Augmentation with Atypical Antipsychotics for Depression: A Review of Evidence‐Based Support from the Medical Literature

Abstract

Major depressive disorder (MDD) is a chronic mental illness that affects an estimated 5-26% of adults at some time in their lives. Treatment is often started as pharmacotherapy using a single drug such as a selective serotonin reuptake inhibitor. If a patient fails to respond adequately to the initial antidepressant, typically three pharmacotherapy options are available to the practitioner. The dose of the current therapy can be maximized, a change can be made to a different drug, or the current regimen can be augmented with another drug. Atypical antipsychotics have recently become a major focus for augmentation of traditional antidepressant therapy. This review summarizes the evidence for efficacy and safety of augmenting treatment-refractory or treatment-resistant depression with atypical antipsychotics. The National Library of Medicine's MEDLINE database was searched for all English-language articles published from January 1966-December 2011 describing the use of atypical antipsychotics in treatment-resistant depression. The literature retrieved was limited to case series, open-label trials, and randomized controlled trials (RCT). Studies of bipolar depression, psychotic depression, or studies conducted in children and adolescents were excluded. Thirty-five studies using atypical antipsychotics for augmentation treatment of depression were included in this analysis. Trials were identified for aripiprazole (six open-label; three RCT), clozapine (one case series), olanzapine (three open-label, including two case series; four RCT), quetiapine (four open-label; five RCT), risperidone (two open-label; five RCT), and ziprasidone (two open-label). The atypical antipsychotics may be effective as adjunctive therapy in MDD; however, their adverse effect profile may be unfavorable to some patients. Trying at least one alternative treatment strategy after an initial antidepressant is indicated before augmentation is implemented with these agents. If atypical antipsychotics are used, safety and efficacy should be frequently reassessed and dosage should be individualized.

Long-Term Efficacy, Safety, and Tolerability of <span style="font-variant:small-caps; "> l</span>-Methylfolate Calcium 15 mg as Adjunctive Therapy With Selective Serotonin Reuptake Inhibitors

“…24,25 Based on these results, adjunctive l-methylfolate can be considered an early option in patients who fail to adequately respond to monotherapy SSRI, with preliminary evidence demonstrating sustained remission and recovery. Further controlled studies are warranted to clarify the acute and long-term benefits of using l-methylfolate in patients with MDD and to ascertain subpopulations who may benefit from early intervention with adjunctive l-methylfolate 15 mg for inadequate response to monotherapy.…”

Efficacy and Safety of Adjunctive Cariprazine in Inadequate Responders to Antidepressants

“…[7][8][9] When adding an antipsychotic to an antidepressant regimen, it is important to consider the risk for adverse effects associated with this class of medication (eg, weight gain, extrapyramidal symptoms). 5,6 Cariprazine, a dopamine D 3 and D 2 receptor partial agonist with preferential binding to D 3 receptors, is an investigational drug in late-stage development for bipolar mania and schizophrenia. Cariprazine differs from other antipsychotics by exhibiting a 10-fold greater in vitro affinity for D 3 versus D 2 receptors 10 and high and balanced in vivo occupancy of both D 2 and D 3 receptors at clinically relevant doses.…”

“…4 Atypical antipsychotics have been used adjunctively with antidepressant treatment to improve response, with some demonstrating efficacy in randomized, controlled trials. 5,6 Currently, aripiprazole, quetiapine extended release, and brexpiprazole are the only antipsychotics approved by the US Food and Drug Administration (FDA) for the adjunctive treatment of MDD. [7][8][9] When adding an antipsychotic to an antidepressant regimen, it is important to consider the risk for adverse effects associated with this class of medication (eg, weight gain, extrapyramidal symptoms).…”

Recent scenario on psychotropic drug usage pattern among patients attending psychiatric outpatient department of a tertiary care teaching hospital in Nepal

“…The efficacy and safety of augmenting treatment-refractory or treatment-resistant depression with atypical antipsychotics has been well established in previous studies. 16,17 They have low propensity to cause extra-pyramidal side effects, efficacy against refractory cases, better tolerance, low relapse rate, and safer adverse effect profile as compared to typical antipsychotics. 18 Olanzapine was the most frequently prescribed antipsychotic in our study.…”