Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures.

OBJECTIVE: To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial. BACKGROUND: We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated. METHODS: Variables analyzed included between-treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache-free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine-Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change. RESULTS: The intent-to-treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate- vs placebo-treated subjects were as follows: for > or =25% reduction: 68.6% vs 51.6% (P = .005); > or =50%: 37.3% vs 28.8% (P = .093); and > or =75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache-free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine-Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine-Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062). CONCLUSIONS: In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events.

Epidemiology, risk factors, and treatment of chronic migraine: a focus on topiramate.

The term chronic daily headache refers to a heterogeneous group of headache disorders characterized by a frequency of headaches on > or = 15 days per month. Chronic migraine is a subtype of chronic daily headache. The prevalence of chronic migraine is approximately 1%. Baseline attack frequency and acute medication overuse have been identified as potential risk factors for the progression of migraine from an episodic disorder to a chronic condition. There is an unmet patient need for effective and safe treatments for patients with chronic migraine, but data from rigorous controlled trials are limited. Previous studies have demonstrated that topiramate is an effective and safe preventive treatment for episodic migraine. In addition, pilot studies have suggested the utility of topiramate for the prevention of chronic migraine. Two randomized, double-blind, placebo-controlled, multicenter trials investigating the efficacy and safety of topiramate in the treatment of patients with chronic migraine have recently been completed. This review presents comparative data from these 2 clinical trials, which suggest that topiramate at a dose of 100 mg daily is effective and generally well tolerated in chronic migraine.

Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia.

OBJECTIVE: Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown. METHODS: We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test. RESULTS: At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance. CONCLUSIONS: This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.