Pilot study of haloperidol, fluoxetine, and placebo for agitation in Alzheimer's disease. Fluvoxamine in the treatment of demented elderly patients: a double-blind, placebo-controlled study. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders. A Nordic multicentre study. A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Sertraline versus small doses of haloperidol in the treatment of agitated behavior in patients with dementia.
This pilot study compared haloperidol, fluoxetine, and placebo for reduction of agitation in 15 outpatients with AD. The two drugs were no more effective than placebo at reducing agitation in these subjects; however, both drugs produced more toxicity than did placebo. The efficacy of fluvoxamine on cognitive functioning and behavioral changes was evaluated in a double-blind, placebo-controlled study of 46 elderly demented patients. The patients had a DSM-III diagnosis of primary degenerative dementia or multi-infarct dementia and were aged greater than or equal to 65 years. Twenty-two patients were given 150 mg fluvoxamine per day and 24 received placebo tablets; 14 and 15 patients, respectively, completed 6 weeks of treatment. Within treatments, there were no significant changes in median scores on neuropsychological tests (picture recall and recognition, trail making and finger tapping) or the GBS scale scores (degrees of dementia) or GBS subscale score (clinical profiles, including symptoms common in dementia, motor, emotional and intellectual functioning). Between treatments, the median changes in psychometric test scores did not differ significantly. However, within and between treatments, there were trends favoring fluvoxamine on symptoms common in dementia (confusion, irritability, anxiety, fear-panic, mood level and restlessness). In conclusion, the study does not support the hypothesis that fluvoxamine improves cognitive functioning or behavioral changes in elderly dementia patients. To compare citalopram and risperidone for the treatment of psychotic symptoms and agitation associated with dementia, with a priori hypotheses that risperidone would be more efficacious for psychosis and citalopram for agitation.
                A 12-week randomized, controlled trial in nondepressed patients with dementia hospitalized because of behavioral symptoms (N = 103) was conducted at the University of Pittsburgh Medical Center. Participants were consecutively recruited on an inpatient unit if they had at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions). Once they improved sufficiently, they were discharged to nursing homes, personal care homes, or residential homes for continued treatment. Planned pre-post and mixed model analyses of the main outcome measures of Neurobehavioral Rating Scale and Side Effect Rating Scale at baseline and at weekly/biweekly intervals were conducted.
                Completion rates did not differ for citalopram and risperidone (overall completion rate: 44%). Agitation symptoms (aggression, agitation, or hostility) and psychotic symptoms (suspiciousness, hallucinations, or delusions) decreased in both treatment groups but the improvement did not differ significantly between the two groups. There was a significant increase in side effect burden with risperidone but not with citalopram such that the two groups differed significantly.
                No statistical difference was found in the efficacy of citalopram and risperidone for the treatment of either agitation or psychotic symptoms in patients with dementia. These findings need to be replicated before citalopram or other serotonergic antidepressants can be recommended as alternatives to antipsychotics for the treatment of agitation or psychotic symptoms associated with dementia. In this multicenter study, the clinical efficacy of citalopram was investigated in 98 patients with moderate AD/SDAT or VD using a combined double-blind and open technique with placebo and citalopram. Analyses were made for each diagnosis after four weeks of double-blind treatment. Patients with AD/SDAT treated with citalopram showed a significant improvement in emotional bluntness, confusion, irritability, anxiety, fear/panic, depressed mood and restlessness. Those improvements were not found after treatment with placebo. There were no significant improvements in patients with VD. No improvements were recorded in motor or cognitive impairment. Citalopram provoked few and comparatively mild side-effects. None of the changes observed during the double-blind withdrawal period were identified as withdrawal symptoms or rebound phenomena. The authors compared the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia. Twenty-eight elderly patients with dementia and agitated behaviors were randomly assigned to double-blind treatment with either trazodone (50-250 mg/day) or haloperidol (1-5 mg/day) for 9 weeks. There was no significant difference in improvement between the medication groups. Adverse effects, however, were more common in the group treated with haloperidol. Improvement in individual areas suggested that repetitive, verbally aggressive, and oppositional behaviors responded preferentially to trazodone, whereas symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol. These results indicate that moderate doses of trazodone and haloperidol are equally effective for treatment of overall agitated behaviors in patients with dementia, but specific symptoms may respond preferentially to a particular agent. Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs.
                To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients.
                A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden.
                Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments.
                Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed. nan
Currently there are relatively few studies of antidepressants for the treatment of agitation and psychosis in dementia. The SSRIs sertraline and citalopram were associated with a reduction in symptoms of agitation when compared to placebo in two studies. Both SSRIs and trazodone appear to be tolerated reasonably well when compared to placebo, typical antipsychotics and atypical antipsychotics. Future studies involving more subjects are required to determine if SSRIs, trazodone, or other antidepressants are safe and effective treatments for agitation and psychosis in dementia.