Many drugs used in the chronic management of neuropsychiatric disorders, including certain anticonvulsants and mood-stabilizing agents, can cause significant weight gain in adults. Because even modest degrees of sustained weight gain are associated with increased risk of complications, drug-induced weight gain may represent a potential safety issue, especially in patients with pre-existing health risks that could be aggravated by added weight. For such patients, therapies that have positive effects on weight control by not causing inappropriate weight gain or by producing weight loss in overweight/obese patients should be considered.
Topiramate is a neurotherapeutic agent approved to treat epilepsy and under investigation for the treatment of other disorders. In previous studies, topiramate was associated with weight loss, suggesting a correlation between the degree of weight loss and both topiramate dose and pretreatment weight. However, these studies were short and were not specifically designed to evaluate the effect of topiramate on weight or factors correlating with weight loss. Therefore, a recent study published in Obesity Research assessed the effects of topiramate on weight and associated physiological and metabolic measures in adults with epilepsy to identify potential predictors of weight loss.
A total of 49 adults with epilepsy were included in this prospective one-year study. Topiramate was added to existing anticonvulsant therapy at a starting dose of 25 mg/ day and increased biweekly in 25- or 50-mg increments to the best tolerated dosage providing maximum seizure control. At the baseline visit and two subsequent visits, body weight was measured and food intake data were collected. Body composition was also measured. Laboratory studies included a 75 g oral glucose tolerance test, thyroid hormones ([T.sub.3], r[T.sub.3], [T.sub.4], TSH), a fasting lipid profile and a leptin radioimmunoassay.
The mean topiramate dose after three months was 81 mg/day. Seizure frequency was reduced by 59%. A clinically significant response was recorded in 53% of patients, with 35% reporting no seizures during the first three months, in patients completing one year of topiramate treatment, mean weight loss was 3 kg after three months and 5.9 kg after one year. In obese patients, mean weight loss was 4.2 kg at 3 months and 10.9 kg at one year. Weight loss was primarily caused by reduction in body fat mass. Early in the therapy, caloric intake paralleled weight loss. However, with continued topiramate treatment, caloric intake returned to baseline levels, whereas weight loss continued. Topiramate treatment was also associated with a significant reduction in fasting total cholesterol at three months and one year and leptin levels were also significantly reduced after one year.
This is the first prospective study specifically evaluating weight change as a result of topiramate treatment. The results suggest that weight loss occurs in most adults and is sustained for at least one year. As expected, weight loss was associated with expected improvements in glucose, insulin, and total cholesterol levels. The combination of weight loss and metabolic improvements seen with topiramate may be the reason to evaluate the potential benefits of this drug for the metabolic syndrome and type 2 diabetes.
Elinor Ben-Menachem, Mette Axelsen, Else Hellebo, et al. Predictors of weight loss in adults with topiramate-treated epilepsy. Obesity Research 11(3): 556-562 (March 2003) [Address correspondence to Elinor Ben-Menachem, Institute of Clinical Neuroscience, Division of Neurology, Sahlgrenska Academy at Goteborg University, Goteborg 413 45, Sweden. E-mail: ebm@neuro.gu.se]
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