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August 1994

Overview of Clinical Trials of Hydergine in Dementia

Author Affiliations

From the University of Southern California School of Medicine, Departments of Psychiatry and Behavioral Sciences (Drs Schneider and Olin) and Neurology (Dr Schneider), Los Angeles.

Arch Neurol. 1994;51(8):787-798. doi:10.1001/archneur.1994.00540200063018

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 that currently approved. The circumstances of the efficacy of Hydergine remain inadequately defined.