Our review found only three randomized, placebo-controlled trials of quetiapine carried out in adult patients with MDD. All studies had the same study designs. The preliminary findings of this meta-analysis suggest that quetiapine monotherapy is effective for adult patients with MDD. Based on the pooled response rates, the NNT of 7.2 indicates that, by average, every 1 in 8 patients with MDD will respond to quetiapine treatment. The high dropout rate due to adverse events suggests that some MDD patients may not be able to tolerate quetiapine XR. Due to the balance of its efficacy benefit and risk of side effects, as the overall discontinuation rate shown, the acceptability of this agent is not more than placebo.
In this review, the pooled response rate for quetiapine monotherapy in MDD patients (51.51%) was superior to placebo (37.55%). Similarly, a meta-analysis of 7 RCTs found that the response rates of bupropion and SSRIs treatment in MDD patients were 62 and 63%, respectively, compared with 51% for placebo . The remission rate of quetiapine treatment (27.31%) is also greater than that of placebo one (21.16%). Previous meta-analyses found that the remission rates of TCAs, SSRIs, and SNRIs were 44.1, 37.7 and 31-55% respectively . It should be noted that not only the response and remission rates of quetiapine treatment but also those of placebo treatment found in this study were lower than previous findings. Therefore, the cross-trial comparisons of the response and remission rates of quetiapine with those of other antidepressants may not be justified.
Absolute risk reduction (ARR) is the difference between the control group’s event rate and the experimental group’s event rate. As a measure of the size of difference between two treatments (e.g., antidepressants and placebo), the ARR may be a logical method for comparing the remission and response rates of antidepressants across studies. Based on the ARR, quetiapine increases the response rate for 13.96% (51.51% for quetiapine group vs. 37.55% for placebo group), while bupropion and SSRIs increase the response rates for 11% and 12%, respectively (62% for bupropion group and 63% for SSRI group vs. 51% for placebo group) . Regarding the response rates of other antidepressants in adults with MDD, the NNTs of fluoxetine and venlafaxine are between 5 and 7, which are comparable to the NNT of 8 for the quetiapine treatment in this population . Not surprisingly, as an inverse of the ARR, the comparable of ARRs between quetiapine and other antidepressants, the NNTs of these agents are, therefore, comparable. However, the ARR for the remission rate of quetiapine treatment [6.15% (27.31% for quetiapine vs. 21.16% for placebo)] is relatively lower than those of SSRIs and bupropion [11% (47% for SSRIs and bupropion vs. 36% for placebo)] . It is not yet known whether these differences reflect the true lower remission rate of quetiapine treatment or only the dissimilarity of participants and study designs among the studies.
Similar to other antidepressants, the acceptability of quetiapine for the treatment of MDD is not higher than that of placebo. The nonsignificant differences in this respect have been found in a number of meta-analyses of paroxetine  and duloxetine  and TCAs  for the treatment of MDD. The low tolerability of quetiapine treatment for MDD is also similar to previous findings of other antidepressants, e.g. TCAs , SSRIs  and SNRIs [46, 47]. These lines of evidence suggest that almost all antidepressants, including quetiapine, have the same profile of comparable acceptability to and less tolerability than placebo.
Sleep disturbance is common in MDD and may complicate its treatment. Up to 31% of MDD patients may have insomnia . In addition, insomnia is a common adverse effect of many antidepressants, e.g., SSRIs  and SNRIs . The findings of sleep quality improved by quetiapine suggests an advantage of quetiapine for the treatment of MDD.
There were several limitations of this review. Firstly, the doses of quetiapine were different across the included studies. While a study used a flexible dose with titration, the others applied fixed and multiple doses in several arms. Secondly, this meta-analysis included only three RCTs sponsored by a pharmaceutical company holding the patent of quetiapine XR. These results, therefore, should be viewed as the very preliminary findings. Thirdly, although all studies adhered to the same methods of double blindness/randomization, had similar baseline characteristics, and applied the intention-to-treat analysis or modified intention-to-treat analysis for the data analyses, 1 of 3 studies did not report an adequate sequence generation of randomization and the allocation concealment. Fourthly, as with all meta-analyses, publication bias must be considered. However, due to the small number of included studies, we did not assess the possibility of publication bias .