Second-Generation Antidepressants for Treating Adult Depression—An Update
Overall Comparative Effectiveness of Second-Generation Antidepressants for Treating Adults With MDD
Efficacy and Effectiveness: Overall, 37 percent of patients did not respond during 6 to 12 weeks of treatment with second-generation antidepressants; 53 percent did not achieve remission. Ninety-one head-to-head trials (i.e., comparisons between medications conducted within trials) provided data on 40 of the potential comparisons between the 13 second-generation antidepressants addressed in this report. Many efficacy trials were not powered to detect statistically or clinically significant differences, leading to inconclusive results. Direct evidence from head-to-head trials was considered sufficient to conduct meta-analyses on the response to treatment (at least 50% improvement from baseline) for six drug-to-drug comparisons. Differences in efficacy reflected in some of these meta-analyses are of modest magnitude, and clinical implications remain to be determined. Findings from indirect comparisons yielded some statistically significant differences in response rates. The magnitudes of these differences, however, were small and are likely not to be clinically significant. Overall, the strength of the evidence supporting no substantial differences in efficacy and effectiveness among second-generation antidepressants for the treatment of major depressive disorder (MDD) in adults was graded as moderate.
Quality of Life: Quality of life or functional capacity was infrequently assessed, usually as a secondary outcome. Seventeen studies (3,960 patients), mostly of fair quality, indicated no statistical differences in efficacy with respect to health-related quality of life. The strength of evidence is moderate.
Speed of Response: Seven studies, all of fair quality and funded by the maker of mirtazapine, reported that mirtazapine had a significantly faster onset of action than citalopram, fluoxetine, paroxetine, and sertraline. The pooled number need to treat to yield one additional responder after 1 or 2 weeks of treatment is 7 (95-percent confidence interval, 5 to 12); after 4 weeks of treatment, however, most response rates were similar. The strength of evidence is moderate.
Age and MDD: Head-to-head trials provided mixed results on differences in benefits and harms in older adults with MDD. The majority of the trials found no differences in efficacy but suggested some differences in adverse events. Two trials comparing fluoxetine, paroxetine, and placebo reported conflicting results. One trial comparing escitalopram with fluoxetine found a significant difference favoring escitalopram over fluoxetine for efficacy; however, this trial also found neither to be significantly better than placebo. Strength of evidence is moderate for comparative efficacy; strength of evidence is low for harms.
- Gartlehner G, Hansen RA, Morgan LC, et al. Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression: An Update of the 2007 Comparative Effectiveness Review. Comparative Effectiveness Review No. 46 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; December 2011. AHRQ Publication No. 12-EHC012-EF. Available at www.effectivehealthcare.ahrq.gov/secondgenantidep.cfm.
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