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Summary of Findings
We found that primary care depression screening programs were likely to be effective when other staff provided part of the depression care, such as assessment and monitoring in coordination with the primary care provider's treatment or when extra efforts were made to enroll patients in specialty mental health treatment. This conclusion is based on 4 newly published trials and 5 trials that were included in the previous review. We found no data that identified harms of depression screening. Harms of screening were not discussed in the previous report. We also found that depression treatment in older adults was effective, which complements the previous reviews finding that depression treatment is effective in general adult populations. Details of these data can be found in the full report of this review (16).
Finally, we examined harms of second-generation antidepressant use in adults, which were not addressed in the previous review. We found that young adults (aged 18 to 29 years) seem to have an increased risk for suicidal behavior (but not suicide deaths), particularly early in the course of treatment. We found no apparent increase or decrease in risk for suicidal behavioral or deaths in middle-aged populations as a result of second-generation antidepressant use. These conclusions are not definitive, however, because suicide deaths were very rare (and therefore power to detect an increased risk was limited) and data on suicidal behavior were not unanimous. Older adults seem to have lower risk for suicidal behavior, although the risk for upper gastrointestinal bleeding is increased and is a particular concern when combined with NSAIDs.
Comparisons With Other Reviews of Depression Screening
In comparison with the 2002 systematic review (62), a 2005 Cochrane review (10), which excluded all studies that included "complex quality improvement/care management" strategies, concluded that screening programs were not effective in improving health outcomes. Our findings both confirm and extend these 2 previous reviews. Consistent with both the USPSTF and Cochrane reviews, the limited evidence we found on screening and feedback without further care supports suggests that this approach is unlikely to have an effect. Our findings show that depression care support programs that include screening can improve depression symptoms and remission in adult populations.
Why Screening Programs Alone May Not Be Effective
It is puzzling, at first glance, why screening and feedback of results alone would not clearly improve depression outcomes, because it is fairly well-established that they do increase recognition of depression (62). Critics of widespread depression screening suggest that the differences between clinically and screen-detected cases could partially explain this discrepancy (63,64). Patients whose depression is undetected in primary care tend to be less impaired and have milder levels of depression than those who are identified without screening (65-68). These patients may not need active treatment or may not respond as well to medication (69).
The greatest barrier to long-term relief from depression is probably insufficient treatment, rather than inadequate identification. In real-world primary care settings, up to 40% to 67% of patients discontinue their antidepressant medication within 3 months, and few receive adequate follow-up (70-72). Thus, efforts to increase appropriate treatment and improve adherence to treatment are likely to provide the greatest effect. Given the burden on the primary care clinician, it is not surprising that the greatest gains are seen in programs in which other staff provides some of the depression care. Considerable research in recent years has focused on treatment approaches that do just this, such as disease management and collaborative care, which are generally effective (11,73-76) and cost-effective (77). There are probably several mechanisms by which these interventions produce benefits; such mechanisms include enhanced treatment adherence through closer monitoring of treatment tolerability and response, treatment adjustments, and psychosocial support.
Age-Related Risks Associated With Second-Generation Antidepressant Use
Two meta-analyses suggested an increased risk for suicidal behavior in younger adults, particularly those with MDD or those receiving paroxetine (34,41), whereas another demonstrates a protective effect of antidepressant treatment of older adults (35). Other studies outside the scope of this review generally confirm a beneficial effect of antidepressants on suicides in older adults (78,79). However, the increased risk for upper gastrointestinal bleeding in older adults is a concern. Concurrent use of NSAIDs, and to a lesser extent low-dose aspirin and other anticoagulants, seemed to further increase bleeding risks. A recently published meta-analysis estimated increased odds of upper gastrointestinal hemorrhage with SSRI use (OR, 2.36 [CI, 1.44 to 3.85]), particularly when NSAIDs were used concurrently (OR, 6.33 [CI, 3.40 to 11.8]) (80). In people aged 50 years or older without other risk factors, but with both SSRI and NSAID use, the number needed to treat to harm was 106. Among postmarketing reports for adults primarily older than 60 years, median time to bleeding was after 25 weeks of SSRI treatment. These findings may have implications for all adults but particularly for vulnerable older adults or those with a history of gastrointestinal bleeding, given the prevalence of use of analgesic medications (over-the-counter as well as prescription) for therapeutic and preventive reasons.
Limitations of the Review and the Literature
This review took a targeted approach that focused on critical key questions and evidence gaps at the time of the last review and limited the evidence reviews for some questions. We limited the evidence for harms of antidepressant treatment to systematic reviews, supplemented by large prospective observational studies to address deficiencies in short-term RCTs. Although this approach was pragmatic (and our consideration of the literature suggested to us that it was generally adequate), it would not have captured rare or emerging serious medical events that were not already well studied or systematically reviewed. Detailed considerations of potential side effect differences were beyond the scope of this report but are considered elsewhere (47,81). Furthermore, studies that probably met the review criteria but would not fundamentally change the review findings were published between the completion of our review and publication of this article. Appendix Table 3 lists these studies, but they were not formally incorporated into this article.
Furthermore, the available evidence base in antidepressant treatments has limitations. Much of the evidence for serious suicide-related harms derives from short-term RCTs conducted for drug development and regulatory approval. This evidence may not be generalizable to primary care because of recruitment of motivated patients, exclusion of patients with the most severe depression or suicidal patients, high withdrawal rates (81), and sponsorship by the drug industry (which has been shown to be more likely to demonstrate positive effects than independent studies) (82). Also, high placebo effects are documented and may be due to several factors, including the trend toward less severely depressed patients in more recent clinical trials and the ameliorating effect on depression stemming from the support of being in a trial (83).
Good evidence supports the health benefits of programs that combine depression screening and feedback with the support of additional staff to provide some depression care in adults who visit primary care. However, available evidence does not support screening and feedback of results to the clinician in the absence of additional staff that provides some depression care support. The most comprehensive programs included clinician training and treatment protocols provided at the point of care, patient educational materials, office staff training and participation in providing post-visit follow-up, and available mental health referral. Closer monitoring may also be important for reducing uncommon, but potentially serious, adverse events.
Concerns about rare, but very serious, suicide-related antidepressant treatment harms have prompted repeated meta-analyses. The most current evidence on completed suicide does not demonstrate an effect of second generation antidepressants compared with placebo. However, several meta-analyses suggest a true short-term increase in suicidal behavior in young adults (aged 18 to 29 years) who receive antidepressants, particularly those with MDD and those receiving paroxetine. Thus, careful monitoring during early treatment, particularly in younger adults, seems prudent.
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Source: O'Connor EA, Whitlock EP, Beil TL, Gaynes BN. Screening for depression in adult patients in primary care settings: a systematic evidence review. Ann Intern Med 2009;151:793-803.
AHRQ Publication No. 10-05143-EF-4
Current as of December 2009
O'Connor EA, Whitlock EP, Beil TL, Gaynes BN. Screening for Depression in Adult Patients in Primary Care Settings: A Systematic Evidence Review. AHRQ Publication No. 10-05143-EF-4, December 2009. http://www.uspreventiveservicestaskforce.org/uspstf09/adultdepression/addeprart.htm