SSRI Comparable to Antipsychotic for Psychosis in Dementia

TORONTO, Sept. 10 -- An antidepressant may be just as effective as an antipsychotic for calming agitation and treating psychotic symptoms in older patients with dementia, investigators here reported.

In a small study comparing the selective serotonin reuptake inhibitor citalopram (Celexa) with the antipsychotic risperdone (Risperdal), the efficacy of the SSRI was comparable at relieving psychotic symptoms, with fewer adverse events, reported Bruce G. Pollock, M.D., Ph.D., of the University of Toronto, and colleagues.

"Contrary to our hypothesis and conventional beliefs that an antipsychotic would be superior for the treatment of psychotic symptoms, a similar improvement was observed with both citalopram (-32.3%) and risperidone

(-35.2%)," the authors wrote in an early online release from the November issue of the American Journal of Geriatric Psychiatry,

Fewer than half of the patients continued the 12-week trial, however, a finding that highlights the difficulties of pharmacotherapy in a frail population, the authors said.

Although current guidelines recommend the use of atypical antipsychotics such as risperidone for pharmacologic treatment of non-cognitive symptoms of dementia such as agitation or psychosis, "there are concerns regarding both their safety and effectiveness in patients with dementia," they wrote. "Sparse and inconclusive evidence support the use of alternative agents such as antidepressants or cognitive enhancers."

Working on the assumption that citalopram would be better at handling the symptoms of agitation and risperidone would be better at treating psychotic symptoms in patients with dementia, the authors conducted a 12-week randomized trial in 103 non-depressed patients with dementia who were hospitalized in a geropsychiatric unit because of behavioral symptoms.

Participants were included if they had at least one moderate to severe target symptom: aggression, agitation, hostility (agitation symptoms), or suspiciousness, hallucinations, or delusions (psychosis symptoms). Patients who improved sufficiently were then discharged to nursing homes, personal care homes, or residential homes for continued treatment.

The patients were randomized to either 10 mg of citalopram or 0.5 mg of risperidone, starting with one capsule at bedtime for three days and then two capsules per day. After at least two weeks, two additional increases (up to a maximum of four capsules a day) were allowed based on assessment of response and treatment-emergent side effects.

Patients could also be given up to 2 mg a day of lorazepam (Ativan) any time during the trial for extreme agitation or aggression.

Only 44% of patients completed the study, with no significant difference in dropout rates between the drug groups.

The researchers found that both the SSRI and the antipsychotic were comparably effective at reducing psychosis. Overall, there was a 32.3% reduction of psychotic symptoms with citalopram and a 35.2% reduction with risperidone.

But citalopram was associated with a significantly lower burden of adverse events (e.g., sedation, tension, apathy) on the side effects rating scale. Total side effect burden scores increased 19% with risperidone, but decreased 4% with citalopram.

The finding that an SSRI could have an antipsychotic effect was surprising, said co-author Benoit H. Mulsant, M.D.

"It reinforces our belief that psychosis and agitation have a different neurochemistry in older patients with dementia and in younger patients with schizophrenia, even though both groups of patients are currently treated with the same medications - antipsychotics," Dr. Mulsant said.

The authors noted that although their sample size was relatively small, the absolute difference between the treatments, 2.9%, was well below the 15% threshold for clinical significance that the study was powered to detect.

They acknowledged, however, that it was limited by lack of a placebo control and by the high number of dropouts - more than 50% of the patients.

"We urge caution in generalizing the results of a single trial or in extrapolating them to other drugs," they wrote. "Nonetheless, considering the better tolerability of citalopram and concerns regarding increased mortality associated with antipsychotics, 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."

Dr. Mulsant has received grants or research support from Eli Lilly, Janssen, and Pfizer, and has been a consultant or on the speaker bureau for AstraZenca, Lundbeck, and Pfizer. Dr. Pollock has received grants or research support from Janssen Pharmaceuticals, 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. Co-authors Jules Rosen, M.D. is on the speakers' bureau of Forest, Janssen, and Pfizer.

Primary source:

American Journal of Geriatric Psychiatry

Source reference:Pollock BG et al. "A Double-Blind Comparison of Citalopram and Risperidone for the Treatment of Behavioral and Psychotic Symptoms Associated with Dementia."

Am J Geriatr Psychiatry

2007; doi:10.1097/JGP.0b013e3180cc1ff5.