archived

Final Evidence Summary

Depression in Adults: Screening

December 15, 2009

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Table of Contents
Expand All

A Systematic Evidence Review

Date: December 2009

By Elizabeth A. O'Connor, PhD; Evelyn P. Whitlock, MD, MPH; Tracy L. Beil, MS; and Bradley N. Gaynes, MD, MPH

Address correspondence to: Elizabeth O'Connor, PhD, Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This article was first published in Annals of Internal Medicine in December 2009 (Ann Intern Med 2009;151:793-803. http://www.annals.org).

Return to Table of Contents

Background: In primary care settings, prevalence estimates of major depressive disorder range from 5% to 13% in all adults, with lower estimates in those older than 55 years (6% to 9%). In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended screening adults for depression in clinical practices that have systems to ensure accurate diagnosis, effective treatment, and follow-up.

Purpose: To conduct a targeted, updated systematic review for the U.S. Preventive Services Task Force about the benefits and harms of screening adult patients for depression in a primary care setting, the benefits of depression treatment in older adults, and the harms of depression treatment with antidepressant medications.

Data Sources: MEDLINE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PsycINFO (1998 to 2007), expert suggestions, and bibliographies of recent systematic reviews.

Study Selection: Fair- to good-quality randomized clinical trials or controlled clinical trials; systematic reviews; meta-analyses; and large observational studies of serious adverse events and early discontinuation due to adverse effects. All studies were published in English.

Data Extraction: Two investigators abstracted, critically appraised, and synthesized 33 articles that met inclusion criteria.

Data Synthesis: Nine fair- or good-quality trials indicate that primary care depression screening and care management programs with staff assistance, such as case management or mental health specialist involvement, can increase depression response and remission. Benefit was not evident in screening programs without staff assistance in depression care. Seven regulatory reviews or meta-analyses and 3 large cohort studies indicate no increased risk for completed suicide deaths with antidepressant treatment. Risk for suicidal behaviors was increased in young adults (aged 18 to 29 years) who received antidepressants, particularly those who received paroxetine, but was reduced in older adults.

Limitation: Examination of harms was limited to serious adverse events, and existing systematic reviews were primarily used. Additional studies published from 2007 to 2008 extend this review.

Conclusion: Depression screening programs without substantial staff-assisted depression care supports are unlikely to improve depression outcomes. Close monitoring of all adult patients who initiate antidepressant treatment, particularly those younger than 30 years, is important both for safety and to ensure optimal treatment.

Return to Table of Contents

Major depressive disorder (MDD) is common, with an estimated lifetime prevalence of 13.2%. In primary care settings, prevalence estimates of MDD range from 5% to 13% in all adults1,2, with lower estimates in those older than 55 years (6% to 9%)3,4. Primary care practitioners manage approximately one third to one half of non elderly adults5,6) and almost two thirds of older adults7 who received treatment for MDD. The severity of depressive symptoms in patients who receive treatment in primary care is equivalent to that of patients treated in psychiatric settings8. For example, approximately 43% of such primary care patients report some degree of suicidal ideation within the previous week8,9.

In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended screening adults for depression in clinical practices that have systems to ensure accurate diagnosis, effective treatment, and follow-up. Subsequent reviewers have concluded that screening does not improve health outcomes10, but care management systems for depressed patients improve depression remission rates11). Commentators on these divergent reviews have been divided12,13).

We conducted this systematic review to aid the USPSTF in updating its 2002 recommendation for adult depression screening in primary care. We sought to 1) identify evidence published since the previous review on the benefits of screening for depression in primary care and integrate it with the previously identified evidence and 2) review the evidence in several areas in which evidence was insufficient at the time of the previous review or not was examined by the previous review14. This includes the benefits of depression treatment in older adults, the harms of depression screening, and the harms of depression treatment with antidepressant medications.

Return to Table of Contents

Scope of the Review

We developed an analytic framework (Appendix Figure 1) and 5 key questions that focused on the evidence that the USPSTF required to update its recommendation by using the USPSTF's methods15.

  1. Is there direct evidence that screening for depression among adults and elderly patients in primary care reduces morbidity and/or mortality?
    1a. What is the effect of clinician feedback of screening test results (with or without additional care management support) on depression response and remission in screening-detected depressed patients receiving usual care?
  2. What are the adverse effects of screening for depressive disorders in adults and elderly patients in primary care?
  3. Is antidepressant and/or psychotherapy treatment of elderly depressed patients effective in improving health outcomes?
  4. What are the adverse effects of antidepressant treatment (particularly selective serotonin reuptake inhibitors [SSRIs] and other second-generation drugs) for depression in adults and elderly patients?

This article discusses methods and results for key questions 1, 1a, and 4. Detailed methods and results for the remaining key questions are in the full report16.

Data Sources and Searches

We used the Database of Abstracts of Reviews of Effects, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, and PsycINFO to search for relevant systematic reviews, meta-analyses, and primary studies published in English from January 1998 to December 2007. The full report provides the search strategies16.

Study Selection

Two investigators reviewed 4088 abstracts published in English and 412 full-text articles (Appendix Figure 2) against key question-specific inclusion and exclusion criteria (Appendix Table 1). Articles for key questions 1 and 1a were limited to randomized and controlled clinical trials that were conducted in primary care or similar settings. Key question 1 trials compared outcomes in screened and unscreened patients. Trials for key question 1a were required to have used the screening results for care decisions for intervention recipients and not for the control participants. Outcomes for these 2 questions were focused on depression response and remission.

We focused our review of harms of treatment (key question 4) on already-synthesized evidence, supplemented by large observational studies. Methods for incorporating systematic reviews and meta-analyses are detailed elsewhere (Appendix Table 2). We examined serious adverse effects associated with antidepressant treatment, including suicide-related events (completed suicide, serious self-harm or attempted suicide, suicidal ideation, or suicidal behavior [usually defined to include suicide attempts, preparatory acts, or nonfatal serious self-harm]), and serious psychiatric events, including hospitalization. For older adults, we also considered evidence of serious medical events (for example, upper gastrointestinal bleeding) that were associated with SSRI and other second-generation antidepressant use. We examined rates of early discontinuation as a proxy for less serious adverse effects, particularly discontinuation due to adverse effects as a measure of tolerability. We focused on second-generation antidepressants (SSRIs in particular) because of their preponderance of use in the United States17,18.

Updated Searching and Study Examination

Because of the delay between completion of the systematic review and publication, we repeated our search strategy through February 2009. We reviewed 800 abstracts against inclusion and exclusion criteria, and 21 seemed to meet criteria for this systematic review. After examining results of each of these new studies (as described in the abstracts), we determined that they would be unlikely to change our conclusions. Appendix Table 3 lists these studies.

Data Extraction and Quality Assessment

Two investigators rated articles for quality by using design-specific quality criteria on the basis of the USPSTF methods15. The National Institute for Health and Clinical Excellence19 criteria (for all study designs) and the Oxman criteria20 (for systematic reviews) supplemented these methods. One investigator abstracted data from included studies into evidence tables and another verified it. The full review shows complete quality criteria20.

Regulatory reviews provided unique challenges and could not be evaluated by using typical quality criteria. For example, their search approach was different because they can mandate that manufacturers supply requested data. Because of the large number of trials (often in the hundreds) and proprietary information involved, however, they did not provide detailed information about individual trials.

Data Synthesis and Analysis

Data synthesis was primarily qualitative because of clinical heterogeneity. For cohort studies included for key question 4, we calculated absolute event rates and CIs for suicide-related events on the basis of reported data if this information was not provided. The 95% CIs were calculated on the basis of a Poisson distribution by using the GENMOD procedure (SAS software, version 8.2, SAS Institute, Cary, North Carolina) with the RISK option. Similarly, for the meta-analyses of antidepressant trials included for key question 4, we calculated missing CIs by using the FREQ procedure.

Role of Funding Source

The Agency for Healthcare Research and Quality funded this work, provided project oversight, and assisted in external review of the draft report but had no role in the design, conduct, or reporting of the review. The authors worked with 4 USPSTF members at key points throughout the review process to develop the analytic framework and key questions and resolve issues about scope and approach. The draft systematic review was reviewed by 6 experts and was revised on the basis of their feedback.

Return to Table of Contents

Key Question 1

Is there direct evidence that screening for depression among adults and elderly patients in primary care reduces morbidity and/or mortality?

One fair-quality randomized, controlled trial (RCT) of primary care patients reported mixed results when screened participants were compared with an unscreened usual care group21 (Table). Concerns about the follow-up sample, however, limit our confidence in the results. At 3-month follow-up, the proportion of people who met criteria for depression, according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, was similar in the screened (37%) and usual care groups (46%) (P = 0.19), although power to detect a population-level effect was inadequate (n = 218). After the investigators controlled for baseline severity of depression (which differed between the screened and usual care groups in the full randomized sample), the mean reduction in symptom counts derived from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, was similar for the 2 groups (1.6 in screened patients vs. 1.5 in unscreened patients; P = 0.21). However, among the subset of patients who were depressed at baseline, screened patients were more likely than unscreened patients to be in complete remission at follow-up (≤1 symptom of depression in 48% of those screened vs. 27% of those not screened; P < 0.05). Only patients from 1 of the 2 study sites were included in the follow-up sample. At this site, only those with a diagnosis of depression at baseline and a random sample of the remaining participants (oversampling those with depressive symptoms at baseline), were reassessed at 3 months, thus limiting the study power to detect group differences and potentially introducing bias. Data were not presented on the baseline similarity between the follow-up sample and the original sample or between the intervention and control groups for the follow-up sample, which would have given some assurance that bias was minimized. This study was also at risk for intervention contamination because providers saw patients in both study conditions.

Key Question 1a

What is the effect of clinician feedback of screening test results (with or without additional care management support) on depression response and remission in screening-detected depressed patients receiving usual care?

Two good-quality22,23 and 6 fair-quality24-29 RCTs reported the effect of depression screening results feedback on health outcomes in screened populations (Table) and generally found that programs involving staff support in depression care can reduce depressive symptoms beyond usual care (Table and Appendix Table 4). Four of these studies involved general adult populations (n = 1908) 22,23,26,27, and 4 focused on older adults (n = 1443)24,25,28,29.

General Adult Populations

In general adult populations, 4 trials 22,23,26,27 screened a total of 38,843 primary care patients to detect 1908 depressed adult patients. Bergus and colleagues26 conducted a small, fair-quality RCT in a rural setting that provided no depression care support beyond simple feedback of screening results and was not effective in reducing symptoms of depression. This trial did not report blinding of outcomes assessment and was underpowered to detect anything other than a very large effect. Another small, fair-quality RCT reported improved depressive symptoms but had a highly selected participant sample because investigators only enrolled screened adults with newly detected depression who were not seeking treatment of depression27. In this trial, clinicians received a detailed depression treatment protocol during the visit that included a recommended follow-up schedule and educational materials for the patient. Providers also received logistical support from other staff for scheduling follow-up visits and facilitating referrals. Both of these trials had very small samples and were vulnerable to contamination because providers saw both intervention and control participants.

Two good-quality trials with considerably higher-intensity interventions involving depression care by other staff were effective in improving depression outcomes22,23, particularly for adults with newly detected depression. These trials included such elements as intensive clinician and office support staff training, support staff or specialty mental health provider participation in ongoing depression care, and several follow-up contacts. The more intensive of these trials23 found that 40% of participants in either of the 2 treatment groups were still positive for depression on the Composite International Diagnostic Interview 2-item screen compared with 50% of usual care participants (P = 0.001). The effect was maintained at 12 months. At 5-year follow-up, program benefits were sustained for 1 of the 2 treatment groups, in which positive Composite International Diagnostic Interview screening scores were 36% among intervention participants and 44% among usual care participants (P = 0.05)30. These results provide good evidence for the effectiveness of their program. It is impossible to determine, however, what role the screening component played in the success of their program. Furthermore, although this intervention was proven feasible for primary care settings, it involved substantial institutional commitment and may not reflect the care that would be found currently in most settings.

Older Adult Populations

In screening focused on older adults, 4 fairly large-scale trials24,25,28,29 screened 12,432 primary care patients to identify 1443 depressed older adults to test the effect of screening feedback with some care supports on remission and symptom reduction. Only 1 of 4 interventions in these trials improved depression beyond usual care29. This trial attempted to identify patients with any of 5 high-risk conditions, 1 of which was depression. It involved the assistance of a case manager, who conducted an in-depth assessment and then referred the patient to primary or specialty care or to a multidisciplinary geriatric assessment team for further assessment. The case manager also provided patient education and follow-up. After 1 year, there was a 1-point difference in improvement between the groups on the 30-point Geriatric Depression Scale (P = 0.05), which may not reflect a clinically important difference. Although the trial was of good quality overall, this specific comparison was not a randomized comparison because it included only participants who had a positive screening result for depression. Data on baseline comparability in this subset were not provided. Also, because the sample was limited to patients who scored in a "high-risk" range for multiple conditions, the generalizability of this trial to the general primary care population of older adults may be limited. The remaining 3 trials in older adults, which found no treatment effects, had either fairly high attrition24, 25 or differential attrition throughout the recruitment process28).

Key Question 2

What are the adverse effects of screening for depressive disorders in adults and elderly patients in primary care?

No evidence was found that addressed harms of screening.

Key Question 3

Is antidepressant and/or psychotherapy treatment of elderly depressed patients effective in improving health outcomes?

We found evidence that pharmacologic and psychotherapeutic approaches are effective in older adults. Details can be found in the full report16.

Key Question 4

What are the adverse effects of antidepressant treatment (particularly SSRIs and other second-generation drugs) for depression in adults and elderly patients?

We found 7 regulatory reviews or published meta-analyses reported in 10 articles 34-43 that each reviewed an average of 326 (range, 57 to 702) short-term RCTs of antidepressant treatment versus placebo in adults with MDD or other psychiatric conditions. Overall, these meta-analyses suggested no increase in suicide but did suggest age-related effects on suicide-related and other outcomes (Appendix Table 5). Most patients (88% to 95%) tolerated these medications, although adverse side effects and overall discontinuation rates were higher in older adults44-51. Large population-based observational studies suggest that upper gastrointestinal bleeding is a concern for older adults, particularly when antidepressants are combined with nonsteroidal anti-inflammatory drugs (NSAIDs).

Completed Suicide

None of the 7 meta-analyses supplied clear evidence that use of second-generation antidepressants (or SSRIs in particular) increased odds of completed suicide in adults of any age compared with placebo. However, power to detect these rare events was limited, given very few suicides (7 to 43 total suicides among all patients per review). In most meta-analyses, pooled rates of suicide ranged from 3.8 to 8.8 per 10,000 adults who received antidepressants compared with 2.3 to 9.3 per 10,000 patients who received placebo. The 2 meta-analyses that represented outliers were probably because of methodological differences in meta-analysis design16. A report by the U.S. Food and Drug Administration estimated many fewer suicides than other reviews and used a hierarchical outcome assignment method administered by trial sponsors, which may have underascertained suicides34,35. The much higher estimates of suicide rates in patients who received antidepressants and placebo in another review37 could reflect the greater disease severity among studied patients. In addition, there were several quality concerns about this review, which include unclear event classification schema and lack of quality appraisal.

To complement short-term data from trials, we examined 3 fair- or good-quality large observational studies that reported suicide with antidepressant treatment in a total of 383,796 patients in a large HMO in the United States and in general practices in the United Kingdom52-54 (Appendix Table 6). Among the 2 highest-quality studies, crude suicide rates were 4.7 and 4.8 per 10,000 persons after 6 to 8 months of receiving treatment primarily with second-generation antidepressants, with slightly higher rates reported among those younger than 30 years. These studies also indicated higher risk for suicide among men compared with women. Although these observational studies do not provide comparative information for persons who were not receiving antidepressants, they give credence to the estimate of approximately 4 per 10,000 suicide cases among patients who received antidepressants, which was found most consistently in the meta-analyses of short-term trial data.

Suicidal Behaviors

Suicidal behaviors were defined differently across studies but usually included suicide attempts, preparatory acts, or serious self-harm. Results from 5 meta-analyses that reported 9 separate pooled estimates showed no statistically significant differences in the odds of suicidal behaviors in adults who received treatment with antidepressants compared with placebo, with several exceptions. In 1 fair-quality systematic review, odds of suicidal behaviors were increased in adults of all ages who were treated with SSRIs for any indication (odds ratio [OR], 2.70 [CI, 1.22 to 6.97])42; this report was limited to published studies only and did not have clear adverse event ascertainment for most patients. In a review of regulatory data of placebo-controlled trials by the U.S. Food and Drug Administration, odds of suicidal behavior were approximately doubled in adults younger than 25 years who received second-generation antidepressants for all psychiatric disorders (OR, 2.31 [CI, 1.02 to 5.64])34. In contrast, the odds of suicidal behaviors were unchanged among middle-aged adults and were greatly reduced in older adults receiving second-generation antidepressants (OR, 0.06 [CI, 0.01 to 0.58])35.

The highest odds of nonfatal suicidal behavior were reported in adults of all ages who received treatment for MDD with paroxetine compared with placebo (OR, 6.70 [CI, 1.1 to 149.4]). The increased risk is assumed to be primarily in young adults because most events (8 of 11) occurred in those aged 18 to 29 years. This good-quality review conducted by the manufacturer used independent, adverse event assignment by experts.

Two good-quality observational studies suggested that, in contrast to a higher risk for suicide in men, there were no sex-based differences in risks for self-harm, but there were age-related differences53,54. Suicide attempts were greater in younger persons (31.4 per 10,000 person-years in those younger than 18 years vs. 7.8 per 10,000 person-years for those 18 years or older)54 and rates of self-harm were higher in those aged 19 to 30 years (214.7 per 10,000 person-years) than those older than 30 years (88.3 per 10,000 person-years)53. For all ages, the highest risk for suicidal behaviors occurred during the month before treatment initiation and the first month of treatment54. Rates of suicidal behaviors in real-world practice situations were similar to trial rates for 1 study54 but were substantially higher in the other53; this higher rate could reflect real differences or may represent study differences in definitions (and perhaps ascertainment).

Suicidal Ideation

Three meta-analyses used a combined end point of suicidal ideation or behavior34,38,41. They found no differences between patients who received treatment with antidepressants or placebo, except for a reduction in older adults who received treatment with second-generation antidepressants for all psychiatric conditions (OR, 0.39 [CI, 0.18 to 0.78])34.

Serious Psychiatric Events

We found no existing systematic reviews that addressed serious psychiatric events, such as psychiatric hospitalization or precipitation of mania. Observational data did not provide reliable estimates of the effect of antidepressant use on these outcomes.

Tolerability

We found 8 systematic reviews44-51 and 2 large cohort or uncontrolled treatment trials55,56 that reported overall discontinuation rates or discontinuation because of adverse effects. Rates of early treatment discontinuation ranged from 16% to 29% in meta-analyses of antidepressant trials in primary care patients with depression, with a best estimate of 20% to 23% in "real-world" trials of primary care. Early discontinuation could be due to lack of effect, adverse effects, or other unknown reasons and therefore does not clearly reflect tolerability. Rates of early discontinuation due to adverse effects were lower (5% to 12%) and are a direct reflection of tolerability. Patients 55 years or older had higher discontinuation rates overall (27% to 36%) and because of adverse effects (17% to 22%). With longer follow-up, adverse event discontinuation rates increased, particularly in those who switched or augmented medications because of lack of efficacy or intolerable side effects.

Older Adults

As reported earlier, older adults were at lower risk for suicide-related harms during antidepressant treatment. For serious medical events in older adults, we found a fair-quality systematic review of 6 large observational studies from Denmark, Canada, the United Kingdom, and Holland that examined bleeding risk with SSRIs57. Among 26,005 Danish patients 16 years or older (almost half of whom were 60 years or older), risk for hospitalization for upper gastrointestinal bleeding was increased compared with nonrecipients during intervals of current SSRI use only, with an excess risk of 3.1 per 1000 treatment-years. In 317,824 Canadian patients 65 years or older who received antidepressants, risk for hospitalization for upper gastrointestinal bleeding increased greatly with age, from 4.1 hospitalizations per 1000 person-years of SSRI treatment in those aged 65 to 70 years to 12.3 hospitalizations per 1000 person-years in octogenarians. Excess hospitalizations for upper gastrointestinal bleeding were increased 5-fold (33.2 per 1000 treatment-years) in persons with previous upper gastrointestinal bleeding. In some studies58-60, but not all61, odds of upper gastrointestinal bleeding among SSRI recipients were further increased at least 2- to 3-fold when SSRI recipients were also receiving NSAIDs, with less risk associated with concurrent use of aspirin or other anticoagulant medications.

Return to Table of Contents

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.

Conclusion

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.

Return to Table of Contents

This document is in the public domain within the United States.

Requests for linking or to incorporate content in electronic resources should be sent via the USPSTF contact form.

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.

Return to Table of Contents
  1. Committee on Safety of Medicines. Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants. London: Medicines and Healthcare products Regulatory Agency; 2004. Accessed at www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf on 29 September 2009
  2. Briefing document: paroxetine adult suicidality analysis: major depressive disorder and non-major depressive disorder. GlaxoSmithKline; 2006. Accessed at http://us.gsk.com/docs-pdf/media-news/briefing_doc.pdf on 29 September 2009.
  3. Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005;330:396. [PMID: 15718539]
  4. Storosum JG, van Zwieten BJ, van den Brink W, Gersons BP, Broekmans AW. Suicide risk in placebo-controlled studies of major depression. Am J Psychiatry 2001;158:1271-5. [PMID: 11481162]
  5. Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord 2000;58: 19-36. [PMID: 10760555]
  6. Arroll B, Macgillivray S, Ogston S, Reid I, Sullivan F, Williams B, et al. Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis. Ann Fam Med 2005;3:449-56. [PMID: 16189062]
  7. Beasley CM Jr, Nilsson ME, Koke SC, Gonzales JS. Efficacy, adverse events, and treatment discontinuations in fluoxetine clinical studies of major depression: a meta-analysis of the 20-mg/day dose. J Clin Psychiatry 2000;61:722-8. [PMID: 11078032]
  8. Gartlehner G, Hansen RA, Thieda P, DeVeaugh-Geiss A, Gaynes BN, Krebs EE, et al. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Review No. 7-EHC007-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2007.
  9. MacGillivray S, Arroll B, Hatcher S, Ogston S, Reid I, Sullivan F, et al. Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis. BMJ 2003;326:1014. [PMID: 12742924]
  10. Mottram P, Wilson K, Strobl J. Antidepressants for depressed elderly. Cochrane Database Syst Rev 2006:CD003491. [PMID: 16437456]
  11. Mulrow CD, Williams JW Jr, Chiquette E, Aguilar C, Hitchcock-Noel P, Lee S, et al. Efficacy of newer medications for treating depression in primary care patients. Am J Med 2000;108:54-64. [PMID: 11059441]
  12. Williams JW Jr, Mulrow CD, Chiquette E, Noël PH, Aguilar C, Cornell J. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med 2000;132:743-56. [PMID: 10787370]
  13. Jick SS, Dean AD, Jick H. Antidepressants and suicide. BMJ 1995;310: 215-8. [PMID: 7677826]
  14. Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, Moseley J, et al. Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study. BMJ 2005;330:389. [PMID: 15718538]
  15. Simon GE, Savarino J, Operskalski B, Wang PS. Suicide risk during antidepressant treatment. Am J Psychiatry 2006;163:41-7. [PMID: 16390887]
  16. Kroenke K, West SL, Swindle R, Gilsenan A, Eckert GJ, Dolor R, et al. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA 2001;286:2947-55. [PMID: 11743835]
  17. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006;163: 1905-17. [PMID: 17074942]
  18. Dalton SO, Sørensen HT, Johansen C. SSRIs and upper gastrointestinal bleeding: what is known and how should it influence prescribing? CNS Drugs 2006;20:143-51. [PMID: 16478289]
  19. de Abajo FJ, Rodríguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999;319:1106-9. [PMID: 10531103]
  20. van Walraven C, Mamdani MM, Wells PS, Williams JI. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ 2001;323:655-8. [PMID: 11566827]
  21. Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62:1097-106. [PMID: 16203955]
  22. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617-27. [PMID: 15939839]
  23. Lyness JM, Caine ED, King DA, Cox C, Yoediono Z. Psychiatric disorders in older primary care patients. J Gen Intern Med 1999;14:249-54. [PMID: 10203638]
  24. Schulberg HC, Mulsant B, Schulz R, Rollman BL, Houck PR, Reynolds CF 3rd. Characteristics and course of major depression in older primary care patients. Int J Psychiatry Med 1998;28:421-36. [PMID: 10207741]
  25. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, et al; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCSR). JAMA 2003;289:3095-105. [PMID: 12813115]
  26. Pincus HA, Tanielian TL, Marcus SC, Olfson M, Zarin DA, Thompson J, et al. Prescribing trends in psychotropic medications: primary care, psychiatry, and other medical specialties. JAMA 1998;279:526-31. [PMID: 9480363]
  27. Harman JS, Veazie PJ, Lyness JM. Primary care physician office visits for depression by older Americans. J Gen Intern Med 2006;21:926-30. [PMID: 16918736]
  28. Gaynes BN, Rush AJ, Trivedi M, Wisniewski SR, Balasubramani GK, Spencer DC, et al. A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial. Gen Hosp Psychiatry 2005;27:87-96. [PMID: 15763119]
  29. Gaynes BN, Rush AJ, Trivedi MH, Wisniewski SR, Balasubramani GK, Spencer DC, et al. Major depression symptoms in primary care and psychiatric care settings: a cross-sectional analysis. Ann Fam Med 2007;5:126-34. [PMID: 17389536]
  30. Gilbody S, House AO, Sheldon TA. Screening and case finding instruments for depression. Cochrane Database Syst Rev 2005:CD002792. [PMID: 16235301]
  31. Gilbody S, Whitty P, Grimshaw J, Thomas R. Educational and organizational interventions to improve the management of depression in primary care: a systematic review. JAMA 2003;289:3145-51. [PMID: 12813120]
  32. Coyne JC, Palmer SC, Sullivan PA. Screening for depression in adults [Letter]. Ann Intern Med 2003;138:767. [PMID: 12729435]
  33. Hickie IB, Davenport TA, Ricci CS. Screening for depression in general practice and related medical settings. Med J Aust 2002;177 Suppl:S111-6. [PMID: 12358569]
  34. Pignone MP, Gaynes BN, Rushton JL, Burchell CM, Orleans CT, Mulrow CD, et al. Screening for depression in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:765-76. [PMID: 12020146]
  35. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al; Methods Work Group, Third US Preventive Services Task Force. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001;20:21-35. [PMID: 11306229]
  36. Whitlock EP, O'Connor E, Beil T, Gaynes B. Screening for Depression in Adults and Older Adults in Primary Care: An Updated Systematic Review. 2009. Agency for Healthcare Research and Quality. Accessed at http://www.uspreventiveservicestaskforce.org/uspstf/uspstopics.htm on 24 September 2009.
  37. Pirraglia PA, Stafford RS, Singer DE. Trends in prescribing of selective serotonin reuptake inhibitors and other newer antidepressant agents in adult primary care. Prim Care Companion J Clin Psychiatry 2003;5:153-157. [PMID: 15213776]
  38. Hansen RA, Gartlehner G, Lohr KN, Gaynes BN, Carey TS. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med 2005;143:415-26. [PMID: 16172440]
  39. National Institute for Clinical Excellence. Guideline Development Methods: Information for National Collaborating Centres and Guideline Developers. London: NICE; 2004. Accessed at www.nice.org.uk/nicemedia/pdf/CG23fullguideline.pdf on 24 September 2009.
  40. Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol 1991;44:1271-8. [PMID: 1834807]
  41. Williams JW Jr, Mulrow CD, Kroenke K, Dhanda R, Badgett RG, Omori D, et al. Case-finding for depression in primary care: a randomized trial. Am J Med 1999;106:36-43. [PMID: 10320115]
  42. Rost K, Nutting P, Smith J, Werner J, Duan N. Improving depression outcomes in community primary care practice: a randomized trial of the quEST intervention. Quality Enhancement by Strategic Teaming. J Gen Intern Med 2001;16:143-9. [PMID: 11318908]
  43. Wells KB, Sherbourne C, Schoenbaum M, Duan N, Meredith L, Unützer J, et al. Impact of disseminating quality improvement programs for depression in managed primary care: a randomized controlled trial. JAMA 2000;283:212-20. [PMID: 10634337]
  44. Whooley MA, Stone B, Soghikian K. Randomized trial of case-finding for depression in elderly primary care patients. J Gen Intern Med 2000;15:293-300. [PMID: 10840264]
  45. Callahan CM, Hendrie HC, Dittus RS, Brater DC, Hui SL, Tierney WM. Improving treatment of late life depression in primary care: a randomized clinical trial. J Am Geriatr Soc 1994;42:839-46. [PMID: 8046193]
  46. Bergus GR, Hartz AJ, Noyes R Jr, Ward MM, James PA, Vaughn T, et al. The limited effect of screening for depressive symptoms with the PHQ-9 in rural family practices. J Rural Health 2005;21:303-9. [PMID: 16294652]
  47. Jarjoura D, Polen A, Baum E, Kropp D, Hetrick S, Rutecki G. Effectiveness of screening and treatment for depression in ambulatory indigent patients. J Gen Intern Med 2004;19:78-84. [PMID: 14748864]
  48. Bosmans J, de Bruijne M, van Hout H, van Marwijk H, Beekman A, Bouter L, et al. Cost-effectiveness of a disease management program for major depression in elderly primary care patients. J Gen Intern Med 2006;21:1020-6. [PMID: 16836625]
  49. Rubenstein LZ, Alessi CA, Josephson KR, Trinidad Hoyl M, Harker JO, Pietruszka FM. A randomized trial of a screening, case finding, and referral system for older veterans in primary care. J Am Geriatr Soc 2007;55:166-74. [PMID: 17302651]
  50. Wells K, Sherbourne C, Schoenbaum M, Ettner S, Duan N, Miranda J, et al. Five-year impact of quality improvement for depression: results of a group-level randomized controlled trial. Arch Gen Psychiatry 2004;61:378-86. [PMID: 15066896]
  51. Sherbourne CD, Wells KB, Duan N, Miranda J, Unützer J, Jaycox L, et al. Long-term effectiveness of disseminating quality improvement for depression in primary care. Arch Gen Psychiatry 2001;58:696-703. [PMID: 11448378]
  52. Rost K, Nutting PA, Smith J, Werner JJ. Designing and implementing a primary care intervention trial to improve the quality and outcome of care for major depression. Gen Hosp Psychiatry 2000;22:66-77. [PMID: 10822094]
  53. Rost K, Nutting P, Smith JL, Elliott CE, Dickinson M. Managing depression as a chronic disease: a randomised trial of ongoing treatment in primary care. BMJ 2002;325:934-7. [PMID: 12399343]
  54. Levenson M, Holland C. Statistical evaluation of suicidality in adults treated with antidepressants. In: Laughren TP, ed. Memorandum: overview for December 13 meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). Silver Spring, MD: Center for Drug Evaluation and Research, U.S. Food and Drug Administration; 2006. Accessed at http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf [PDF file, 1 MB; PDF Help] on 29 September 2009.
  55. Stone M, Jones ML. Clinical review: relationship between antidepressant drugs and suicidality in adults. In: Laughren TP, ed. Memorandum: overview for December 13 meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). Silver Spring, MD: Center for Drug Evaluation and Research, U.S. Food and Drug Administration; 2006. Accessed at http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf [PDF file, 1 MB; PDF Help] on 29 September 2009.
  56. Hammad TA, Laughren TP, Racoosin JA. Suicide rates in short-term randomized controlled trials of newer antidepressants. J Clin Psychopharmacol 2006;26:203-7. [PMID: 16633153]
  57. Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry 2003;160:790-2. [PMID: 12668373]
  58. Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ 2005;330:385. [PMID: 15718537]
  59. Saperia J, Ashby D, Gunnell D. Suicidal behaviour and SSRIs: updated meta-analysis [Letter]. BMJ 2006;332:1453. [PMID: 16777898]
  60. Möller HJ, Baldwin DS, Goodwin G, Kasper S, Okasha A, Stein DJ, et al; WPA Section on Pharmacopsychiatry. Do SSRIs or antidepressants in general increase suicidality? WPA Section on Pharmacopsychiatry: consensus statement. Eur Arch Psychiatry Clin Neurosci 2008;258 Suppl 3:3-23. [PMID: 18668279]
  61. Papakostas GI, Nelson JC, Kasper S, Möller HJ. A meta-analysis of clinical trials comparing reboxetine, a norepinephrine reuptake inhibitor, with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Eur Neuropsychopharmacol 2008;18:122-7. [PMID: 17719752]
  62. Rahme E, Dasgupta K, Turecki G, Nedjar H, Galbaud du Fort G. Risks of suicide and poisoning among elderly patients prescribed selective serotonin reuptake inhibitors: a retrospective cohort study. J Clin Psychiatry 2008;69:349-57. [PMID: 18278986]
  63. Dalton SO, Johansen C, Mellemkjaer L, Nørgård B, Sørensen HT, Olsen JH. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003; 163:59-64. [PMID: 12523917]
  64. Tata LJ, Fortun PJ, Hubbard RB, Smeeth L, Hawkey CJ, Smith CJ, et al. Does concurrent prescription of selective serotonin reuptake inhibitors and nonsteroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding? Aliment Pharmacol Ther 2005;22:175-81. [PMID: 16091054]
  65. Pignone MP, Gaynes BN, Rushton JL, Burchell CM, Orleans CT, Mulrow CD, et al. Screening for depression in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:765-76. [PMID: 12020146]
  66. Gilbody S, Sheldon T, Wessely S. Should we screen for depression? BMJ 2006;332:1027-30. [PMID: 16644833]
  67. Palmer SC, Coyne JC. Screening for depression in medical care: pitfalls, alternatives, and revised priorities. J Psychosom Res 2003;54:279-87. [PMID: 12670603]
  68. Simon GE, VonKorff M. Recognition, management, and outcomes of depression in primary care. Arch Fam Med 1995;4:99-105. [PMID: 7842160]
  69. Goldberg D, Privett M, Ustun B, Simon G, Linden M. The effects of detection and treatment on the outcome of major depression in primary care: a naturalistic study in 15 cities. Br J Gen Pract 1998;48:1840-4. [PMID: 10198504]
  70. Thompson C, Ostler K, Peveler RC, Baker N, Kinmonth AL. Dimensional perspective on the recognition of depressive symptoms in primary care: The Hampshire Depression Project 3. Br J Psychiatry 2001;179:317-23. [PMID: 11581111]
  71. Schwenk TL, Coyne JC, Fechner-Bates S. Differences between detected and undetected patients in primary care and depressed psychiatric patients. Gen Hosp Psychiatry 1996;18:407-15. [PMID: 8937906]
  72. Oxman TE, Sengupta A. Treatment of minor depression. Am J Geriatr Psychiatry 2002;10:256-64. [PMID: 11994212]
  73. Olfson M, Marcus SC, Tedeschi M, Wan GJ. Continuity of antidepressant treatment for adults with depression in the United States. Am J Psychiatry 2006; 163:101-8. [PMID: 16390896]
  74. Simon GE. Evidence review: efficacy and effectiveness of antidepressant treatment in primary care. Gen Hosp Psychiatry 2002;24:213-24. [PMID: 12100832]
  75. Solberg LI, Trangle MA, Wineman AP. Follow-up and follow-through of depressed patients in primary care: the critical missing components of quality care. J Am Board Fam Pract 2005;18:520-7. [PMID: 16322414]
  76. Badamgarav E, Weingarten SR, Henning JM, Knight K, Hasselblad V, Gano A Jr, et al. Effectiveness of disease management programs in depression: a systematic review. Am J Psychiatry 2003;160:2080-90. [PMID: 14638573]
  77. Gensichen J, Beyer M, Muth C, Gerlach FM, Von Korff M, Ormel J. Case management to improve major depression in primary health care: a systematic review. Psychol Med 2006;36:7-14. [PMID: 16356292]
  78. Neumeyer-Gromen A, Lampert T, Stark K, Kallischnigg G. Disease management programs for depression: a systematic review and meta-analysis of randomized controlled trials. Med Care 2004;42:1211-21. [PMID: 15550801]
  79. Williams JW Jr, Gerrity M, Holsinger T, Dobscha S, Gaynes B, Dietrich A. Systematic review of multifaceted interventions to improve depression care. Gen Hosp Psychiatry 2007;29:91-116. [PMID: 17336659]
  80. Wang PS, Simon G, Kessler RC. The economic burden of depression and the cost-effectiveness of treatment. Int J Methods Psychiatr Res 2003;12:22-33. [PMID: 12830307]
  81. Juurlink DN, Mamdani MM, Kopp A, Redelmeier DA. The risk of suicide with selective serotonin reuptake inhibitors in the elderly. Am J Psychiatry 2006; 163:813-21. [PMID: 16648321]
  82. Barak Y, Olmer A, Aizenberg D. Antidepressants reduce the risk of suicide among elderly depressed patients. Neuropsychopharmacology 2006;31:178-81. [PMID: 16123751]
  83. Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2008;27:31-40. [PMID: 17919277]
  84. National Collaborating Centre for Mental Health. Depression: Management of Depression in Primary and Secondary Care. Clinical Guideline 23. 1-63. London: NICE; 2004.
  85. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 2003;326: 1167-70. [PMID: 12775614]
  86. Ernst CL, Goldberg JF. Antisuicide properties of psychotropic drugs: a critical review. Harv Rev Psychiatry 2004;12:14-41. [PMID: 14965852]
  87. Whitlock EP, Lin JS, Chou R, Shekelle P, Robinson KA. Using existing systematic reviews in complex systematic reviews. Ann Intern Med 2008;148: 776-82. [PMID: 18490690]
  88. Schreuders B, van Marwijk H, Smit J, Rijmen F, Stalman W, van Oppen P. Primary care patients with mental health problems: outcome of a randomised clinical trial. Br J Gen Pract 2007;57:886-91. [PMID: 17976289]
  89. van Marwijk HW, Ader H, de Haan M, Beekman A. Primary care management of major depression in patients aged > or = 55 years: outcome of a randomised clinical trial. Br J Gen Pract 2008;58:680-6, I-II; discussion 687. [PMID: 18826778]
  90. Wang PS, Simon GE, Avorn J, Azocar F, Ludman EJ, McCulloch J, et al. Telephone screening, outreach, and care management for depressed workers and impact on clinical and work productivity outcomes: a randomized controlled trial. JAMA 2007;298:1401-11. [PMID: 17895456]
  91. Nelson JC, Delucchi K, Schneider LS. Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am J Geriatr Psychiatry 2008;16:558-67. [PMID: 18591576]
  92. Pinquart M, Duberstein PR, Lyness JM. Effects of psychotherapy and other behavioral interventions on clinically depressed older adults: a meta-analysis. Aging Ment Health 2007;11:645-57. [PMID: 18074252]
  93. Sneed JR, Rutherford BR, Rindskopf D, Lane DT, Sackeim HA, Roose SP. Design makes a difference: a meta-analysis of antidepressant response rates in placebo-controlled versus comparator trials in late-life depression. Am J Geriatr Psychiatry 2008;16:65-73. [PMID: 17998306]
  94. Wilson KC, Mottram PG, Vassilas CA. Psychotherapeutic treatments for older depressed people. Cochrane Database Syst Rev 2008:CD004853. [PMID: 18254062]
  95. Aursnes I, Gjertsen MK. Common adverse events associated with an SSRI: meta-analysis of early paroxetine data. Pharmacoepidemiol Drug Saf 2008;17: 707-13. [PMID: 18383561]
  96. Barbui C, Esposito E, Cipriani A. Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies. CMAJ 2009;180: 291-7. [PMID: 19188627]
  97. Beasley CM Jr, Ball SG, Nilsson ME, Polzer J, Tauscher-Wisniewski S, Plewes J, et al. Fluoxetine and adult suicidality revisited: an updated meta-analysis using expanded data sources from placebo-controlled trials. J Clin Psychopharmacol 2007;27:682-6. [PMID: 18004137]
  98. Cipriani A, Geddes JR, Furukawa TA, Barbui C. Metareview on short-term effectiveness and safety of antidepressants for depression: an evidence-based approach to inform clinical practice. Can J Psychiatry 2007;52:553-62. [PMID: 17953159]
  99. Cooper-Kazaz R, Lerer B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol 2008;11:685-99. [PMID: 18047754]
  100. de Abajo FJ, García-Rodríguez LA. Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents. Arch Gen Psychiatry 2008;65:795-803. [PMID: 18606952]
  101. Deshauer D, Moher D, Fergusson D, Moher E, Sampson M, Grimshaw J. Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials. CMAJ 2008;178:1293- 301. [PMID: 18458261]
  102. Hansen R, Gaynes B, Thieda P, Gartlehner G, Deveaugh-Geiss A, Krebs E, et al. Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants. Psychiatr Serv 2008;59:1121-30. [PMID: 18832497]
  103. Katzman MA, Tricco AC, McIntosh D, Filteau MJ, Bleau P, Chokka PR, et al. Paroxetine versus placebo and other agents for depressive disorders: a systematic review and meta-analysis. J Clin Psychiatry 2007;68:1845-59. [PMID: 18162015]
  104. Marcinko D. Antidepressants and suicidality: the basis of controversies. Psychiatr Danub 2007;19:238-40. [PMID: 17914327]
  105. Marks DM, Park MH, Ham BJ, Han C, Patkar AA, Masand PS, et al. Paroxetine: safety and tolerability issues. Expert Opin Drug Saf 2008;7:783-94. [PMID: 18983224]
Return to Table of Contents

KQ1 and KQ1a: Screening trials

Inclusion criteria

  1. Screening: study of depression screening.
  2. Requires 1 of the following outcomes: depressive symptoms, quality-of-life ratings, assessments of functioning, depressive illness diagnosis, suicidality (attempts or ideation), change in health status (e.g., death, improvement in comorbid disorders, and reduction in physical symptoms).

Exclusion criteria

  1. Focus on inpatient, residential treatment, psychiatric, or community settings.
  2. Focus on interventions that are not primary care feasible or referable (e.g., electroconvulsive therapy).
  3. Does not meet quality criteria, including follow-up <6 wk.
  4. Focus on children or adolescents.
  5. None of the outcomes listed above.
  6. Focus on pregnancy-related screening.
  7. Examination of genetic modifiers.
  8. Does not meet any inclusion criterion.
  9. Not a general primary care population.
  10. Not English language or nondeveloped country.
  11. Noncomparative study or excluded design.
  12. Comparative effectiveness study.
  13. Missing both depression-specific screen and depression-specific outcome.
  14. Screen not used in clinical care.

KQ4: Harms of depression treatment with antidepressants

Inclusion criteria

  1. Systematic review; regulatory review; large cohort, or large, prospective observational study addressing adverse events associated with depression treatment or screening.
  2. For studies of suicidality
    1. Minimum of 10 000 participants for cohort or observational study.
    2. Minimum follow-up of 6 months.
  3. For studies of nonsuicidality harms
    1. Minimum of 1000 participants for cohort or observational studies.
    2. Minimum follow-up of 3 months.
    3. May include comparative effectiveness without control group if absolute rates of harms in an understudied population are provided.

Exclusion criteria

  1. Focus on inpatient, residential treatment, psychiatric, or community settings.
  2. Focus on interventions that are not primary care feasible or referable (e.g., electroconvulsive therapy).
  3. Does not meet quality criteria.
  4. Focus on children or adolescents.
  5. None of the adverse effects of interest to our review above.
  6. Focus on pregnancy-related screening.
  7. Updated or covered by another more recent meta-analysis or systematic review.
  8. Does not meet any inclusion criterion.
  9. Not a general primary care population.
  10. Not English language or nondeveloped country.
  11. Not a study design specified above.
  12. Comparative effectiveness study.

KQ = key question.
*Go to full report for other KQ criteria16.

Return to Table of Contents

Figure 1. Analytic framework and key questions. Go to Text Description for details.

Text Description

The figure depicts the analytic framework. At the top of the figure is a circle with a "1" in it for key question 1. It points to a rectangle on the right side that reads:

"Diagnosis of a depressive illness
Symptoms of depression
Quality-of-life ratings
Assessments of functioning
Suicidality (attempts or ideation)
Change in health status (e.g., death, improvement in comorbid disorders, reduction in physical symptoms) "

On the left side is the text which reads: "Adults aged 18-64 y; Adults aged ≥65 y." From that text is an arrow which points both to a pill-shaped box and down to an oval text box and the number "2" (for key question 2); the arrow points down to the oval which states "Adverse effects". The pill-shaped box states "Patients identified with depression". Another arrow labeled "3" points from this box to the box on the right, and also down to an oval text box and the number "4" (for key question 4). This second oval also reads, "Adverse effects".

Key Questions

  1. Is there direct evidence that screening for depression among adults and elderly patients in primary care reduces morbidity and/or mortality?
    1. What is the effect of clinician feedback of screening test results (with or without additional care management support) on depression response and remission in screening-detected depressed patients receiving usual care?
  2. What are the adverse effects of screening for depressive disorders in adults and elderly patients in primary care?
  3. Is antidepressant and/or psychotherapy treatment of elderly depressed patients effective in improving health outcomes?
  4. What are the adverse effects of antidepressant treatment (particularly SSRIs and other second-generation drugs) for depression in adults and elderly patients?

SSRI = selective serotonin reuptake inhibitor.

Return to Table of Contents

Flow chart showing process and criteria of which literature was included in this analysis. Abstracts reviewed from searches for KQ1, 1a, 2, 3, and 4 (n = 4088); Articles reviewed from outside sources: 2001 review, experts, reference lists, and others (n = 296); Total articles reviewed (n = 412); Articles reviewed for KQ1, 1a, and 2 (n = 248); Articles reviewed for KQ3 (n = 83); Articles reviewed for KQ4 (n = 98). Articles excluded (n = 236)* 1 article excluded for quality. Articles excluded (n = 80)* 1 article excluded for insufficient information to assess quality. Articles excluded (n = 73)* 4 articles excluded for insufficient quality. Trials included: KQ1: 1, KQ1a: 8 (in 11 articles), KQ2: 0. Studies included (n = 3). Studies included (n = 21 in 25 publications), Suicide: 10 (in 14 articles), Tolerability: 10 (in 10 articles), Older adults: 1.

KQ = key question.
* Numbers differ slightly from the full report 16 because only articles relevant to the more limited body of literature discussed in this publication are included in this figure.

Return to Table of Contents

Consistent with recently articulated methods84, we initially conducted a comprehensive search of systematic reviews by using MEDLINE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Health Technology Assessments, and PsycINFO from 1998 to August 2006. We identified reviews that were relevant to 1 or more KQ on the basis of populations, interventions, and outcomes in the scope of the current review and then assessed the quality of those that were identified as relevant. Strategies for using systematic reviews were different for KQ1, KQ1a, and KQ4.

KQ1 and KQ1a: Effectiveness of depression screening
One recent good-quality review10 examined questions similar to those addressed in our review but had more restrictive inclusion and exclusion criteria. Therefore, we proceeded with our systematic review of primary evidence by using the bibliography of this review and all others with potential relevance to KQ1 and KQ1a to identify primary evidence.

KQ4: Harms of depression treatment with antidepressants
We identified relevant systematic reviews and included them as evidence for KQ4, given the large number of regulatory studies used. We included all fair- or good-quality systematic reviews that reported on suicidality (completed suicide, suicidal behavior, or suicidal ideation), tolerability (operationalized as rates of overall discontinuation and discontinuation due to adverse effects), or risk for gastrointestinal bleeding in our report. We reported specific analyses of most relevance where possible. For example, if a systematic review ran separate meta-analyses of all antidepressant recipients and the subgroup of antidepressant recipients who received them for depression, we reported the latter analysis.

KQ = key question.

Return to Table of Contents
Study, Year (Reference) Brief Summary or Analysisb
KQ1
No studies were found. NA
KQ1a
Schreuders et al, 200785 Primary care patients were screened. Those with ≥3 primary care visits in the previous 6 mo who screened high on a general mental health instrument (not depression-specific) were recruited. Results show that additional problem-solving treatments by nurse specialists did not improve mental health outcomes. The depressed sample could not be identified at baseline to determine effect for these persons.
van Marwijk et al, 200886 Primary care practices screened patients, providers conducted consultation, and antidepressant treatment was proposed. A small effect was found at 6-mo follow-up but disappeared at 12-mo follow-up. This was consistent with other results that no long-term effect was sustained without additional care supports for providers.
Wang et al, 200787 Depression outreach and care management program in a worksite setting was effective. This was consistent with other results that showed that care management involving ongoing monitoring and communication with providers was effective. The generalizability of results to primary care was questionable.
KQ2
No studies were found. NA
KQ3
Nelson et al, 200888 Meta-analysis of second-generation antidepressants in older adults concluded that second-generation antidepressants were more effective than placebo in older depressed adults.
Pinquart et al, 200789 Meta-analysis of psychotherapy and other behavioral interventions for depression in older adults concluded that cognitive behavioral therapy and reminiscence therapy are effective.
Sneed et al, 200890 Meta-analysis of clinical trials that compared antidepressants with placebo or an active comparator in older adults. The response rates were higher in the active comparator trials compared with the placebo trials. This was not relevant to our report because our focus was on establishing efficacy rather than comparative efficacy or effectiveness.
Wilson et al, 200891 Reviewed psychotherapy for depression in older adults and included far fewer studies than the reviews used in the full report16. Cognitive behavioral therapy was more effective than wait-list controls (5 trials) and active controls for outcomes measured by 1 instrument but not another (3 trials total).
KQ4
Aursnes and Gjertsen, 200892 Reviewed regulatory data and compared results with published SPC. Five of 19 adverse effects were found in data but not mentioned in SPC. The abstract did not mention any serious adverse events.
Barbui et al, 200993 Systematic review of observational studies that reported suicide attempts of those receiving SSRIs vs. those who did not. Use of SSRIs may be associated with reduced risk for suicide in adults with depression but may increase suicidality in adolescents.
Beasley et al, 200794 Assessed suicidality emergence reported in the largest available double-blind, placebo-controlled fluoxetine trials in adults with major depression. Fluoxetine led to greater benefit rather than risk for suicidality.
Cipriani et al, 200795 Review of reviews of acute-phase treatment with antidepressants. Some evidence supports that SSRIs may increase suicidal thoughts, but not actual suicide. Uncertainty remains, and balance between risks and benefits should be considered for each individual patient.
Cooper-Kazaz and Lerer, 200896 Examined the thyroid hormone triiodothyronine as a supplement to antidepressant treatment. Triiodothyronine was well tolerated in most studies and adverse effects were not an impediment to its use, but more research is needed for definitive conclusions.
de Abajo and Garcìa-Rodrìguez 200897 Used a large general practice database to examine upper gastrointestinal effects of second-generation antidepressants. Antidepressants with relevant blockade action on the serotonin reuptake mechanism increase risk for upper gastrointestinal bleeding, particularly in association with nonsteroidal anti-inflammatory drugs. Use of acid-suppressing agents limits increased risk.
Deshauer et al, 200898 Meta-analysis of placebo-controlled SSRI trials ≥6 mo. Evidence supports the current recommendation of continued treatment for 6-8 mo after initial recovery, but no data were found for treatment that lasted >1 y. Withdrawal was reported as proxy for tolerability. No mention of serious adverse effects was found in the abstract.
Hansen et al, 2008 99 Meta-analysis for use of second-generation antidepressants for relapse prevention. Withdrawal due to adverse effects (7% receiving active treatment and 5% receiving placebo, which is in the range of those reported in this report) was reported. No mention of serious adverse effects was found in the abstract.
Katzman et al, 2007100 Meta-analysis comparing paroxetine with placebo and other active agents. A consistently better effect occurred with paroxetine than placebo. Inconsistent results were found when placebo was compared with other active agents. The abstract had minimal mention of tolerability and no mention of serious adverse effects.
Marcinko, 2007101 Estimates of risk-benefit ratio. No description of data sources or suggestion that new data were presented in this publication.
Marks et al, 2008102 Review of paroxetine. This study did not seem to be a systematic review.
Möller et al, 2008103) Review of publications (RCTs and observational designs) related to antidepressants and suicide, suicidality, suicidal behavior, and aggression. Antidepressants, including SSRIs, carry a small risk for inducing suicidal thoughts and attempts in patients younger than 25 years but must be balanced against well-known beneficial effects.
Papakostas et al, 2008104 Review compared reboxetine with SSRIs and found tolerability better for SSRIs, although some mild adverse effects were more common in SSRI recipients. Efficacy seems to be similar. No mention of serious adverse effects was found in the abstract.
Rahme et al, 2008105 Used a large Canadian health care database to compare risk for suicide death and poisoning during periods of antidepressant treatment vs. periods without treatment in older patients. No differences were found in suicide rates between SSRI use vs. nonuse. Higher rates among those who received both SSRIs and other antidepressants may be due to severity of an underlying disorder. Poisoning is higher during SSRI use vs. nonuse for some agents.

KQ = key question; NA = not applicable; RCT = randomized, controlled trial; SPC = Summary of Product Characteristics; SSRI = selective serotonin reuptake inhibitor.
a From January 2008 to February 2009.
b Based on abstract review or brief examination of publication.

Return to Table of Contents
Category of Depression Care Depression Care Component Studies in the General Adult Population Studies in Older Adults
Bergus et al, 200526 Jarjoura et al, 2004[[27,a]] Wells et al, 200023 and 200430; Sherbourne et al, 2001[[31,a]] Rost et al, 200122, 200032, and 2002[[33,b]] Bosmans et al, 200628 Whooley et al, 200024 Callahan et al, 199425 Rubenstein et al, 2007[[29,a]]
Screening Screening results given to provider for review Yes Yes Yes Yes Yes Yes Yes Yes
Improve quality of PCP care Provider prompted or trained in further assessment - Yes - Yes Yes Yes - -
Provider given generic treatment protocol and depression management training - Yes Yes Yes Yes Yes Yes -
Provider given patient-specific treatment recommendations - - - - - - Yes -
Logistical support to PCP Support or study staff provided proactive logistical help, e.g., with follow-up appointments and referrals - Yes Yes Yes - - Yes Yes
Other staff provide some or most of depression care Psychoeducational classes - - - - - Yesc - -
Support or study staff provided monitoring and/or case management - - Yes Yes - - - Yes
Routine referral to behavioral counseling - Yes - - - - - -
Study, mental health, or other specialty staff provided depression care or medication management - Partial Yes - - - - Partial
Other Financial commitment by provider's institution - - Yes - - - - -

PCP = primary care provider.
a Statistically significant group differences.
b Group differences were significant only for the subgroup or participants with newly identified depression.
c This program offered a group psychoeducational class that only 12% of the intervention participants attended.

Return to Table of Contents
Study, Year (Reference); Search Dates Treatment Completed Suicide Suicidal Behaviors Suicidal Behavior or Ideation
Events/ Persons, n/n Rate per 10 000 Persons Odds Ratio (95% CI) Events/ Persons, n/n Rate per 10 000 Persons Odds Ratio (95% CI) Events/ Persons, n/n Rate per 10 000 Persons Odds Ratio (95% CI)
Levenson and Holland, 200634, and Stone and Jones, 200635; through September 2006
MDD only (162 RCTs) 2nd-gen AD Placebo 4/22 379
1/14 873		 1.79

0.67

 2.66a (0.26-130.9) - - - 163/22 309
123/14 728		 73.1
83.5		 0.86 (0.67-1.10)
All psychiatric indications (295 RCTs) 2nd-gen AD Placebo 5/39 799
2/27 309		 1.3

0.73

 1.72a (0.28-18.01) 79/39 729
49/27 164		 19.9
18.0		 1.11 (0.77-1.61) 248/39 729
196/27 164		 62.4
72.2		 0.84 (0.69-1.02)
All psychiatric indications for patients aged 18-24 y (272 RCTs) 2nd-gen AD Placebo - - - 23/3810
8/2604		 60.4
30.7		 2.31 (1.02-5.64)b 47/3810
21/2604		 123.4 80.6 1.55 (0.91-2.70)
All psychiatric indications for patients aged 25-30 y (295 RCTs) 2nd-gen AD Placebo - - - - - 1.03 (0.68-1.58)c 41/5558
27/3772		 73.8
71.6		 0.79 (0.64-0.98)c
All psychiatric indications for patients aged 31-64 y (295 RCTs) 2nd-gen AD Placebo - - - - - 1.03 (0.68-1.58)c 147/27 086
124/18 354		 54.3 67.6 0.79 (0.64-0.98)c
All psychiatric indications for patients aged ≥65 y (233 RCTs) 2nd-gen AD Placebo - - - - - 0.06 (0.01-0.58)b 12/3227
24/2397		 37.1 100.1 0.39 (0.18-0.78)b
Hammad et al, 200636; through 2000
MDD only (207 RCTs) SSRIs only SSRI/other Placebo 6/14 675 15/25 604 2/8868 4.1 5.9 2.3 SSRI vs. placebo, 1.81a (0.32-18.37); SSRI + other vs. placebo, 2.60a (0.60-23.4) - - - - - -
Khan et al, 200337; January 1985 to January 2000
Indications not stated (total RCTs not reported) SSRIs Placebo 38/26 109 5/4895 14.6 10.2 1.43a (0.56-4.64) - - - - - -
Indications not stated (number of RCTs not reported) SSRIs Active controls 38/26 109
34/17 273		 14.6 19.7 0.74a (0.45-1.21) - - - - - -
Gunnell et al, 200538, Saperia et al, 200639, and CSM, 200440; through 2003
All indications (439 RCTs) SSRIs Placebo 9/23 804
7/17 022		 3.8
4.1		 0.85 (0.20-3.40) 128d/30 814
75d/21 689		 41.5
34.6		 1.21 (0.87-1.83) 97e/26 882
80e/18 822		 36.1
42.5		 0.80 (0.49-1.30)
GlaxoSmithKline, 200641; through December 2004
MDD cases (19 RCTs) Paroxetine Placebo - - - 11/3455
1/1978		 31.8
5.1		 6.7 (1.10-149.4)b 31/3455
11/1978		 89.7
55.6		 1.3 (0.7-2.8)
MDD cases for patients aged 18-30 y (number of RCTs not reported) Paroxetine Placebo - - - 8/612
0/339		 130.7
0		 Cannot calculate - - -
Fergusson et al, 200542; 1967 to June 2003
All indications (411 RCTs) SSRIs Placebo 4/10 557
3/7 856		 3.8
4.0		 0.95 (0.24-3.78) 23/10 557

6/7856

 21.8
7.6		 2.70 (1.22-6.97)b - - -
Storosum et al, 200143; 1983 to 1997 Probable MDD cases (77 short-term RCTs) SSRIs Placebo 7/7944
4/4302		 8.8
9.3		 0.95a (0.24-4.42) 29/7944
17/4302		 36.5
39.5		 0.92a (0.49-1.79) - - -

2nd-gen AD = second-generation antidepressant; CSM = Committee on Safety of Medicines; MDD = major depressive disorder; RCT = randomized, controlled trial; SSRI = selective serotonin reuptake inhibitor.
a Calculated.
b P < 0.05.
c Patients aged 25-64 y. Cited in reference 35.
d Nonfatal self-harm; also includes fluoxetine-related suicides for reference 38.
e Ideation only.

Return to Table of Contents
Study, Year (Reference); Subgroup Treatment Completed Suicide Suicidal Behaviors
Events/Persons, n/n Rate per 10 000 Persons (95% CI) Events/Persons, n/n Rate per 10 000 Persons (95% CI)
Simon et al, 200654; MDD only in prepaid group practice 2nd-generation antidepressant and TCAs 31/65 103 4.8 (3.3-6.8)b 76/65 103 11.7 (9.3-14.6)b
Martinez et al, 200553; patients aged <90 y with new antidepressant prescription Any antidepressant (primarily 1st-generation) 69/146 095 4.7 (3.7-6.0)b 1968/146 095c 134.7 (128.9-140.8)b
Martinez et al, 200553; patients aged 19-30 y with new antidepressant prescription Any antidepressant (primarily 1st-generation) 19/34 792 5.5 (3.5-8.6)b 747/34 792 214.7 (199.8-230.7)b
Jick et al, 199552; pharmaceutical event monitoring data for all indications Any antidepressant (primarily 1st-generation) 143/172 598 8.3 (7.0-9.8)b - -

MDD = major depressive disorder; TCA = tricyclic antidepressant.
a Includes 95% CI around event rate if no comparison.
b Calculated.
c Nonfatal harms.

Return to Table of Contents
Study, Year (Reference) Setting Approach to Intervention Beyond Screening Results Feedback Sample Characteristics Length of Follow-up Patients Depressed at Follow-up Scale Score Decrease from Baseline
IV Group, % UC Group, % Measure IV Group, % UC Group, % Measure
General adult population
Williams et al, 199921 Multisite, Veterans Affairs, community health clinic None (KQ1: included unscreened control group) 863 participants; 71% women; calculated age, 58 y; proportion treated, not reported 3 mo (all patients)

3 mo (those depressed at baseline)

 37

52a

 46

73a

 MDD per DIS

≥2 MDD symptoms per DIS

 1.6 1.5 Number of MDD symptoms per DIS
Bergus et al, 200526 Rural None 59 participants; 67% women (calculated); calculated age, 41 y; 38% received medication for depression or anxiety 10 wk

6 mo

 46

48

 63

62

 PHQ ≥6

PHQ ≥6

 5.8

5.7

 5.8

5.0

 PHQ-9
Jarjoura et al, 200427 Urban, indigent Improve quality of provider's care; logistic support for provider; other staff provide some depression care 61 participants; 69% women (calculated); calculated age, 45 y; 0% currently treated 6 mo

12 mo

 -

-

 -

-

 -

-

 7.6a

6.5a

 0a

0a

 Z-BDI
Wells et al, 200023 and 200430; Sherbourne et al, 200131 Multisite, urban, rural Improve quality of provider's care; logistic support for provider; other staff provide some depression care 1356 participants; 71% women; age 44 y; proportion treated, not reported 6 mo

12 mo

57 mo

24 mo

 40b d

42b d

38 (IV1)a

36 (IV2)

39 (IV1)

31 (IV2)

 50b

51b

44a

44

34

34

 CIDI-2

CIDI-2

CIDI-2

CIDI-2

CIDI

CIDI

 -

-

-

-

 -

-

-

-

 -

-

-

-
Rost et al, 200122 and 2000 32; cases in which depression was identified by the provider as part of usual care before the study Multisite, urban, rural Improve quality of provider's care; logistic support for provider; other staff provide some depression care 243 participants; 84% womenc; age 43 yc; 100% recently treated 6 mo - - - 14.5 11.0 CES-D
Rost et al, 200122, 200032 and 200233 cases in which depression was newly identified by screening related to the study Multisite, urban, rural Improve quality of provider's care; logistic support for provider; other staff provide some depression care 189 participants; 84% womenc; age 43 yc; 0% recently treated 6 mo

24 mo

 -

26a

 -

59a

 -

CES-D ≥15

 21.7a

-

 13.5a

-

 CES-D

-
Older adult population
Bosmans et al, 200628) Urban, the Netherlands Improve quality of provider's care 145 participants; 60% women; calculated age, 65 y; 0% currently treated; 83% history of depression 12 mo 57 52 PRIME-MD 7.8 7.2 MADRS
Whooley et al, 200024 Urban Improve quality of provider's care; other staff provide some depression care (minimally implemented) 331 participants; 61% women; calculated age, 76 y; 20% received antidepressants for ≥12 mo 24 mo 42 50 GDS ≥6 1.8 2.2 GDS
Callahan et al, 199425 Urban Improve quality of provider's care; logistic support for PCP 175 participants; 76% women; age 65 y; 11.4% received antidepressants 6 mo

9 mo

 87

-

 88

-

 HDRS ≥16

-

 -e

-

 -

-

 CES-D

CES-D
Rubenstein et al, 200729 Urban, Veterans Affairs Logistical support for PCP; other staff provide some depression care 792 participants (206 screened positive for depression); 3.2% women; age 74 y; proportion treated, not reported 12 mof - - - 3.7a 2.7a GDS

CES-D = Center for Epidemiological Studies depression scale; CIDI = Composite International Diagnostic Interview, full interview; CIDI-2 = Composite International Diagnostic Interview, 2-item depression screen; DIS = diagnostic interview schedule for Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised; GDS = Geriatric Depression Scale; HDRS = Hamilton Depression Rating Scale; IV1= psychotherapy, IV2 = medication support; IV = intervention; KQ = key question; MADRS = Montgomery-Asberg Depression Rating Scale; MDD = major depressive disorder; PCP = primary care provider; PHQ-9 = Patient Health Questionnaire-9 item; PRIME-MD = Primary Care Evaluation of Mental Disorders, Mood Module screening items; UC = usual care; Z-BDI = Beck Depression Inventory, standardized on control group change.
a P <0.05.
b P <0.01.
c These statistics refer to the entire study sample.
d Results for the 2 intervention groups were reported combined at 6- and 12-mo follow-up. They were reported separately at 24- and 57-mo follow-up.
e Reported that groups did not differ at 6 or 9 mo, but did not provide exact scores.
f Results only for subgroup that screened positive for depression.

Return to Table of Contents