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Up to one in eight individuals may require treatment for depression during their lifetimes. The direct costs of treatment for major depressive disorder combined with the indirect costs from lost productivity are significant, accounting for approximately $16 billion per year in 1980 dollars.
Despite the high prevalence of depressive symptoms and major depressive episodes in patients of all ages, depression is underdiagnosed and undertreated by primary care and other nonpsychiatric practitioners, who are, paradoxically, the providers most likely to see these patients initially. Depression may co-occur with other nonpsychiatric, general medical disorders or with other psychiatric disorders; it may also be brought on by the use of certain medications. Major risk factors for depression include a personal or family history of depressive disorder, prior suicide attempts, female gender, lack of social supports, stressful life events, and current substance abuse. The social stigma surrounding depression is substantial and often prevents the optimal use of current knowledge and treatments. The cost of the illness in pain, suffering, disability, and death is high.
Once identified, depression can almost always be treated successfully with medication, psychotherapy, or a combination of both. Not all patients respond to the same therapy, but a patient who fails to respond to the first treatment attempted is highly likely to respond to a different treatment. The threshold for accepting a scientific report regarding treatment efficacy was the randomized controlled clinical trial, as this methodology is the most stringent test of treatment efficacy. Therefore, where studies are cited and data are available, conclusions are virtually certain.
Once major depressive disorder is diagnosed, interventions that predictably decrease symptoms and morbidity earlier than would occur naturally in the course of the illness are logically tried first. The key initial objectives of treatment, in order of priority, are (1) to reduce and ultimately to remove all signs and symptoms of the depressive syndrome, (2) to restore occupational and psychosocial function to that of the asymptomatic state, and (3) to reduce the likelihood of relapse and recurrence.
All treatments are administered in the context of clinical management, which is defined as education of an discussion with patients and, when appropriate, their families about the nature of depression, its course, and the relative costs and benefits of treatment options. Clinical management is to be distinguished from formal supportive therapy; the latter focuses on the management and resolution of current difficulties and life decisions using the patient's strengths and available resources. Supportive therapy is often combined with medication and clinical management in more severe, complex, or chronic cases. However, good clinical management is important with all depressed patients, whose pessimism, low motivation and energy, and sense of social isolation or guilt may lead them to give up, not to adhere to treatment, or even to drop out of treatment.
Effective treatment rests on accurate diagnosis. The practitioner must first distinguish clinical depression, which is sufficiently severe and disabling to require intervention, from sadness or distress that is a normal part of the human experience. A formal mood syndrome should be treated. Treatments with established efficacy are preferred initially over less well tested or untested interventions.
In selecting an appropriate treatment, the clinician weighs the certainty of treatment response against the likelihood and severity of potential adverse treatment effects. The optimal treatment is highly acceptable to patients, predictably effective, and associated with minimal adverse effects. It results in complete removal of symptoms and restoration of psychosocial and occupational functioning. Treatment proceeds in three phases: acute treatment, continuation treatment, and maintenance treatment.
Acute treatment aims to remove all signs and symptoms of the current episode of depression and to restore psychosocial and occupational functioning (a remission). A remission (absence of symptoms) may occur either spontaneously or with treatment. If the patient improves significantly, but does not fully remit with treatment, a response is declared. If the symptoms return and are severe enough to meet syndromal criteria within 6 months following remission, a relapse (return of symptoms of the current episode) is declared.
Continuation treatment is intended to prevent this relapse. Once the patient has been asymptomatic for at least 4 to 9 months following an episode, recovery from the episode is declared. At recovery, continuation treatment may be stopped. For those with recurrent depressions, however, a new episode (recurrence) may occur months or years later. Maintenance treatment is aimed at preventing a new episode of depression and may be prescribed for 1 year to a lifetime, depending on the likelihood of recurrences.
Formal treatments for major depressive disorder fall into five broad domains: medication, psychotherapy, the combination of medication and psychotherapy, electroconvulsive therapy (ECT), and light therapy. Each domain has benefits and risks, which must be weighed carefully in selecting a treatment option for a given patient. Once selected, the initial treatment should be applied for a sufficient length of time to permit a reasonable assessment of the patient's response (or lack of response). If the treatment is going to be effective, a 4- to 6-week trial of medication or a 6- to 8-week trial of psychotherapy usually results in at least a partial symptomatic response; a 10- to 12-week trial usually results in a symptomatic remission, though full recovery of psychosocial function appears to take longer. The selection of the first and subsequent treatments should, whenever possible, be a collaborative decision between practitioner 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 (MAOls) or selective serotonin reuptake inhibitors (SSRls) 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, non psychotic, 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 non psychiatric, 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.
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