Augmentation and combination strategies for depression.
ABSTRACT Treatment-resistant depression represents a common problem, with the vast majority of depressed patients showing incomplete response to antidepressant trials. Augmentation and combination strategies are commonly employed to address this problem, but there are few randomized, controlled studies to guide treatment choice. Indeed, some of the most common augmentation strategies in depression are those with the least controlled evidence. The popularity of bupropion, psychostimulants and atypical antipsychotics as augmentors may not be warranted by existing controlled studies, whereas two less commonly used augmentors-lithium and thyroid hormone- have substantial controlled evidence to support their use. This paper summarizes the state of the evidence for commonly used augmenting strategies and explores preliminary findings for more investigational approaches.
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ABSTRACT: Objective:Recommendations for treatment of chronic major depressive disorder (cMDD) are mostly based on clinical experiences and on the literature on treatment-resistant depression (TRD) but not on a systematic review of the literature. Method: We conducted a systematic review of 10 randomized controlled trials (RCTs), with 17 comparisons between antidepressants (ADs), psychotherapy, or the combination of both interventions. Results: The best evidence is for the combination of psychotherapy and ADs, and especially for the combination of the cognitive behavourial analysis system of psychotherapy and ADs. Evidence is very weak for both ADs alone and psychotherapy alone. Assessment of TRD was mostly absent in the studies. Conclusion: The best treatment for cMDD is a combination of psychotherapy and ADs. However, there is a lack of well-performed RCTs in both ADs and psychotherapy and their combination for cMDD. Therefore, the conclusions are preliminary.Canadian journal of psychiatry. Revue canadienne de psychiatrie 07/2013; 58(7):386-92. · 2.41 Impact Factor
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ABSTRACT: The efficacy, safety, and tolerability of combined bupropion versus placebo using duloxetine as active reference drug, in patients with a DSM-IV diagnosis of major depression with atypical features and a history of treatment resistance, were evaluated in this preliminary six-week study. Patients (n=46) had a baseline Hamilton Depression Scale (HAM-D) ≥14 and were randomly assigned to 150/300 mg/day bupropion vs. placebo, which was added to 60 to 120 mg/day duloxetine depending on baseline depression severity. Atypical features of depression were assessed using the additional eight-item module of the Structured Interview Guide for the HAM-D with the Atypical Depression Supplement. By week 6, only five (21.7%) patients receiving duloxetine+placebo vs. six (26.1%) patients on the bupropion combination achieved response. No significant difference in final HAM-D scores between the two groups was observed between those patients achieving response. The presence of a higher number of atypical features significantly predicted non-response, with the relevant binary logistic regression model correctly classifying 17 out 22 (77.3%) of non-responders [Exp(B)=0.294; p=.016] vs. 17 out 23 (73.9%) [Exp(B)=0.353; p=.028] non-responder cases in the “+placebo” and “+bupropion” groups, respectively. In those patients receiving bupropion, treatment-emergent adverse events leading to withdrawal were more common among those receiving lower doses of the combination drug, and no life-threating dangers were noted. Additional studies, including an adequate course of duloxetine trial, are nonetheless aimed to allow a firm conclusion about the usefulness of the combination of duloxetine and bupropion for treatment-resistant cases of major depression with atypical features.European Neuropsychopharmacology 08/2014; DOI:10.1016/j.euroneuro.2014.04.004 · 5.40 Impact Factor