Abstract and Introduction

Abstract

Purpose of review The aim of this systematic review was to examine the efficacy and safety of second-generation antipsychotics (SGAs) in nonpsychotic major depressive disorder (MDD).
Recent findings In MDD, SGA monotherapy or adjunctive therapy to conventional antidepressants showed rapid onset of antidepressant efficacy. Although maintenance data are limited, quetiapine monotherapy, risperidone adjunctive therapy, and amisulpride adjunctive therapy significantly delayed the time to relapse as compared with placebo. In general, extrapyramidal symptoms appeared to be low with SGAs, but a higher incidence of akathisia was observed with aripiprazole. An elevated risk of weight gain was observed with olanzapine–fluoxetine combination, risperidone, aripiprazole, and quetiapine compared with placebo. At present, there are insufficient data to confidently distinguish between different SGAs in the treatment of MDD. A recent meta-analysis found that adjunctive SGAs were significantly more effective than placebo, but differences in efficacy were not identified among the studied agents, nor were outcomes affected by trial duration or the method of establishing treatment resistance.
Summary Both SGA monotherapy and adjunctive therapy showed greater efficacy in the treatment of MDD than placebo, but augmentation is more widely utilized in treatment-resistant depression. Clinicians should routinely monitor for cardiometabolic side-effects and extrapyramidal symptoms during SGA therapy.

Introduction

Major depressive disorder (MDD) is an impairing, common and costly mental disorder, representing one of the most prevalent psychiatric conditions in the USA.^[1] Affecting approximately 16% of individuals over their lifetime, MDD frequently assumes a recurrent course and is associated with substantial disability and role impairment. MDD ranks fourth worldwide as the leading cause of total disease burden according to a World Health Organization report and is associated with an earlier mortality both from suicide and natural causes, including cardiovascular disease.^[2]

Over the past several decades, there has been a substantial growth in the number of medications approved by the US Food and Drug Administration for the treatment of acute MDD. Nevertheless, results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, one of the largest 'real-world' clinical studies conducted to date, suggest that only one-third of patients will achieve remission after an adequate course of antidepressant treatment.^[3] Among patients who did not remit after two treatment strategies in the STAR*D study, the likelihood of achieving remission significantly declined. As a consequence, several treatment strategies have evolved for difficult-to-treat forms of depression,^[4] including switching to another class of antidepressants or augmenting with agents such as thyroid hormone, lithium, and second-generation antipsychotics (SGAs). In addition, some traditional antidepressants are limited by their slower onset of action.

The evidence base for SGAs in the treatment of MDD has grown at a rapid pace. Given the expansion of clinical trials in this area, the aim of the present systematic review was to examine the efficacy and safety of SGAs in the treatment of patients with MDD and to provide an updated clinical perspective to guide prescribers.

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