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

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, 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

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).

Figures

Figure 1
Figure 1
Patient disposition (randomized sample). SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Figure 2
Figure 2
Mean MGH-SFI overall improvement score over the course of treatment by ADT group and week (safety sample, OC). ADT, antidepressant treatment; MGH-SFI, Massachusetts General Hospital Sexual Functioning Inventory; OC, observed case; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Figure 3
Figure 3
Mean change in CGI-S from baseline to Week 52 by ADT group and week (efficacy sample, OC). Mean (SE) baseline CGI-S scores: bupropion plus aripiprazole, 4.2 (0.1); SSRI/SNRI plus aripiprazole, 4.2 (0.0). ADT, antidepressant treatment; CGI-S, Clinical Global Impressions–Severity score; OC, observed case; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

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Source: PubMed

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