Are antipsychotics effective adjunctive Tx for patients with moderate-to-severe depression?
EVIDENCE-BASED ANSWER:
YES. Augmentation with second- generation antipsychotics, especially aripiprazole and quetiapine, appears to be effective in patients with moderate-to-severe depression who have had a suboptimal response to a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor (strength of recommendation [SOR]: A, based on a systematic review of randomized controlled trials [RCTs] and an individual RCT). Augmenting antidepressant therapy with cariprazine, ziprasidone, or olanzapine also appears to improve depressive symptoms over the short term. All antipsychotics studied carried an increased likelihood of adverse effects that could lead to discontinuation (SOR: A, based on a systematic review of RCTs).
Patients were randomly assigned to 1 of 3 different treatment groups, which included switching to a different antidepressant (bupropion sustained release 150-500 mg/d); augmenting current treatment with bupropion; or augmenting with an atypical antipsychotic (aripiprazole 2-15 mg/d) for 12 to 36 weeks. The primary outcome was remission rate at 12 weeks, which was defined as a score ≤ 5 on the Quick Inventory of Depressive Symptomatology–Clinician Rated (QIDS-C; range, 0-27) at 2 consecutive visits. The secondary outcome, symptom response to treatment, was defined as ≥ 50% reduction on QIDS-C score.
The augment-aripiprazole group (N = 146) exceeded the switch group (N = 114) in remission rate (absolute remission rates = 28.9% vs 22.3%; relative risk [RR] = 1.3; 95% CI, 1.1-1.6; number needed to treat [NNT] = 15), but had similar remission rates to the augment-bupropion group (N = 136; absolute remission rate = 26.9%; RR = 1.1; 95% CI, 0.88-1.3). Symptom response in the augment-aripiprazole group (74.3%) was higher than in either the switch group (62.4%; RR = 1.19; 95% CI, 1.09-1.29; NNT = 8) or the augment-bupropion group (65.6%; RR = 1.13; 95% CI, 1.0-1.2; NNT = 11). There was no difference noted in response rate between the switch group and the augment-bupropion group (RR = 1.05; 95% CI, 0.96-1.15).3
The adverse events that occurred more often in the augment-aripiprazole group than in the other groups included weight gain ≥ 7% (25% at 36 weeks) and extrapyramidal symptoms (19%).3 Limitations of the study included the evaluation of only 1 antipsychotic and 1 antidepressant, the dropout rate (only 75% of patients completed the 12-week follow-up), and the homogeneity of the patient population (older, male, veterans), all of which may limit the effect size.
Editor’s takeaway
Multiple trials show that adjunctive antipsychotic medications such as aripiprazole and quetiapine more effectively treat resistant depression than adding a placebo, increasing antidepressant dosage, switching to a different antidepressant, or adding another antidepressant. However, while primary care physicians should be comfortable with this option, the magnitude of difference between these options was modest, and adverse effects were common. All options can still be reasonably considered.
