Love the medication but hate the weight gain?

Nicole Mori RN, MSN, APRN-BC
Nurse Practitioner
Lindner Center of HOPE

Obesity is an important comorbidity among psychiatric patients and is associated with increased morbidity and a complicated clinical course.  Many frequently used psychotropic medications can contribute to weight gain, which commonly accompanies adverse metabolic outcomes.  Weight gain is distressing to patients and leads to decreased quality of life and lower adherence.  Psychotropic-mediated weight gain is particularly problematic for patients with bipolar disorder who, regardless of treatment status, experience higher rates of overweight and metabolic abnormalities than the general population.  Patients with bipolar disorder face additional risks for weight gain because the mainstay treatments for bipolar disorder such as mood stabilizers (e.g., Lithium and Valproate) and atypical antipsychotics carry a risk for accelerated weight gain and metabolic disturbances. The effect of many psychotropic medications on histamine, alpha-1 and serotonin 5HT 2A and 5HT 2C receptors has been associated with higher weight gain potential.  In addition, many psychotropic medications can interfere with the activity of leptin, which regulates food intake.  The effects of antipsychotics and mood stabilizers can also lead to dysregulation in lipid biosynthesis, insulin resistance and increased risk for type 2 diabetes.

Strategies for managing weight changes include lifestyle interventions aimed at improving diet and increasing physical activity, selecting medications with a lower weight gain liability and prescribing medications aimed at promoting weight loss or mitigating the weight gain effects of psychotropics.  Selecting medications with lower risk for weight gain or switching medications can be helpful but this may not always be possible due to efficacy considerations.  Studies show that lifestyle modifications can be modestly helpful in mitigating the effects of psychotropic medications on weight, but weight loss is often insufficient and difficult to maintain.

Some medications have been studied and used off label for their potential to attenuate the effects of antipsychotics and mood stabilizers on weight.  Metformin has the most data for efficacy and safety, especially when used in combination with lifestyle modification.  In addition, metformin has shown significant benefits in improving glycemic control and dyslipidemia.  Metformin requires monitoring of renal function and carries a risk for metabolic acidosis (rare) and hypoglycemia.  Gastrointestinal adverse effects associated with metformin (flatulence and diarrhea) can be a barrier to dose escalation and tolerability.  There is some evidence supporting the use of topiramate for mitigating the weight gain effect of psychotropics.  However, rates of discontinuation are high due to adverse events such as dizziness, paresthesia and cognitive impairment.  Norepinephrine reuptake inhibitors have shown a marginal effect on weight gain, and carry a potential for adverse effects on heart rate, blood pressure and psychiatric symptoms, which limits their use.

Although the FDA has approved a handful of new antiobesity medications in the past decade (lorcaserin (Belviq), topiramate/phentermine (Qsymia), bupropion/naltrexone (Contrave) and liraglutide (Saxenda)) there is little research on the efficacy and safety of anti-obesity medications in patients for bipolar disorder.  Orlistat is one of the few FDA-approved medications with clinical trial data for use in psychiatric patients but study results were mixed and the subject population was limited to patients with schizophrenia.  Although orlistat carries a relatively low risk for mood destabilization, it can decrease the absorption of certain medications (including antiepileptics, warfarin and levothyroxine) and is associated with intolerable gastrointestinal side effects (flatulence and incontinence) that lead to discontinuation.  There is no published data on the use of the new antiobesity medications for patients with bipolar disorder.   Most antiobesity medications are combinations of drugs that target the central nervous system and modulate neurotransmitters, raising concerns for risk of destabilization and drug-drug interactions for patients with bipolar disorder.  Liraglutide is the only recently approved medication that primarily targets the gastrointestinal system, and in theory, carries a lower potential for effects on the central nervous system.

There is a need for safe and effective treatments to prevent psychotropic-induced weight gain or enhance weight loss in overweight patients with bipolar disorder. Until research brings new treatments to market, timely detection and management of weight gain and metabolic abnormalities remains the most important intervention to reverse or attenuate these undesirable effects from psychotropic medications.


Dent, R., Blackmore, A., Peterson, J., Habib, R., Kay, G. P., Gervais, A., … & Wells, G. (2012). Changes in body weight and psychotropic drugs: a systematic synthesis of the literature. PLoS One7(6), e36889.

G Fiedorowicz, J., D Miller, D., R Bishop, J., A Calarge, C., L Ellingrod, V., & G Haynes, W. (2012). Systematic review and meta-analysis of pharmacological interventions for weight gain from antipsychotics and mood stabilizers. Current psychiatry reviews8(1), 25-36.

Saunders, K. H., Umashanker, D., Igel, L. I., Kumar, R. B., & Aronne, L. J. (2018). Obesity pharmacotherapy. Medical Clinics102(1), 135-148.

The Lindner Center of HOPE is conducting a randomized, placebo-controlled study of Liraglutide in overweight patients with Bipolar disorder.  For information, please call 513-0704 or visit