The authors reported that eight (although nine or ten appeared to be tabulated) acute phase RCTs with ten comparisons were included (762 patients). Four trials provided four comparisons with antipsychotics. Five trials provided six comparisons with antidepressants. Trial sample size ranged from 36 to 259 patients.
Antidepressant-antipsychotic co-therapy significantly reduced inefficacy in the acute phase of psychotic depression compared with antipsychotic monotherapy (RR 0.73, 95% CI 0.63 to 0.84; four comparisons; Ι²=0%) and antidepressant monotherapy (RR 0.76, 95% CI 0.59 to 0.98; six comparisons; Ι²=34%).
Antidepressant-antipsychotic co-therapy significantly reduced depression in the acute phase compared with antipsychotic monotherapy (Hedges g -0.49, 95% CI -0.75 to -0.23; four comparisons; I2=27%,) but there was no difference when compared with antidepressant monotherapy (five comparisons). Antidepressant-antipsychotic co-therapy significantly reduced Clinical Global Impressions-Severity Illness score in the acute phase compared with antidepressant monotherapy (Hedges g -0.25, 95% CI -0.49 to -0.02; four comparisons; Ι²=0%); data were not available for the antipsychotic monotherapy comparison. There was no significant difference in terms of psychosis or anxiety.
The rates of discontinuation and adverse events were similar, except for somnolence which was statistically significantly more likely with antipsychotic-antidepressant co-therapy compared with antidepressant monotherapy (RR 2.79, 95% CI 1.14 to 6.79; three comparisons; Ι²=15%).
Further results, including subgroup results, were reported in the review.