A Good research-based evidence, with some panel opinion, to support the guideline statement. B Fair research-based evidence, with substantial panel opinion, to support the guideline statement. C Guideline statement based primarily on panel opinion, with minimal research-based evidence, but significant clinical experience. This synopsis of diagnostic issues is not based on reviews of the evidence for or against the validity of specific diagnostic entities. (For such reviews, see DSM-IV Sourcebook [Frances and Widiger, in press].) Rather, the panel reviewed the epidemiology of major depressive disorder in community samples and primary care settings and the course, cooccurrence, and co-morbidity of depressive and other medical conditions. The panel also reviewed literature on the role of self-reports and clinician ratings as tools for detecting or differentially diagnosing depression. The role of laboratory tests in differential diagnosis of the medical causes of depression was illustrated by using the example of thyroid function testing. This synopsis describes the various forms of depression; their course, epidemiology, and common clinical expression in different age groups; the co-occurrence of depressive symptoms or formal syndromes with other psychiatric or nonpsychiatric medical conditions; the role of medications in causing depression; and the role of clinical and laboratory procedures in the detection and differential diagnosis of depression. The depression guidelines were drafted in four different formats: (1) the full Depression Guideline Report; (2) the Clinical Practice Guideline, which condenses pertinent information from the report into two volumes for easy use by practitioners; (3) the summary Quick Reference Guide for Clinicians; and (4) A Patient's Guide. The literature reviews, drafts of the full Depression Guideline Report, and all four shorter versions were sent to 14 scientific reviewers, who critiqued them. The guidelines were revised and sent to the original 14 reviewers, plus 14 new scientific reviewers for further critique and subsequent revision. Peer review was requested for both the diagnosis and treatment volumes, as well as for A Patient's Guide and the Quick Reference Guide for Clinicians, from 73 professional organizations and 3 patient advocacy groups. In addition, independent family, general medical, and nurse practitioners reviewed these guidelines for ease of use, feasibility, and utility. These reviews provided the basis for final guideline revisions (Figure 1). Additional revisions to these guidelines are anticipated, based on further comments from practitioners, new scientific evidence, studies of the impact of these guidelines on primary care practice, and new reviews to address areas not yet discussed. For example, the panel has not reviewed treatment of certain conditions, such as bipolar disorder; certain treatments, such as use of lithium alone; or certain patient groups, such as children and adolescents. These topics were deferred to subsequent years either NLM literature searches conducted using key words selected for each topic by panel/reviewers with MEDLINE and Psychiatric Abstracts for each topic Abstracts reviewed for inclusion/exclusion criteria by literature reviewers Full copy of each article selected read by literature reviewers Depression Guideline Report synopsized to Clinical Practice Guideline, Peer review requested from 73 organizations and 14 new scientific reviewers, pilot review of A Patient's Guide, Quick Reference Guide for Clinicians, and Clinical Practice Guideline in nine sites Final copy of all versions of guidelines submitted to AHCPR because they are less common in primary care or because logistic constraints made deferral necessary. The panel invites correspondence from users to help in these future revisions. Interpretation of the Scientific Literature Several limitations to the available scientific literature made the development of guidelines for primary care providers difficult: ■ Most studies on diagnosis and treatment of depression come from nonprimary care settings (usually psychiatric or psychological practice settings). ■ Only modest data are available on the usefulness of DSM-III-R in patients with depression and concurrent medical disorders. ■ Only a few randomized controlled treatment trials have been conducted in patients with depression and concurrent significant medical disorders. ■ The long-term outcomes of treated and untreated mood disorders seen in primary care settings are relatively unstudied. ■ While a moderate number of randomized controlled acute treatment trials using medication and some trials using psychotherapy have been conducted in geriatric patients, only seven trials were conducted in primary care settings, though geriatric patients are common in primary care. ■ Even fewer randomized controlled trials with depressed children and adolescents are available, and none have been conducted in primary care settings. ■ While many patients with mood disorders seen in primary care settings have DNOS or "minor" forms of depression, very few randomized controlled trials on these patients have been undertaken. Although several authors have questioned the generalizability of research findings from psychiatric to primary care settings, many difficulties encountered in primary care are also found in psychiatric settings. These include distinguishing depressions from underlying medical disorders, identifying medical disorders that present with depressive symptoms, treating mood disorders in patients with other general medical illnesses, and identifying and treating depressive psychological reactions to nonpsychiatric medical disorders. The panel believes it essential to highlight the impact of current social and cultural forces, as well as current reimbursement policies, on timely diagnosis and treatment of depressive and other psychiatric conditions. Social stigma contributes to: ■Resistance of patients to seek treatment. ■Reluctance of practitioners to look for and formally diagnose depressions. ■ Poor adherence by patients during long-term treatment of more chronic forms of depression. ■Low reimbursement rates by third-party payors for these conditions. Inappropriate emphasis on depression and other psychiatric disorders on applications for driver's license, employment, security clearance, and other "routine" purposes (a situation that may be improved with the recent enactment of the Americans with Disabilities Act). Because of the current discrimination against persons with depressive and other psychiatric conditions, appropriate diagnosis and treatment may carry a far greater personal cost for patients with depression than for those with other medical conditions. In some cases, acknowledgment of diagnosis and treatment of depression can actually worsen an individual's social, occupational, and economic status. The ultimate long-term consequences of this stigma must be addressed to ensure accurate, early diagnosis and effective, early treatment. The implementation of these guidelines may require one or more of the following: Increased reimbursement for those time-intensive tasks recommended in these guidelines. ■ Educational efforts aimed at primary care practitioners. ■ Patient/family education. On the other hand, use of these guidelines may reduce overall medical costs, since patients with clinical depression may be identified and treated earlier in the course of the illness, thus reducing the need for multiple physician visits for various somatic symptoms of depression (e.g., tension headaches, abdominal pain, joint pain, insomnia) and the need for eventual, more complex and expensive treatments for more chronic depressions. Indirect cost savings, such as fewer days lost from work, less disability, and less pain and suffering, are additional benefits of effective treatment. Guideline: 2 Overview of Mood Disorders Guideline: Depressive disorders should not be confused with the depressed or sad mood that normally accompanies specific life experiences-particularly losses or disappointments. Mood disorders involve disturbances in emotional, cognitive, behavioral, and somatic regulation. A clinical depression or a mood disorder is a syndrome (a constellation of signs and symptoms) that is not a normal reaction to life's difficulties. A sad or depressed mood is only one of many signs and symptoms of a clinical depression. In fact, the mood disturbance may include apathy, anxiety, or irritability in addition to or instead of sadness; also, the patient's interest or capacity for pleasure or enjoyment may be markedly reduced. Not all clinically depressed patients are sad, and many sad patients are not clinically depressed. (Strength of Evidence = A.) Primary mood disorders include both depressive (unipolar) and manicdepressive (bipolar) conditions. Most mood disorders seen in primary care settings are thought by some to be at an early, poorly organized stage of the illness. These disorders are often mixed with anxiety symptoms and accompanied by vague somatic complaints. Furthermore, they may be less profoundly severe, but more chronic, than those mood disorders encountered primarily by mental health care providers. Patients initially seeking care from primary care providers may be less inclined toward a psychological explanation or conceptualization of their depression. Guideline: Major depressive disorder (sometimes called unipolar depression) is characterized by one or more episodes of major depression without episodes of mania or hypomania (low-level mania). By definition, major depressive episodes last at least 2 weeks (and typically much longer). (Strength of Evidence = A.) A sad mood or a significant loss of interest is required, along with several associated signs and symptoms (Table 1), to diagnose a major depressive episode. Guideline: A major depressive episode can occur as part of a primary mood disorder (e.g., major depressive or bipolar disorder), as part of other nonmood psychiatric conditions (e.g., eating, panic, or obsessivecompulsive disorders), in cases of drug or alcohol intoxication or withdrawal, as biologic or psychological consequences of various nonpsychiatric general medical conditions or as consequences of the |