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Objective: To examine the effect of risperidone on specific behavioral and psychological symptoms of dementia (BPSD)., Method: We conducted a post hoc exploratory analysis of an integrated database from 3 randomized, controlled trials of risperidone versus placebo in treating 1150 nursing home residents with BPSD. Changes in scores were measured for items on the Cohen-Mansfield Agitation Inventory (CMAI) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD)., Results: On the CMAI, risperidone was significantly more effective in treating hitting (p = .000), hurt self or other (p = .005), cursing or verbal aggression (p = .000), repetitive sentences or questions (p = .001), scratching (p = .041), general restlessness (p = .001), grabbing onto people (p = .028), constant request for attention (p = .041), pacing and aimless wandering (p = .013), and performing repetitious mannerisms (p = .045). On the BEHAVE-AD, risperidone was significantly more effective in treating physical threats and/or violence (p = .000), verbal outbursts (p = .000), other anxieties (p = .01), agitation (p = .000), tearfulness (p = .03), and nonparanoid delusions (p = .02)., Conclusions: The items from the BEHAVE-AD and CMAI that were improved with risperidone included psychotic, agitated, and aggressive symptoms. These data suggest that risperidone is more effective than placebo in treating a variety of symptoms associated with dementia.

Background: In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents., Method: The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial., Results: Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers., Conclusion: In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.

Background: We report the findings from the first large, double-blind, placebo-controlled study conducted to evaluate the efficacy and safety of risperidone in the treatment of psychotic and behavioral symptoms in institutionalized elderly patients with dementia., Method: 625 patients (67.8% women; mean age = 82.7 years) with DSM-IV diagnoses of Alzheimer's disease (73%), vascular dementia (15%), or mixed dementia (12%) and significant psychotic and behavioral symptoms were included. Each patient was randomly assigned to receive placebo or 0.5 mg/day, 1 mg/day, or 2 mg/day of risperidone for 12 weeks. The primary outcome measure was the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD)., Results: The study was completed by 70% of the patients. Baseline Functional Assessment Staging scores were 6 or 7 in more than 95% of the patients, indicating severe dementia. At endpoint, significantly greater reductions in BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day of risperidone than in placebo patients (p = .005 and p < .001, respectively). At week 12, 0.5 mg/day of risperidone was superior to placebo in reducing BEHAVE-AD aggression scores (p = .02). More adverse events were reported by patients receiving 2 mg/day of risperidone than 1 mg/day. The most common dose-related adverse events were extrapyramidal symptoms, somnolence, and mild peripheral edema. The frequency of extrapyramidal symptoms in patients receiving 1 mg/day of risperidone was not significantly greater than in placebo patients., Conclusion: Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia. Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia.

Depressive disorders--both major depression and other less severe but nonetheless clinically significant depressions--are common comorbidities, components, or complications of dementia. Depression with reversible cognitive impairment may be a prodrome for dementia rather than a separate and distinct disorder. Recent research has demonstrated that both the diagnosis of major depression and the assessment of typical depressive symptoms can be conducted reliably, even in patients with mild-to-moderate levels of cognitive impairment. Self-ratings of depressive symptoms with the Geriatric Depression Scale remain valid in patients with Mini-Mental State Examination scores of at least 15. Among interviewer-administered instruments, the Hamilton Rating Scale for Depression and the Cornell Scale are the best established. Potential difficulties with assessment include problems with ascertainment (because families, in general, report greater depression in patients than do clinicians) and the ambiguity of symptoms (because apathy and related symptoms can result from both depression and Alzheimer's disease). Brain changes due to Alzheimer's disease may lead to fundamental differences in drug responses. Nevertheless, randomized clinical trials have demonstrated that depression in dementia responds to specific psychopharmacologic or psychosocial treatments.

A significant drug-placebo difference was found in a double-blind, placebo-controlled study of nortriptyline for treatment of major depression among frail elderly patients living in an institutional setting. This finding confirms the validity of the DSM-III-R diagnosis of major depression and establishes the need for specific psychiatric services for the chronically ill elderly living in nursing homes and congregate housing facilities. The incidence of adverse events requiring early termination of treatment was 34%, demonstrating the vulnerability of these patients and their need for careful monitoring during treatment. High levels of self-care disability and low levels of serum albumin were both associated with decreased therapeutic responses, demonstrating the need for further research on psychopathology in these settings.

Seven schizophrenic (according to DSM-III criteria) inpatients completed a two-phase study; each phase had a 1-week drug-free period followed by 6 weeks of a drug trial. The first phase uniformly involved treatment with chlorpromazine, and in the second phase patients received either mesoridazine (N = 3) or thioridazine (N = 4). Clinical ratings (Brief Psychiatric Rating Scale and Clinical Global Impressions) and neuroleptic blood levels were obtained weekly throughout the study. Whereas patients failed to respond to chlorpromazine 1800 mg/day, response to mesoridazine 400 mg/day and to thioridazine 800 mg/day was established on all Brief Psychiatric Rating Scale factors except for anxiety-depression. A higher neuroleptic blood level was achieved with mesoridazine or thioridazine at less than half the reference chlorpromazine dosage. Correlations between neuroleptic blood level and clinical response were positive for mesoridazine, negative for chlorpromazine, and nonsignificant for thioridazine. These findings are consistent with earlier research. We conclude that drug-resistant schizophrenics seem to improve clinically with mesoridazine or thioridazine, unlike with chlorpromazine, and that for mesoridazine this difference may be a function of selective dopamine receptor blockade.

Impairment of memory by muscarinic anticholinergic drugs has been demonstrated with a variety of agents using both acute administration in normal volunteers and chronic treatment in patients. Cognitive toxicity must be considered in the evaluation of the risks versus the benefits of psychopharmacologic treatment. The relationship between serum levels of anticholinergic drugs measured by radioreceptor assay and performance on the Buschke Selective Reminding Test were investigated to develop strategies for identifying patients with drug-related cognitive impairment. The radioreceptor assay may be of value in screening for patients at high risk for cognitive toxicity. However, there appears to be no alternative to careful longitudinal evaluation of learning and memory in patients after appropriate trial modifications of their medication regimens to identify patients with drug-related impairment.