A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia.

OBJECTIVE: To compare effects of risperidone with placebo (efficacy and tolerability) and haloperidol (tolerability) for treating demented patients with aggression and other behavioral symptoms. METHODS: A 13-week double-blind study involving 344 patients with dementia randomly assigned to receive placebo or flexible doses (0.5 to 4 mg/d) of risperidone or haloperidol. Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression (CGI) scale. Tolerability assessments included the Extrapyramidal Symptom Rating Scale, sedation levels, Functional Assessment Staging, Mini-Mental State Examination, and incidence of adverse events. RESULTS: The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Although not significant, a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement (> or =30% reduction from baseline to endpoint in BEHAVE-AD total score) at endpoint and week 12. Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12. In a further analysis of aggression, the most dominant symptom in these patients, BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12. CGI scores were also significantly reduced at endpoint and week 12. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12. CONCLUSION: Low-dose risperidone (mean 1.1 mg/d) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms, particularly aggression, in elderly patients with dementia.

[Circadian rhythm disorders, motivation and Alzheimer's disease]. / Troubles du rythme nycthéméral, motivation et maladie d'Alzheimer.

In Alzheimer's disease, when the breakdown of the sleep's circadian rythm is sudden, it reflects frequently a concomitant somatic or psychiatric disorder. If the trouble appears progressively, there is less pathological or disturbing behaviors in the beginning. Later, it is often associated with a loss of interest for the daily living activities (perte de motivation).

Depression and cognitive impairment in the elderly: a multicentre study.

The present study, conducted in collaboration between the Departments of Psychiatry in Swiss Universities and the World Health Organization, had two main goals: to develop assessment methods which could subsequently be used in the Swiss centres in a standard manner; and to make arrangements for continuing collaboration between the centres in Switzerland and the acquisition of new knowledge about the distinctions between depression and cognitive impairment. For this aim, three different groups of elderly patients of either sex were selected during the period of November 1989 to July 1991 for inclusion in the study. The first two groups included the first ten patients of either sex over 60 years of age consecutively contacting the participating institutions and showing depression with or without clinically significant symptoms of cognitive impairment; the control group included patients showing no depression or clinically significant symptoms of cognitive impairment. A total of 125 patients were included in the initial evaluation, 69 of which were reassessed at a seven-month follow up (on average). Each patient was administered a number of clinician-rated or self-report instruments for the assessment of depression, cognitive impairment, disabilities, physical status and onset of disorders. The study has shown that a variety of instruments can be used for the reliable assessment of depression or cognitive impairment in the elderly; but the instruments for the assessment of depression differentiate only poorly between patients with or without cognitive impairment. Because of the importance of identifying both depressed and cognitively impaired patients among the elderly, different assessment instruments targeted at the different symptom clusters need to be administered simultaneously.

Clomipramine therapy in the geriatric hospital: experience with therapeutic drug monitoring.

Sixty-nine patients, aged 63-98 years and admitted at the Geneva Geriatric Hospital, were included in the present retrospective study. They received clomipramine orally, 50 or 75 mg/day. Blood concentrations of clomipramine were measured as part of a routine drug monitoring program. Comparison with a reference population of patients aged < or = 65 years indicated that elderly patients with concomitant somatic diseases reach higher dose-normalized concentrations of clomipramine and increased parent drug to demethylated metabolite ratios, as a consequence of impaired demethylation (approximately 50%) and hydroxylation (approximately 25%). Sixty-five percent of patients showed clinical improvement, with a maximum rate of satisfactory response observed in major depression. Severe side effects, such as symptomatic hypotension or confusion, were seen in 20% of patients. Because of 10- and 15-fold interindividual variations in the concentrations of clomipramine and its metabolite, respectively, therapeutic drug monitoring can provide valuable assistance to clinical judgment in individual dose adjustment for patients whose old age, associated somatic diseases, and comedication necessitate additional precautions.