DIHYDROERGOCRISTINE IN THE TREATMENT OF ELDERLY PATIENTS WITH COGNITIVE DETERIORATION - A DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RESPONSE STUDY

The efficacy and safety of three dose levels of dihydroergocristine (D HEC) and placebo were compared in this double-blind, placebo-controlle d, randomized study with four parallel groups. A total of 80 patients of both sexes, aged 50 years or older, with degenerative cerebral impa irment and mild-to-moderate symptoms of cognitive deterioration were i ncluded in the study. All eligible patients received placebo for a run -in period of 15 days before entry into the study. They were then rand omly assigned to receive one of the following treatments: DHEC 6 mg/d, DHEC 12 mg/d, DHEC 20 mg/d, or placebo for 3 months. The Sandoz Clini cal Assessment Geriatric (SCAG) scale was administered on entry and af ter 30, 45, and 90 days of treatment; at each visit, physical examinat ion and monitoring of adverse events were performed. Before and at the end of the study period systolic and diastolic blood pressures and he art rate were measured and samples were taken for routine laboratory t ests. The four treatment groups were well matched as to sex, age, body weight, concomitant diseases and therapies, history of disease, and S CAG total scores. In all three DHEC-treated groups, a progressive impr ovement of symptoms, as assessed by using SCAG total scores, was obser ved. Clinically relevant or statistically significant differences from baseline values and a clear dose-response relationship were seen in t hese groups. Conversely, in the placebo group the symptoms remained al most unchanged throughout the study. The mean times to obtain a 50% re duction of all symptoms, as calculated by regression analysis of SCAG total score for each group, were significantly lower after treatment w ith DHEC 20 mg than after treatment with DHEC 6 mg and DHEC 12 mg; the same evaluation performed on single clusters showed a significant dos e-effect relationship. Three types of adverse events were reported in 5 patients (nausea in 1 placebo patient, gastric pain in 1 patient tre ated with DHEC 12 mg and 1 with DHEC 20 mg, and dyspepsia in 1 treated with DHEC 6 mg and 1 with DHEC 12 mg). All symptoms were mild, short lasting, and self-limiting, except dyspepsia in the 1 patient given DH EC 12 mg, which was moderate and lasted until the discontinuation of t he treatment. The results of this study confirm that DHEC is effective and safe in the treatment of patients with organic psychosyndrome and suggest the usefulness of administering the drug at 20 mg/d to patien ts with a high degree of cerebral impairment.