Chronic tension-type headache, mood depression and serotonin: therapeutic effects of fluvoxamine and mianserine. Fluoxetine prophylaxis of migraine. Antidepressant treatment of chronic tension-type headache: a comparison between fluoxetine and desipramine. Amitriptyline versus amitriptyline combined with fluoxetine in the preventative treatment of transformed migraine: a double-blind study. A comparative study of amitriptyline and fluvoxamine in migraine prophylaxis. Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial. Fluoxetine for migraine prophylaxis: a double-blind trial. Use of amitriptyline and fluoxetine in prophylaxis of migraine and tension-type headaches. S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study. Selective serotonin reuptake inhibitors for migraine prophylaxis.
Forty out-patients affected by chronic tension-type headache were selected according to the diagnostic criteria of International Headache Society (IHS) Headache Classification Committee. In a controlled trial patients received placebo for a four-week baseline period, then they were randomized in double-blind fashion to therapy with mianserine (30-60 mg/day) of fluvoxamine (50-100 mg/day) for another eight-week period. Frequency of headache, pain severity and analgesic consumption were evaluated using a self-monitoring system. Mood depression was evaluated at 0, 4 and 8 weeks by using Zung's Self-Rating Depression Scale and Hamilton Rating Scale for Depression. Both drugs were beneficial in the treatment of chronic tension-type headache. Non-depressed subjects with more severe headache responded best to fluvoxamine, whereas mianserine was more effective in the treatment of depressed patients with moderate headache. These results suggest that central serotoninergic neurotransmission can play a role in the pathophysiology of chronic tension-type headache also in non-depressed patients. Many patients with severe migraine remain refractory to the current treatment regimens or cannot tolerate the side effects. Since current research implicates serotonin dysregulation in migraine pathogenesis, we investigated in a double blind, placebo controlled study the prophylactic effect of the serotonergic drug fluoxetine. Sixteen subjects were randomly assigned to 8 week fluoxetine treatment and 16 to the placebo group; nine subjects in each group completed the study. Migraine headache scores were obtained for two weeks prior to commencement of treatment, and then for each successive two week period. Zung depression scores were obtained before and after completion of the study. Fluoxetine caused significant reduction in headache scores starting with weeks 3-4 of treatment; there was no significant change with placebo. Depression scores did not differ between groups before treatment, and did not significantly change with either treatment. Fluoxetine appears to be a safe and effective drug for migraine prophylaxis, and deserves further therapeutic trials with larger groups for longer periods of time. Amitriptyline, which is a noradrenaline reuptake and 5-HT reuptake inhibitor, has an established role in the management of chronic tension-type headaches. In a single-blind study, patients with chronic tension-type headache were randomized to either fluoxetine 20 mg (a selective 5-HT reuptake inhibitor) or desipramine 75 mg (a selective noradrenaline reuptake inhibitor) and followed for 12 weeks to compare the effectiveness of the two drugs in improving headache, and to assess whether pain control is related to changes in depression. Patients were evaluated at weekly intervals on an analog pain-rating scale and at 4-weekly intervals on the Montgomery and Asberg Depression Rating Scale (MADRS), the MOS general health status questionnaire (SF36), the Hospital Anxiety and Depression Scale (HADS), and a side effects checklist. Eighteen patients were randomized to take fluoxetine and 19 to take desipramine. Of the 25 patients who completed the trial, 12 were on fluoxetine and 13 were on desipramine. There was no significant difference between the two groups at baseline nor in change of pain; reduction in use of analgesic medication; nor change in the HADS, MADRS, or SF36 scores at 12 weeks, but 72% of patients who completed the study improved, and this improvement almost exactly mirrored the improvement on the MADRS. The results from this trial are compatible with the notion that the beneficial effect of antidepressants in chronic tension-type headache is indirect, mediated by an effect on depression, and not more,dependent on serotonin reuptake inhibition than noradrenaline reuptake inhibition. Antidepressants are often used to treat chronic daily headache disorders such as transformed migraine, in part because of the high prevalence of associated mood disorder. We conducted this study to evaluate the efficacy and tolerability of combined treatment with amitriptyline and fluoxetine compared with amitriptyline alone for chronic daily headache due to transformed migraine.
                Thirty-nine patients, 26 women and 13 men, aged 20 to 69 years (mean, 36.4; SD, 2.5) who fulfilled criteria for transformed migraine proposed by Silberstein et al were studied prospectively. Amitriptyline was dosed as follows: 8 mg/day for 6 days, 8 mg twice a day for 6 days, 20 mg/day for 6 days, and 20 mg twice a day for 45 days. In the group receiving combination therapy, fluoxetine was dosed and administered identically. The initial and end of the study (9 weeks) headache indices (frequency x intensity) were compared between groups.
                Twenty-seven patients completed the study, 13 in the amitriptyline-alone group (group 1) and 14 in the combination-therapy group (group 2). The most frequent adverse event in both groups was dry mouth, and there was no significant difference in the occurrence of this or other adverse events between the two groups. Initial headache indices were similar for groups 1 and 2. The mean difference between the initial and final headache index for group 1 was 513.5 (P<.0005) and 893 (P<.0017) for group 2. The difference between the final headache index for the two groups was not significant (P>.207).
                We were unable to demonstrate any significant benefit from amitriptyline plus fluoxetine over amitriptyline alone in the treatment of chronic daily headache/transformed migraine. Because of the small number of subjects involved and the short duration of our study, a type II error cannot be excluded. Current treatment of migraine either abortive or prophylactic is often unsatisfactory. Prophylactic treatment of severe migraine may reduce attack frequency, and current therapy centers on beta-blockers, serotonin (5-HT) reuptake blockers and 5-HT2 receptor antagonists. The author compared the efficacy and safety of amitriptyline and fluvoxamine among migraine patients (24F, 8M vs. 23F, 9M) in a double blind study. The efficacy of amitriptyline has already been established by earlier clinical studies. The other investigated drug, fluvoxamine, has a more selective 5-HT reuptake blocking property than amitriptyline. In this study, amitriptyline significantly reduced the number of headache attacks, but it caused severe drowsiness in many migraineurs. The fluvoxamine also favorably influenced on the number of headache attacks and caused only slight side effects. These findings suggest, that fluvoxamine may be an alternative drug in migraine prophylaxis, however, further studies should be performed with more subjects. Drugs influencing monoaminergic pathways are of potential use in the treatment of pain. A serotonin re-uptake inhibitor, paroxetine (20-30 mg daily), and a dopamine antagonist, sulpiride (200-400 mg daily) were compared in a randomized, double-blind, response-conditional cross-over pilot study in 50 non-depressed patients with chronic tension-type headache. Headache was scored daily on a 5-point verbal scale during 4-weeks baseline and during 8 weeks of treatment for each drug. A 5-point 'Global' assessment was obtained for each drug. In both treatment groups headache score decreased compared to baseline. Group comparison of 24 patients first treated with paroxetine and 24 patients first treated with sulpiride showed a non-significant trend in favor of sulpiride by 'Global' evaluation and by evaluation of the available diary records (18 paroxetine-treated and 19 sulpiride-treated). Cross-over analysis of 'Global' records from 20 patients treated with paroxetine followed by sulpiride and 17 patients treated in the reverse order showed better relief from sulpiride compared to paroxetine in patients having tested both drugs (P = .03). A similar difference was reflected in available headache scores (13 and 10 patients respectively; P = .03). Predominant side effects were sedation and depression, for paroxetine also nausea and head pain. None of the drugs improved headache more than one score-point on average. A placebo controlled trial of sulpiride may be warranted. Selective serotonin reuptake inhibitors have recently been used in the treatment of migraine.
                We studied the safety and efficacy of fluoxetine in the prevention of migraine.
                Between February 1997 and December 1997, we examined 52 patients (33 women) at the Headache Diagnosis and Therapy Service of the Second University of Naples. Ages ranged from 18 to 65 years, and all patients suffered from migraine without aura according to IHS 1988 criteria. The sample was divided into two groups: group A included 32 patients (19 women; mean age, 36.8 years [SD 12.4]) who received fluoxetine at a dosage of 20 mg per day; group B included 20 patients (14 women; mean age, 38.8 years [SD 15.6]) who received placebo.
                Our study was a single-center, randomized, double-blind, parallel study of fluoxetine for the prophylactic control of migraine and consisted of two phases: 30 days of pharmacological wash out and 6 months of therapy with monthly follow-up. Patients were randomly assigned to two groups: A, fluoxetine or B, placebo. At the first visit, patients provided a detailed history and underwent neurological evaluation and a Zung test for depression. No pathological values were revealed. In order to monitor symptomatology, all patients received a form for the calculation of the total pain index at monthly follow-up.
                A comparison of the total pain index between basal values (calculated during the period of wash out) and monthly follow-up (calculated monthly during the period of 6 months of the therapy) showed significant reduction (P < .05) beginning from the third month of treatment in the fluoxetine group and no significant reduction in the placebo group.
                Even if preliminary and to be confirmed, these data seem to support the use of fluoxetine in the treatment of migraine. nan S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placebo-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F = 4.93; p = 0.033) and month 4 (F = 4.55; p = 0.041). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should be interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study. The objective of this study was to assess the efficacy of sertraline in migraine prophylaxis. Other selective serotonin reuptake inhibitors have been studied for migraine prophylaxis, but this is the first report with sertraline. Twenty-seven subjects were enrolled and baseline assessment of migraine frequency and severity were measured over a 4-week period. Subjects were then randomized to receive placebo or sertraline in a double-blind fashion with headache frequency and severity measured over an 8-week period. Subjects completed a daily diary reporting the occurrence, severity, and degree of impairment associated with migraine. The headache index, a composite measure of migraine frequency and severity, scores did not significantly improve between assessments at baseline (20.8 +/- 14.88), 8 weeks (17.6 +/- 12.27), and 12 weeks (16.7 +/- 6.38) in the treatment group (n=6) (P=0.956). This finding is compared to other studies with the serotonin selective reuptake inhibitors, fluoxetine, fluvoxamine, and paroxetine. The authors believe that the selective serotonin reuptake inhibitors are not as effective as conventional migraine prophylaxis medications such as beta-blockers, tricyclic antidepressants, or divalproex sodium, but that in patients with comorbid depression who have failed conventional therapy selective serotonin reuptake inhibitors may be effective.
Over 2 months of treatment, SSRIs are no more efficacious than placebo in patients with migraine. In patients with chronic TTH, SSRIs are less efficacious than tricyclic antidepressants. In comparison with SSRIs, the burden of adverse events in patients receiving tricyclics was greater. These results are based on short-term trials and may not generalise to longer-term treatment.