Mathew 1995.
| Methods | Prospective, 2:1 randomised, double‐blind, parallel trial. 5 half‐lives washout period for previous migraine prophylactic medication. Total duration then 16 weeks: 4‐week single‐blind, placebo‐only baseline period. 4 weeks titration, then 8 weeks stable dosage Discontinuation rate: dropout 17% for active treatment, 14% for placebo Compliance (adherence) data: compliance data available only as mean blood valproate levels Rules for use of acute medication: reported as exclusions; analgesics and triptans permitted (but not daily) Methodological quality score: 4 |
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| Participants | Inclusion: migraine according to ICHD‐I; migraine onset more than 6 months prior to study; 2 or more attacks per month for previous 3 months Exclusion: secondary headaches, daily headaches, and analgesic overuse headache were adequately excluded. Other exclusions: migraine symptoms without headache, significant other medical or psychiatric disorder, history of poor compliance, history of valproate use, women of childbearing potential, failure of more than 2 other migraine prophylactic agents Setting: multi‐centre Country: USA 107 migraine patients participated; 95% had had attacks without aura and 27% with aura. 83 females and 24 males; allowed age range 16 to 75 |
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| Interventions | Divalproex sodium versus placebo (12 weeks). Dosage titrated to maintain plasma concentration at 70 to 120 mg/L. Mean dose 1087 mg/day | |
| Outcomes | Number of migraine attacks per 28 days. Number of migraine days per 28 days. Peak headache severity (0 to 4 scale). Headache duration (hours). Average analgesic use. Other composite measures Time point(s) considered in the review: entire 3‐month treatment phase |
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| Notes | Funders of the trial: Abbott Laboratories | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Description of method for random sequence generation (2:1 ratio of verum to placebo within each centre) is lacking |
| Allocation concealment (selection bias) | Unclear risk | No information |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Single‐blind baseline phase (patient was blinded, clinician was not) followed by double‐blind treatment phase. Placebo tablets were identical in appearance to verum and dose‐adjusted in a similar fashion. An unblinded designee reviewed plasma concentrations and informed personnel at each clinic of the results in a blinded manner. For patients receiving placebo, sham valproate concentrations were reported by the unblinded designee according to an algorithm designed to maintain the blind |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | No information |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Analyses were performed using all data from randomised patients |
| Selective reporting (reporting bias) | Low risk | No suspicion of selective reporting of outcomes, time points, subgroups, or analyses |