Antidepressants, antipsychotics and mood stabilizers can be a big help for people dealing with depression and other psychiatric disorders, but can sometimes lead to weight gain and obesity.

Finding ways to minimize and mediate this side effect is a major puzzle for scientists, psychiatrists and drug companies alike. And it’s not just a cosmetic concern: Even modest weight gain can spark a more troubling problem – “psychotropic medication nonadherence,” which in plain English means that some patients stop taking their pills.

Currently prescribed psychotropic drugs may cause anywhere between 4 and 37 pounds of weight gain over the course of clinical treatment, according to a 2011 review article from SUNY Upstate Medical University researchers in the Journal of Obesity.

There are different families of psychotropic medication, so it’s hard to pin down a single cause for weight gain from them all. Unfortunately, there aren't a lot of large clinical studies examining weight gain in the medicated mentally ill population. But there are some studies that point to how the ingredients in antidepressants and antipsychotics affect both metabolism and appetite.

A small study of adolescent male schizophrenia patients published in the American Journal of Psychiatry in 2002 found that the patients being treated with the drug olanzapine (sold commercially as Zyprexa) gained more weight than the boys treated with another drug. The researchers found that the primary cause of weight gain was increased caloric intake, though the study also showed that Zyprexa affected the patient’s resting energy expenditure and slowed their metabolism.

Many antipsychotics, including Zyprexa, and some antidepressants, block activity at a kind of neurotransmitter receptor called 5-HT2C, which has been shown to be a trigger for eating behavior and obesity in mice. Other drugs may act on other kinds of receptors involved in weight gain, such as the beta-3 adrenergic receptors in fat tissue. The beta-3 receptors play a role in converting fat into energy, and some psychotropics known to have greater affinity for these receptors are associated with a greater risk of weight gain, according to the SUNY Upstate team.

Sometimes switching drugs helps. Some drugs within the same class have differing effects – among selective serotonin reuptake inhibitors, Paxil is more likely to cause weight gain than another SSRI, Zoloft.

For some patients, especially younger ones that cannot switch to second-generation antipsychotics, a psychiatrist may also prescribe the anti-diabetic drug metformin to counter the weight gain. A trial of 128 schizophrenia patients in China, published in 2008 in the Journal of the American Medical Association, showed that metformin could be a powerful tool. The group that was treated just with metformin saw an average body-mass index drop of 1.2, while metformin combined with lifestyle interventions saw an average BMI decrease of 1.8.

Other off-label options for doctors include orlistat, which prevents people from absorbing fats from food, and the anti-eplipepsy drug topiramate.

Losing weight is hard enough for the neurotypical population, and for people on antidepressants, there’s additional hardships for doctors to consider in their prescriptions.

“A combination of diet, exercise and medications would be the ideal approach for combating the weight gain seen in the mentally ill population, but we often find these patients unable to comply with rigorous diet and exercise regimens due to their psychiatric symptoms,” the SUNY Upstate team wrote.

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