Antidepressant shows early promise in treating agitation and psychotic symptoms of dementia
May one day offer an alternative to antipsychotic

Toronto, ONT – Researchers have found surprising evidence that an antidepressant (citalopram) may perform as well as a commonly-prescribed antipsychotic (risperidone) in the alleviation of severe agitation and psychotic symptoms of dementia. Researchers also found that the antidepressant was associated with “significantly lower” adverse side effects.
The study, published in the online American Journal of Geriatric Psychiatry (in advance of the November 2007 issue), is believed to be the first head-to-head comparison of an SSRI (selective serotonin reuptake inhibitor) with one of the more commonly prescribed second generation antipsychotics in older, non-depressed patients.
The findings are exciting because they raise the possibility of a new direction in drug treatment for psychotic disorders related to dementia in the elderly. However, the researchers caution that more studies are needed to replicate their early findings and that second generation antipsychotics continue to be a first-line pharmacological treatment, despite growing scientific evidence that they can be associated with serious side effects, including death.
“We are encouraged by this early data, but we need to learn more in further trials that include a placebo group before we can say with confidence that antidepressants are an effective and safe treatment for agitation and psychosis in patients suffering from dementia,” says lead investigator Dr. Bruce Pollock, who teamed up with colleague Dr. Benoit Mulsant to conduct the study.
Both scientists are internationally recognized for their research in geriatric psychopharmacology – the study of the effects of drugs on mood, behavior and cognition in late life. They are now with leading Toronto-based research institutes – Dr. Pollock with the Rotman Research Institute at Baycrest and the Geriatric Mental Health Program at the Centre for Addiction and Mental Health (CAMH), and Dr. Mulsant with the Geriatric Mental Health Program at CAMH. They also have academic appointments with the Department of Psychiatry, University of Toronto (UofT).
Drs. Pollock and Mulsant conducted a double-blind randomized control trial of citalopram (antidepressant) and risperidone (antipsychotic) to compare the efficacy and safety of the two drugs in 103 patients who were hospitalized with psychiatric disturbances related to dementia at the University of Pittsburgh Medical Centre.
In this 12-week clinical trial, 53 patients were given daily doses of citalopram and 50 received daily doses of risperidone. Overall, 43% of the participants completed the trial: 47% in the citalopram group and 40% in the risperidone group. The dropout rate is typical for this vulnerable population, according to Dr. Pollock, and does not undermine the scientific validity of the findings.
The researchers were surprised to find that citalopram and risperidone had similar efficacy in reducing psychosis (hallucinations, delusions, suspicious thoughts) and agitation. Overall, there was a 32% reduction of symptoms with citalopram and a 35% reduction with risperidone. Citalopram was associated with a significantly lower burden of adverse side effects, such as sedation, tension and apathy. Total side effect burden scores increased 19% for risperidone and decreased by 4% with citalopram.
“We didn’t expect that an antidepressant would have so-called antipsychotic properties,” adds Dr. Mulsant. “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).”
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The study was funded by the National Institute of Health (NIH) in the U.S. The two researchers have submitted a grant proposal on behalf of Baycrest/CAMH/UofT to the NIH for a larger, multi-centre follow-up study that will include a placebo group.
Baycrest is one of the world’s premier academic health sciences centres, focused on aging and diseases of the brain. CAMH is a Pan American Health Organization and World Health Organization Collaborating Centre. Baycrest and CAMH are fully affiliated with the University of Toronto.