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@ARTICLE{Maier:151663,
      author       = {Maier, Franziska and Spottke, Annika and Bach, Jan-Philipp
                      and Bartels, Claudia and Bürger, Katharina and Dodel,
                      Richard and Fellgiebel, Andreas and Fliessbach, Klaus and
                      Frölich, Lutz and Hausner, Lucrezia and Hellmich, Martin
                      and Klöppel, Stefan and Klostermann, Arne and Kornhuber,
                      Johannes and Laske, Christoph and Peters, Oliver and
                      Priller, Josef and Richter-Schmidinger, Tanja and Schneider,
                      Anja and Shah-Hosseini, Kija and Teipel, Stefan and von
                      Arnim, Christine A. F. and Wiltfang, Jens and Jessen, Frank},
      title        = {{B}upropion for the {T}reatment of {A}pathy in {A}lzheimer
                      {D}isease},
      journal      = {JAMA network open},
      volume       = {3},
      number       = {5},
      issn         = {2574-3805},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DZNE-2020-01242},
      pages        = {e206027},
      year         = {2020},
      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},
      cin          = {Patient Studies (Bonn) / AG Teipel / AG Höglinger / AG
                      Spottke / Clinical Research (Munich) / AG Gasser / AG Peters
                      / AG Priller / AG Wiltfang / AG Jessen},
      ddc          = {610},
      cid          = {I:(DE-2719)1011101 / I:(DE-2719)1510100 /
                      I:(DE-2719)1110002 / I:(DE-2719)1011103 / I:(DE-2719)1111015
                      / I:(DE-2719)1210000 / I:(DE-2719)5000000 /
                      I:(DE-2719)5000007 / I:(DE-2719)1410006 /
                      I:(DE-2719)1011102},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32463470},
      doi          = {10.1001/jamanetworkopen.2020.6027},
      url          = {https://pub.dzne.de/record/151663},
}