Treating Depression After Initial Treatment Failure Directly Comparing Switch and Augmenting Strategies in STAR*D

Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Journal of clinical psychopharmacology (Impact Factor: 5.09). 12/2011; 32(1):114-9. DOI: 10.1097/JCP.0b013e31823f705d
Source: PubMed

ABSTRACT Augmenting and switching antidepressant medications are the 2 most common next-step strategies for depressed patients failing initial medication treatment. These approaches have not been directly compared; thus, our objectives are to compare outcomes for medication augmentation versus switching for patients with major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial.
We conducted a retrospective analysis of participants aged 18 to 75 years with DSM-IV nonpsychotic depression who failed to remit with initial treatment in the STAR*D clinical trial (N = 1292). We compared depressive symptom remission, response, and quality of life among participants in each study arm using propensity score matching to minimize selection bias.
The propensity-score-matched augment (N = 269) and switch (N = 269) groups were well balanced on measured characteristics. Neither the likelihood of remission (risk ratio, 1.14; 95% confidence level, 0.82-1.58) or response (risk ratio, 1.14; 95% confidence level, 0.82-1.58), nor the time to remission (log-rank test, P = 0.946) or response (log-rank test, P = 0.243) differed by treatment strategy. Similarly, quality of life did not differ. Post hoc analyses suggested that augmentation improved outcomes for patients tolerating 12 or more weeks of initial treatment and those with partial initial treatment response.
For patients receiving and tolerating aggressive initial antidepressant trials, there is no clear preference for next-step augmentation versus switching. Findings tentatively suggest that those who complete an initial treatment of 12 weeks or more and have a partial response with residual mild depressive severity may benefit more from augmentation relative to switching.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Few studies have compared simultaneously different antidepressants in long-term treatment of major depressive disorder (MDD). Long-term prevention of recurrences should be the main goal of MDD treatment. The purpose of this study was to compare antidepressants of different pharmacological classes in terms of retention in treatment (no discontinuation for recurrences, hospitalizations, side effects). Methods One hundred and fifty outpatients with an MDD diagnosis, treated with antidepressants in mono-therapy, were included. Follow-up period was set at 24months, and information have been obtained from charts, interviews with patients and their relatives, and from the Lombardy regional register. A survival analysis (Kaplan-Meier) was performed, considering recurrences, hospitalizations, or discontinuation due to side effects as death' events. ResultsIn our sample, 48.7% of the patients presented a recurrence within the first 2years of treatment. Bupropion appears less effective in long-term treatment of MDD than the other compared antidepressants, with exception of fluoxetine (p=0.09), amitriptyline (p=0.13), fluvoxamine (p=0.83), venlafaxine (p=0.5), and trazodone (p=0.58). Fluvoxamine appears to be less effective than citalopram (p=0.036), paroxetine (p=0.037), clomipramine (p=0.05), sertraline (p=0.011), and duloxetine (p=0.024). Conclusions Bupropion and fluvoxamine appear less effective in long-term treatment of MDD. These results should be confirmed by randomized placebo-controlled prospective studies with larger samples. Copyright (c) 2014 John Wiley & Sons, Ltd.
    Human Psychopharmacology Clinical and Experimental 01/2015; 30(1). DOI:10.1002/hup.2447 · 2.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Major depressive disorder (MDD) is a highly prevalent chronic psychiatric illness associated with significant morbidity, mortality, loss of productivity, and diminished quality of life. Typically, only a minority of patients responds to treatment and meet criteria for remission as residual symptoms may persist, the result of an inadequate course of treatment and/or the presence of persistent side effects. The foremost goal of treatment should be to restore patients to full functioning and eliminate or relieve all MDD symptoms, while being virtually free of troublesome side effects. The current available pharmacological options to manage persistent depressive symptoms include augmentation or adjunctive combination strategies, both of which target selected psychobiological systems and specific mood and somatic symptoms experienced by the patient. As well, non-pharmacological interventions including psychotherapies may be used in either first-line or adjunctive approaches. However, the evidence to date with respect to available adjunct therapies is limited by few studies and those published have utilized only a small number of subjects and lack enough data to allow for a consensus of expert opinion. This underlines the need for further longer term, large population-based studies and those that include comorbid populations, all of which are seen in real world community psychiatry. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research 12/2014; 220S1:S15-S33. DOI:10.1016/S0165-1781(14)70003-4 · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The efficacy of adjunctive aripiprazole in patients with major depressive disorder (MDD) with no improvement after 8 weeks of prior antidepressant monotherapy has not been evaluated.MethodsA post hoc analysis of three similarly designed, randomised, double-blind, placebo-controlled, phase III studies was conducted investigating the efficacy and safety of aripiprazole adjunctive to standard antidepressant treatment (ADT) in MDD patients with a prior inadequate response to one to three ADTs. Minimal improvement to antidepressant monotherapy was defined as a Clinical Global Impressions – Improvement (CGI-I) score of 3 and non-improvement as a CGI-I of 4 at weeks 6 and 8 of antidepressant monotherapy.ResultsThe end-point response rate for ADT minimal improvers receiving adjunctive aripiprazole was 38.8% vs. 26.6% for adjunctive placebo (p < 0.05; number needed to treat [NNT] = 9 [95% confidence interval: 4.8–27.7]), and for ADT non-improvers receiving adjunctive aripiprazole was 24.0% vs. 10.3% for adjunctive placebo (p < 0.05; NNT = 8 [95% confidence interval: 4.4–21.5]). ADT minimal improvers and non-improvers demonstrated significant improvements in response vs. ADT alone as early as after 1 and 2 weeks of adjunctive treatment, respectively. The end-point remission rate for ADT minimal improvers receiving adjunctive aripiprazole was 34.2% vs. 21.0% for adjunctive placebo (p < 0.05; NNT = 8), and for ADT non-improvers receiving adjunctive aripiprazole was 16.0% vs. 5.9% for adjunctive placebo (p < 0.05; NNT = 10). The most common adverse events for ADT minimal improvers and non-improvers receiving adjunctive aripiprazole were akathisia, restlessness and insomnia.Conclusion Patients with minimal or no improvement after 8 weeks of antidepressant monotherapy significantly benefited from adjunctive aripiprazole treatment, supporting the efficacy of this treatment for MDD patients with all levels of response to ADT.
    International Journal of Clinical Practice 09/2014; 68(11). DOI:10.1111/ijcp.12480 · 2.54 Impact Factor