Overview of clinical trials of hydergine in dementia
L. S. Schneider and J. T. Olin
Department of Psychiatry, University of Southern California School of Medicine, Los Angeles.
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.
