Prophylactic treatment of migraine with bisoprolol: a placebo-controlled study

The objective of the present study was to assess the efficacy of bisoprolol in migraine prophylaxis. A double-blind placebo-controlled study was conducted in 226 patients with migraine with or without aura, a migraine history of at least 2 years and at least 3 documented attacks during the 28 days run-in period. The duration of treatment was 12 weeks following an initial 28 days' run-in period. Patients reported the number of attacks and their severity in a diary. Treatment with bisoprolol 5 mg resulted in a significant reduction in the frequency of migraine attacks (39% vs 22%) compared to placebo treatment ( p <0.05). Treatment had no effect on the duration and severity of the attacks. Bisoprolol was well tolerated.     

A thromboembolic predisposition and the effect of anticoagulants on migraine

OBJECTIVE: To investigate the presence of thromboembolic risk factors and the effect of low-dose acenocoumarol therapy on migraine in patients who spontaneously reported a reduction of their migraine attacks during previous therapeutic use of anticoagulants. BACKGROUND: The positive effect of anticoagulants on migraine has been described in case reports and observational studies. It remains unclear whether this concerns only a select group of migraineurs with certain common characteristics. METHODS: In 4 migraineurs with a self-reported reduction of attack frequency during previous use of anticoagulants (international normalization ratio [INR], 2.5:4.0), the presence of thromboembolic risk factors and the effect of low-dose acenocoumarol therapy (INR, 1.5:2.0) on migraine attacks were prospectively investigated in an open study. RESULTS: All patients had one or more thromboembolic risk factors. Two patients, both with factor V Leiden heterozygosity, experienced a clear improvement of migraine during low-dose acenocoumarol therapy. CONCLUSIONS: Our findings support the hypothesis that migraine, as a phenotype, has different underlying mechanisms, amongst which a thromboembolic tendency. In this group of patients, oral anticoagulants may be a suitable form of migraine prophylaxis, but this needs further clinical investigation.     

Long Acting Propranolol in the Prophylaxis of Migraine. Comparison of the Daily Doses of 80 mg and 160 mg

SYNOPSIS
The efficacy of long acting propranolol in a dosage of 80 mg once daily in comparison to 160 mg once daily was assessed in the prophylactic treatment of migraine in a double-blind cross-over trial. 48 patients with classic or common migraine were included in the investigation, 6 patients withdrew, but only one because of side-effects. A four week run-in placebo period preceded the drug treatments, the duration of drug treatments was 12 weeks and there was a wash-out placebo period of 4 weeks between the treatments.
The two long acting propranolol doses, 80 mg and 160 mg once daily seemed to be equally effective. There was no difference in the antimigraineous effect. Long acting propranolol decreased both the frequency and severity of migraine attacks. Side-effects reported during the trial were mild, both doses were well tolerated. The treatment compliance during the once daily treatment was very good.     

Long-acting propranolol in migraine prophylaxis: results of a double-blind, placebo-controlled study

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.     

Metoprolol and propranolol in the prophylactic treatment of classical and common migraine. A double-blind study

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.     

Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily

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.     

Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a double-blind study versus placebo

Omega-3 polyunsaturated fatty acids (OPFA) have beneficial effects on inflammatory reactions and production of cytokines. They decrease the release of 5HT by platelets and possess vasorelaxant activity. This led them to be tried in the prophylactic treatment of migraine. After 4 weeks of a single-blind placebo run-in period, patients were randomized and treated in double-blind condition by placebo or OPFA 6 g a day for 16 weeks, followed by a 4-week placebo run-out period. The intention to treat population included 196 patients. Those who received all four treatment periods included 96 patients taking OPFA and 87 taking placebo. The primary efficacy analysis was the number of migraine attacks during the last 4 weeks of treatment. During this period, the mean number of attacks was 1.20 +/- 1.40 in the OPFA group and 1.26 +/- 1.11 in the placebo group (NS). The total number of attacks during the 4-month period of the study was significantly different between groups: 7.05 in the placebo group, 5.95 in the OPFA group (P = 0.036). Mean intensity, mean duration of the attacks and rescue medication use, were not significantly different between the two groups. Except for a significant difference against OPFA for eructations, the tolerance was satisfying. Despite a run-in placebo period of 1 month, a very strong placebo effect was observed in this trial: 45% reduction of the attacks between run-in and 4-month treatment period (55% in the OPFA group, P = 0.058). Finally, this large study did not confirm two previous studies based on a small number of patients.     

Montelukast for migraine prophylaxis: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of montelukast 20 mg in the prophylactic treatment of migraine. BACKGROUND: A previous small open-label study in migraine patients suggested prophylactic efficacy for montelukast, an antagonist of the cysteinyl leukotriene receptor that is used in the treatment of asthma. We sought to confirm these findings in a randomized controlled trial. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-groups study enrolled adult migraine outpatients who experienced > or =3 and < or =8 migraine attacks per month for the last 6 months. Patients were entered into a 2-month, single-blind, placebo run-in phase. Only patients who experienced > or =3 migraine attacks in the second month were eligible to enter the subsequent 3-month, double-blind treatment phase of the study. The primary efficacy endpoint was the percentage of patients reporting at least a 50% decrease in migraine attack frequency per month during the double-blind treatment period (months 3-5) compared to baseline (run-in month 2). RESULTS: A total of 93 patients were randomized to montelukast 20 mg and 84 patients to placebo at the end of the placebo run-in month 2; 76 patients on montelukast and 72 patients on placebo completed the double-blind treatment period. Over 3 months of treatment, there was no significant difference between the two groups in the percentage of patients who reported at least a 50% decrease in migraine attack frequency per month: 15.4% for montelukast versus 10.3% for placebo (P= .304). In addition, montelukast 20 mg was not significantly superior to placebo on any of the secondary endpoints. There were no differences between treatment groups for adverse events. CONCLUSION: Montelukast 20 mg was well tolerated in migraine patients but was not an effective prophylactic for prevention of migraine.     

Flunarizine Versus Metoprolol in Migraine Prophylaxis: A Double-Blind, Randomized Parallel Group Study of Efficacy and Tolerability

The prophylactic effect of flunarizine and metoprolol was studied in a multi-center randomized, double-blind trial of 149 patients with migraine with or without aura. After a 4-week placebo run-in period, patients were randomly allocated to treatment with flunarizine 10 mg daily or metoprolol 200 mg daily for 16 weeks (parallel group design). Both drugs reduced the number of migraine days per month by 37% (95% confidence interval 21-53%) compared with the placebo run-in period. All efficacy parameters were significantly reduced by both drugs and no significant difference was found between the two drugs at any time of the treatment period. However, calculation of the 95% confidence limits showed that each drug may have a superiority of more than 100% on a single main effect parameter. The most common adverse experiences were day-time sedation (both drugs) and weight gain (flunarizine). Depression was the most serious side-effect occurring in 8% on flunarizine and 3% on metoprolol. We conclude that both drugs are effective in the prevention of migraine attacks but a higher number of dropouts occurred on flunarizine because of depression or weight gain.     

A Placebo-Controlled Crossover Trial Using Trazodone in Pediatric Migraine

SYNOPSIS
An 8-month, double-blind, placebo-controlled cross-over trial was carried out on the use of trazodone in pediatric migraine prophylaxis. It involved 40 patients aged 7 to 18 years old and suffering from migraine without aura, randomly divided into 2 groups.
After a 4-week run-in period, Group A received oral trazodone (1 mg/kg a day divided into 3 doses) for 12 weeks, while Group B received a placebo. After a further 4-week washout period, Group A was given the placebo and Group B was treated with trazodone for a further 12 weeks. The trial was completed by 35 patients, the number of drop-outs being comparable in the two groups.
During the first treatment period, both the frequency and the duration of the migraine episodes were significantly reduced in both groups. During the second, a significant further improvement in both parameters was only observed in Group B. No side-effects were observed at any time. Our results showed that, like other antidepressants, trazodone is a valid prophylactic agent for juvenile migraine.     

Topiramate prophylaxis and response to triptan treatment for acute migraine

OBJECTIVE: To evaluate the effect of topiramate migraine prophylaxis on subject responsiveness to triptans used for acute symptomatic migraine treatment. BACKGROUND: Clinical experience suggests that prophylactic migraine treatment may enhance the efficacy of symptomatic medications used to treat acute migraine attacks. METHODS: This open-label, single-arm multicenter study consisted of a 6-week baseline period followed by a 16-week topiramate treatment period. Subjects meeting International Headache Society (IHS) criteria for migraine with and without aura signed consent and entered the baseline period. Those with 3 to 12 migraine periods per month during baseline received topiramate prophylactic treatment. Only patients who completed at least 12 weeks of topiramate treatment were included in the data analysis. RESULTS: Of 55 patients screened, 40 subjects entered the topiramate treatment period and 21 subjects received at least 12 weeks of treatment. Mean final dose of topiramate was 124 mg per day (range 50 to 200 mg per day). During the baseline period, the mean percentage of attacks rendered pain-free at 2 hours for the 21 subjects was 46.9% (SD = 31.9), while during the topiramate treatment period it was 44.6% (SD = 32.2) (P= .8). On topiramate, after the first 8 weeks of dosage titration, patients experienced a mean of 3.68 migraine attacks/month, compared to 4.31 during the baseline period (P < .03). Thirteen subjects discontinued because of adverse events. The most commonly reported adverse events were paresthesia, fatigue, anxiety, and dizziness. CONCLUSION: Although topiramate prophylaxis did reduce migraine attack frequency, in this pilot study topiramate prophylactic migraine treatment did not increase the proportion of patients pain-free 2 hours after symptomatic triptan therapy.     

Patients with acenocoumarol treatment and migraine

OBJECTIVE: The aim of our study was to investigate the possible effect of acenocoumarol, which is indicated for nonneurological disease, on headache. BACKGROUND: It has been suggested that anticoagulation can have beneficial effects in the control of migraine attacks. METHODS: Four hundred randomized patients on oral anticoagulant therapy were asked to complete a questionnaire regarding their headaches. RESULTS: Headache was present before or during oral anticoagulation in 166 (66 migraineurs and 100 nonmigraineurs) of 326 respondents. The major finding was that oral anticoagulation produced improvement in 63% of patients with migraine versus 38% of patients with nonmigranous headache. Improvement was related to the severity of migraine but not to age. CONCLUSIONS: Oral anticoagulant therapy can improve migraine. The way in which anticoagulant therapy acts on migraine is unknown, but potential mechanisms include its effect on platelet aggregability and pharmacological effects such as suppression of enhanced nitric oxide.     

Propranolol in the treatment of acute migraine attacks

The efficacy of the beta-adrenoceptor antagonist propranolol in the acute treatment of patients in attacks of either classical (migraine with aura) or common migraine (migraine without aura) headache was assessed in a double-blind placebo-controlled crossover trial with fixed doses. The trial was carried out on 25 patients. The treatment period was set at eight weeks, with the provision of shortening or lengthening it if necessary with a maximum period of seventeen weeks. A minimum of three migraine attacks were treated during each treatment period. Patients were assessed according to: the mean duration and mean severity per treatment period of migraine attacks. The secondary efficacy assessment was made on the basis of the percentage of attacks requiring escape medication per treatment period. The study, based on the t-distribution statistical model with a confidence level of 95%, showed that propranolol had no significant effect in aborting acute attacks of migraine when compared with placebo.     

Effectiveness of lamotrigine in the prophylaxis of migraine with aura: an open pilot study

We report a small open pilot study to evaluate the efficacy of lamotrigine (100 mg/day) in the prevention of migraine with aura attacks. We studied 24 patients affected by migraine with aura with a high frequency of attacks. Following a 1-month run-in period, the patients took lamotrigine for 3 months. Mean attack number per month was reduced from 6.1 +/- 4.1 during the run-in period to 0.7 +/- 1.3 at the 3rd month of treatment (p < 0.0001). In 13 out of 21 patients who completed the study, the attacks were completely abolished at the 3rd month of treatment, while only one patient was completely unresponsive to the drug. Lamotrigine seems worthy of a controlled trial as prophylaxis of a migraine with aura.     

Responders and non-responders to metoprolol, propranolol and nifedipine treatment in migraine prophylaxis: a dose-range study based on time-series analysis

The aim of the present study was to ascertain, on the basis of single case statistics and time-series analysis, responder and non-responder rates for metoprolol, propranolol and nifedipine in migraine prophylaxis. In addition, an attempt was made to identify the dose relationship for the various drugs on headache parameters. In a double-blind dose-finding study, 58 patients were treated in five consecutive dosage steps each lasting 1-3 months. All patients kept a headache diary before, during and after treatment. Serum drug levels were also determined. The data were assessed by time-series analysis, as well as by multiple regression and analysis of variance. A significant improvement was noted in 54.4% of patients with migraine during treatment with metoprolol. The study did not confirm the high success rates in migraine prophylaxis of nifedipine and propranolol quoted in the literature. Administration of nifedipine led to an increase in migraine attacks in 71% of the patients. Nifedipine was of no value in the prophylaxis of migraine. Only 32% of patients showed a reduction in frequency of migraine attacks during administration of propranolol. The analysis of variance failed to show any significant difference between the responder rates for metoprolol and propranolol. Higher doses of propranolol and metoprolol were more effective. Multiple regression analysis explained a considerable part of variance for propranolol (but not for metoprolol) as a result of reduced intake of ergotamine preparations and analgesics. It can therefore be concluded that part of the prophylactic effect of propranolol is attributable to a reduction in the use of migraine medication.     

Propranolol in the Prophylaxis of Migraine - Evaluation by Spectral Analysis of Beat-to-Beat Heart Rate Fluctuations

Migraine patients seem to suffer from a continuous autonomic imbalance. Sympathetic instability, expressed by enhanced low frequency fluctuations, which exists during the headache free intervals, was observed in our previous study by spectral analysis of heart rate (HR) fluctuations. Propranolol--a beta adrenoceptor antagonist, is widely used in migraine prophylaxis. In order to specify and quantitate propranolol efficacy in migraine, spectral analysis of heart rate fluctuations was performed on 10 migraine patients before and during the treatment with propranolol. They were compared to 10 healthy control patients and 6 migraine patients who were treated for several months with propranolol and then discontinued the medication. The analysis was carried out on a 24h Holter ECG recording, which was performed for each subject during a headache free interval. Short 256 sec subtraces, taken every 30 min from the 24h ECG signal, were submitted to A/D conversion, R wave detection and computation of heart rate power spectrum. Propranolol achieved a marked effect, when comparing the power spectra of HR fluctuations in treated versus untreated migraine patients. A strong reduction (to normal level) in the low frequency HR fluctuations in the range below 0.1 Hz., was apparent in patients treated with propranolol. Subjects who had received propranolol in the past and discontinued the drug, displayed a carry-over effect of reduced fluctuations even 2-3 months after its discontinuation. It seems that the propranolol efficacy in migraine is associated with the mechanism of stabilizing the fluctuations within the frequency band related to sympathetic activity, hereby moderating the vascular instability in migraine.     

European Multicenter Trial of Nimodipine in the Prophylaxis of Common Migraine (Migraine Without Aura)

SYNOPSIS
This double blind, randomized study of the calcium antagonist Nimodipine 40 mg t.i.d. vs placebo in the prophylaxis of common migraine (migraine without aura) included 192 patients. Patients with 2–8 migraine days/4 weeks, age 18–60, who had no other types of recurring headaches except up to 6 interval headaches/4 weeks were included. The study was carried out at 11 European centers. After a 4 week run-in period, patients were randomly allocated to Nimodipine or placebo for 12 weeks (parallel groups). There were 19 drop-outs, 12 on Nimodipine and 7 on placebo, A gradual and marked improvement was seen both with Nimodipine and with placebo amounting to approximately 60% during the last 4 weeks. Statistical analysis on all included patients (intention to treat) revealed no difference between Nimodipine and placebo for migraine days (P = 0.69) or migraine index (p = 0.91). In patients "valid for analysis of efficacy" there were also no significant differences. Due to a very marked placebo effect and use of the parallel groups design, the present trial was not very powerful despite the large number of patients and a satisfactory compliance. We cannot rule out that Nimodipine might have up to 30% effect on a single main outcome parameter, but the uniform lack of response in all tested parameters makes this unlikely. Therefore Nimodipine probably has only a small or no effect in common migraine (migraine without aura).     

Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study

OBJECTIVE: This exploratory trial evaluated the safety and efficacy of multiple treatments of botulinum toxin type A (BoNTA; BOTOX, Allergan, Inc., Irvine, CA, USA) as prophylactic treatment of episodic migraine headaches. DESIGN AND METHODS: This was an 11-month randomized, double-blind, placebo-controlled, exploratory study. Patients were screened during a 30-day baseline period, and eligible patients with 4 or more migraine episodes and < or =15 headache days entered a single-blind 30-day placebo run-in period. Patients were classified as placebo nonresponders (PNR) if they had at least 4 moderate-to-severe migraine episodes and did not experience at least a 50% decrease from baseline in the frequency of migraine episodes following their placebo treatment. All other subjects were classified as placebo responders (PR). Patients were randomized within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA per treatment cycle) or placebo at 90-day intervals using a modified follow-the-pain treatment paradigm. The primary efficacy outcome measure was the mean change from baseline in the frequency of migraine episodes for the 30 days prior to day 180 in the PNR group. Secondary efficacy measures included the proportion of patients with a decrease from baseline of 50% or more migraine episodes per 30-day period. Patients were allowed to take concomitant acute and prophylactic headache medications. Adverse events were reported. RESULTS: A total of 809 patients were screened and 369 patients (89.2% female; mean age, 45 years; range, 20 to 65 years) entered the placebo run-in period and were subsequently randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U) (range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met. Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were observed (P > .999). From day 180 through the end of the study (day 270) at least 50% of all patients in each treatment group had a decrease from baseline of 50% or more migraine episodes per 30-day period. However, in the group of patients with > or =12 headache days at baseline (and < or =15 headache days), BoNTA patients experienced a mean change from baseline of -4.0 headache episodes at day 180 compared with -1.9 headache episodes in the placebo group (P= .048). The majority of treatment-related adverse events were transient and mild to moderate in severity. Only 7 patients (1.9%) discontinued the study due to adverse events (6 BoNTA, 1 placebo). CONCLUSION: There were no statistically significant between-group differences in the mean change from baseline in the frequency of migraine episodes per 30-day period. There were substantial, sustained improvements during the course of the study in all groups. Multiple treatments with BoNTA were shown to be safe and well tolerated over an active treatment period lasting 9 months.     

An analysis of the "carry-over effect" following successful short-term treatment of transformed migraine with divalproex sodium

OBJECTIVE: To determine whether successful short-term prophylactic treatment of transformed migraine may be followed by a continued respite from headaches once the treatment has been discontinued ("carry-over effect"). BACKGROUND: The optimal duration of prophylactic treatment for pervasive headache and for migraine, in particular, is unknown. METHODS: We prospectively evaluated a series of patients with transformed migraine, all of whom were managed according to a uniform treatment protocol involving prophylactic therapy with divalproex sodium for a period not exceeding 12 weeks. All patients reporting a positive treatment response were followed for at least 2 months after the discontinuation of divalproex sodium, and the incidence of the carry-over effect in that group was assessed. RESULTS: A short-term carry-over effect occurred in 12 (60%) of 20 patients, but more sustained relief occurred in only 8 (40%). CONCLUSIONS: The successful short-term treatment of transformed migraine with divalproex sodium will often produce a short-term carry-over effect, but this response will be sustained only in a minority of patients.     

Prophylactic botulinum type A toxin complex (Dysport®) for migraine without aura

(Headache 2011;51:52‐63) Objective.— To evaluate the efficacy, safety, and optimum dose of a highly purified Clostridium botulinum type A toxin‐hemagglutinin complex (Dysport) for migraine prophylaxis. Background.— Botulinum toxin type‐A has demonstrated good efficacy in several open‐label studies of patients with migraine, involving either individualized or standardized protocols, although data from placebo‐controlled trials have been conflicting. Methods.— A 12‐week, double‐blind, randomized trial of Dysport (120 or 240 units) vs placebo was conducted in 6 centers in Thailand to evaluate the efficacy, safety, and optimum dose of botulinum toxin type‐A (Dysport) for migraine prophylaxis. A total of 128 patients with migraine without aura were enrolled. The primary end point was the change in the mean number of migraine attacks per 4‐week period from the pre‐treatment period to 8‐12 weeks post injection. Secondary efficacy measures included the change in the mean total intensity score from the pre‐treatment period to 8‐12 weeks, the investigator and patient global assessments of change at each visit compared with pre‐treatment, and Migraine Disability Assessment and Short Form‐36 scores. Results.— Change in number of migraine attacks from pre‐treatment to weeks 8‐12 was not significantly different. There was a greater improvement in total intensity score at weeks 8‐12 with Dysport‐240 (not significant), and interim visit data showed that this was significant at weeks 0‐4 (P = .03 Dysport‐240 vs placebo). The mean duration of headache during weeks 0‐4 was lower with Dysport‐240 (P = .04 vs placebo). Improvements in patient and investigator global assessments of change between weeks 0‐4 and 8‐12 were significant for the Dysport‐240 group (both P < .05 vs placebo). Conclusions.— Limitations in study design and assessment tools employed may have contributed to the inconclusive nature of the primary end point data. Dysport‐240 showed significant benefit over placebo at some end points and further trials with more appropriate outcome measures are required to evaluate effectively this treatment.