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A Double-Blind Comparison of Citalopram and Risperidone for the Treatment of Behavioral and Psychotic Symptoms Associated With Dementia

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Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Section snippets

Setting and Participants

Participants of this 12-week clinical trial were recruited upon admission to the geropsychiatric unit of an academic hospital providing treatment to a large urban and suburban population. If they improved sufficiently, participants were discharged to nursing homes, personal care homes, or residential homes for continued treatment under double-blind conditions.

Admissions were eligible if they had a dementia of the Alzheimer type (DAT), vascular dementia, dementia with Lewy bodies, mixed

RESULTS

Of the randomized participants, 53 were randomized to citalopram and 50 to risperidone. The sex distribution and baseline NBRS total scores differed significantly between the two groups (Table 1). Thirty participants continued a stable dose of a cholinesterase inhibitor: 16 (30.2%) randomized to citalopram and 14 (28.0%) randomized to risperidone (Fisher exact p = 0.83). No participant was on memantine during the study. Mean (SD) maximum doses were 31.1 (8.7) mg/day of citalopram and 1.36

DISCUSSION

In patients with dementia hospitalized for the treatment of behavioral or psychotic symptoms, citalopram and risperidone had similar efficacy but citalopram was associated with a lower burden of side effects. To our knowledge, this study is the first head-to-head comparison of a selective serotonin reuptake inhibitor (SSRI) and a second-generation (atypical) antipsychotic in the treatment of noncognitive symptoms associated with dementia. Contrary to our hypothesis and conventional beliefs that

CONCLUSION

We urge caution in generalizing the results of a single trial or in extrapolating them to other drugs. Nonetheless, considering the better tolerability of citalopram and concerns regarding increased mortality associated with antipsychotics,5., 6. our findings should encourage the conduct of additional trials of citalopram and other agents in the treatment of behavioral and psychotic symptoms associated with dementia. Given the current view of questionable risk-benefit ratio of second-generation

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    This work was supported by grants from the U.S. Public Health Service (MH59666, MH65416, MH69430, M01RR0056) and the Sandra A. Rotman Program in Neuropsychiatry (Toronto).

    Presented in part at the 159th Annual Meeting of the American Psychiatric Association, Toronto, Ontario, Canada, May 20 to 25, 2006.

    The authors thank Jennifer Maurer of the University of Pittsburgh Medical Center for database management, and Christina Pataky of the Rotman Research Institute at Baycrest for assistance in preparation of the manuscript.

    This trial is registered at Clinical Trials.gov (http://www.clinicaltrials.gov/); identifier:NCT00073658.

    Richard Blakesley, Kimberly Huber, and Patricia Houck have no conflicts of interest or financial interests to disclose. Sati Mazumdar has directly purchased stocks of Forest. Benoit Mulsant has received grants or Research Support from the National Institute of Health, Eli Lilly, Janssen, and Pfizer. He has been a consultant for Lundbeck and Pfizer. He is on the speakers' bureau of AstraZeneca and Pfizer. He has directly purchased stocks (all below $10,000) of Akzo-Nobel, Alkermes, AstraZeneca, Biogen Idec, Celsion, Elan, Eli Lilly, Forest, General Electric, Immune Response, Pfizer. Bruce Pollock has received grants or research support from the National Institute of Health and Janssen Pharmaceuticals. He has served on the advisory board of Forest Laboratories and is a faculty member of the Lundbeck Institute. He is on the speakers' bureau of Forest and Lundbeck. Jules Rosen is on the speakers' bureau of Forest, Janseen, and Pfizer. He has directly purchased stocks of Forest.

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