Galantamine Versus Risperidone Treatment of Neuropsychiatric Symptoms in Patients with Probable Dementia: An Open Randomized Trial Yvonne Freund-Levi, M.D., Ph.D., Erik Jedenius, Ph.D., Ann Christine Tysen-Bäckström, R.N., Marie Lärksäter, R.N., Lars-Olof Wahlund, M.D., Ph.D., Maria Eriksdotter, M.D., Ph.D. Objective: To examine the effects of galantamine and risperidone on neuropsychi- atric symptoms in dementia (NPSD) and global function. Methods: Using a randomized, controlled and open-blind, one-center trial at an in- and outpatient clinic at a university hospital, we studied 100 adults with probable dementia and NPSD. Participants received galantamine (N ¼ 50, target dose 24 mg) or risperidone (N ¼ 50, target dose 1.5 mg) for 12 weeks. The primary outcome was effects on NPSD assessed by the Neuropsychiatric Inventory (NPI). Secondary measures included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating, Clinical Global Impression, and Simpson Angus scales. All tests were performed before and after treatment. Results: Outcome measures were analyzed using analysis of covariance. Ninety-one patients (67% women, mean age 79  7.5 years) with initial NPI score of 51.0 ( 25.8) and MMSE of 20.1 ( 4.6) completed the trial. Both galantamine and risperidone treatments resulted in improved NPSD symptoms and were equally effective in treating several NPI domains. However, risperidone showed a significant treatment advantage in the NPI domains irritation and agitation, F(1, 97) ¼ 5.2, p ¼ 0.02. Galantamine treatment also ameliorated cognitive functions where MMSE scores increased 2.8 points compared with baseline (95% confidence interval: 1.96e3.52). No treatment-related severe side effects occurred. Conclusions: These results support that galantamine, with its benign safety profile, can be used as first- line treatment of NPSD symptoms, unless symptoms of irritation and agitation are prominent, where risperidone is more efficient. (Am J Geriatr Psychiatry 2013; -:-e-) Key Words: Neuropsychiatric symptoms, dementia, NPSD, NPI, galantamine, risperidone Received August 26, 2012; revised April 25, 2013; accepted May 15, 2013. From the Division of Clinical Geriatrics, Department of Neuro- biology, Caring Sciences and Society (NVS) (YF-L, EJ, L-OW, ME), Karolinska Institutet, Stockholm, Sweden; and Department of Geriatric Medicine (YF-L, ACT-B, ML, L-OW, ME), Karolinska University Hospital, Stockholm Sweden. Send correspondence and reprint requests to Yvonne Freund-Levi, M.D., Ph.D., Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, SE, 146 86 Stockholm, Sweden. e-mail: Yvonne.Freund-Levi@ki.se Ó 2013 American Association for Geriatric Psychiatry http://dx.doi.org/10.1016/j.jagp.2013.05.005 FLA 5.2.0 DTD  AMGP257_proof  5 September 2013  6:26 pm  ce Am J Geriatr Psychiatry -:-, - 2013 1