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.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT00095745 (November 9, 2004).

• Authors: Anita H Clayton, Ross A Baker, John J Sheehan, Zachary J Cain, Robert A Forbes, Sabrina Vogel Marler, Ronald Marcus, Robert M Berman, Michael E Thase
• Journal: BMC research notes (BMC Res Notes) Vol. 7 Pg. 459 (Jul 18 2014) ISSN: 1756-0500 [Electronic] England
• PMID: 25037144 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antidepressive Agents
• Piperazines
• Quinolones
• Serotonin Uptake Inhibitors
• Bupropion
• Serotonin
• Aripiprazole
• Norepinephrine

Topics

• Adult
• Antidepressive Agents (therapeutic use)
• Aripiprazole
• Bupropion (therapeutic use)
• Depressive Disorder, Major (drug therapy, metabolism, physiopathology)
• Drug Therapy, Combination
• Female
• Humans
• Male
• Middle Aged
• Norepinephrine (metabolism)
• Piperazines (therapeutic use)
• Quinolones (therapeutic use)
• Serotonin (metabolism)
• Selective Serotonin Reuptake Inhibitors (therapeutic use)
• Sexual Behavior (drug effects)
• Treatment Outcome