While antipsychotics are a proven treatment for schizophrenia, patients often trade their symptoms for unpleasant side effects such as weight gain, which puts them at risk for conditions like diabetes, high blood pressure, and certain cancers. This trade-off frequently leads to treatment non-adherence, a significant hurdle in mental health care. However, the rise in popularity of obesity medications such as semaglutide may offer a solution for patients struggling with these metabolic side effects.
The results of a new systematic review and network meta-analysis published in JAMA Psychiatry suggest that several drugs currently used for weight management could be repurposed to help patients with schizophrenia maintain better metabolic health while on antipsychotics. Dr. Mahavir Agarwal, a psychiatrist and scientist at the Centre for Addiction and Mental Health (CAMH) in Toronto, led the research alongside Dr. Maggie Hahn.
The study analyzed 95 trials involving 39 different interventions. The researchers aimed to provide a ranking of treatments based on their relative efficacy in preventing or treating antipsychotic-induced weight gain. Dr. Agarwal sat down with Managed Healthcare Executive to discuss the findings.
The analysis identified the top five most effective drugs for this specific use case. Three of these are GLP-1 receptor agonists, the newer class of drugs driving the current obesity treatment market. Semaglutide, liraglutide, and exenatide were found to be highly effective, with metformin and topiramate rounding out the top five.
Addressing the side effects
Antipsychotics are often the cornerstone of treatment for severe mental illness, managing symptoms and improving daily functioning. Despite their efficacy, they are associated with significant metabolic risks, including weight gain, insulin resistance, and hypertension. Dr. Agarwal explained that the mechanism behind this weight gain is not fully understood but likely involves a disruption of the body’s appetitive machinery. Antipsychotics can interfere with hunger cues and insulin release, creating a physiological environment that promotes weight accumulation.
The impact of these side effects on patient care is substantial. Dr. Agarwal noted that weight gain is a leading reason why young people discontinue their antipsychotic medications. The physical changes can affect a patient’s self-perception and quality of life, making adherence difficult. According to the study, roughly seven or eight out of every ten young people starting their first antipsychotic will experience clinically significant weight gain of at least 5%.
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It is a familiar pattern in the history of pharmacotherapy: as treatments for one condition improve, they often introduce new, difficult-to-manage complications. In this case, the “cure” for severe mental illness brings a metabolic burden that can sometimes undermine the very treatment meant to help. The challenge for clinicians is now finding the right balance between mental stability and metabolic health, a balance that often requires a multi-drug approach.
Treating the problem
Dr. Agarwal outlined how these drugs can be used in a clinical setting. Metformin, the oldest and most studied of the top five, is often recommended as an early intervention. It is low cost, well-tolerated, and effective, making it a suitable starting point for patients beginning antipsychotic therapy or those at high risk for metabolic issues.
For patients where metformin is not sufficient, GLP-1 receptor agonists like semaglutide become the next option. These drugs are highly effective for significant weight loss but face challenges regarding accessibility and cost. Dr. Agarwal noted that while generic versions are now available in Canada, making them more affordable, they still are not covered by most public plans, creating a barrier to access. Topiramate serves as a third option, particularly for patients on disability programs who may not have the financial means for GLP-1 drugs. The study showed that topiramate can lead to approximately five kilograms of weight loss in one in three patients.
Looking ahead, Dr. Agarwal believes the field needs longer-term studies and research into newer agents, such as tirzepatide. The current body of evidence, while robust, relies heavily on trials that lasted less than six months. He emphasized the need for more data on the long-term safety and efficacy of these treatments in this specific population.
Efforts to support metabolic health are ongoing. The potential benefits of these treatments extend beyond weight management, touching on broader physical well-being. This approach aligns with the goal of maintaining overall health while managing mental health conditions. Good Vibrations and a Healthy Body suggest that physical wellness is deeply connected to mental stability. Patients can benefit from holistic strategies that address both physical and psychological needs simultaneously.
