Several attempts to improve antidepressants have recently led to the availability of some newer antidepressants (NAs) including nefazodone, mirtazapine, and venlafaxine. The author proposed to compare both efficacy and discontinuation rates between these NAs and older antidepressants (OAs) which include tricyclic antidepressants (TCAs), nontricyclic antidepressants (NTCAs), and selective serotonin reuptake inhibitors (SSRIs). In each comparison, the author analyzed the heterogeneity of outcomes and computed the pooled odd ratio (OR) with 95 per cent confidential interval (95% CI) by using Peto method. The results show that NAs have slightly higher efficacy than OAs. The overall discontinuation rate of the NA group was also lower than that of the TCA group but not that of NTCA-SSRI group. In conclusion, NAs have slightly but significantly superior efficacy to OAs which probably include SSRIs. They are also more tolerable than TCAs but not NTCAs-SSRIs. However, the efficacy difference between NAs and SSRIs should be viewed as a preliminary result since very few studies have compared their efficacy.