Year: 2020
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed. Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type. Design, Setting, and Participants: This 12-week, multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in a psychiatric and neurological outpatient setting between July 2010 and July 2014 in Germany. Patients with mild-to-moderate dementia of Alzheimer type and clinically relevant apathy were included. Patients with additional clinically relevant depressed mood were excluded. Data analyses were performed between August 2018 and August 2019. Interventions: Patients received either bupropion or placebo (150 mg for 4 weeks plus 300 mg for 8 weeks). In case of intolerability of 300 mg, patients continued to receive 150 mg throughout the study. Main Outcomes and Measures: Change on the Apathy Evaluation Scale-Clinician Version (AES-C) (score range, 18-72 points) between baseline and week 12 was the primary outcome parameter. Secondary outcome parameters included measures of neuropsychiatric symptoms, cognition, activities of daily living, and quality of life. Outcome measures were assessed at baseline and at 4, 8, and 12 weeks. Results: A total of 108 patients (mean [SD] age, 74.8 [5.9] years; 67 men [62%]) were included in the intention-to-treat analysis, with 54 randomized to receive bupropion and 54 randomized to receive placebo. The baseline AES-C score was comparable between the bupropion group and the placebo group (mean [SD], 52.2 [8.7] vs 50.4 [8.2]). After controlling for the baseline AES-C score, site, and comedication with donepezil or galantamine, the mean change in the AES-C score between the bupropion and placebo groups was not statistically significant (mean change, 2.22; 95% CI, -0.47 to 4.91; P = .11). Results on secondary outcomes showed statistically significant differences between bupropion and placebo in terms of total neuropsychiatric symptoms (mean change, 5.52; 95% CI, 2.00 to 9.04; P = .003) and health-related quality of life (uncorrected for multiple comparisons; mean change, -1.66; 95% CI, -3.01 to -0.31; P = .02) with greater improvement in the placebo group. No statistically significant changes between groups were found for activities of daily living (mean change, -2.92; 95% CI, -5.89 to 0.06; P = .05) and cognition (mean change, -0.27; 95% CI, -3.26 to 2.73; P = .86). The numbers of adverse events (bupropion group, 39 patients [72.2%]; placebo group, 33 patients [61.1%]) and serious adverse events (bupropion group, 5 patients [9.3%]; placebo group, 2 patients [3.7%]) were comparable between groups. Conclusions and Relevance: Although it is safe, bupropion was not superior to placebo for the treatment of apathy in patients with dementia of Alzheimer type in the absence of clinically relevant depressed mood. Trial Registration: EU Clinical Trials Register Identifier: 2007-005352-17.
Source: JAMA Network Open
Authors: Franziska Maier, Annika Spottke, Jan-Philipp Bach, Claudia Bartels, Katharina Buerger, Richard Dodel, Andreas Fellgiebel, Klaus Fliessbach, Lutz Frölich, Lucrezia Hausner, Martin Hellmich, Stefan Klöppel, Arne Klostermann, Johannes Kornhuber, Christoph Laske, Oliver Peters, Josef Priller, Tanja Richter-Schmidinger, Anja Schneider, Kija Shah-Hosseini, Stefan Teipel, Christine A. F. von Arnim, Jens Wiltfang, Frank Jessen
Institutions: University Hospital Cologne, University of Bonn, German Center for Neurodegenerative Diseases, Philipps University of Marburg, Essen University Hospital, Universitätsmedizin Göttingen, University of Göttingen, Institut für Schlaganfall- und Demenzforschung, Ludwig-Maximilians-Universität München, University Medical Center of the Johannes Gutenberg University Mainz, Heidelberg University, Central Institute of Mental Health, University of Cologne, University of Bern, Stiftung Charité, Charité – Universitätsmedizin Berlin, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hertie Institute for Clinical Brain Research, University of Tübingen, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Universitätsmedizin Rostock, University Hospital Ulm
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funder: Biogen
OpenAlex ID: W3032608964