- Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression: An update of the 2007 Comparative Effectiveness Review [Entered Retrospectively]
- Background: Depressive disorders such as major depressive disorder (MDD), dysthymia, and subsyndromal depression may be serious disabling illnesses. MDD affects more than 16 percent of adults at some point during their lifetimes. Second-generation antidepressants dominate the medical management of depressive disorders. These drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other drugs with related mechanisms of action that selectively target neurotransmitters. Objectives: The objective of this report was to compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of depressive disorders, including variations of effects in patients with accompanying symptoms and patient subgroups. Data Sources: We updated a comparative effectiveness review published in 2007 by the Agency for Healthcare Research and Quality searching PubMed, Embase, The Cochrane Library, and International Pharmaceutical Abstracts up to January 2011. Review Methods: Two people independently reviewed the literature, abstracted data, and rated the risk of bias. If data were sufficient, we conducted meta-analyses of head-to-head trials of the relative benefit of response to treatment. In addition, we conducted mixed treatment comparisons to derive indirect estimates of the comparative efficacy among all second-generation antidepressants. Results: From a total of 3,722 citations, we identified 248 studies of good or fair quality. Overall, no substantial differences in efficacy could be detected among second-generation antidepressants for the treatment of acute-phase MDD. Statistically significant differences in response rates between some drugs are small and likely not clinically relevant. No differences in efficacy were apparent in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbidities, although evidence within these subpopulations was limited. Differences exist in the incidence of specific adverse events and the onset of action. Venlafaxine leads to higher rates of nausea and vomiting, sertraline to higher rates of diarrhea, and mirtazapine to higher rates of weight gain than comparator drugs. Bupropion causes lower rates of sexual dysfunction than other antidepressants. The evidence is insufficient to draw conclusions about the comparative efficacy and effectiveness for the treatment of dysthymia and subsyndromal depression. Conclusions: Our findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy and effectiveness. Differences with respect to onset of action and adverse events may be taken into consideration for the choice of a medication.
- Authors of Report
- Methodology description
- We have made only a few changes to the methods used for the CER published in 2007. They involve drugs, approaches to the literature searches, articles included or excluded, techniques for quantitative synthesis, and grading strength of evidence for the overall body of evidence. Specific changes are noted here; longer documentation will be found in later parts of this methods chapter.
We added one drug—desvenlafaxine—to the literature searches and analyses (we used the same search strategy in electronic databases as for the original report). For manual literature searches, we changed the process to semi-automatic searches using the ScopusTM abstraction and citation database (www.scopus.com/home.url). The method is described below in the section on Literature Searches. We did not make any changes to the eligibility criteria (Table 4 in the Introduction). We used the same approach as in the 2007 report to select literature, assess the quality of individual studies (i.e., appraise their risk for bias), and extract relevant data.
Despite using identical methods to select relevant evidence, however, we removed some studies in the 2007 report from the current update. These studies had not met eligibility criteria in the 2007 report to begin with, but because they represented the only available evidence to answer a particular question at the time we had retained them. In the 2007 report we also had briefly summarized findings of such studies to provide a synopsis of the best available evidence (best- evidence approach). When, for this update, we have identified newer evidence that meets our eligibility criteria, we excluded the other "ineligible" studies from the current update.
For indirect comparisons we changed our statistical methods. Specifically, we now use a Bayesian mixed-treatment comparisons approach rather than meta-regressions and network meta-analyses. A detailed description of this approach appears in the section below on Data Synthesis.
We changed our method for rating the strength of evidence. In 2007 we used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. For this update, we follow the principles outlined for use by the AHRQ Evidence-based Practice Centers in AHRQ’s Methods Guide for Effectiveness and Comparative Effectiveness Reviews20 (www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and- reports/?pageaction=displayproduct&productid=318). Details are summarized below in Grading Strength of a Body of Evidence.
- The following Key Questions addressed in this report:
1a. For adults with major depressive disorder (MDD), dysthymia, or subsyndromal
depressive disorders, do commonly used medications for depression differ in efficacy
or effectiveness in treating depressive symptoms?
1b. If a patient has responded to one agent in the past, is that agent better than current
alternatives at treating depressive symptoms?
1c. Are there any differences in efficacy or effectiveness between immediate-release and
extended-release formulations of second-generation antidepressants?
2a. For adults with a depressive syndrome that has responded to antidepressant treatment, do second-generation antidepressants differ in their efficacy or effectiveness for preventing relapse (i.e., continuation phase) or recurrence (i.e., maintenance phase) when a patient
o Continues the drug they initially responded to, or
o Switches to a different antidepressant?
2b. For adults with a depressive syndrome that has not responded to acute antidepressant treatment or has relapsed (continuation phase) or recurred (maintenance phase), do alternative second-generation antidepressants differ in their efficacy or effectiveness?
3. In depressed patients with accompanying symptoms such as anxiety, insomnia, and neurovegetative symptoms, do medications or combinations of medications (including tricyclics in combination) differ in their efficacy or effectiveness for treating the depressive episode or for treating the accompanying symptoms?
4a. For adults with a depressive syndrome, do commonly used antidepressants differ in safety, adverse events, or adherence? Adverse effects of interest include but are not limited to nausea, diarrhea, headache, tremor, daytime sedation, decreased libido, failure to achieve orgasm, nervousness, insomnia, and more serious events including suicide.
4b. Are there any differences in safety, adverse events, or adherence between immediate- release and extended-release formulations of second-generation antidepressants?
5. How do the efficacy, effectiveness, or harms of treatment with antidepressants for a depressive syndrome differ for the following subpopulations?
o Elderly or very elderly patients
o Other demographic groups (defined by age, ethnic or racial groups, and sex) o Patients with medical comorbidities (e.g., ischemic heart disease, cancer)
o Patients with psychiatric and behavioral comorbidities (e.g., substance abuse
o Patients taking other medications
*** The systematic review data of this published project was retrospectively imported into SRDR by the Brown EPC on behalf of the Research Triangle Institute International-University of North Carolina (RTI-UNC ) Evidence-based Practice Center and the Agency for Healthcare Research and Quality (AHRQ). For access to the full report available on the AHRQ website, follow this link: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=863&pageaction=displayproduct ***
- Funding Source
- The Agency for Healthcare Research and Quality (AHRQ)