the weight-loss benefits of metformin. Although the dose of semaglutide was low, participants lost 8.7 percent of their body weight after one year. This amount of weight loss is likely to improve general medical health and decrease mortality. With higher doses, it is possible that weight loss would be greater. Also, newer, more powerful weight loss drugs may be even more effective.

There are risks associated with taking GLP-1 agonists for all individuals. Gastrointestinal side effects, including pancreatitis and gastroparesis (markedly slowed emptying of the stomach) can occur. There have been conflicting reports that semaglutide may also increase suicide risk. Moreover, these medications are currently very expensive, and there is evidence that people often regain weight after discontinuing semaglutide.

Agarwal and Hahn’s main point is that “Although the concerns about long-term risks are real and should be investigated, they should not be the reason to selectively prevent patients with severe mental illness from accessing the drug in research and clinical contexts. Mental health stands to gain much from an improvement in physical health.”

We fully concur with this conclusion. These new weight loss medicines may be helpful in the treatment of several chronic medical conditions in obese individuals. There is no reason for those with psychiatric disorders to be excluded from such benefits. Carefully done, larger clinical trials are needed to understand more completely the benefits and risks of these important medications.