Weight Reducing and Metabolic Effects of Topiramate in Patients with Migraine – an Observational Study

Abstract

Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine, which also induces weight reduction by an unknown mechanism. We investigated the effect of topiramate on metabolic and endocrine parameters in patients with migraine independently of any intention to lose body weight. Six patients (26-61 years old, body mass indices [BMI] 20.9-32.1 kg/m(2)) with migraine were treated with an average dose of 100 mg topiramate/day over a period of 20 weeks. The following parameters were measured every 4-8 weeks: BMI, body fat proportion, waist and hip circumference, HOMA insulin resistance, fasting serum-/plasma concentrations of adiponectin, leptin, ghrelin, vascular endothelial growth factor (VEGF), cortisol, interleukin-6 and tumor necrosis factor (TNF)-alpha. Profound metabolic changes were observed for the whole treatment period. Compared with the baseline value, 20 weeks of treatment reduced the BMI by 7.2+/-1.4%, body fat proportion by 11.6+/-3.6%, waist circumference by 4.2+/-1.2%, leptin by 39.2+/-6.5% and HOMA insulin resistance by 37.3+/-5%, while adiponectin was increased by 69.9+/-17.3% (P<0.05, respectively). VEGF concentrations increased during the week 2-4 by 177.4+/-39.4% (P<0.05) followed by a continuous decrease. There were trends for a reduction in ghrelin concentration, whereas cortisol, interleukin-6 and TNF-alpha values were unchanged. In summary, in this small sample of migraine patients topiramate treatment was associated with increased insulin sensitivity, increased adiponectin concentration and a reduction of body fat in all treated patients. The role of increased VEGF concentrations prior to these metabolic changes is not clear and might, hypothetically, involve a centrally mediated effect of topiramate on body weight regulation.

Effectiveness of topiramate in lipomatosis comorbid with agoraphobia and migraine. Case study

“…The exact metabolic mechanism has not been elucidated yet, although effects of topiramate on the hypothalamus are discussed by Yaman et al [24]. Other studies suggest a significant role of increased adiponectin in conjunction with lower leptin levels responsible for weight loss after topiramate intake [25,26]. Adiponectin -secreted almost exclusively by the adipose tissue itself -is postulated to play a decisive role in weight reduction [27].…”

“…A third hypothesis suggests that carboanhydrase, particularly isoenzyme II (CA II), may be involved in lipogenesis and therefore CA-inhibitors such as topiramate or zonisamide show anorectic properties [28]. The role of vascular endothelial growth factor, which transiently increases after intake of topiramate, needs clarification [26].…”

Migraine and Obesity: Possible Link to Inflammation

“…Berilgen et al [72] have evaluated leptin levels in the patients with migraine before and after amitriptyline hydrochloride therapy and their results suggest that serum leptin levels were higher at 4-and 12-week follow-up when compared to baseline levels. Schutt et al [54] reported that leptin was decreased from baseline following 20 weeks of treatment with topiramate in case series. Bernecker et al [73] reported the crude leptin levels in non-obese female migraineurs participants were higher than controls, but this relationship was no significant after adjustment for age and BMI.…”

“…Recently Food and Drug Administration approved "topiramate" drug for migraine prevention in adolescents which has well-established appetite-suppressant side effects that eating disorder symptoms due to topiramate therapy draw the attention to the relation between appetite and migraine [53][54].…”

Ictal adipokines are associated with pain severity and treatment response in episodic migraine

“…[5][6][7] Studies evaluating interictal LEP levels in migraineurs have been inconclusive. [8][9][10][11][12] No previous studies have evaluated ictal LEP or resistin levels in migraineurs. …”