femoxetine and Migraine-Disorders

In a randomized general practice study, the prophylactice effect of femoxetive (a 5HT uptake inhibitor) was compared with placebo in migraine patients. Treatment, with separate randomization schedules in each practice, was allocated to 65 patients. Each patient was treated for 16 weeks with 200 mg increasing during the first nine days to 600 mg daily. No effect of femoxetine could be demonstrated in attack frequency and headache index. Separate analysis of maximum reduction in serotonin concentration during treatment revealed no difference in efficacy when compared with placebo. This supports earlier studies that femoxetine generally exerts no prophylactic effect on migraine, and the hypothesis that platelet 5HT might be of major importance in the pathogenesis of migraine is not supported.

Topics: Adolescent; Adult; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Migraine Disorders; Piperidines

The amplitude of visual evoked potentials (VEPs) for flickering light has been reported to be increased in migraine. In the present study, we have examined whether the VEPs are attenuated when the clinical state of the patient improves during a double-blind experiment with propranolol and femoxetine. VEPs for sinusoidally-modulated light were measured by spectral analysis, and an index depicting the visual reaction type was calculated. The group mean VEP index closely followed the group mean attack frequency, but individual variance was considerable. The changes were most evident in VEPs elicited by stimuli of about 20 Hz. During the treatments, the VEP and headache were also significantly correlated among subjects. The results suggest a close relationship between the enlarged VEPs and the headache mechanisms.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Evoked Potentials, Visual; Female; Humans; Male; Middle Aged; Migraine Disorders; Piperidines; Propranolol; Visual Pathways

The prophylactic effect in migraine of femoxetine, a 5-HT-uptake inhibitor, was compared to that of placebo in a double-blind group-comparative study. A total of 59 patients, referred to the department from general practitioners, was stratified according to age, sex, duration, and frequency of attacks and then allocated at random to treatment with either femoxetine or placebo. Each patient was treated for 12 weeks with 200 mg in the first week and 300 in the remaining weeks. Ten patients on femoxetine and four patients on placebo failed to complete the study. Headache index as well as number and severity of attacks showed a significant reduction with time. The patients on femoxetine showed the greatest improvement over time. It was, however, not statistically significant. Direct comparison between femoxetine and placebo revealed no statistically significant difference. Three patients in the femoxetine group withdrew due to side-effects combined with lack of therapeutic effect. Other side-effects were slight and infrequent. They did not interfere with the treatment. These results indicate that femoxetine could be useful in migraine as a prophylactic drug.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; Piperidines; Placebos; Random Allocation; Serotonin; Serotonin Antagonists

The prophylactic effect of the 5-HT uptake inhibitor femoxetine was compared with propranolol (Frekven R) in a double-blind crossover trial of 6 months duration. Forty-nine patients commenced the trial. Twelve patients withdrew because of drug failure or failure to attend checkups (6), side effects (4) or other non-drug related causes (2). In the 37 patients who completed the trial there was no significant difference between propranolol 160 mg and femoxetine 400 mg with respect to the number of headache days or the number of migraine attacks during the last 2 months of each treatment, Propranolol, however, was superior to femoxetine when the headache index was used (P less than 0.05). The study has shown that partial depletion of thrombocyte 5-HT by a 5-HT uptake inhibitor does not lead to a marked improvement in all patients contrary to what might be expected from the 5-HT hypothesis of migraine. Nevertheless, due to the infrequent subjective side effects associated with femoxetine treatment it may be a valuable prophylactic drug to a subgroup of migraine patients.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; Piperidines; Propranolol; Serotonin Antagonists

The prophylactic effect of a 5-HT uptake inhibitor, femoxetine, was compared with that of propranolol in a double-blind crossover study of 6-months duration. 29 patients commenced the experiment. 3 subjects withdrew because of side effects and 2 because the program was inconvenient for them. In the 24 patients who continued the study to the end, the periods of propranolol (administered 160 mg daily) and of femoxetine (given 400 mg daily) differed significantly from each other with respect to the attack frequency and headache index. A significant reduction in the use of medication relieving attacks was observed during the propranolol treatment as compared with the pre-treatment period. The study showed that partial depletion of thrombocyte 5-HT uptake inhibitor did not lead to a marked improvement in headache, contrary to what might be expected on the grounds of the 5-HT hypothesis of migraine.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; Piperidines; Propranolol; Serotonin Antagonists; Time Factors

Reports have indicated that patients with migraine have abnormalities in platelet function and in the metabolism of vasoactive monoamines. On the basis of these findings, a number of compounds with a stabilizing effect on the level of free vasoactive monoamines in plasma or with anti-platelet effects have been evaluated with regard to their prophylactic effect in migraine. Femoxetine, a new phenylpiperidine derivative and a potent selective serotonin uptake inhibitor, has been suggested as a useful prophylactic drug in migraine. The present studies were designed to evaluate platelet function and blood serotonin levels in patients with migraine before and during femoxetine treatment. During the treatment of 11 patients with migraine with 300 mg femoxetine daily, blood serotonin decreased from 0.17 +/- 0.06 microgram/ml (mean +/- SD) to 0.06 +/- 0.02 microgram/ml. In 8 patients treated with 300 mg femoxetine daily for 12 weeks, 14C-serotonin uptake into platelets in vitro was reduced significantly. Unlike most drugs used in migraine prophylaxis, femoxetine did not influence platelet aggregation in vitro. The demonstration of a certain prophylactic effect of femoxetine in some patients lends support to theories of a serotonin involvement in the pathogenesis of migraine. It does not, however, exclude the possibility of a platelet abnormality as the primary cause of migraine. A hypothesis combining the 2 theories is put forward.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Platelets; Female; Humans; Middle Aged; Migraine Disorders; Piperidines; Platelet Function Tests; Serotonin