Bupropion for the treatment of apathy in Huntington’s disease: A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

Abstract

ObjectiveTo evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington’s disease (HD).MethodsIn 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).ResultsAt 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.ConclusionBupropion 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.Trial registrationClinicalTrials.gov 01914965

Pharmacologic Approaches for the Management of Apathy in Neurodegenerative Disorders

“…In Huntington disease, the use of bupropion (a norepinephrine dopamine reuptake inhibitor) did not show a significant effect in reducing levels of apathy, globally or by domain (cognitive, behavioral, and emotional) (Gelderblom et al, 2017). This RCT targeting apathy as primary outcome (using the Apathy Evaluation Scale AES) over a 10-week period of treatment with bupropion (150 or 300 mg/day vs placebo).…”

Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD)

“…This was not seen and is in line with a recent trial showing that bupropion was ineffective for treating this symptom. 34 However, randomised controlled trials, which include detailed scales to assess these conditions, are needed to more thoroughly explore the role of DA in depression and apathy in HD.…”

Leitlinien „Chorea/Morbus Huntington“ für die deutschsprachigen Länder neu überarbeitet

“…Bislang gibt es keine evidenzbasierte Behandlung der Apathie bei der Huntington-Erkrankung. In Einzelfällen wurden Bupropion und Modafinil eingesetzt, eine Phase-II-Studie (NCT01914965) erbrachte aber keinen Wirksamkeitsnachweis für Bupropion [4].…”

“…▪ Eine Verbesserung der klinischen Symptomatik durch den Phosphodiesterase-10a-Hemmer PF-02545920 konnte nicht nachgewiesen werden; der primäre Endpunkt wurde nicht erreicht. ▪ Eine randomisierte, kontrollierte Phase-II-Studie zur Behandlung von Apathie bei der Huntington-Erkrankung mit Bupropion (NCT01914965) konnte den primären Endpunkt nicht erreichen [4]. ▪ In einer randomisierten, placebokontrollierten Phase-II-Studie konnte bei HK-Patienten keine Symptomverbesserung durch Memantine nachgewiesen werden (MITIGATE-HD, NCT01458470).…”