Comparing Augmentation with Non-Antidepressants over Sticking to Antidepressants after Treatment Failure in Depression: A Naturalistic Study

Abstract

Introduction: Non-response to an antidepressant monotherapy in unipolar depression is quite common. Therefore strategies for subsequent treatment steps are necessary. However, there is a lack of direct comparisons of these different strategies. In this naturalistic study we compared the outcome to different strategies after failure of the primary antidepressant treatment. Methods: Failure of primary antidepressant monotherapy occurred in 135 patients. 98 of these patients have been administered 4 treatment strategies of the physicians? choice: lithium augmentation (Li-Augm), switching to another antidepressant (AD-Switch), combination of 2 antidepressants (AD-Comb) or augmentation with second generation antipsychotic (SGA-Augm). Primary outcome measure was the 17-item Hamilton rating scale for depression (HRSD). Results: Patients who received Li-Augm or augmentation with SGAs showed significantly greater improvement in HRSD and BDI compared to patients with antidepressant switch or antidepressant combination. Remission rates for Li-Augm and SGA-Augm were 89.3% and 86.2% compared to 40.7% for AD-Switch and 42.9% for AD-Comb. Discussion: Changing to another pharmacological class (Li-Augm or augmentation with SGAs) showed better treatment results than sticking to the class of antidepressants (AD-Switch and AD-Comb) after primary failure in response to antidepressant monotherapy in unipolar depression. The lack of randomization and absence of a non-response definition are design flaws. Controlled studies are required to confirm the findings of this trial.

Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: From Clinical Trials to Clinical Practice

“…However, the small sample size (total n=98) is an important limitation of this study. 28 In line with the findings by Köhler et al, 28 a recent Korean naturalistic study 55 also found that patients have chosen AA therapy more than antidepressant combination and switching therapies when experiencing nonresponse to initial antidepressant treatment. In addition, AA therapy was shown to have more clinical benefit than antidepressant combination and switching.…”

“… 27 Anecdotal data support the usefulness of switching or combining antidepressant strategies; however, few clinical trials of such therapies have been conducted and the results are inconsistent. 18 28 29 30 31 32 A number of small RCTs have investigated the efficacy of switching therapy for depression (10 RCTs and 30 open-label studies). 27 33 34 35 According to these controlled clinical trials, the remission rates after switching therapy ranged from 10% to 80%.…”

“…According to a recent survey study, 59 the rates of AAs used for MDD in Taiwan were aripiprazole (78.2%), quetiapine (62%), olanzapine (34.6%), risperidone (30.2%), and sulpiride (27.4%) which is in line with previous studies. 28 60 However, no direct comparison studies have been conducted. Clinical considerations on the use of aripiprazole augmentation will be discussed in detail in the later section.…”

Study supports augmentation with a non-antidepressant agent over combining or switching antidepressants in unipolar depression

“…Only 74% of patients reached the study endpoint. These aspects are significantly different from other depression trials, such as the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial,2 and limit the generalisability of the results. Of note, augmentation with antipsychotics might increase the risk of some undesired but clinically significant side effects, for example, on metabolic or motor function, as also indicated by this study.…”

“…Even after several treatment approaches, the rate of patients with refractory depression is still 30% 1. In case of non-response to therapy, adding a drug from a different pharmaceutical class to the antidepressant treatment has been shown to have an augmentative effect 2. Most evidence is available for augmentation with lithium3 and atypical antipsychotics 4.…”