Overview of clinical trials of hydergine in dementia

Abstract

Objective: To assess the overall effect of Hydergine (a combination drug called ergoloid mesylates) on patients with possible dementia and to investigate potential moderators of an effect.

Data sources: MEDLINE, EMBASE, and two proprietary databases were searched for reports of clinical trials.

Study selection: Included were randomized, placebo-controlled, double-blind, parallel-group trials in subjects with symptoms consistent with dementia performed with specified outcome instruments and sufficient statistical information to calculate effect sizes. Forty-seven (31%) of 151 trials reviewed met selection criteria.

Data extraction: Potential moderating variables were extracted from each trial: sample size, inpatient-outpatient status, trial duration, age, gender, medication dose, publication year, and diagnostic grouping. Outcome measures were extracted with their associated statistics.

Data synthesis: The overall combined treatment effects ("adjusted d") for three types of outcome measures were calculated. Overall, Hydergine was more effective than placebo as assessed by comprehensive ratings (d = 0.47; 95% confidence interval [CI], 0.38 to 0.56; P = .0001), clinical global ratings (d = 0.56; 95% CI, 0.44 to 0.68; P = .0001), and combined neuropsychological measures (d = 0.27; 95% CI, 0.22 to 0.32; P = .0001). Inpatient status, daily doses of 4 mg or more, and vascular dementia were generally associated with larger effects. The effect in patients with possible Alzheimer's dementia was significant only for combined neuropsychological measures in five trials (d = 0.30; 95% CI, 0.16 to 0.44; P = .0001; and with a dose-response, P = .001).

Conclusions: Overall, ergoloid mesylates were more effective than placebo. However, the effect in patients with possible Alzheimer's dementia was very modest at best. The dose-response relation suggests that potentially effective doses may be higher than the currently approved. The circumstances of the efficacy of Hydergine remain inadequately defined.