Comparison of the Effects of Amitriptyline and Flunarizine on Weight Gain and Serum Leptin, C Peptide and Insulin Levels when used as Migraine Preventive Treatment

Abstract

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.

Adipokines and Migraine: A Systematic Review

“…Review of references in these manuscripts and related‐reviews identified 2 additional studies . Of these 21 manuscripts, 6 were reviews, 3 were non‐adipokine studies, and 1 utilized an animal model of aura and were thus excluded, leaving 12 studies which evaluated blood levels of leptin in those with migraine . Of these 11 manuscripts, 6 included crude interictal leptin evaluations in those with migraine as compared to controls and 5 evaluated leptin levels before and after abortive or preventive therapy in those with migraine.…”

Obesity and Headache: Part II – Potential Mechanism and Treatment Considerations

“…42 A second study which evaluated serum leptin levels in migraineurs before and after preventive treatment (tx) with amitriptyline reported increased leptin levels after treatment (pre-tx: 7.15 ± 1.12; post-tx: 16.85 ± 2.38, P < .01). 43 However, one small case series of 6 migraine patients reported that leptin was decreased by 39.2 ± 6.5% from baseline following 20 weeks of treatment ( P = .013). 44 Most recently Bernecker et al evaluated fasting leptin levels in 40 non-obese female migraineurs.…”

Low Leptin Levels in Migraine: A Case Control Study

“…Leptin levels of migraine patients, however, have not yet been explored fully. Berilgen et al 14 found elevated leptin levels in migraine patients in the third month of preventive treatment with amitriptyline and flunarizine when compared with baseline levels, probably as a physiological response to counterbalance the weight gain. In this study, we aimed to assess leptin levels in a headache‐free period of migraine patients who did not use any medication interfering in leptin levels, and investigate the relation to vascular risk factors.…”