Metoprolol and propranolol in migraine prophylaxis: a double-blind multicentre study. Comparison of propranolol LA 80 mg and propranolol LA 160 mg in migraine prophylaxis: a placebo controlled study. The difference between non-selective and beta 1-selective beta-blockers in their effect on platelet function in migraine patients. Propranolol and acetylsalicylic acid in migraine prophylaxis. Double-blind crossover study. Cyclandelate in the prophylaxis of migraine: a randomized, parallel, double-blind study in comparison with placebo and propranolol. The Study group. Propranolol prophylaxis of migraine. Cyclandelate versus propranolol in the prophylaxis of migraine--a double-blind placebo-controlled study. Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. A double-blind trial. Propranolol in prophylaxis of migraine. [Betablocker vs placebo in vasomotor headache. A double-blind crossover study]. Propranolol (Inderal) and clonidine (Catapressan) in the prophylactic treatment of migraine. A comparative trial. A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura. Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily. Propranolol for migraine prophylaxis. Long-term outcome of migraine therapy: predictive value of the frontotemporal nitroglycerin test. Comparative study of nadolol and propranolol in prophylactic treatment of migraine. A comparative trial of flunarizine and propranolol in the prevention of migraine. Propranolol and femoxetine, a HT-uptake inhibitor, in migraine prophylaxis. A double-blind crossover study. [Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine]. Timolol vs propranolol vs placebo in common migraine prophylaxis: a double-blind multicenter trial. Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine. Flunarizine and propranolol in the treatment of migraine. Flunarizine vs. propranolol in the prophylaxis of migraine: two double-blind comparative studies in more than 400 patients. Propranolol in the treatment of migraine. Comparative efficacy of nadolol and propranolol in the management of migraine. Long-acting propranolol in migraine prophylaxis: results of a double-blind, placebo-controlled study. Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials. Short-term clinical trial of phopranolol in racemic form (Inderal), D-propranolol and placebo in migraine. Prophylaxis of migraine and mixed headache. A randomized controlled study. Nadolol and propranolol in migraine management. Alpha-dihydroergocryptine and predictive factors in migraine prophylaxis. Nimodipine in migraine: clinical efficacy and endocrinological effects. Prophylactic propranolol in the treatment of headache. Comparison of mefenamic acid and propranolol with placebo in migraine prophylaxis. [Propranolol for prophylaxis of migraine (author's transl)]. Tolfenamic acid versus propranolol in the prophylactic treatment of migraine. Prophylactic treatment of migraine with propranolol. A clinical trial. Nifedipine versus propranolol for the initial prophylaxis of migraine. Long-term study of propranolol in the treatment of migraine. Migraine prophylaxis. A comparison of propranolol and amitriptyline. Double blind study of propranolol for migraine prophylaxis. A comparison of naproxen sodium to propranolol hydrochloride and a placebo control for the prophylaxis of migraine headache. The treatment of migraine with propranolol. The way to serotonergic use and abuse in migraine. Propranolol and migraine. A clinical trial. Comparative trial of Tenormin (atenolol) and Inderal (propranolol) in migraine. Propranolol in the prophylaxis of migraine. Prophylactic treatment of migraine with tolfenamic acid, propranolol and placebo. Femoxetine - a new 5-HT uptake inhibitor - and propranolol in the prophylactic treatment of migraine. Metoprolol and propranolol in the prophylactic treatment of classical and common migraine. A double-blind study.
In a double-blind, cross-over multicentre trial, the prophylactic antimigraine effect of the beta 1-selective beta-blocker metoprolol was evaluated and compared with that of the non-selective beta-blocker propranolol. Metoprolol was used in a dosage of 50 mg b.i.d. and propranolol in 40 mg b.i.d. 56 patients with classical or common migraine were included in the double-blind part of the investigation. 3 patients withdrew, but none because of side-effects. The data suggest that metoprolol is clinically equivalent in effectiveness to propranolol in migraine prophylaxis regarding parameters such as attack frequency, improvement in sum of severity score and subjective evaluation. Both drugs were generally well tolerated and the number of reported side-effects was similar to those reported during the run-in period (placebo). Thirty patients with severe classical and common migraine participated in a double-blind placebo-controlled cross-over study of migraine prophylaxis with propranolol LA (long-acting) 80 mg once daily, or propranolol LA 160 mg once daily or placebo. Each treatment was given for two months. There were no significant differences between the three treatment periods in headache frequency, headache severity, nausea frequency or severity. There was a non-significant trend for reduced duration of headache with the two doses of propranolol. The possible reasons for this negative effect are discussed. The safety of propranolol and its lack of serious side effects were demonstrated. Platelet function has been postulated as playing a role in the pathogenesis of migraine. This study aimed to investigate to what extent beta 1-selective and non-selective beta-blockers interfere with the platelet function in migraine patients. Twelve patients with classical migraine were included. After a 2-week drug-free period, the patients were randomly allocated to either beta 1-selective metoprolol (50 mg b.i.d.) or non-selective propranolol (40 mg b.i.d.) treatment for one month. After a wash-out period, the patients were changed to the corresponding beta-blocker for one month. ADP-induced platelet aggregability, platelet cAMP, ATP and ADP levels, plasma cAMP and TxB2 concentration, as well as the serum production of TxB2 were measured before and after each treatment period. After propranolol treatment, the patients showed lower ADP threshold values for producing irreversible platelet aggregation and lower platelet and plasma cAMP levels as compared to metoprolol. Neither of the beta-blockers induced any change in the plasma concentration or serum production of TxB2. In conclusion, non-selective beta-blockade (propranolol) significantly increases the platelet aggregability compared to beta 1-selective blockade (metoprolol). The aim of this double-blind crossover study was to compare the prophylactic effect of acetylsalicylic acid (ASA) with that of propranolol (PRP) in the treatment of migraine. Plasma concentrations of the two drugs were measured in order to investigate a possible relationship to the clinical effect. Compared to the pretreatment period, PRP and ASA reduced migraine index, frequency, duration, severity of attacks and headache days. Due to the limited number of patients, our results should be cautiously interpreted, however relevant the clinical improvement seemed. Improvement of migraine index was not related to different plasma levels of the two drugs. Cyclandelate inhibits calcium-induced contraction of vascular smooth muscle cells, platelet aggregation induced by thrombin, platelet-activating-factor and adenosine, and also suppresses a provoked 5HT release from platelets. This pharmacological profile suggests that cyclandelate may have a potential prophylactic effect in migraine. To test this hypothesis, a double-blind multicentre study was performed in 214 patients to investigate the efficacy and tolerability of cyclandelate compared to placebo and propranolol. After a 4-week baseline period, eligible patients (randomization 3:2:3) were treated for 12 weeks with daily doses of 1.200 mg cyclandelate (n = 81), placebo (n = 55) or 120 mg propranolol (n = 78). The number of migraine attacks (> or = 50% responders) and the migraine duration/month were compared based on the difference between baseline and the last 4 weeks of prophylactic treatment. The percentage of patients with a reduction in migraine attacks of > or = 50% treated with cyclandelate (37.0%) or propranolol (42.3%) was not significantly superior to placebo (30.9%; p > 0.025). The mean duration of migraine in hours (h) per month decreased in both active treatment groups (cyclandelate: 36.8 h, p = 0.046; propranolol: 34.4 h, p = 0.039) compared to placebo (13.7 h) without reaching statistical significance (alpha/2 = 0.025). The clinical efficacy of cyclandelate and propranolol was comparable. Adverse experiences were reported by 13 patients (16.0%) treated with cyclandelate, by 5 patients (9.1%) treated with placebo and by 19 patients (24.4%) treated with propranolol. These were drug-related in 7.1% (n = 6) of patients treated with cyclandelate and in 9% (n = 7) of patients treated with propranolol. In summary, cyclandelate has a comparable efficacy to that of propranolol, an established drug of first choice in the prophylaxis of migraine. Both drugs were better than placebo, but not significantly so. Both active treatments were well tolerated. nan The aim of the present study was to ascertain the comparative efficacy of cyclandelate, a migraine prophylactic with calcium overload blocking properties, versus propranolol, a non-selective beta-adrenergic blocker, and placebo. Based on different statistical analysis procedures (including time series analysis) a responder and nonresponder evaluation for cyclandelate and propranolol was performed. In addition, an attempt was made to identify the dose relationship of the various drugs on headache parameters. In a double-blind placebo-controlled study 84 patients were treated in a placebo run-in phase (4 weeks). The patients were then randomized by the statistical criterion of placebo responder and nonresponder to either the cyclandelate or the propranolol group. The total treatment period included a low-dosage phase (8 weeks) and high-dosage phase (8 weeks). All patients kept a headache diary before, during and after treatment. The data were assessed by time series analysis (ARIMA), as well as by analysis of variance and nonparametric statistics. Based on ARIMA statistics, 39.3% of the patients showed a significant improvement of migraine during treatment with cyclandelate compared with 29.4% placed on propranolol. Higher doses of cyclandelate and propranolol were more effective. Using the qualitative response-criterion of a 50% reduction in migraine symptoms, cyclandelate showed a response in 67.9% and propranolol in 41.2% of all cases. It can therefore be concluded that cyclandelate as well as propranolol are two comparable substances in the prophylactic treatment of migraine, with cyclandelate showing fewer side effects. Fourty-five migraine without aura patients underwent a parallel double-blind trial aiming the comparison of the effects of propranolol 60 mg/day to flunarizine 10 mg/day and to propranolol 60 mg/day plus flunarizine 10 mg/day simultaneously. There were 3 groups, each one with 15 patients. After a 20-day-baseline period, each group received one kind of treatment during 120 days. Migraine index on propranolol was 23.4*, on flunarizine 18.7* and on both drugs 14.4*, mean frequency of attacks on propranolol was 1.26**, on flunarizine 1.2** and on both drugs 1.13** (*p < 0.05, **p < 0.01 compared to baseline) and global evaluation was reduced with all forms of treatment. It was not found statistical differences between groups, nevertheless there was a trend in the group using two drugs reaching lower values in migraine index, frequency of attacks and global evaluation. In individuals using flunarizine (alone or associated with propranolol) the therapeutic effect was largely maintained up to 45 days after drug withdrawal. nan Vasomotor headaches are commonly, especially in the international literature, classified under ordinary migraine. Since beta-blockers seem to be the drug of choice in the prevention of migraine, 30 patients were given placebo and three times 40 mg propranolol in a double-blind cross-over trial. Among 24 fully assessable sets of tests only four showed a decrease in the frequency of headaches by more than 50%. In three patients the frequency actually increased over the placebo effect. Twenty-one patients continued a double-blind crossover study to compare the prophylactic effect on migraine of propranolol and clonidine. The daily dosage of propranolol and clonidine was 160 mg and 100 microgram, respectively. Statistical analysis did not show any significant difference between the two drugs in respect to headache or nausea. The number of sickleave days and the use of symptomatic drugs were both less on propranolol treatment than on clonidine, but there was no statistically conclusive difference. To compare the efficacy of divalproex sodium (Depakote) with that of propranolol hydrochloride (and placebo) for the prophylaxis of migraine without aura.
                Single-investigator, randomized, single-blind, placebo-controlled study with 5 phases: baseline (weeks 1-4); placebo (weeks 5-8); first treatment, 1 agent (weeks 9-20); washout (weeks 21-24); and second treatment, crossover to other agent (weeks 25-36).
                Private practice of a general neurologist with a special interest in headache disorders.
                Of 37 patients (30 women and 7 men) selected, 32 completed the study. All received placebo, after which half were randomized to receive divalproex or propranolol, then crossed over after washout.
                Divalproex and propranolol doses were titrated during the initial 8 weeks of each 12-week treatment cycle. For divalproex, doses were titrated to 1500 mg/d in 23 patients, to 2000 mg/d in 2, and downward in 7; the mean valproate sodium trough level was 68.5 mg/L. Propranolol was titrated to 180 mg/d in 28 patients, to 240 mg/d in 1, and downward in 3.
                Migraine frequency was reduced in 19% (6/ 32) of placebo-treated, 66% (21/32) of divalproex-treated, and 63% (20/32) of propranolol-treated patients. Assessment of migraine-days per month revealed significant response to placebo in 22% (7/32) of patients, to divalproex in 66% (21/32), and to propranolol in 69% (22/32). When results were limited to the third month of each active-agent treatment phase, 75% (24/ 32) of patients receiving divalproex and 78% (25/32) of those receiving propranolol had reduction in migraine frequency.
                No significant difference was identified between divalproex and propranolol for the prophylaxis of migraine without aura. This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n=58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P<0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe. nan We evaluated whether type of response to the migraine-induction test with a nitroglycerin ointment applied to the frontotemporal head region could predict the efficacy of antimigraine therapy. Forty-two patients with migraine without aura underwent the test before and 2 months after antimigraine therapy. Two and 4 months after treatment withdrawal, most subjects with a negative response to the post-treatment test maintained treatment benefit, whereas benefit was lost in patients with an early onset migraine response. Forty-eight patients (13 men and 35 women) took part in a double-blind randomized study. All patients received a placebo daily for 4 weeks (period A), at the end of which the frequency and severity of headaches experienced by each patient were assessed. Patients then received an active drug for 12 weeks (period B). Sixteen patients received nadolol, 80 mg/day; 16 received nadolol, 160 mg/day; and 16 received propranolol, 160 mg/day. The frequency and severity of headaches in the three groups were tabulated at the end of period B, as were the side effects. Only three subjects dropped out during the study, and one of these needed abdominal surgery. All three groups reported improvement, the most noticeable being in those patients who received 80 mg of nadolol daily. The calcium-entry blocker flunarizine (Sibelium; Janssen) was compared with the beta-adrenoreceptor-blocking agent propranolol in the prophylaxis of migraine. Fifty-eight patients were entered into a double-blind 4-month treatment trial. Patients in whom beta-blockers were contraindicated were excluded from the trial. At the end of the trial 28 patients had received 10 mg flunarizine at night during the study, 29 patients had received 60 mg propranolol 3 times a day and 1 patient was withdrawn. Both groups responded well; and there was a 4-fold drop in frequency of attacks. There was no significant difference between the two groups in terms of patient profile, onset of response to therapy, final response to therapy, incidence of dropout from the trial or incidence of side-effects. Side-effects for flunarizine were weight gain (9 patients) and tiredness (6), and for propranolol sleep disturbances including nightmares (6), tiredness (8), mental changes (e.g. irritability) (3) and weight gain (4). Both flunarizine and propranolol are useful drugs for migraine prophylaxis and can be used effectively as first-line drugs. The low incidence of generally mild side-effects with flunarizine may make it preferable to many of the agents at present in use for migraine prophylaxis. 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. The efficacy of 5-hydroxytryptophan and propranolol has been studied in the interval treatment of migraine. 39 migraine patients have participated in a double-blind trial. After a placebo run-in of one month, the patients received either 5-hydroxytryptophan or propranolol for 4 months. The treatment with both substances resulted in a statistically significant reduction in frequency of migraine attacks. Furthermore, in the propranolol group the duration of the attacks and the number of analgesics used for treatment of the attacks were significantly reduced. Although propranolol, which is considered a reference for the interval treatment of migraine, is more effective, 5-hydroxytryptophan is a possible alternative for many patients. Common migraine sufferers (25 males, 71 females) with a history of 2-6 attacks per month participated in a 4-centre trial comparing the prophylactic effect of timolol (10 mg b.i.d.) and propranolol (80 mg b.i.d.) to placebo. After a pretreatment period of 4 weeks they entered a double-blind 3-way cross-over trial with 3 treatment periods of 12 weeks each. 83 patients received all 3 treatments. The mean frequency of attacks per 28 days was 3.35 on timolol, 3.69 on propranolol and 4.83 on placebo. Mean severity of attacks (0-3) was 1.75 on timolol, 1.83 on propranolol, and 1.93 on placebo. Mean duration of attacks was 7.41 h on timolol, 7.38 on propranolol and 7.95 on placebo. The headache index (frequency times severity) was 5.71 on timolol, 6.66 on propranolol and 9.03 on placebo (P less than 0.05, P less than 0.01 compared to placebo). The difference between propranolol and timolol was non-significant: frequency of attacks 0.34 (95% confidence limits - 0.26; 0.89). Headache index 0.95 propranolol and 23 patients on placebo experienced side effects (P less than 0.05). It is concluded that timolol and propranolol are equally effective in the used doses (1:8) for common migraine prophylaxis. This study was designed to compare flunarizine, a cerebro-specific calcium channel antagonist, and propranolol in the prophylaxis of migraine with or without aura. Following a 1 month single-blind placebo baseline period, 94 patients were equitably randomised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months. Neither treatment affected the severity nor duration of migraines. Overall, 67% of flunarizine patients and 51% of propranolol patients responded positively. Propranolol significantly reduced blood pressure and heart rate; flunarizine had no effect on cardiovascular function. Weight gain was noted with both treatments. Flunarizine is at least as effective as propranolol in the prophylactic treatment of migraine and may have a better safety profile. The clinical efficacy of flunarizine and of propranolol for the prevention of migraine attacks was assessed in a multicenter double-blind study lasting four months which was preceded by a single-blind placebo period of one month. For both drugs, more than half of the patients judged the effect to be good or very good. When considering the patients' daily logs, both drugs produced a significant reduction of the number of attacks. Propranolol furthermore significantly reduced the severity of attacks and the number of analgesics used during the attacks. In both groups no severe side effects were observed. In the course of a 16 weeks' interval treatment of migraine in connection with two multicenter double-blind studies, flunarizine was compared with propranolol in patients suffering predominantly from "classical migraine". Eighty-seven patients from 12 outpatient departments were admitted to the first study, while 434 patients from 99 medical practices participated in the second study. After each month of treatment, the patients were clinically evaluated, and the number, duration, and severity of attacks were documented. Concerning the frequency and intensity of attacks, additional analgesics consumption and overall evaluation, both drugs proved to be highly effective in the practice as well as in the hospital study. The percentage and severity of side-effects were comparable in the two treatment groups. Summarizing, it may be stated that the studies proved the efficacy of flunarizine to be rather similar to that of propranolol in the prophylactic treatment of migraine. nan nan The efficacy and safety of long-acting propranolol (LA.P), 160 mg once-daily, in the prophylactic treatment of migraine have been tested against placebo in a multicentric, double-blind, randomized study. The two groups are compared in a parallel manner over a treatment period of 12 weeks, following a 4-week placebo run-in period. Fifty-five of the 74 patients who entered the trial were included at the end of the run-in period. Forty-one patients completed the study. None of the 14 patients who withdrew from the study did so because of side effects. The statistical analysis was done according to the "intention to treat" principle. LA.P was significantly more effective than placebo in reducing the frequency of migraine attacks (p = 0.01 by variance analysis). LA.P reduced the average number of monthly crises by 48% on day 84. There was a slight but significant reduction of the systolic blood pressure and heart rate in the erect position, but there was no significant difference between LA.P and placebo regarding either the number of complaints or the number of side effects elicited out of a 17-item questionnaire. None of the observed side effects led to a withdrawal from treatment. The present study used recordings of visual potentials evoked by pattern reversal (VEPs) to investigate the central effects of three drugs used in migraine prophylaxis: the calcium channel blocker nifedipine, the beta-1-selective blocker metoprolol, and the nonselective beta adrenoreceptor blocker propranolol. The study involved 58 patients with common or classical migraine who were treated in a double-blind randomized study over a period of 7 months, while the effectiveness of prophylactic treatment was recorded in headache diaries that were subjected to time series analysis. VEPs were recorded at the beginning of a 2-month baseline period without treatment, after 4 months of treatment, and at the end of a 3-month washout period. At baseline, migraine patients had significantly higher VEP amplitudes and longer latencies than did a group of 87 healthy control subjects. Patients were separated by statistical analysis into responders and nonresponders to each prophylactic treatment. Nifedipine had no effects on the frequency, intensity, and duration of migraine attacks, nor on amplitude and latency of the VEPs. In contrast, the use of beta blockers resulted in a significant decrease in VEP amplitude, both in responders and nonresponders, whereas VEP latency remained unchanged. VEP amplitudes returned to the initial values at follow-up in the nonresponders, but stayed at lower levels in responders. Beta blockers thus appear to have a significant effect on the increased excitability of the visual system in patients with migraine, although their action is not directly related to their reduction of migraine frequency. Propranolol penetrates the blood brain barrier, whereas mainly the racemic form, Inderal, possesses beta-receptor blocking properties. A comparison between d-propranolol and Inderal might therefore indicate the relative importance of the beta blocking properties and possible "central" effects mediated by propranolol and of importance in migraine prophylaxis. The effects of propranolol in racemic form (Inderal) 40 mg q.i.d., d-propranolol 40 mg q.i.d. and placebo were compared in 20 migraine patients. Inderal as well as d-propranolol were significantly superior to placebo. Inderal seemed to be more effective than d-propranolol, but the difference was not statistically significant (P greater than 0.05). The results indicate that beta-receptor blocking properties, but possibly also properties other than the beta-blocking ones, may be of importance for the anti-migraine effect of propranolol. nan nan A double-blind, crossover study was carried out to compare the efficacy of alpha-dihydroergocryptine mesylate (10 mg twice daily) vs propranolol (40 mg twice daily) in the prophylaxis of migraine without aura, and to identify possible predictors of therapeutic response by evaluating the symptomatological profile of individual migraine attacks and the autonomic cardiovascular response to noradrenergic and dopaminergic (cold pressor, bromocriptine) tests.
                Forty migraineurs (10 males, 30 females) were randomized according to a two-period (3-month), two-treatment, crossover design. Efficacy was assessed using quantitative data recorded in the patient's headache diary. Data were evaluated using the Wallenstein's method.
                Both drugs showed a significant reduction in all the efficacy variables (headache attacks, days with headache, analgesic consumption) with no difference between treatments. Neither a bromocriptine test, nor a cold pressor test nor the symptomatological profile of individual migraine attacks differed between the two groups of migraine patients. Ten patients experienced at least one adverse drug reaction during the first period of the crossover design, 5 being treated with alpha-dihydroergocryptine and 5 with propranolol.
                It is concluded that alpha-dihydroergocryptine is an effective medication for migraine prophylaxis. The biochemical tests and the type of psychological profile cannot be used to predict drug response. Serum prolactin is increased during chronic flunarizine treatment of patients suffering from migraine. In order to clarify the role of calcium in control of the secretion of anterior pituitary hormones, a study has now been made of the effects of chronic nimodipine and propranolol treatment of migraine patients on prolactin (PRL), luteinizing hormone (LH) and growth hormone (GH) levels. 11 patients were treated with nimodipine and 8 with propranolol for four months. A statistically significant reduction in the frequency of the attacks was demonstrated in both groups. No significant change was found in the hormones levels during nimodipine treatment. nan The prophylactic effects of the antiprostaglandin agent mefenamic acid on migraine attacks were compared with propranolol or placebo in a double-blind crossover study of 29 patients. In the 17 patients who completed the trial the frequency of attacks and their total duration were significantly reduced during mefenamic acid therapy or propranolol therapy as compared to placebo. There were no significant effects of mefenamic acid or propranolol on average duration or severity of migraine attacks. The study suggests that mefenamic acid and propranolol are equally effective for migraine prophylaxis. The prophylactic effectiveness of propranolol (80 to 120 mg per day) in 18 migraine patients was compared with a placebo group of 19 migraine patients in a double blind study without cross over for a treatment period of six and twelve weeks. A statistically significant difference in effect could not be ascertained. The results and methodological assumptions of the double blind studies with cross over already under consideration in the literature are discussed. The prophylactic effect of tolfenamic acid and propranolol was studied in a randomized double-blind cross-over trial of 76 patients with migraine with or without aura. After a 4-week run-in period patients were randomly allocated to treatment with either tolfenamic acid 100 mg three times daily or propranolol 40 mg three times daily for 12 weeks. After a placebo wash-out period of 4 weeks the patients got the alternative drug for 12 weeks; 56 patients completed the study. Both drugs significantly reduced migraine attacks as judged from the reduction in the efficacy parameters (migraine hours, migraine days, and migraine intensity) in the treatment periods compared with the run-in period. No statistical significant difference in any efficacy parameter was found between the two drugs (level 2 alpha = 0.05, alpha = 0.10). The adverse effects showed no statistical difference in frequency between the 2 treatments. Twenty patients discontinued the study: 12 patients on propranolol and 8 patients on tolfenamic acid. Side effects were the cause of premature discontinuation of study medicine in 9 patients during propranolol treatment (dizziness, fatigue, and fall in blood pressure) and in 5 patients during tolfenamic acid treatment (gastrointestinal symptoms). nan We conducted a randomized open-labeled study of nifedipine versus propranolol for the initial prophylaxis of migraine. Propranolol was effective in 67% of patients (12/18) and well tolerated. Nifedipine was effective in only 30% of patients (6/20). The lack of overall efficacy of nifedipine was attributable to a high incidence of side effects, including an unusual symptom complex resembling erythromelalgia. These side effects led 45% (9/20) of the nifedipine patients to withdraw from the study within two weeks. By contrast, no patient (0/18) withdrew from the study within the first 2 weeks of propranolol therapy. We conclude that nifedipine is not an agent of first choice for the prophylaxis of migraine. nan The comparative efficacy of propranolol and amitriptyline in the prophylaxis of migraine headache was studied in 30 patients in a double-blind, placebo-controlled, crossover design. Headache response to medication was measured monthly by compilation of headache scores derived from quantitative data recorded by patients in a daily diary; at each visit, Zung and Hamilton tests for depression and the Spielberger state test for anxiety were performed. In the absence of clinical toxicity at monthly visits, the decision to maintain the current dose or raise it was made by a computer, which compared current headache score with that of the previous month. Both drugs were superior to placebo. Neither drug was superior to the other. The effectiveness of neither drug correlated with a decrease in anxiety or depression demonstrated by psychological testing. nan nan nan 5-HT is currently indicated to play a role in migraine (M). Previously evidenced 5-HT supersensitivity which characterizes M is insufficient to compensate for a possible deficit in 5-HT bioavailability. Inducing a further up-regulation of 5-HT receptor can yield improvement of M syndrome. Chronic treatments of methysergide and propranolol, drugs exerting antagonist action at 5-HT receptors, induced a significant amelioration in 256M sufferers. On the contrary, chronic treatments of ergotamine and sumatriptan, both provided with a 5-HT1 agonist activity, induced a worsening of M in 134 M sufferers. The M worsening was paralleled by an increase in consumption of analgesic drugs. Discussion concerns the effects of the chronically given 5-HT agonists and antagonists as well as the possible receptor mechanism underlying "craving for serotonin" in severe M. The increase of 5-HT supersensitivity evidenced at the end of M attacks is also discussed and its role in determining the interruption of the attack is here suggested. nan nan nan In 31 patients with at least 3 migraine attacks per month the prophylactic effect of tolfenamic acid 300 mg/day, propranolol 120 mg/day, and placebo was compared in a randomized double-blind cross-over study. The patients were treated for 12 weeks with each drug, but only the last 11 weeks were used for evaluation. Both tolfenamic acid and propranolol significantly reduced the number of attacks, the total duration of attacks and additional drugs taken when compared with placebo. Tolfenamic acid, but not propranolol, significantly reduced the median intensity of pain and the number of attacks confining the patients to their beds when compared with placebo. Only mild adverse reactions occurred with no significant difference between the drugs. It was concluded that the prophylactic effect of tolfenamic acid 300 mg/day in migraine was at least as good as propranolol 120 mg/day. 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. In a double-blind, cross-over study the effect and tolerance of the non-selective beta-blocker propranolol in a dosage of 80 mg twice daily was compared to that of the beta 1-selective beta-blocker metoprolol 200 mg once daily in Durules (a controlled-release formulation). The attack frequency, migraine days, severity score, consumption of acute medication and subjective evaluation were the main parameters used for evaluation. Thirty-six patients with classical or common migraine were included. Thirty-three completed the investigation. It is concluded from the results that there are no differences in efficacy between metoprolol and propranolol regarding the studied parameters. Both drugs reduced the migraine symptoms compared to the run-in period and were generally well tolerated.