Comparison of propranolol LA 80 mg and propranolol LA 160 mg in migraine prophylaxis: a placebo controlled study

Thirty patients with severe classical and common migraine participated in a double-blind placebo-con-trolled 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.     

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.     

Comparative Efficacy of Nadolol and Propranolol in the Management of Migraine

SYNOPSIS
A multicenter randomized double-blind study was conducted on 140 patients with classic and/or common migraine who received either nadolol (80 mg or 160 mg OD) or propranolol (80 mg bid). Admission into the 12-week active treatment period required at least 3 attacks per month during a placebo lead-in period. Abortive headache therapy was allowed at the patients' discretion, each keeping a diary of migraine attacks and use of medications. Clinical assessments were performed monthly.
Data from 42 patients were excluded from the evaluation of efficacy, mainly because of non-adherence to protocol requirements. Drug efficacy evaluation in the remaining 98 patients was based on 4 separate migraine indices: frequency of attacks, intensity of attacks, days of pain, and need for relief medication, with success being defined as a reduction in an index of at least 50% relative to baseline. A successful response in at least I index was found in 48% of patients on nadolol 80 mg (p=NS vs propranolol 160 mg) and in 69% of the patients on nadolol 160 mg compared with 54% on propranolol 160 mg (p<0.05). Success in all 4 indices was found in 21% of patients on nadolol 80 mg (p=NS vs propranolol 160 mg) and in 41% of patients on 160 mg nadolol as compared to 15% on propranolol 160 mg (p<0.05).
Adverse reactions required discontinuation from therapy in 2 of 48 patients on nadolol 80 mg (4.1%), 2 of 47 patients on nadolol 160 mg (4.3%), and 4 of 44 patients on propranolol 160 mg (9.1%).
This study indicates that, in the prophylaxis of migraine, 80 mg of nadolol administered once daily is equivalent in efficacy and safety to propranolol 80 mg administered twice daily. Furthermore, nadolol given as a single daily dose of 160 mg is superior to an equal total daily dose of propranolol administered twice daily.     

DOUBLE BLIND STUDY OF PROPRANOLOL FOR MIGRAINE PROPHYLAXIS

SYNOPSIS
Eighty-three migraine patients were admitted to a double-blind, single cross-over, propranolol vs. placebostudy. Sixty-two patients completed the trial. The daily dosage was either 80 or 160 mg. propranolol, or an equivalent number of placebo capsules, for 4 to 8 weeks for the first medication and 8 weeks for the second one. At the end of the trial, 32 patients preferred propranolol and 18 placebo. Those who preferred propranolol had greater reduction in severity and frequency of headaches and less consumption of analgesics and ergotamine than patients who preferred placebo. Side effects were benign. Propranolol issafe and effective for the prophylaxis of migraine if patients are carefully selected.     

Effects of atenolol and propranolol when added to long-term antihypertensive diuretic therapy.

The antihypertensive effects of atenolol and propranolol were compared in a double-blind crossover study of 19 patients with essential hypertension (World Health Organization, I and II) who were receiving long-term diuretic treatment (chlorthalidone, 50 mg daily) during the study. After a 3-wk placebo period, a beta-adrenergic antagonist was administered once daily (atenolol, 50 mg daily, or propranolol, 80 mg daily) for a week. If the MAP was more than 108 mm Hg at the end of the week, dosage of the beta-blocker was doubled the following week; when necessary, doubling was repeated to a maximum dose of 640 mg propranolol and 400 mg atenolol daily. Fifty milligrams atenolol had a greater effect than 80 mg propranolol and was as effective as 160 mg propranolol. The dose-response curve flattened off after 160 mg propranolol and 50 mg atenolol daily. The two highest doses of atenolol lowered MAP more than the highest doses of propranolo. Heart rate slowing was the same for both drugs and did not correlate with the fall in blood pressure. PRA was suppressed by all doses of propranolol, whereas atenolol suppressed PRA only at the 2 highest doses, (200 and 400 mg daily). With the lower propranolol doses, the percent MAP change correlated weakly with the percent PRA change (80 mg--r = 0.41, p less than 0.1; 160 mg--r = 0.64, p less than 0.05). Side effects were minimal, and were noted only with 640 mg propranolol; with this exception, the percentage of patients with no complaints rose when placebo was replaced by beta-blockers.     

A double-blind comparison of acebutolol (Sectral) and propranolol (Inderal) in the treatment of hypertension in black Nigerian patients

Acebutolol and propranolol were compared in forty-five Black African patients in a double-blind randomized trial carried out at Ahmadu Bello University Teaching Hospital in Kaduna, Nigeria. After a wash-out period of 6 weeks, including placebo administration for the last 4 of those weeks, twenty-seven patients were given acebutolol once daily and eighteen were given propranolol twice daily for 12 weeks, followed by a tapering-off period of 2 weeks, making a total of 14 weeks on active treatment. The two beta-receptor blocking drugs were effective in controlling hypertension with final daily doses ranging from 160 to 320 mg in the propranolol group and 400 to 800 mg in the acebutolol group. The supine systolic blood pressure responses with acebutolol were statistically significant and better than those elicited by propranolol. Acebutolol produced less (resting) bradycardia than did propranolol; this may be related to acebutolol's intrinsic sympathomimetic activity. The only unpleasant side-effects reported in this study were slight dizziness in two patients treated with propranolol and slight tiredness in one patient treated with acebutolol. No significant abnormal changes were noted in laboratory tests or chest X-rays. Electrocardiography detected supraventricular tachyarrythmia in five patients: this disappeared by the end of the study. Acebutolol was shown to be a safe, effective and reliable antihypertensive drug, at least comparable to and probably slightly better than, propranolol in the treatment of hypertension in Black Nigerians. It has the added advantage of a once-daily dose schedule.     

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.     

Efficacy of nimodipine in comparison with pizotifen in the prophylaxis of migraine

The efficacy of nimodipine in comparison with that of pizotifen was assessed in the prophylaxis of migraine in a double-blind cross-over study, in which a double-dummy technique was also utilized. The study was carried out on 43 migraine patients, of whom 15 had classic and 28 had common migraine. A 4-week run-in placebo period preceded the drug treatments, the drug treatments lasted 12 weeks, and there was a washout placebo period of 4 weeks between nimodipine and pizotifen treatments. The dosages used were 40 mg three times daily for nimodipine and 0.5 mg three times daily for pizotifen. Both nimodipine and pizotifen proved to be better than placebo, the number of migraine attacks showing a significant reduction. There was no difference between nimodipine and pizotifen in antimigrainous efficacy, but there were fewer side effects during the nimodipine period. The results suggest that nimodipine is an effective drug for the prophylaxis of migraine, with few side effects and therapeutic efficacy equal to that of pizotifen.     

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses

A randomized double-blind, cross-over study using treatment periods of 12 weeks with a 2-week washout, comparing two long-acting formulations of propranolol ('Inderal' LA 160 mg daily and Half-'Inderal' LA 80 mg daily) was performed after a placebo run-in of 4 weeks on 51 patients. The study indicated that both long-acting formulations were significantly better than placebo in reducing the frequency of migraine attacks (p less than 0.01). After 12 weeks there was a significantly lower (p = 0.03) frequency of migraine attacks in patients on the higher dose formulation than in those on the lower dose formulation. There was no significant difference in the frequency of side effects produced by the two formulations.     

Nadolol and propranolol in the treatment of hypertension: a double-blind comparison

Nadolol and propranolol were compared in seventy-five hypertensive patients in a double-blind randomized study conducted at Ain-Shams Hospital. After an initial wash-out period of 5 weeks, including 3 weeks of placebo administration, forty-five patients were given nadolol once daily and thirty patients received propranolol four times per day for 12 weeks, followed by a tapering-off period of 2 weeks. Both beta-blocking agents were effective in controlling hypertension with final daily doses ranging from 80 to 320 mg. Of statistical significance, however, were the better responses of supine systolic blood pressure elicited by nadolol. The only adverse reactions that occurred in this series were slight weight gains in two patients treated with nadolol and moderate dizziness in one patient treated with propranolol. Nadolol was proved to be a safe antihypertensive drug, at least comparable to propranolol in efficacy, with the advantages of a once-daily dose and a lack of direct depressant action on the heart.     

Propranolol in the Prophylaxis of Migraine

SYNOPSIS
This 34-week, placebo-controlled, single crossover study with a double-blind randomized treatment sequence evaluated the effects of propranolol as a prophylactic agent in individualized doses ranging from 60–320 mg/day given to 62 patients who had common and/or classic migraine. Variables reflecting efficacy were the frequency, severity, and persistency of acute migraine attacks expressed as Headache Unit Index (HUI) and the therapeutic medication required for acute attacks during the study expressed as the Relief Medication Unit Index (RMUI). Both HUI and RMUI were significantly reduced from baseline after the six weeks of propranolol titration (p<0.0001) reflecting fewer and/or less severe headaches. During the crossover treatment periods, propranolol, in comparison with placebo, was significantly more effective in the reduction of HUI (p<0.01) and RMUI (p<0.05). Data at the end of the dose finding (titration) period were analyzed separately for patients whose final prescribed doses were 60-240 mg or 320 mg/day propranolol. Significant reductions in HUI and RMUI (p< 0.0001) were shown at this time at each dose level. At all dose levels, propranolol was well tolerated. This was the first study in which the propranolol dose for migraine extended above the usual recommended 240 mg/day, i.e., up to 320 mg/day. This higher dose was administered if the drug had been well tolerated, even if only one headache in 2 weeks occurred at lower doses. The data suggest that there is an option to prescribe propranolol at higher doses as a preventive measure, thus reducing the need for ancillary medications.     

A placebo-controlled, double-blind, cross-over trial of flunarizine in common migraine

After four weeks of medication-free baseline observation, 29 patients with common migraine randomly received flunarizine (10 mg daily) or placebo for a 16-week period. After four weeks wash-out they crossed treatments for another 16 weeks; 27 patients completed the trial. Compared with placebo, flunarizine significantly reduced the frequency of migraine attacks and the derived headache indices, but the duration and severity of single attacks remained unchanged (Mann-Whitney U-test). The effect of flunarizine increased during the 16-week treatment period and during the last four weeks the number of migraine attacks reduced to 50% compared to the wash-out period. The only side-effect of flunarizine was mild daytime sedation in three patients. It is concluded that flunarizine is a valuable new prophylactic agent for common migraine.     

An assessment of Half-Inderal LA and Inderal LA in the treatment of hypertension in elderly subjects

Twenty-three elderly hypertensive patients, who remained hypertensive despite treatment with 2.5 mg bendrofluazide once daily, were randomised to receive, in addition to the diuretic, placebo, or a low-dose (80 mg) or a high-dose (160 mg) of long-acting propranolol once daily in a double-blind crossover study. Each randomised treatment period was of four weeks' duration. Blood pressure was assessed in the supine and standing positions, as well as after an individualised exercise test. Evaluations were carried out at least 24 hours after the last dose of medication. Sitting blood pressure fell from 196.2 +/- 21.3/107.2 +/- 11.3 mmHg to 193.1 +/- 17.5/106.0 +/- 15.9 mmHg for bendrofluazide alone, 193.2 +/- 24.76/97.3 +/- 11.9 mmHg for bendrofluazide plus long-acting propranolol (80 mg) and 187.2 +/- 19.6/102.1 +/- 11.2 mmHg for bendrofluazide plus long-acting propranolol (160 mg). The three randomised treatments yielded standing pressures of 191.3 +/- 20.5/106.2 +/- 13.5 mmHg, 192.4 +/- 29.0/99.6 +/- 12.6 mmHg and 192.4 +/- 28.0/106.0 +/- 8.6 mmHg for bendrofluazide alone, and bendrofluazide plus low- and high-dose, long-acting propranolol respectively, compared with the pretreatment standing blood pressure of 193.4 +/- 18.4/108.4 +/- 14.8 mmHg. There appeared to be no significant effect of any treatment on systolic blood pressures in either sitting or standing positions. No statistically significant differences between the three randomised treatments with regard to post-exercise diastolic pressure were observed, except for a small but significantly greater reduction during treatment with the low-dose, long-acting propranolol compared with the high-dose, long-acting propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerivastatin, a New Potent Synthetic HMG Co-A Reductase Inhibitor: Effect of 0.2 mg Daily in Subjects With Primary Hypercholesterolemia

BACKGROUND: Reduction of serum cholesterol, most notably low-density lipoprotein cholesterol is associated with reductions in cardiovascular morbidity and mortality. Statins have been shown to effectively reduce low-density lipoprotein cholesterol via inhibition of the hydroxymethyl-coenzyme A (HMG-CoA) reductase. Cerivastatin is the most potent HMG-CoA reductase inhibitor currently under study in the United States. METHODS AND RESULTS: A parallel group, randomized, placebo-controlled, double-blind, multicenter study was conducted to compare the efficacy and safety of three different dosing regimens of 0.2 mg/day of cerivastatin, a new HMG-CoA reductase inhibitor, in patients with hypercholesterolemia. After a 10-week diet-placebo lead-in period, 319 patients with low-density lipoprotein cholesterol >160 mg/dL were randomized to 4 weeks of treatment with one of the following regimens: cervastatin 0.1 mg twice daily, cerivastatin 0.2 mg once daily with the evening meal, cerivastatin 0.2 mg once daily at bedtime or placebo. All three active treatment groups produced statistically significant (P <.05) changes compared to aseline and placebo in total cholesterol (0.1 mg twice daily \_18.9%; 0.2 mg once daily with the evening meal: \_21.9%; 0.2 mg once daily at bedtime: \_22.1%; placebo: 0.0%), low-density lipoprotein cholesterol (0.1 mg twice daily: \_25.7%; 0.2 mg once daily with the evening meal: \_29.4%; 0.2 mg once daily at bedtime: \_30.4%; placebo: 1.4%) and high-density lipoprotein cholesterol (0.1 mg twice daily: 5.3%; 0.2 mg once daily with the evening meal: baseline and placebo, were also reduced by all active treatments (0.1 mg twice daily: \_11.6% [P =.05]; 0.2 mg once daily with the evening meal: \_11.6% [P =.05]; and 0.2 mg at bedtime: \_10.9% [P =.07]). The percentage change in total cholesterol and low-density lipoprotein cholesterol after 4 weeks of therapy for the once-daily cerivastatin groups was statistically significantly greater (P <.05) than the cerivastatin twice daily regimen. A treatment responser was seen by 1 week of therapy and was maximal by 3 weeks. The drug was well tolerated in all three dosing regimens and resulted in no significant increase in biochemical or clinical side effects compared to placebo. CONCLUSION: Cerivastatin is a novel, highly potent, well-tolerated HMG-CoA reductase inhibitor that produces low-density lipoprotein cholesterol reductions of approximately 30% when administered at 0.2 mg once a day in the evenings.     

L-5-Hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study

L-5HTP was tested versus placebo in a double-blind crossover study of 27 migraine children aged 6-12 years, who recorded their headaches in a headache diary for 1 month. Twenty-one patients subsequently started the trial. The mean daily dose of L-5HTP was 5 mg/kg body weight, and each treatment period with either L-5HTP or placebo lasted 12 weeks. In group A (L-5HTP-placebo; 10 patients) and group B (placebo-L-5HTP; 11 patients) both L-5HTP and placebo led to a significant reduction of the migraine index and frequency of migraine attacks during the 3rd month of each treatment period. However, we found a treatment X period interaction because the efficacy determinants decreased significantly during the first and the second treatment periods in both groups irrespective of the sequence of treatments. No differences were found between L-5HTP (first period of group A) and placebo (first period of group B).     

Classic migraine: Effective prophylaxis with metoprolol

Metoprolol slow-release tablets (Durules®), 200 mg, given once daily in the morning were compared with placebo in the prophylaxis of classic migraine. The trial comprised eight Scandinavian neurologic centres and was designed as a double-blind cross-over study with 4 weeks' run-in, four weeks washout, and 8 weeks of either treatment. Seventy-seven patients with two to eight migraine attacks per month were entered in the trial, and 73 completed it. A total of 1119 attacks with aura symptoms and 374 without were recorded. Metoprolol was significantly better than placebo with regard to the total frequency of attacks (1.8 versus 2.5 attacks/4 weeks), mean duration of attacks (6.0 versus 8.0 h/attack), mean global rating, and consumption of analgesics per attack: Similar differences could be shown for attacks with aura symptoms alone, except for the duration of attacks. Metoprolol is the first drug for which a prophylactic effect in classic migraine has been convincingly demonstrated.     

Diclofenac-K (50 and 100 mg) and placebo in the acute treatment of migraine

The aim of the present study was to assess the efficacy and tolerability of single oral doses of 50 mg and 100 mg of diclofenac-K compared to placebo in migraine sufferers during three attacks. The study was conducted in a double-blind, randomized, placebo-controlled, three-period, within-patient comparative trial; 72 migraine patients were treated with diclofenac-K (50 mg or 100 mg) or placebo at six centres (1 in Sweden and 5 in Finland). The primary efficacy end-point was the change in pain intensity assessed on a 100 mm Visual Analogue Scale (VAS) at 120 min after taking the study medication. We found that 50 mg and 100 mg of diclofenac-K reduced the pain intensity significantly better than placebo (p = 0.003 and p = 0.001, respectively), without difference between the doses; 100 mg diclofenac-K was significantly better than placebo in improving phonophobia, photophobia, working ability and need for rescue medication. Diclofenac-K 50 mg or 100 mg is an effective and well-tolerated acute treatment for migraine headache and its associated symptoms. The higher dose of diclofenac-K was only marginally more effective than the lower dose.     

Crossover Comparison of Rizatriptan 5 mg and 10 mg Versus Sumatriptan 25 mg and 50 mg in Migraine

Rizatriptan is a selective 5-HT_1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.     

Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group

Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.     

Comparison of rizatriptan 5 mg and 10 mg tablets and sumatriptan 25 mg and 50 mg tablets

This randomized, double-blind, two-attack, placebo-controlled, crossover study explored the efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 50 mg as well as rizatriptan 5 mg compared with sumatriptan 25 mg in the acute treatment of migraine. Following randomization to one of six possible treatment sequences, patients (n = 1447) treated two sequential attacks, of moderate or severe intensity, separated by at least 5 days. Patients assessed pain severity, migraine-associated symptoms, and functional disability at 0.5, 1, 1.5, and 2 h post treatment. Compared with placebo, all treatments were effective. On the primary endpoint of time to pain relief, rizatriptan 10 mg was not statistically different from sumatriptan 50 mg [odds ratio (OR) 1.10, P = 0.161], and rizatriptan 5 mg was statistically superior to sumatriptan 25 mg (OR 1.22, P = 0.007). In general, rizatriptan 10 mg and 5 mg treatment resulted in improvement compared with the corresponding doses of sumatriptan on measures of pain severity, migraine symptoms, and functional disability and the 5-mg dose reached statistical significance on almost all measures. All treatments were generally well tolerated.