| Comparison and Outcome of Interest | Strength of Evidencea | Findings | |
|---|---|---|---|
| SGA versus CBT monotherapy | Remission | Low | Results from direct comparisons in 3 trials indicate that no substantial differences in remission exist between SGAs and CBT monotherapy. |
| Response | Moderate | Results from direct comparisons in 5 trials indicate that no substantial differences in response exist between SGAs and CBT monotherapy. | |
| Functional capacity | Low | Results from 1 trial indicate that no substantial differences in functional capacity exist between SGAs and CBT monotherapy. | |
| Overall risk of adverse events | Insufficient | Based on 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| Overall discontinuation of treatment (8–14 weeks) | Moderate | Results from direct comparisons in 4 trials indicate that no significant differences exist in overall discontinuation between patients treated with SGAs and those treated with CBT. | |
| Overall discontinuation of treatment (24 weeks) | Low | Results from 1 trial indicate that patients treated with SGAs are more likely to discontinue treatment for any reason than those treated with CBT. | |
| Discontinuation of treatment because of adverse events | Low | Results from direct comparisons in 3 trials indicate that patients treated with SGAs experience a numerically but not statistically significant higher rate of discontinuation because of adverse events than those treated with CBT. | |
| Serious adverse events | Insufficient | Based on 2 trials with few events, the evidence is insufficient to draw conclusions. | |
| Suicidal ideas and behavior | Insufficient | Based on 3 trials with few events, the evidence is insufficient to draw conclusions. | |
| SGA versus SGA + CBT | Remission | Low | Results from direct comparisons in 2 trials indicate that no substantial differences in remission exist between SGAs and SGAs combined with CBT. |
| Response | Low | Results from direct comparisons in 2 trials indicate that no substantial differences in response exist between SGAs and SGAs combined with CBT. | |
| Functional capacity | Low | Results from 1 trial indicate that the combination of SGA with CBT results in greater improvement on 3 of 4 work functioning measures than SGA alone. | |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 2 head-to-head trials indicate that no significant differences exist in overall discontinuation between patients treated with SGAs and those treated with CBT. | |
| Discontinuation of treatment because of adverse events | Low | Results from direct comparisons in 2 head-to-head trials indicate that no significant differences exist in discontinuation because of adverse events between patients treated with SGAs and those treated with CBT. | |
| SGA versus IT monotherapy | Remission | Low | Results from direct comparisons in 2 trials indicate that no substantial differences in remission exist between SGAs and interpersonal therapy monotherapy. |
| Response | Low | Results from 1 trial indicate that no substantial differences in response exist between SGAs and interpersonal therapy monotherapy. | |
| Overall discontinuation of treatment | Insufficient | Based on 2 trials with few events, the evidence is insufficient to draw conclusions. | |
| Discontinuation of treatment because of adverse events | Insufficient | Based on 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| Suicidal ideas and behavior | Insufficient | Based on 2 trials with few events, the evidence is insufficient to draw conclusions. | |
| SGA versus SGA + IT | Remission | Low | Results from 1 trial indicate that a substantial difference in remission favoring SGAs combined with interpersonal therapy exists, but the confidence interval is very wide. |
| Overall discontinuation of treatment | Insufficient | Based on 1 with very few events, the evidence is insufficient to draw conclusions. | |
| Subgroup with anxiety | Insufficient | Based on 1 trial, the evidence is insufficient to draw conclusions for benefits or harms. | |
| SGA versus PSYD monotherapy | Remission | Low | Results from 1 trial indicate that no substantial differences in remission exist between SGAs and PSYD monotherapy. |
| Functional capacity | Low | Results from direct comparisons based on 2 trials indicate that few substantial differences in functional capacity exist between SGAs and PSYD monotherapy. | |
| Overall discontinuation of treatment (8 to 16 weeks) | Insufficient | Results from direct comparisons in 3 head-to-head trials indicate that no significant differences exist in overall discontinuation after 8–16 weeks of followup between patients treated with SGAs and those treated with PSYD monotherapy. | |
| Overall discontinuation of treatment (48 weeks) | Low | Results from direct comparisons in 1 head-to-head trial indicate that no significant differences exist in overall discontinuation after 48 weeks of followup between patients treated with SGAs and those treated with PSYD monotherapy. | |
| Overall discontinuation of treatment (96 weeks) | Low | Results from direct comparisons in 1 head-to-head trial indicate that no significant differences exist in overall discontinuation after 96 weeks of followup between patients treated with SGAs and those treated with PSYD monotherapy. | |
| Suicidal ideas and behavior | Insufficient | Based on 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| SGA versus SGA + PSYD | Functional capacity | Low | Results from 1 trial indicate that no substantial differences in the effects on WAIS-III measures exist between patients treated with SGAs and those treated with SGAs plus PSYD. |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 1 head-to-head trial indicate that overall discontinuation is more likely among patients treated with SGAs than those treated with SGAs plus PSYD. | |
| Suicidal ideas and behavior | Low | Results from direct comparisons based on a single head-to-head trial indicate that no significant differences exist in suicidal ideas and behavior between patients treated with SGAs and those treated with SGAs plus PSYD. | |
| SGA versus third-wave CBT | Remission | Insufficient | Based on 2 trials, the evidence is insufficient to draw conclusions. |
| Response | Insufficient | Based on 2 trials, the evidence is insufficient to draw conclusions. | |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 2 head-to-head trials indicate that overall discontinuation is significantly more likely among patients treated with SGAs than those treated with third-wave CBT. | |
| Discontinuation of treatment because of adverse events | Low | Results from direct comparisons in 2 head-to-head trials indicate that discontinuation of treatment because of adverse events is significantly more likely among patients treated with SGAs than those treated with third-wave CBT. | |
| Suicidal ideas and behavior | Insufficient | Based on 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| SGA versus acupuncture monotherapy | Response | Low | Results from direct comparisons based on 2 head-to-head trials, as well as network meta-analysis, indicate that no substantial differences in response exist between patients treated with SGA and those treated with acupuncture monotherapy. |
| Overall risk of adverse events: direct evidence | Insufficient | Based on 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| Overall risk of adverse events: indirect evidence | Moderate | Results from a systematic review of 21 trials indicate that patients treated with SGAs experience a significantly higher overall risk of adverse events than those treated with acupuncture. However, this systematic review of 21 trials did not meet our eligibility criteria because some trials included depressive disorders other than MDD. | |
| Overall discontinuation of treatment | Insufficient | Based on 1 of 2 available trials with few events, the evidence is insufficient to draw conclusions. | |
| SGA versus SGA + acupuncture | Remission | Low | Results from direct comparisons in 1 head-to-head trial indicate that no substantial differences in remission exist between patients treated with SGAs and those treated with acupuncture combination therapy. |
| Response | Low | Results from direct comparisons in 2 head-to-head trials indicate higher response rates for patients treated with SGAs plus acupuncture than patients treated with SGAs alone. | |
| Overall risk of adverse events | Low | Results from direct comparisons based on 1 head-to-head trial indicate that no significant differences exist in overall risk of adverse events between patients treated with SGAs and those treated with acupuncture plus SGAs. | |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 2 head-to-head trials indicate that no significant differences exist in overall discontinuation between patients treated with SGAs and those treated with SGAs plus acupuncture. | |
| Discontinuation of treatment because of adverse events | Low | Results from direct comparisons based on 2 head-to-head trials indicate that no significant differences exist in discontinuation because of adverse events between patients treated with SGAs and those treated with SGAs plus acupuncture. | |
| SGA versus Omega-3 fatty acids monotherapy | Response | Low | Results from network meta-analysis indicate higher response rates for patients treated with SSRIs than for those receiving omega-3 fatty acids. |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 1 head-to-head trial indicate that no substantial differences exist in overall discontinuation between patients treated with SGAs and those treated with omega-3 fatty acids. | |
| Discontinuation of treatment because of adverse events | Low | Results from direct comparisons in 1 head-to-head trial indicate that no substantial differences exist in overall discontinuation between patients treated with SGAs and those treated with omega-3 fatty acids. | |
| Suicidal ideas and behavior | Insufficient | Based on 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| SGA versus SGAs + Omega-3 fatty acids | Remission | Insufficient | Based on 1 trial, the evidence is insufficient to draw conclusions. |
| Response | Insufficient | Based on 2 trials, the evidence is insufficient to draw conclusions. | |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 2 head-to-head trials indicate that no substantial differences in overall discontinuation between patients treated with SGAs and those with treated with SGAs plus omega-3 fatty acids. | |
| Discontinuation of treatment because of adverse events | Insufficient | Results from direct comparisons in 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| SGAs versus SAMe monotherapy | Remission | Insufficient | Based on 1 trial, the evidence is insufficient to draw conclusions. |
| Response | Low | Results from direct comparisons in 1 trial and our network meta-analysis indicate that no substantial differences in response exist between SGA and SAMe monotherapy. | |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 1 head-to-head trial indicate that no significant differences exist in overall discontinuation between patients treated with SGAs and those treated with SAMe. | |
| Discontinuation of treatment because of adverse events | Insufficient | Based on 1 trial with few events, the evidence is insufficient to draw conclusions. | |
| SGA versus St. John’s wort monotherapy | Remission | Low | Results from direct comparisons based on 5 head-to-head trials indicate that no substantial differences in remission exist between patients treated with SGA and those treated with St. John’s wort monotherapy. |
| Response | Low | Results from direct comparisons in 9 head-to-head trials indicate that no apparent differences in response exist between patients treated with SGAs and those treated with St. John’s wort monotherapy. | |
| Overall risk of adverse events | Moderate | Results from direct comparisons in 8 head-to-head trials indicate that patients treated with SGAs experience a significantly higher overall risk of adverse events than those treated with St. John’s wort. | |
| Overall discontinuation of treatment | Moderate | Results from direct comparisons in 9 head-to-head trials indicate that patients treated with SGAs experience significantly higher rates of overall discontinuation than those treated with St. John’s wort. | |
| Discontinuation of treatment because of adverse events | Moderate | Results from direct comparisons in 9 head-to-head trials indicate that patients treated with SGAs experience significantly higher rates of discontinuation because of adverse events than those treated with St. John’s wort. | |
| Serious adverse events | Low | Results from direct comparisons in 4 head-to-head trials indicate that no significant differences exist in the occurrence of serious adverse events between patients treated with SGAs and those treated with St. John’s wort. | |
| Suicidal ideas and behavior | Insufficient | Based on 2 trials with few events, the evidence is insufficient to draw conclusions. | |
| Subgroup based on older age | Low | Results from 1 trial in older adults indicate similar response rates and discontinuation rates because of adverse events for patients treated with SGAs and those treated with St. John’s wort. | |
| SGA versus exercise monotherapy | Remission | Low | Results based on direct comparisons in 2 trials reveal no significant difference in remission between patients treated with SGAs and those treated with exercise therapy. |
| Response | Low | Estimates based on network meta-analysis reveal no significant difference in response between patients treated with SGAs and those treated with exercise therapy. | |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 2 head-to-head trials indicate that no significant differences exist in overall discontinuation between patients treated with SGAs and those treated with exercise. | |
| Discontinuation of treatment because of adverse events | Low | Results from direct comparisons in 2 head-to-head trials indicate that patients treated with SGAs experience significantly higher rates of discontinuation because of adverse events than those treated with exercise. | |
| SGA versus exercise + SGA | Remission | Low | Results based on direct comparison from 1 trial reveal no significant difference in effectiveness between SGA and SGAs plus exercise. |
| Overall discontinuation of treatment | Low | Results from direct comparisons in 1 head-to-head trial indicate that no significant differences exist in overall discontinuation between patients treated with SGAs and those treated with SGAs plus exercise. | |
| Discontinuation of treatment because of adverse events | Low | Results from direct comparisons in 1 head-to-head trial indicate that no significant differences exist in discontinuation because of adverse events between patients treated with SGAs and those treated with SGAs plus exercise. | |
CBT = cognitive behavioral therapy; IT = integrative therapies; MMD = major depressive disorder; PSYD = psychodynamic therapies; SAMe = S-adenosyl-L-methionine; SGA = second-generation antidepressant; SOE = strength of evidence; SSRI = selective serotonin reuptake inhibitor; third-wave CBT = third-wave cognitive behavioral therapy; vs. = versus
SOE grades (high, moderate, low, or insufficient) are based on methods guidance for the AHRQ EPC program.83
From: Discussion
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.