Bupropion for the treatment of apathy in Huntington's disease: A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial.
OBJECTIVE
To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD).


METHODS
In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI).


RESULTS
At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator.


CONCLUSIONS
Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD.


BACKGROUND
ClinicalTrials.gov 01914965.
Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Harald
H
Gelderblom
Department of Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Torsten
T
Wüstenberg
European Huntington's Disease Network, Ulm, Germany.
Tim
T
McLean
European Huntington's Disease Network, Ulm, Germany.
Lisanne
L
Mütze
Department of Neurology, University of Ulm, Ulm, Germany.
Wilhelm
W
Fischer
Department of Neurology, Huntington-Center NRW, St. Josef Hospital, Ruhr-University, Bochum, Germany.
Carsten
C
Saft
Department of Neurology, Huntington-Center NRW, St. Josef Hospital, Ruhr-University, Bochum, Germany.
Rainer
R
Hoffmann
European Huntington's Disease Network, Ulm, Germany.
Sigurd
S
Süssmuth
Institute of Medical Statistics, Computer Sciences and Documentation, Jena Universityhospital, Jena, Germany.
Peter
P
Schlattmann
Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands.
Erik
E
van Duijn
European Huntington's Disease Network, Ulm, Germany.|Department of Neurology, University of Ulm, Ulm, Germany.
Bernhard
B
Landwehrmeyer
Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Cluster of Excellence NeuroCure, DZNE and BIH, Berlin, Germany.
Josef
J
Priller
D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D057565:Apathy / Q000187:drug effects*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D016642:Bupropion / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012201:Reward; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion