Abstract and Introduction
Major depressive disorder (MDD) is a chronic and recurrent mental condition leading to huge impacts on direct and indirect personal and public medical costs. To overcome such a serious mental disorder, we currently have a number of different classes of antidepressants, such as selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, noradrenergic and specific serotonin receptor antagonists, dopamine and norepinephrine reuptake inhibitors, along with newly introduced antidepressants (e.g., vilazodone and agomelatine). However, a number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that only a third of such MDD patients remit following adequate antidepressant treatment, while most MDD patients suffer from significant core depressive or residual symptoms during their clinical course. There have been some treatment approaches to overcome such a shortage of antidepressant efficacy, such as augmentation of psychotropics other than antidepressants, switching to a different antidepressant and combinations of different antidepressants. Among these different second treatment options, augmentation treatment has some favorable points compared with the combination and switching option (e.g., maintaining previous antidepressant partial response, synergistic effect between different pharmacological profile and no need to wash out previous antidepressants). Recently, second-generation antipsychotics (SGAs), olanzapine plus fluoxetine, quetiapine extended release and aripiprazole have clearly demonstrated efficacy in the treatment of MDD patients through a number of small-scale, open-label studies or randomized, placebo-controlled clinical trials. Eventually, in November 2007, aripiprazole was the first approved by the US FDA as an adjunctive treatment to antidepressants for treating MDD, followed by the approval of quetiapine and olanzapine plus fluoxetine at 2009. This comprehensive review provides an overview of the clinical trial data of SGAs for treating MDD and clinical issues raised in the use of SGA therapy in patients with MDD in clinical practice.
Major depressive disorder (MDD) is a common, chronic, recurrent and debilitating psychiatric condition, leading to significant impairments in personal functional capacities, which also eventually impact directly and indirectly on public medical costs.
After the advent of the older antidepressants such as monoamine oxidase inhibitors and tricyclic antidepressants for the treatment of MDD, newer antidepressants with improved tolerability such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors, dopamine and norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressant medications have been introduced and flourished as the first-line treatments options for patients with MDD in clinical practice. However, despite sufficient availability of different classes of antidepressants to date, most patients with MDD do not achieve an adequate response or remission with such antidepressant treatment. The lack of satisfactory clinical efficacy of first-line antidepressant treatment is clearly evidenced in a number of case studies, randomized, double-blind, placebo-controlled clinical trials (RCTs), meta-analyses and practical clinical trials. For instance, a 12-week treatment with SSRI monotherapy (citalopram) showed only a 30% remission rate in MDD patients in the STAR*D trial. In addition, in a recent meta-analysis including 182 antidepressant RCTs (n = 36,385), the response and remission rates were approximately 54 and 37%, respectively. Such inadequate antidepressant efficacy results in significant residual symptoms, functional incapacity, increased utilization of medical services, and frequent recurrence and relapse.[4–6]
According to the cumulative evidence in the last decade, augmentation strategies including second-generation antipsychotic (SGA) augmentation, switching to different antidepressants, or a combination of different antidepressant strategies are recommended in most guidelines for partial or non responders in clinical practice.[7–10] Among such second-treatment steps, the augmentation strategy has proven its usefulness for enhancing the antidepressant effect, showing increased remission rates and early treatment effects on core depressive symptoms and comorbid symptoms without losing previous antidepressant response as well as minimizing antidepressant-mediated side effects (e.g., sexual dysfunction).[7–10] Although classical augmentation agents including lithium and thyroid hormones have been commonly used for patients with inadequate response from antidepressant first-line therapy, they were supported by limited data and none of those augmentation agents has been officially approved by the national authority such as the US FDA.
Recently, SGAs including olanzapine, quetiapine extended release (XR) and aripiprazole have clearly demonstrated efficacy as an augmentation agent for MDD patients through a number of small-scale, open-label studies or randomized, placebo-controlled clinical trials (RPCTs). In November 2007, aripiprazole was the first approved by the US FDA as an augmentation therapy to antidepressants for treating MDD, followed by approval of quetiapine XR and olanzapine in 2009.
Expert Rev Neurother. 2013;13(7):851-870. © 2013 Expert Reviews Ltd.