Duloxetine prophylaxis for episodic migraine in persons without depression: a prospective study.

OBJECTIVE: The objective of this pilot study is to evaluate the effects of daily duloxetine, 60-120 mg, on the frequency, duration, and severity of migraine attacks and the level of disability in episodic migraineurs. BACKGROUND: There is a need for more proven effective migraine preventive medications. Two antidepressants, both of which block serotonin and norepinephrine reuptake, have been shown to be effective in the preventive treatment of migraine. Neither has earned a level A recommendation in the 2012 guidelines of the American Academy of Neurology. Duloxetine also blocks serotonin and norepinephrine reuptake. METHODS: This was a prospective, 5-visit study on duloxetine treatment of episodic migraine headache with 4-10 migraine days, and less than 15 headache days per month. Patients were titrated to a goal dose of 120 mg. They were excluded if they had depression. RESULTS: There were 22 completers plus 5 subjects who took at least 1 dose of drug. The mean duloxetine dose was 110 mg. In a modified intent-to-treat analysis, subjects went from 9.2 ± 2.7 headache days per month at baseline to 4.5 ± 3.4 headache days per month (P < .001). There were no significant differences in the average headache duration, average headache severity, maximum headache attack severity, and level of functioning. Fifty-two percent of subjects had a 50% or greater improvement in headache days. CONCLUSIONS: Migraine prophylactic treatment with high-dose duloxetine may be effective in a nondepressed individual. The reported treatment response is in line with other commonly used migraine preventives.

Correlation of increase in phosphene threshold with reduction of migraine frequency: observation of levetiracetam-treated subjects.

OBJECTIVES: To correlate the reduction in migraine frequency with change in phosphene threshold of transcranial magnetic stimulation during levetiracetam treatment. BACKGROUND: Several case series have suggested levetiracetam efficacy may be effective in the management of migraine. Phosphene threshold is reduced in patients with migraine with aura, migraine without aura, and menstrual migraine. Preventive treatment may raise phosphene threshold while reducing headache frequency. METHODS: Subjects experiencing 4-10 migraine attacks per month and not currently receiving preventive treatment for the indication of migraine were recruited into an open-label trial using levetiracetam, and asked to record headache symptoms, severity, duration, and acute medication use in a daily diary. Following a 28-day qualifying baseline period, subjects were titrated over 6 weeks to either a total daily dose of 3000 mg or their maximum tolerated dose (minimum tolerated daily dose of 1000 mg required). Transcranial magnetic stimulation was performed at day 28 and days 26, 28, 84, and 154. The visual cortex of each subject was stimulated 2 times at 20% power. Power was increased by 10% increments until at least one of the 2 stimulations produced a positive phosphene response. Once a positive response was achieved, a random order of 5 stimulation intensities surrounding the initial positive threshold was generated and given 3 times per session. Stimulation intensities were -10%, -5%, 0%, +5%, and +10% in relation to the positive threshold achieved. To eliminate a learning curve distortion, only observations at days 28, 84, and 154 were used for analysis. The mean phosphene threshold was defined as the average of the lowest positive threshold of the 3 stimulation sequences per visit. Ordinary least squares regression was used to evaluate the association between the change in mean daily headache rate from visit 3 to visit 7 and the change in mean transcranial magnetic stimulation threshold during the same period. RESULTS: Sixty-one subjects were enrolled. Twenty-one subjects were discontinued (because of poor study compliance or attack frequency) during the baseline phase prior to study drug initiation, and an additional subject whose data were not analyzed because of suspect quality. During the first 6 weeks on study drug (titration phase), 8 subjects dropped out (20.5%). Full analysis of the remaining 31 subjects, who reached a maintenance dose after 6 weeks on study medication, was performed. Subjects were largely white, female, and had a mean age of 41 +/- 13 years. Increasing age (beta = 1.27, P = .09), nonwhite race (beta = 6.90, P = .03), and diagnosis of tension-type headache (beta = 6.12, P = .095) were found to be associated with a higher mean transcranial magnetic stimulation threshold. Conversely, increasing body mass index was found to be associated with a lower mean transcranial magnetic stimulation threshold (beta = -1.19, P = .005). The number of migraine attacks decreased from 4.24 during the baseline interval to 2.53 during the interval preceding visit 7 (P = .001). There was a small but significant increase in transcranial magnetic stimulation threshold from visit 3 to visit 5 (P = .03) and visit 3 to visit 7 (P = .03 omnibus test). However,the difference between visit 5 and visit 7 was not statistically significant (P = .88). The mean transcranial magnetic stimulation threshold did not change from visit 5 to visit 7. CONCLUSION: Phosphene threshold increased during treatment with levetiracetam. At the 10% significance level, headache frequency and phosphene threshold were negatively correlated.

Dihydroergotamine for early and late treatment of migraine with cutaneous allodynia: an open-label pilot trial.

OBJECTIVE: To explore whether dihydroergotamine (D.H.E. 45) is equally effective and safe for migraine with allodynia, when administered either early or late in an attack. BACKGROUND: Central sensitization may account for the extracranial tenderness and cutaneous allodynia that can occur with migraine. Once allodynia is established, triptans are less effective. Dihydroergotamine is often effective for patients whose refractory headaches have failed prior triptan therapy. METHODS: In this single-center, open-label pilot trial, patients with episodic migraine associated with cutaneous allodynia were treated on 2 occasions with dihydroergotamine 1.0 mg intramuscularly. One attack was treated within 2 hours (early) and a second attack at 4 hours (late) after the onset of throbbing pain. Headache pain and any associated symptoms, subjective cutaneous allodynia, and mechanical (brush) allodynia were assessed. All data were analyzed using the Fisher's exact test. RESULTS: Thirteen patients met the entry criteria; however, data from only 9 patients, those who completed treatment for 2 migraine attacks, were used to evaluate the efficacy and safety of dihydroergotamine. Whether they took dihydroergotamine early or late in the attack, most patients (>55%) had headache relief within 2 hours, and at least 44% of patients achieved headache-free status by 8 hours postdose. Subjective cutaneous allodynia started to decline after 30 minutes postdose in the early treated group and after 120 minutes postdose in the late-treated group. Brush allodynia began to decline after 15 minutes postdose in the early treated group and after 90 minutes postdose in the late-treated group. Six of 9 patients (67%) reported at least 1 adverse event. CONCLUSIONS: The results of this pilot trial provide proof of concept for the headache-relief benefit of dihydroergotamine in patients with migraine headache and allodynia. A large, placebo-controlled trial of dihydroergotamine in allodynic patients is warranted.

Evaluation of an electronic diary as a diagnostic tool to study headache and premenstrual symptoms in migraineurs.

OBJECTIVE: To evaluate an electronic diary as a tool to evaluate the occurrence and relationship of headaches and premenstrual syndrome (PMS) symptoms throughout the menstrual cycle in women with migraine. BACKGROUND: Menstrually related headache and PMS significantly impact the quality of life of many women. The time relationship of these 2 menstrually related problems is not well understood and not well described. METHODS: Twenty women with migraine experiencing regular menstrual cycles were enrolled in a prospective study designed to date- and time-stamp data, both self- and computer-prompted, headache and PMS symptoms, for 3 consecutive months. A previously validated PMS score was calculated by grading 23 PMS criteria on a scale of 0 to 3 (0 = no symptoms, 3 = severe symptoms). RESULTS: The total number of data entries recorded was 2009, composed of 56 menstrual cycles in 20 migraineurs. Five hundred forty-four entries reported a current, prodromal, or previous headache. The mean daily occurrence of headache increased beginning on cycle day -5, peaked on days +1 to +5, and returned to baseline by day +7. Mean daily PMS scores ranged from 2.4 to 12. Mean daily PMS scores peaked on days -6 to +2 and returned to baseline by day +8. CONCLUSIONS: An electronic diary may have potential as a diagnostic tool in studying headaches and PMS symptoms throughout the menstrual cycle. The occurrence of headache and PMS symptoms in migraineurs follows similar time courses.

Patients' preference for migraine preventive therapy.

OBJECTIVE: Preventive treatment is an important part of migraine therapy. When prescribing medication, physicians should understand patients' treatment preferences and select drugs that most closely meet their patients' needs. Understanding the factors that influence patients' preference increases physicians' ability to select appropriate migraine therapy. However, unlike acute migraine treatment, patients' preferences for migraine preventive treatment have never been studied. METHODS: We enrolled 250 patients who attended the Jefferson Headache Center and Sao Paulo Headache Center and had a primary headache diagnosis. Patients' age, gender, body mass index (BMI), headache diagnosis, headache frequency, duration, and intensity, headache disability (by MIDAS), and current preventive treatments were ascertained. Patients were asked to rate 7 aspects of headache prevention (efficacy, speed of onset, out-of-pocket expenses, adverse events, formulation of therapy, type of treatment, and frequency of dosing) in order of importance (1-7). Each patient also evaluated 12 different clinical scenarios, each one containing a simulation of 2 hypothetical headache preventive treatments, wherein patients could choose Product A, Product B, or neither. Patients were informed of each product's efficacy data (50%, 75%, or 100% headache elimination), adverse event profile (weight gain, concentration difficulty, and/or fatigue), and dosing frequency (once every 3 months, once per day, or twice per day). RESULTS: Most patients were Caucasian. Mean BMI was 26.55 +/- 5.34, range (17-45). Mean history of headache was 20.93 years. Fifty patients (40%) had 45 or more headache days in the past 3 months. Mean headache intensity score (0-10 scale) was 5.7 +/- 1.8. Patients were on various preventive treatments, including beta-blockers (48 [41%]), calcium-channel blockers (19 [16%]), antidepressants (52 [44%]), antiepileptics (46 [39%]), neurotoxins (16 [14%]), vitamins/herbal therapies (28 [24%]), and nonmedicinal therapy (38 [32%]). Of the 7 aspects of migraine prevention that patients were asked to rate, 72% rated effectiveness the most important aspect. Twelve percent rated speed of onset most important, 6% rated absence of adverse events most important, 3% rated formulation of therapy most important, 3% rated out-of-pocket expenses most important, and 2% rated type of treatment (prescription/vitamin) most important. None rated frequency of dosing as the most important factor. In the area of preventive treatment scenarios, patients were more likely to choose treatments with higher efficacy rates, fewer adverse events and less frequent dosing schedule. Patients indicated that they preferred the treatment options with higher efficacy rates even if side effects were present and a more frequent dosing schedule was necessary. CONCLUSION: Patients' preference regarding migraine prevention is very important in headache management. Patients rated efficacy the most important aspect in preventive therapy and preferred treatment options with higher efficacy rates. Future studies are needed for a better understanding of patients' preference for migraine prevention.

Consecutive transcranial magnetic stimulation: phosphene thresholds in migraineurs and controls.

OBJECTIVE: To characterize the temporal course of transcranial magnetic stimulation-induced phosphene thresholds in subjects with migraine and in controls. METHODS: Eleven subjects with migraine with aura, 10 subjects with migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no history of migraine and without migraine during the study) were studied. Subjects were not on preventive medication. Transcranial magnetic stimulation was performed, and a phosphene threshold was measured 3 times a week over 3 weeks in a manner timed to incorporate the menstrual period in females. A headache calendar was kept during the study. RESULTS: Mean transcranial magnetic stimulation thresholds were lower for each migraine group compared with controls (P <.001) for each comparison. There was a trend for lower thresholds among subjects with migraine with aura compared with subjects with migraine without aura (P <.10), but not subjects with menstrual migraine. There was consistent lowering of thresholds from the first to the last stimulation in all migraine groups and in the controls. Maximum and minimum thresholds did not predict headache occurrence, nor did the occurrence of headache predict an ensuing maximum or minimum phosphene threshold. CONCLUSIONS: Transcranial magnetic stimulation thresholds are lower in subjects with migraine compared with controls. The reported phosphene threshold is lowered with repeated measurement. Neither high nor low phosphene thresholds predict a subsequent headache, nor do migraines predict a subsequent high or low threshold.