Atypical antipsychotics are effective adjuncts for treatment resistant depression

Atypical antipsychotics are effective adjuncts for treatment resistant depression but increase discontinuation due to adverse effects: review

Question:
How effective are atypical antipsychotics as adjunctive therapy for treatment resistant depression?

Outcomes:
Primary outcome: remission rates using the Hamilton Rating Scale for Depression (HAM-D) or Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes: discontinuation rates and response rates.

MAIN RESULTS

Ten randomised controlled trials of 1500 outpatients were included (4 using olanzapine in combination with fluoxetine; 4 using quetiapine in combination with an SSRI or SNRI; and 2 with risperidone plus various antidepressants). Trial durations ranged from 4–12 weeks. Adjunctive antipsychotic treatment increased remission and response rates compared with adjunctive placebo (RR for remission: 1.75, 95% CI 1.36 to 2.24; p<0.001; RR for response: 1.35 95% CI 1.13 to 1.63; p = 0.001). Tests for heterogeneity were non-significant for both remission and response rates. Overall rates of discontinuation were not significantly different between antipsychotic and placebo groups (RR 1.18, 95% CI 0.93 to 1.49; p = 0.133). However, discontinuation due to adverse effects was higher with antipsychotics than placebo (RR 3.38; 95% CI 1.98 to 5.76; p<0.001).

CONCLUSIONS

Antipsychotics (olanzapine, quetiapine and risperidone) are effective adjunctive treatment for depression that has failed to respond to an adequate trial of standard treatment. However, they do increase discontinuation due to adverse effects. No studies of adjunctive aripiprazole or ziprasidone were identified so results may not apply to these drugs.

ABSTRACTED FROM

Papakostas GI, Shelton RC, Smith J, et al. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry 2007;68:826–31.

Notes: Studies used different depression scales and defined remission using different cut-offs (4 studies used HAM-D score <8; 3 used MADRS score <9 and 3, MADRS score <11). All included studies defined response as a 50% reduction in primary depression scale score from baseline.

Commentary

A Cipriani, MD, M Dieterich, MD, C Barbui, MD University of Verona, Verona, Italy

When dealing with treatment resistant depression, one of the most compelling clinical issues is to decide whether to switch to another antidepressant or to augment antidepressant treatment with an agent belonging to a different class. In this meta-analysis the benefit of adjunctive treatment of standard antidepressants with an atypical antipsychotic for treatment resistant depression was assessed. Despite some interesting findings, careful consideration of the analysis is needed before drawing conclusions for clinical practice.