and patient. Such shared decision making is likely to increase patient adherence and, therefore, treatment effectiveness.

If the patient shows a partial response to treatment by 4 to 6 weeks, the same treatment should be continued for 4 or 6 more weeks. If the patient does not respond at all by 6 weeks or responds only partially by 10 to 12 weeks, other treatment options should be considered. If the initial treatment is the administration of an antidepressant medication, available evidence suggests that both partial responders and nonresponders will benefit from either switching to a different medication class or adding a second medication to the first. If psychotherapy alone is the initial treatment and it produces no response at all by 6 weeks or only a partial response by 12 weeks, clinical experience and logic suggest a trial of medication, given the strong evidence for the specific efficacy of medication. If the initial acute treatment is combined treatment and it produces no response by 6 weeks, switching to another medication is a strong consideration. For some patients, especially those who have had previous medication trials, medication augmentation rather than switching may be preferred.

Medications have been shown to be effective in all forms of major depressive disorder. Given the evidence to date, it is appropriate to treat patients with moderate to severe major depressive disorder with medication whether or not formal psychotherapy is also used. Medication is administered in dosages shown to alleviate symptoms. No one antidepressant medication is clearly more effective than another, and no single medication results in remission for all patients. The specific medication choice is based on side-effect profiles, patient's history of prior response, family history of response, and type of depression. Some patients respond well to one antidepressant medication, while others respond to a different medication. If the patient has previously responded well to and has had minimal side effects with a particular drug, that agent is preferred. Similarly, if the patient has previously failed to respond to an adequate trial of or could not tolerate the side effects of a particular compound, that agent should generally be avoided.

In general, of the tricyclics, the secondary amines (e.g., desipramine, nortriptyline) have equal efficacy, but fewer side effects, than do the parent tertiary amines (e.g., imipramine, amitriptyline). The newer antidepressants (e.g., bupropion, fluoxetine, paroxetine, sertraline, trazodone) are associated with fewer long-term side effects, such as weight gain, than are the older tricyclic medications. Patients whose disorder has atypical features appear to fare better on monoamine oxidase inhibitors (MAOIs) or selective serotonin reuptake inhibitors (SSRIs) than on tricyclic antidepressants (TCAs).

A history of failure to respond to a truly adequate trial of a drug in one class strongly suggests that it would be appropriate to try a medication from a different class rather than another drug from the same class. If the patient has not responded at all or has only a modest symptomatic

response to medication by 6 weeks, the practitioner is advised to reevaluate the accuracy of diagnosis and the adequacy of treatment. Options for further treatment include continuing the current medication at a corrected dosage, discontinuing the first medication and beginning a second, augmenting the first medication with a second, adding psychotherapy to the initial medication, or obtaining a consultation/referral.

Patients with milder forms of major depressive disorder may be unwilling to tolerate medication side effects, and those with certain coexisting medical conditions may be physically unable to tolerate these drugs. Psychotherapy alone to reduce the symptoms of major depressive disorder may be considered a first-line treatment if (1) the depression is mild to moderate, nonpsychotic, not chronic, and not highly recurrent and (2) the patient desires psychotherapy as the first-line therapy. Preferred psychotherapy approaches are those shown to benefit patients in research trials, such as interpersonal psychotherapy, cognitive therapy, behavioral therapy, and marital therapy. The therapies that target depressive symptoms (i.e., cognitive or behavioral therapies) or specific interpersonal or current psychosocial problems related to the depression (i.e., interpersonal psychotherapy) are more similar than different in efficacy.

The efficacy of long-term psychotherapies for the acute phase treatment of major depressive disorder is not known; therefore, these therapies are not recommended for first-line treatment. The psychotherapy should generally be time-limited, focused on current problems, and aimed at symptom resolution rather than personality change. The therapist should be experienced and trained in the use of the therapy with patients who have major depressive disorder. Regular visits once or twice a week are typical.

If the patient being treated with psychotherapy fails to show any improvement in depressive symptoms by 6 weeks or only partial response by 12 weeks, a reevaluation and potential switch to, or addition of, medication are indicated. Medication is almost always recommended for those who do not respond to therapy at all. Given the evidence for the efficacy of medication and the lack of information regarding the efficacy of formal psychotherapy alone, the panel does not advise practitioners to treat severe and/or psychotic major depressive disorders with psychotherapy alone.

Combined treatment with both medication and psychotherapy may have an advantage for patients who have responded partially to either treatment alone or who have a history of chronic episodes or poor interepisode recovery, a history of chronic psychosocial problems (both in and out of episodes of major depression), and/or a history of treatment adherence difficulties. However, combined treatment may provide no unique advantage for patients with uncomplicated, nonchronic major depressive disorder. The possibility that these patients need adjunctive psychotherapy may be better gauged once the depressive syndrome has largely resolved with medication, since medication that induces a

symptomatic remission also, as a consequence, improves psychosocial difficulties in many patients. The condition of patients given the

combination of medication and psychotherapy who have not responded at all by week 6 or only partially by week 12 should be reevaluated to ensure that an alternative cause of symptoms has not been overlooked.

Electroconvulsive therapy is not recommended as first-line therapy for uncomplicated, nonpsychotic cases of major depressive disorder in primary care, as effective treatments that are less invasive and less expensive are available. It is a first-line option for patients suffering from severe or psychotic forms of major depressive disorder, whose symptoms are intense, prolonged, and associated with neurovegetative symptoms and/or marked functional impairment, especially if these patients have failed to respond fully to several adequate trials of medication. Electroconvulsive therapy may also be considered for patients who do not respond to other therapies, those at imminent risk of suicide or complications, and those with medical conditions precluding the use of medications. Very few patients will be sufficiently ill to require ECT. However, when ECT is indicated, it must be provided by a specialist.

Light therapy—a relatively new treatment option—is a consideration only for well-documented mild to moderately severe seasonal, nonpsychotic, winter depressive episodes in patients with recurrent major depressive or bipolar II disorders. Training in the administration and potential risks of light therapy is requisite to its use. Medication may also be effective for seasonal depression.

If a patient has a major depressive episode thought to be biologically caused by a nonpsychiatric, general medical disorder, the practitioner is advised to (1) treat optimally the associated general medical condition, (2) reevaluate the patient's condition, and (3) treat the major depression as an independent disorder if it is still present. In some cases, treatment of the major depression must proceed simultaneously with efforts to optimize treatment of the general medical condition. When major depressive disorder occurs with another psychiatric disorder, the practitioner has three options: (1) to treat the major depressive disorder as the primary target and reevaluate the patient's condition once he or she has responded to determine whether additional treatment is needed for the associated condition (for example, major depressive disorder with personality disorder or generalized anxiety disorder), (2) to treat the associated condition as the initial treatment focus (for example, major depression co-occurring with anorexia nervosa, bulimia nervosa, obsessive-compulsive disorder, or substance abuse), or (3) to attempt to decipher which condition is "primary" and select it as the initial treatment target (for example, major depressive disorder with panic disorder). The option selected will depend on the nature and severity of the co-occurring disorder.

Patients who respond to acute phase medication are generally continued on the drug at the same dosage for 4 to 9 months after they have returned to the clinically well state (continuation treatment). Unless

maintenance treatment is planned, antidepressant medication is

discontinued at 4 to 9 months or tapered over several weeks (depending on the type of medication). Patients are followed during the next several months to ensure that a new depressive episode does not occur. If a recurrence does begin, the patient is likely to respond to the same medication at the same dosage that was effective previously, which should then be continued for 4 to 9 months.

Although antidepressant medications are generally safe, even with long-term use, they should be discontinued if they are not required. All patients who have had a single episode of major depressive disorder are advised to discontinue medication after 4 to 9 months of continuation treatment, since only 50 percent will have another episode of major depressive disorder. Even then, the next episode may be years hence. If the full depressive episode recurs during or shortly after the discontinuation of medication, the depressive episode has not "run its course," and the full therapeutic dosage is generally reinstated.

The decision to implement continuation phase psychotherapy depends on the patient's residual symptoms, psychosocial problems, history of psychological functioning between episodes, and the practitioner's and patient's judgment about the need for such treatment. Continuation psychotherapy can be added to continuation medication following acute phase response to either medication alone or combined treatment.

Patients who relapse once continuation medication is ended may require long-term maintenance medication to prevent a new episode of depression. Patients who have had three or more episodes of major depression have a 90 percent chance of having another and are, therefore, potential candidates for long-term maintenance antidepressant medication. The maintenance medication given is generally the same type and dosage found effective in acute phase treatment. Maintenance psychotherapy does not appear to be effective in preventing a recurrence, although it may delay the onset of the next episode in those with highly recurrent major depressive disorder.

Mental health care professionals must be readily available (same day or next day) to provide a consultation (second opinion) or to receive a referral from busy primary care providers. The consultation is most useful when the mental health care professional outlines specific options or steps for the primary care provider and provides patients with the same

information. Mental health care professionals should be open to subsequent patient visits, if needed.

Overview

The clinical practice guideline statements contained in Depression in Primary Care were developed to assist both patients and primary care practitioners in the diagnosis of depressive conditions and the treatment of major depressive disorder. This guideline is an abbreviated version of a far larger Depression Guideline Report and is divided into two volumes: this one, Volume 2: Treatment of Major Depression, and its companion volume, Volume 1: Detection and Diagnosis. The Depression Guideline Report contains more than 3,500 relevant references.

Treatment of Major Depression systematically reviews the indications, contraindications, benefits, and harms of the four major treatments for major depressive disorder: medication, psychotherapy, combined medication and psychotherapy, and electroconvulsive therapy (ECT). It also makes brief reference to other less frequently used treatments and the special circumstances in which they may be appropriate. The guideline considers the three phases of treatment for major depressive disorderacute, continuation, and maintenance-and the indications for each.

Major depressive disorder consists of one or more episodes of major depression with or without full recovery between episodes. The clinically depressed patient must suffer either a sustained sad mood or a significant loss of interest/pleasure plus associated criterion symptoms for a period of 2 weeks or more. Nearly all patients with major depressive disorder also report significant life stresses. Up to one in eight individuals may require treatment for depression during their lifetimes; up to 70 percent of psychiatric hospitalizations are associated with mood disorders. According to data obtained from a 1980 population base, the total number of cases of major depressive disorder among those 18 or older in a 6-month period would be 4.8 million; in addition, over 60 percent of suicides can be attributed to major depressive disorder.

Based on 1980 data, mood disorders account for more than 565,000 hospital admissions, 7.4 million hospital days, and 13 million physician visits annually. The total cost of mood disorders to society, including the indirect costs that result from lost productivity, is estimated to be $16 billion annually. In addition to economic costs, depression can carry great personal costs because of the social stigma associated with the diagnosis and treatment of a "mental" illness. This stigma likely plays a large role in patients' reluctance to seek, accept, and adhere to treatment. Yet, when identified, depression can almost always be treated successfully, either with medication, psychotherapy, or a combination of the two. The potential savings to be derived from the appropriate treatment of people who suffer from depression are socially and economically significant.

The high prevalence of depression and the success of available treatments prompted these guidelines. The Depression Guideline Panel that prepared them is composed of experts from various mental health and