flunarizine and Weight-Gain

Migrainous vertigo is a common cause of dizziness presenting to an otorhinolaryngology/otoneurology clinic. Although it causes a substantial burden to the individual and society there are no randomized controlled trails on prophylactic medication for this condition. Flunarizine, a calcium channel blocker has been used effectively in both migraine and vestibular conditions. This randomized control trial was undertaken in a tertiary academic referral center to evaluate the efficacy of flunarizine in patients with migrainous vertigo when compared to non-specific vestibular treatment of betahistine and vestibular exercises. The effect of flunarizine on two particularly disabling symptoms of vertigo and headache was studied. A total of 48 patients who were diagnosed with definitive migrainous vertigo completed the study of 12 weeks duration. Patients in arm A received 10-mg flunarizine daily along with betahistine 16 mg and paracetamol 1 gm during episodes, and arm B received only betahistine and paracetamol during episodes. Symptom scores were noted at the start of the study and at the end of 12 weeks. Analysis of the frequency of vertiginous episodes showed a significant difference between arm A and arm B (p = 0.010) and improvement in severity of vertigo between the two groups (p = 0.046). Headache frequency and severity did not improve to a significant degree in arm A as compared to arm B. The main side effects were weight gain and somnolence and this was not significantly different between the two groups. Flunarizine (10 mg) is effective in patients with migrainous vertigo who suffer from considerable vestibular symptoms.

Topics: Acetaminophen; Adolescent; Adult; Aged; Betahistine; Calcium Channel Blockers; Disorders of Excessive Somnolence; Drug Therapy, Combination; Female; Flunarizine; Histamine Agonists; Histamine Antagonists; Humans; Male; Middle Aged; Migraine Disorders; Vertigo; Weight Gain; Young Adult

This study was aimed to verify changes in the levels of hypothalamic neuropeptides in migraineurs under preventive treatment with amitryptiline and flunarizine. Thirty-nine migraine patients with a body mass index <25 kg/m(2) and without endocrinological or metabolic diseases were assigned to two treatment groups, one receiving amitryptiline, the other flunarizine, for 3 months. Orexin-A, orexin-B and neuropeptide-Y plasma levels were measured at the basal time, at the 1st, 2nd and 3rd months of preventive treatment.. A statistically significant reduction in plasma orexin-A and orexin-B levels emerged in both groups. Conversely, plasma neuropeptide-Y levels were markedly increased, with the highest levels at the 2nd and 3rd months, in both patient groups. Orexin-A levels were also negatively correlated to weight gain in both groups during the treatment period.. These results suggest that changes in the levels of hypothalamic orexinergic peptides may contribute to body weight increase occurring in migraineurs during amitryptiline or flunarizine prophylactic treatment.

Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Female; Flunarizine; Humans; Hypothalamus; Male; Middle Aged; Migraine Disorders; Neuropeptides; Pilot Projects; Radioimmunoassay; Weight Gain; Young Adult

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.

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Body Mass Index; C-Peptide; Female; Flunarizine; Humans; Insulin; Leptin; Male; Migraine Disorders; Vasodilator Agents; Weight Gain

A comparative post-marketing surveillance study of the safety and efficacy of flunarizine and propranolol in the treatment of migraine was carried out. General practitioners in Belgium and the Netherlands each recruited patients for whom they would prescribe one of the study medications in the normal course of their treatment and recorded all medical events on follow-up forms for up to 8 months. A total of 1601 migraine patients were enrolled; 838 in the flunarizine cohort and 763 in the propranolol cohort. Propranolol was somewhat better than flunarizine in reducing the severity of migraine attacks, although this may have been due to a selection bias. Discontinuations of therapy due to events considered likely to be treatment-related were mostly due to the recognized side effects of the two drugs. As regards the occurrence of depressions, a total of 58 patients had depressive events, 34 in the flunarizine cohort and 24 in the propranolol cohort. Whereas migraine itself appears to be associated with an increased risk of depression, the number of previous migraine treatments was shown to be an additional risk factor for the development of depression in patients receiving flunarizine as was a history of depression. Overall, there was no appreciable difference in the risk/benefit ratio between flunarizine and propranolol.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Belgium; Child; Cohort Studies; Depression; Fatigue; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Netherlands; Propranolol; Prospective Studies; Risk Factors; Safety; Treatment Outcome; Vasodilator Agents; Weight Gain

Fourteen ambulatory children and adolescents with intractable epilepsy were studied in an open phase II study to investigate the pharmacokinetics and pharmacodynamics of flunarizine as an add-on treatment. Flunarizine was given in increasing doses starting with 0.1-0.3 mg/kg/day until effect was observed or a steady-state plasma concentration of 50-60 ng/ml was reached. Treatment was continued for 3 months at steady state. Pharmacokinetics were determined during the immediate posttreatment period. Positive antiepileptic effect (> or = 50% reduction in seizure frequency) was observed in 4 of 14 patients (29%; 95% CI: 52-5). Independently of antiepileptic effect, 10 of 14 parents (71.4%; 95% CI: 95-48) observed positive cognitive effects. In all patients treatment was withdrawn due to either lack of effect or weight gain. Flunarizine was rapidly absorbed; mean time of peak concentration (Tmax) was 2.7 hours (range: 1-8). The mean terminal half-life was 23.2 days (range: 7-48), the total plasma clearance of flunarizine per fraction of the dose absorbed (CLp/F) was 0.28 ml/min/kg (range: 0.07-042), and the volume of distribution of flunarizine per fraction of the dose absorbed (Vd/F) was 187 L/kg (range: 99-348). We conclude that flunarizine (0.1-0.3 mg/kg/day) seems to be of limited antiepileptic value in children with intractable epilepsy. The pharmacokinetic profile of flunarizine complicates its clinical use.

Topics: Adolescent; Anticonvulsants; Biological Availability; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Epilepsy; Female; Flunarizine; Half-Life; Humans; Male; Metabolic Clearance Rate; Weight Gain

The use of flunarizine, a drug which has proven its efficacy in migraine, is often associated with important side effects. The aim of this paper has been to check their incidence at different dose levels (5 mg vs 10 mg). Our data confirm the occurrence of important side effects (in particular weight gain); on the other hand, they emphasize the dose-dependency of the side effects.

Topics: Adult; Analgesics; Dose-Response Relationship, Drug; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Weight Gain

Topics: Adolescent; Adult; Appetite; Blood Glucose; C-Peptide; Dietary Carbohydrates; Female; Flunarizine; Humans; Insulin; Male; Middle Aged; Migraine Disorders; Time Factors; Weight Gain