Although major depressive disorder (MDD) is one of the world’s great public health problems, the morbidity and increased mortality associated with this common illness can be attenuated by the large number of effective treatments that are now widely available. It is therefore important to ensure that efficient methods for population screening are in place and directly linked to health care systems so depressed patients receive appropriate treatment. This is particularly important because effective treatments of depression not only reduce symptoms associated with the disease and reduce the risk of suicide, but also can improve functioning and offset the negative effects that depressive symptoms can have on physical well-being. In the United States, like many other economically developed nations, primary care practices represent the best place for implementation of these methods, because it is the only venue where both screening and, if clinically indicated, treatment can be provided. With this ideal in mind, in 20021 and 20092 the US Preventive Services Task Force (USPSTF) published systematic reviews and recommendations for such screening for adults. In this issue of JAMA, Siu and colleagues3 provide the second update on this important topic.
Michael E. Thase, MD1,2
As the field has evolved, some aspects have changed since publication of the USPSTF’s first report in 2002. Nevertheless, the 2 most essential recommendations are unchanged: (1) sufficiently reliable patient-reported screening scales for depression are readily available and feasible in primary care, and (2) such screening can lead to accurate diagnosis and treatment in primary care. With respect to specific screening tools, the 9-item depression scale of the Patient Health Questionnaire (PHQ-9) has emerged as the first choice for most primary care settings and adult populations; this instrument can accurately identify about 80% of “true” cases, with a positive predictive value of about 50%.3 Clinicians should be aware that such sensitivity, while acceptable for screening, does not mean that a lower score rules out a diagnosis of depression (about 1 in 5 true cases score below the threshold) and that about half the time a “positive” score will result from symptoms that are attributable to other disorders. Thus, as emphasized in the original report,1 screening does not obviate the need for a diagnostic evaluation. The USPSTF concluded that additional work is necessary to confirm the utility of screening in languages other than English and Spanish and notes that another measure, the Edinburgh Postnatal Depression Scale, is better validated for use in pregnant or postpartum populations. Although it is not absolutely necessary to have “1 scale that fits all,” it would not be difficult to ascertain if the PHQ-9 likewise performs well among women who are pregnant or during the immediate postpartum period.
One area of clear progress in the field reflected in the current report pertains to the USPSTF’s statement about “…adequate systems… to ensure accurate diagnosis, effective treatment, and appropriate follow-up.”3When the recommendations were first published in 2002, some of the seminal studies of the ambulatory care models that are now referred to by names such as collaborative care or depression care management were still under way, and it was not yet clear that the outcomes of depression treatment in primary care could be meaningfully enhanced by relatively simple, cost-effective strategies. The current USPSTF report implicitly incorporates the relatively consistent findings from a large number of studies that have been published over the past several decades4 and now asserts that these forms of targeted clinical support have become the standard for ambulatory care. Indeed, the STAR*D study5 showed that patients treated in primary care practices who were provided with a moderate level of clinical support had the same chances for response and remission as patients treated in psychiatric practices.
Although progress has been made, there is still much work to be done, as reflected by the USPSTF’s assessment of a B grade for the overall weight of evidence in support of depression screening in primary care. In part, the B grade reflects the nature of MDD, ie, a clinically heterogeneous group of conditions that respond variably to a diverse group of interventions. The symptom severity spectrum of MDD includes both a milder group of depressions that are quite responsive to many interventions and a more persistent and disabling group of depressions that are more likely to be resistant to standard treatments. Within this context, it is widely known that first-line antidepressant medications have relatively modest specific effects in controlled studies of ambulatory populations (ie, intent-to-treat response rates of about 50%),6 and no valid biomarkers are available to help guide the selection of specific treatments.7 Moreover, in controlled studies, the specific effects of antidepressants are typically smaller than the effects that are attributable to placebo expectancy and other nonspecific factors.6,8,9 Thus, for some depressed patients at the milder end of the symptom severity spectrum, prompt diagnosis and expeditious treatment may not appreciably improve on a favorable natural history (ie, a short, self-limiting episode with a high likelihood of spontaneous remission). For some patients at the more severe end of the severity spectrum, first-line therapies often are not effective. Being better able to match patients to particular treatments could significantly improve the performance of an efficient screening system.
When clinicians consider what to do for a given patient, the results of studies that use a placebo control condition should not be conflated with those that use no treatment or watchful waiting conditions. Patients being cared for by physicians who are prescribing treatments that are expected to work have a better chance of benefitting than individuals who are enrolled in a clinical trial and receive a double-blind placebo, who in turn have at least twice the chance of remitting as a study participant who is allocated to a waiting list.6Thus, the decision to treat includes both the modest specific benefit of the intervention and the substantial nonspecific benefits associated with receiving care.
It also may be true that patients respond better to treatments that are matched to their preferences and that preference may matter more for patients who have more severe and persistent depressive episodes.10 In this regard, the USPSTF’s updated recommendations, which emphasize both newer-generation antidepressants and empirically supported psychotherapies, either singly or in combination, make good clinical sense and are fully consistent with contemporary North American practice guidelines.11,12 Care systems also need to take into account that some patients will not respond to multiple adequate trials of standard antidepressants or psychotherapies and may require sequential trials of alternate or more complex treatment regimens.13
Until there are better methods to match patients with specific forms of treatment, the best hope to improve on a B grade for patients with depression may be to adapt care systems to respond more flexibly and decisively to key events that are associated with nonadherence or treatment failure. For example, if the clinicians working within a collaborative care model could rapidly incorporate the information that an initial prescription was not filled or was not refilled, it may be possible to diminish the chances that nonadherence will compromise treatment outcome. Likewise, given evidence that nonresponse is predicted by a lack of symptom improvement during the first 14 days of therapy,14 web-based monitoring of symptoms early in the course of therapy may enable physicians and other mental health professionals to intervene more rapidly and reduce the chances of treatment failure. The same approach to ongoing care could be used to facilitate a more timely transition through treatment algorithms13 and more expeditious referral to specialty care.