Overview of clinical trials of hydergine in dementia.
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.


METHODS
MEDLINE, EMBASE, and two proprietary databases were searched for reports of clinical trials.


METHODS
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.


METHODS
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.


RESULTS
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.
Schneider
L S
LS
Department of Psychiatry, University of Southern California School of Medicine, Los Angeles.
Olin
J T
JT
D000544:Alzheimer Disease / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003704:Dementia / Q000188:drug therapy*; D015140:Dementia, Vascular / Q000188:drug therapy; D004311:Double-Blind Method; D004877:Ergoloid Mesylates / Q000627:therapeutic use*; D006801:Humans; D015201:Meta-Analysis as Topic; D010919:Placebos; D016032:Randomized Controlled Trials as Topic
D010919:Placebos; D004877:Ergoloid Mesylates