title: Comparison of adjunctive use of aripiprazole with bupropion or selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors: analysis of patients beginning adjunctive treatment in a 52-week, open-label study.
abstract: BACKGROUND
  This post hoc analysis assessed the safety, tolerability and effectiveness of long-term treatment with aripiprazole adjunctive to either bupropion or selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD).
  
  
  METHODS
  Data from de novo patients (did not participate in 2 previous studies) in a 52-week, open-label safety study of adjunctive aripiprazole after documented inadequate response to 1-4 antidepressant treatments (ADTs; SSRI, SNRI, or bupropion) were analyzed post hoc. Assessments included safety and tolerability, sexual functioning (Massachusetts General Hospital Sexual Functioning Inventory [MGH-SFI]) and Clinical Global Impressions-Severity (CGI-S).
  
  
  RESULTS
  Forty-seven patients received bupropion plus aripiprazole and 245 received an SSRI/SNRI plus aripiprazole; 19 (40.4%) and 78 (31.8%), respectively, completed 52 weeks of treatment, and 46 and 242, respectively, received ≥1 dose of study medication (safety sample). Median time to discontinuation (any reason) was 184.0 days. Overall, 97.8% of patients in the bupropion group and 93.8% in the SSRI/SNRI group experienced ≥1 adverse event. The most common treatment-emergent adverse events were fatigue (26.1%) and somnolence (21.7%) with bupropion and fatigue (23.6%) and akathisia (23.6%) with an SSRI/SNRI. Mean change in body weight at week 52 (observed cases) was +3.1 kg for bupropion and +2.4 kg for an SSRI/SNRI. Treatment-emergent, potentially clinically relevant abnormalities in fasting glucose occurred in 8.3% of patients with bupropion and 17.4% with an SSRI/SNRI; for abnormalities in fasting total cholesterol, the incidence was 25.0% and 34.7%, respectively. Mean (SE) change from baseline in fasting glucose was 1.4 (1.9) mg/dL with bupropion and 2.7 (1.5) mg/dL with an SSRI/SNRI. Baseline MGH-SFI item scores indicated less severe impairment with bupropion versus an SSRI/SNRI; in both groups most MGH-SFI items exhibited improvement at week 52. Mean CGI-S improvement at week 52 (last observation carried forward) was -1.4 with bupropion and -1.5 with an SSRI/SNRI (efficacy sample).
  
  
  CONCLUSIONS
  There were no unexpected AEs with long-term adjunctive aripiprazole therapy when added to either bupropion or SSRIs/SNRIs, and symptom improvement was similar between ADT groups. Sexual functioning in patients with MDD on antidepressants was also modestly improved after adding aripiprazole.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00095745 (November 9, 2004).
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, The University of Virginia, Charlottesville, 2955 Ivy Rd, Northridge Suite 210, Charlottesville VA 22903, USA. ahc8v@virginia.edu.
authors.forename: Anita H
authors.initials: AH
authors.lastname: Clayton
authors.forename: Ross A
authors.initials: RA
authors.lastname: Baker
authors.forename: John J
authors.initials: JJ
authors.lastname: Sheehan
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Cain
authors.forename: Robert A
authors.initials: RA
authors.lastname: Forbes
authors.forename: Sabrina Vogel
authors.initials: SV
authors.lastname: Marler
authors.forename: Ronald
authors.initials: R
authors.lastname: Marcus
authors.forename: Robert M
authors.initials: RM
authors.lastname: Berman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D016642:Bupropion / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012725:Sexual Behavior / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000068180:Aripiprazole; D016642:Bupropion; D009638:Norepinephrine; D010879:Piperazines; D015363:Quinolones; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors