Jamie S. Street

Efficacy of Olanzapine in the Treatment of Psychosis in Dementia with Lewy Bodies

Objective: This study sought to determine whether patients with dementia with Lewy bodies (DLB) and psychosis responded to treatment with olanzapine. Methods: This was a post hoc analysis of a subgroup of patients with DLB included in a larger double-blind, placebo-controlled, randomized parallel group trial of olanzapine for the treatment of psychosis in patients with Alzheimer’s disease. Patients meeting the consensus criteria for DLB and exhibiting parkinsonism and visual hallucinations were selected from the initial study. Psychosis was assessed with the Neuropsychiatric Inventory/Nursing Home (NPI-NH) version and the Brief Psychiatric Rating Scale (BPRS). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale. Results: Twenty-nine patients met the criteria for DLB; 10 were randomized to placebo, 5 received 5 mg of olanzapine, 7 received 10 mg of olanzapine and 7 received 15 mg of olanzapine. Patients with DLB treated with 5 mg of olanzapine showed significant reductions in delusions and hallucinations. Patients treated with 10 mg showed a significant reduction in the NPI-NH delusion subscale score. No significant differences were found between the 15-mg group and the placebo group. Confirmatory findings emerged from an analysis of the BPRS. Caregivers reported decreased disruptions in their occupational routines for the group receiving 5 or 10 mg of olanzapine. There was no significant exacerbation of parkinsonian symptoms in any study group, no decrement in Mini-Mental State Examination scores in any of the treatment groups, and symptoms suggestive of anticholinergic toxicity did not differ among treatment groups. Conclusions: This preliminary analysis suggests that olanzapine (5 or 10 mg) reduces psychosis in patients with DLB without worsening parkinsonism.

Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in nursing home patients with Alzheimer's dementia

Psychotic symptoms and behavioral disturbances are a leading cause of institutionalization in elderly patients with Alzheimers disease (AD).

Olanzapine in the treatment of anxiety symptoms due to Alzheimer's disease: a post hoc analysis

Alzheimers disease (AD) is associated with both cognitive and behavioral symptoms. Agitation, hallucinations, delusions, aggression, irritability, and anxiety are observed in up to 90% of patients with dementia. Although new information has emerged in recent years on the treatment of psychosis and agitation in dementia, very little information is available about the treatment of anxiety symptoms in this population.

532. Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in patients with Alzheimer’s dementia

(Campbell and Feinberg, 1995). Their action on sleep-endocrine regulation has never been studied in the elderly. We examined the effect of the natural NMDA-antagonist Mg in 12 elderly subjects of both gender (range 60–80 years) without sleep disturbances. A placebo controlled randomized crossover design with two treatment intervals of 20 days duration separated by 2 weeks washout was used. Mg was administered as effervescent tablets in a creeping dose of 10 mM and 20 mM each for 3 days followed by 30 mM for 14 days. At the end of each interval after an accommodation night a sleep EEG was recorded from 23.00 h to 7.00 h. Blood samples were taken every 20 min between 22.00 h and 7.00 h for the analysis of ACTH, C, R and AL. Mg led to an increase in SWS (16.5 6 20.4 min vs. 10.1 6 15.4 min, p , 0.05) and delta power. R(3.7 6 2.3 mM/ml 3 min vs. 2.3 6 1.0 mM/ml 3 min, p , 0.05) and AL(3.6 6 4.7 mM/ml 3 min vs. 1.1 6 0.9 mM/ml 3 min, p , 0.05) concentration increased throughout the night, whereas C showed a decrease in the first half of the night around the time of its nadir (8.3 6 2.4 mM/ml 3 min vs. 11.8 6 3.8 mM/ml 3 min, p , 0.01). ACTH remained unchanged. Our data suggest that Mg can reverse some age-related changes of sleep-endocrine activity, possibly via its NMDA-antagonistic effect.

Analysis of Mortality in Pergolide-Treated Patients with Parkinson's Disease

Parkinsons disease, because of its progressive degenerative nature, is associated with increased disability and mortality compared with mortality in the general population. We examined mortality data from three clinical trials involving 1,330 patients with Parkinsons disease treated with pergolide as an adjunct to levodopa or levodopa/carbidopa therapy. The ratio of observed deaths to expected deaths in the general population of the same age, gender, race distribution, and period of observation was 2.3 for the 3 studies combined. The ratio is lower than that in Parkinsons disease patients treated prior to the introduction of levodopa, consistent with ratios with levodopa and levodopa combination therapy. The ratio is slightly higher than in Parkinsons disease patients treated with levodopa and levodopa combination therapy, which may be attributable to differing patient characteristics in the populations studied.

534. Reduction of psychotic symptoms in patients with Lewy body-like symptoms treated with olanzapine

A double-blind 6-week study of nursing home patients (n 5 206) with moderate to severe dementia indicated that 5 mg/day olanzapine provided superior efficacy compared to placebo in reducing psychosis and behavioral disturbances associated with Alzheimer’s disease. Additional analyses assessed the effect of 5 mg/day olanzapine relative to placebo on psychosis and EPS in patients who had possible dementia with Lewy bodies (n 5 29) determined by a nonzero score on the Simpson-Angus Scale, a nonzero score on the Hallucinations item of the NPI/NH and no reported neuroleptic use prior to study entry. Patients treated with olanzapine had a 82.9% mean improvement in the NPI/NH Delusions and Hallucinations combined score compared to a 17.4% mean improvement for placebo (p 5 .015). On the NPI/NH Delusions item, olanzapine-treated patients had a 77.8% mean improvement, compared to a 29.0% mean improvement for placebo (p 5 .012). For all psychiatricrelated NPI/NH items, olanzapine produced at least a 3-fold improvement in scores relative to placebo. In addition, the olanzapine-treated group had an 85.7% improvement in Occupational Disruptiveness related to the NPI/NH Delusions and Hallucinations combined items while the placebo-treated group had only a 14.0% improvement (p 5 .002). Significant improvement (p 5 .042) was also found on the Mini-Mental State Exam for patients treated with olanzapine (2.4-point mean improvement) compared to placebo (0.1-point mean worsening). Changes in EPS were not clinically significantly different for patients treated with olanzapine compared to placebo.