Drug-induced weight gain is a common problem for patients, especially those with severe mental illnesses who must take their medications indefinitely to reduce the risk of symptom relapse. Patients taking antipsychotics typically gain more than 10 pounds during the initial phase of treatment. The impact is usually dose-dependent, however, even low doses of some of the most prescribed drugs in this class caused significant weight gains. All the newer atypical antipsychotics tested cause weight gain, some more than others.
Patients with major depressive disorder also frequently require long-term drug treatment, especially those with recurrent or severe depressive episodes. There is considerable evidence that long-term treatment with many, but not all, antidepressant drugs that target serotonin reuptake can result in significant weight gain. Unfortunately, weight gain is one of the major reasons that people decide to stop taking antidepressants, even if they’re otherwise working well.
Most weight gain occurs at the onset of treatment. For example, patients taking atypical antipsychotics had a statistically significant weight gain of an average of 10 to 14 percent above their baseline body weight within the first six months of treatment.
Longer treatment durations were also associated with larger weight gains. However, it’s not possible, using currently available data, to extrapolate the impact for specific patients who may be treated with atypical antipsychotics or the newer antidepressants for many years. The response produced by different drugs was also quite variable. Complicating the problem further is the fact that mental illness symptoms are frequently treated with multiple medications. One study found that patients taking a combination of drugs (which is extremely common today), including antipsychotics, benzodiazepines (for treatment of anxiety), and an antihypertensive to control blood pressure, experienced a much larger weight gain.
The percentage of weight gain is usually greater in patients with a lower baseline BMI, as compared to patients who are overweight or obese. This difference in response due to BMI may be related to the effects of specific medications on the function of feeding centers in the brain. The responsiveness of feeding centers to food reward, as well as dopamine-acting drugs, becomes blunted in obese people. In addition, it may be that larger doses of certain drugs are necessary to cause statistically significant increases in weight in already obese individuals.
Why do these drugs induce weight gain?
Antipsychotic and antidepressant drugs alter energy intake and energy expenditure by altering neurotransmitter-receptor interactions, particularly involving dopamine and serotonin release in the appetite and reward control centers in the brain. As a result, patients report changes in their appetite and other feeding behaviors. These drugs also alter the release of appetite-regulating hormones such as leptin and orexin, and fat cell-related adipokines. Another potential mechanism to explain why antipsychotic drug therapies induce weight gain is a recent finding that they have antimicrobial properties that induce changes in the gut microbiome that are obesogenic.
Fortunately, it now appears as though the new GLP-1 agonists that have become popular can induce weight loss in patients taking antipsychotics. Potential treatments also include drugs that can suppress increases in leptin that can lead to weight gain. As well, switching to different medications can take advantage of potential individual variations in drug response. In short, three primary strategies are available to mitigate weight gain: lifestyle changes that include dietary changes and increased aerobic exercise; medication switching; and weight loss medication, such as the new glucagon-like peptide receptor agonists.
