Adding Topiramate to the Obesity Treatment Toolbox

As the prevalence of overweight and obese patients continues to surge in developed countries alongside corresponding increases in life-shortening comorbidities, an efficacious pharmacological treatment for obesity is desperately needed in everyday clinical practice.

Behavioral modifications alone are rarely effective in the short-term, and long-term success is even rarer. While bariatric surgery is an option for some patients, body mass index (BMI), comorbidity requirements, and general unsuitability for surgery exclude many patients from this risky, costly, and invasive procedure.

Current drug therapy for obesity is also less effective than desired, though the US Food and Drug Administration (FDA) approval of combination phentermine/topiramate (Qsymia) may usher in a new era of drug treatment. While topiramate alone has not been approved as an obesity agent, one meta-analysis supports its use as a potential solution for patients in whom phentermine is contraindicated, for providers who do not feel comfortable with the use of phentermine, or for those who have not completed the additional training to prescribe Qsymia.

For that systematic review, Caroline K. Kramer, MD, PhD, and colleagues from the Division of Endocrinology at the Hospital de Clínicas de Porto Alegre in Brazil analyzed data from 10 randomized controlled trials (RCTs) representing a total of 3,320 obese adults. Each study lasted at least 16 weeks and reported the effect of topiramate (Topamax) on weight loss, as well as the drug’s adverse events in obese patients.

The researchers found patients who were treated with topiramate in combination with dietary counseling lost an average of 5.34 kg of additional weight (95% confidence interval [CI] -6.12 to -4.56) compared to patients who received placebo — an effect that increased with treatment duration and dosage. In addition, topiramate dosages between 96-200 mg/day resulted in more weight loss in RCTs up to or longer than 28 weeks (-6.58 kg [95% CI -7.48 to -5.68]) compared to trials of less than 28 weeks (-4.11 kg [95% CI -4.92 to -3.30]).

The adverse events most frequently observed across the trials included paraesthesia, taste impairment, and psychomotor disturbances. In the treatment arms, the odds ratio for adverse events that led to topiramate withdrawal was 1.94 (95% CI 1.64—2.29) compared to the control groups. While the risk for adverse events was increased in comparison to placebo, the side effects were reversible.

Taken altogether, the data from this meta-analysis supported the use of topiramate as a potential adjunctive medication in the treatment of obesity. However, patients with type 2 diabetes seemed to lose less weight than non-diabetic patients, and glycated hemoglobin reduction tended to be less than 0.5%, so the drug’s efficacy in the diabetic population may be limited. Fortunately, the unknown mechanism of topiramate and its lack of FDA approval as an obesity treatment should encourage further research on its use in all types of obese patients. Until then, adding topiramate to behavioral and nutritional counseling in motivated patients may increase weight loss and improve health.

This study offers a very safe and potentially effective drug to add to our weight loss toolbox. However, its use in obese patients should only be considered after informed consent discussions regarding its lack of FDA approval and side effects, as well as in conjunction with structured weight loss goals that include 40 minutes of exercise 5 times a week, dietary counseling to increase fruit and vegetable intake, tracking oral consumption, and drug discontinuation if side effects develop or if patients do not comply with agreed upon components.

About the Authors

Tassy Hayden, MD, is a third-year resident in Family Medicine at the University of Massachusetts Medical School in Worcester, MA.

She was assisted in writing this article by Frank J. Domino, MD, Professor and Pre-Doctoral Education Director for the Department of Family Medicine and Community Health at the University of Massachusetts Medical School and Editor-in-Chief of the 5-Minute Clinical Consult series (Lippincott Williams & Wilkins).