By Chris Berrie
PRAGUE, Czech Republic -- March 16, 2009 -- Galantamine shows good safety and tolerability and generally equal effects to risperidone in the treatment of behavioural and psychological symptoms of dementia (BPSD), according to a randomised, parallel-group, controlled, phase 2 study.
The findings were presented on March 15 here at the 9th International Conference on Alzheimer's and Parkinson's Diseases (ADPD).
"Alzheimer's disease [AD] affects 10% to 15% of the population over the age of 65 years, and the number affected by AD is estimated to be 100 million individuals by the 2050s," noted principal investigator Yvonne Freund-Levi, MD, PhD, Section of Clinical Geriatrics, Karolinska University Hospital, NOVUM Karolinska Institute, Stockholm.
Although more than 50% of patients with AD show BPSD, currently available therapies provide limited symptomatic benefits for both cognitive and neuropsychiatric symptoms, Dr. Freund-Levi said in a presentation.
Treatment of BPSD involves the use of acetylcholinesterase inhibitors, but these agents appear to have effects mainly on apathy, anxiety, and depression, she said.
Therefore, Dr. Freund-Levi and her colleagues conducted their study to compare the standard treatment, risperidone, with the alternative acetylcholinesterase inhibitor galantamine in the control of BPSD.
They enrolled 100 patients aged more than 45 years diagnosed with BPSD, Neuropsychiatric Inventory (NPI) score greater than 10, and cognitive dysfunction, defined as a Mini-Mental State Examination (MMSE) score of 10 to 25. They excluded patients with other psychiatric disorders or severe somatic disease.
Patients were randomised to up-titration of risperidone at 0.25 mg daily on week 1, 0.5 mg on week 2, and 1.0 mg on weeks 3 to 12, or to galantamine 4 mg daily on week 1, 8 mg on week 2, and 12 mg on weeks 3 to 12.
The primary outcome measure was the NPI score, with particular focus on cognitive defects, aggressiveness, depression, agitation, hallucinations, delusions, and apathy. Secondary outcomes included the treatment's impact on patient neuropsychiatric status and caregiver burden (using the Psychological General Well-Being Index [PGWBI]).
Patient baseline characteristics were similar in the risperidone and galantamine groups: mean age was 78 and 80 years, respectively; women made up 60% and 66% of the groups, respectively; and apolipoprotein E E4 carriers made up 65% and 52% of the groups, respectively.
Diagnostic characteristics were mild cognitive impairment (8% and 16%, respectively); early/late/mixed AD (2%/28%/26% and 2%/34%/30%, respectively); Lewy body dementia (2% and 2%, respectively); and other dementias (34% and 16%, respectively).
Nine patients dropped out of the trial, with no treatment bias.
Within the NPI, risperidone showed significantly better treatment effects for irritation and agitation (P = .02), with a positive trend for aberrant motor behaviour (P = .08). Conversely, galantamine showed positive trends over risperidone for appetite (P = .06), sleeping disorders (P = .07), and apathy (P = .09).
Within the Cohen-Mansfield Agitation Inventory, risperidone treatment saw significant benefits for verbal aggressive behaviour (P = .01). Significant improvement was seen in the MMSE score with galantamine (P < .001) that was not seen with risperidone, and although the PGWBI showed improvements with both treatments, there were no significant different between treatments.
Dr. Freund-Levi concluded, "Our data suggest that galantamine could be used as a first line treatment of BPSD, unless we have prominent aggressive symptoms."
Funding for this study was provided by Janssen-Cilag.
[Presentation title: Galantamine Compared to Risperidone in BPSD Symptoms: A One-Centre Clinical Trial in 100 Patients.]
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