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Guideline: The objectives of acute phase treatment with medication, psychotherapy, the combination, or ECT are, in order of priority, (1) reduction and, wherever possible, removal of all signs and symptoms of the depressive syndrome, and (2) restoration of occupational and other psychosocial functioning to that of the asymptomatic state. (Strength of Evidence = A.)
A secondary, hoped-for consequence of acute treatment is prevention of relapse and recurrence. Table 1 shows the four most common acute phase treatment options and the suspected mechanisms by which each treatment is thought to achieve its objectives. Relapse/recurrence may occur once medication is discontinued. Theoretically, psychotherapy may prevent relapse/recurrence if patients have learned new skills or if situations have been modified. This latter notion is not fully tested or supported with evidence to date in those with recurrent major depressive disorders. One study (Frank, Kupfer, Perel, et al., 1990) indicates that recurrence may be delayed, but not prevented, with psychotherapy.
Table 1. Objectives and effects of different treatments
| Objective | Treatment | |||
| Medication | Psychotherapy | Combined | ECT | |
| Symptom reduction | Direct effect | Direct effect (cognitive) (behavioral) (Ineterpersonal) |
Direct effect | Direct impact |
| Improved function | Indirect effect (secondary to less depression) |
Direct effect (martial) |
Indirect and direct effects | Indirect effect (secondary to less depression) |
| Recurrence prevention | Direct effect (Maintenance medication) |
Direct effect (continued therapy) Indirect effect (learned skills following therapy) |
Direct effect (maintenance medication or psychotherapy) |
Direct effect (maintenance medication after ECT) |
Note: ECT = Electroconvulsive therapy
Guideline: The practitioner must distinguish between major depression, which is sufficiently severe to require intervention, and the sadness or distress that is a normal part of the human experience. If a formal mood syndrome is present, treatment is indicated. (Strength of Evidence = A.)
Effective treatment rests on accurate diagnosis. The practitioner must first determine whether the patient has a clinical depression or is simply suffering normal sadness and distress. This distinction is analogous to others made in general medicine. When the patient’s condition is primarily sadness, supportive discussions and/or the passage of time may be all that is necessary to resolve the symptoms. On the other hand, if a formal mood syndrome is present, specific treatments are usually indicated because there is clear evidence for their efficacy, because untreated major depressive episodes exact a high cost in pain and disability, and because the long-tern prognosis for untreated major depressive disorder is poor (NIMH, 1985; Prien and Kupfer, 1986).
For patients who have very mild cases of major depression or whose diagnosis is unclear (e.g., major depression versus adjustment reaction with depressed mood) and who are not in immediate danger or are not suffering significant functional impairment, the practitioner may want to schedule one to two additional weekly evaluation visits to determine whether symptoms will abate without formal treatment or to discuss treatment options with the patient. There is evidence that clinical management leads to remission in 20 to 30 percent of cases (Elkin, Shea, Watkins, et al., 1989). However, several cautions are in order regarding extended evaluations:
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. For milder cases of major depressive disorder, there is some (albeit less clear-cut) evidence for the efficacy of medication versus placebo. Medication is administered in dosages shown to alleviate symptoms. The specific medication choice is based on side-effect profiles, history of prior response, family history of response, and type of depression. Typically, no one antidepressant medication exceeds the others in efficacy; some patients respond well to one, while others respond to a different treatment.
In general, the objectives of the formal psychotherapies in the treatment of major depressive disorder are similar to those of medication: symptom remission, improved psychosocial functioning, and prevention of relapse/recurrence. Most of the limited available data (see Table 12, page 76) have established that formal psychotherapy as the sole acute treatment for major depressive disorder is more effective than a wait-list control in outpatients with mild to moderate, nonpsychotic major depressive episodes.
Most psychotherapy efficacy studies have focused on symptom amelioration either by direct, time-limited, symptom-targeted psychological treatments, such as cognitive or behavioral therapy, or by time-limited treatments targeted at resolution of current interpersonal difficulties (interpersonal psychotherapy) or psychological conflicts (brief dynamic psychotherapy) assumed to act as vulnerability or precipitating factors or to maintain the syndrome once it has been established.
Preferred psychotherapeutic approaches are those shown to benefit patients in research trials, such as interpersonal, cognitive, behavioral, brief dynamic, and marital therapies. Because untested therapies are not, by definition, known empirically to be either effective or ineffective, these guidelines recommend choosing tested therapies over untested therapies, when available. The therapy should be limited to 20 sessions, since efficacy research on longer forms of therapy is not available and since strong evidence for the efficacy of medication with clinical management is available.
A second objective of formal psychotherapies is to address the patient’s associated psychosocial problems, even if symptom control is largely accomplished with medication. In these patients, it is important to identify the objectives of therapy before selecting the specific treatment. Often, these associated problems are consequences of the depressive episode itself. If the depressive episode is effectively relieved with medication alone, the associated psychosocial problems often abate without additional psychotherapy (Mintz, Mintz, Arruda, et al., 1992). Thus, a reassessment of the patient’s condition is advisable once symptom relief has been obtained with medication. The continued presence of associated psychosocial problems provides a reasonably strong rationale for augmenting treatment with formal psychotherapy aimed at the residual problems, even though sequential, randomized trials to support this stepwise approach are largely lacking to date.
Several general principles guide the selection of the first acute treatment:
Table 2 shows the four main acute treatment choices for major depressive disorder and factors to be considered in their selection. The advantages and disadvantages of each should be evaluated by the practitioner and patient. Brief discussions of these treatment options are found in the sections that follow, and detailed descriptions appear in the chapters on each option. (The empirical evidence for these recommendations is found in the Depression Guideline Report.)
Table 2. Strategic choices in the acute treatment of major depressive disorder
|
Define Treatment Phases, Objectives, and Options with Patient (and Family, Where appropriate) |
|||
| Medication class1 | Formal Psychotherapy | Combined Treatment | ECT4 |
| More severe Chronic Recurrent Psychotic Melancholic Prior positive response Family history Patient preference Failure to respond to psychotherapy. |
Less severe Less chronic Nonpsychotic Prior positive response Availability Medical contraindication to medications Patient preference class2 |
More severe Chronic Partial response to either alone Availability Peronality disorder3 Patient preference |
Psychotic Severe or extremely severe Prior positive response Failure on several medications or combined treatment trails Need for rapid response Medical contraindication to medications |
1 Medication is always combined with clinical management.
2 Patient preference applies more if depression is milder, nonpsychotic.
3 This recommendation has not been empirically tested. It rests solely on clinical experience.
4 Electroconvulsive therapy (ECT) is very rarely required for patients seen in primary care settings. It is reserved nearly always for those who have severe, often chronic, often psychotic depressions that have not responded to several trails of different standard medications.
Guideline: Patients with moderate to severe major depressive disorder are appropriately treated with medication, whether or not formal psychotherapy is also used Medication is administered in dosages shown to alleviate symptoms. The specific medication choice is based on side-effect profiles, history of prior response, family history of response, type of depression, concurrent general medical or psychiatric illnesses, and concurrently prescribed medications. (Strength of Evidence = A.)
Most randomized controlled trials on the efficacy of medication were performed with the goal of obtaining FDA approval for these drugs. Therefore, data documenting efficacy apply most directly to patients who have moderate to severe depression, are free of other psychiatric and eneral medical conditions, and are seen in psychiatric settings. Only 24 studies have tested the efficacy of medication for major depressive disorder in primary care settings. Although, to date, efficacy is the same or slightly higher in primary care settings than in psychiatric settings, the placebo response rate may also be slightly greater. Most randomized controlled trials include a 7- to 10-day “washout” or “placebo run-in” period. Such a period includes at least two visits to ensure that the major depressive disorder does not remit either spontaneously or with the nonspecific aspects of treatment and to allow patients time to weigh the treatment options. A similar procedure in routine practice for patients who are not severely ill, psychotic, or acutely suicidal is a reasonable option since, in the psychiatric setting, substantial improvement may be seen in 15 to 25 percent of such patients without medication (Fairchild, Rush, Vasavada, et al., 1986); the improvement rate may be even higher in general medical settings (Kathol and Wenzel, 1992).
The decision to use medication depends on the patient’s physical capacity and willingness to risk the possibility of and to tolerate the potential side effects of antidepressant medications. Patients with milder forms of major depressive disorder may be unwilling to tolerate side effects. Those with certain coexisting general medical conditions may be physically unable to tolerate these drugs.
Guideline: Patients with mild to moderate major depression who prefer psychotherapy alone as the initial acute treatment choice may be treated with this option. Psychotherapy alone is not recommended for the acute treatment of patients with severe and/or psychotic major depressive disorders. (Strength of Evidence = B.)
Randomized controlled trials of psychotherapy have been largely limited to a number of short-term, structured forms, including cognitive, interpersonal, behavioral, brief dynamic, and marital psychotherapy. These trials have generally enrolled patients with less severe forms of major depressive disorder than those in medication trials. In general, the formal, time-limited psychotherapies are equivalent to each other and are significantly better than wait-list comparisons. In trials comparing therapy alone to standard antidepressant medication, the therapy and medication have often been equal, though only one trial has used a pill placebo contrast cell (Elkin, Shea, Watkins, et al., 1989).
Many forms of psychotherapy have not been subjected to clinical trials. Without data, scientifically based recommendations for or against these as first-line single or adjunctive treatments for major depressive disorder cannot be provided. The general absence of randomized controlled trials evaluating the efficacy of psychotherapy alone for patients with severe major depressive disorder also precludes a definitive statement regarding this option. Nevertheless, clinical experience clearly indicates that patients whose conditions have psychotic features or severe vegetative symptoms are less able to engage in the activities thought essential to the psychotherapeutic process. Given 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.
The decision to use medication or a proven form of psychotherapy is best made with the patient. It should take into consideration the severity of the depression, the urgency of successful treatment, and the probability of and tolerance for potential harms of treatment.
Guideline: Combined treatment may have an advantage for patients with partial responses to either treatment alone (if adequately administered) and for those with a more chronic history or poor inter episode recovery. However, combined treatment may provide no unique advantage for patients with uncomplicated, nonchronic major depressive disorder. (Strength of Evidence = B.)
Randomized trials of the combination of medication and psychotherapy compared to medication or psychotherapy alone reveal only a modest advantage at best for the combination, especially regarding symptom reduction. On the other hand, there is some evidence that combined treatment may have a broader effect than does medication alone (Friedman, 1975; Weissman, 1979; Weissman, Kasl, and Klerman, 1976; Weissman, Klerman, Prusoff, et al., 1981). One study is consistent with tile widely held clinical belief that combined treatment has a particular advantage for complicated, chronic major depressions (Blackburn, Bishop, Glen, et al., 1981).
Guideline: Electroconvulsive therapy is a first-line treatment option only for patients with more severe or psychotic forms of major depressive disorder, those who have failed to respond to other therapies, those with medical conditions precluding the use of medications, and those with an essential need for rapid response. (Strength of Evidence = A.)
Electroconvulsive therapy is not recommended as first-line therapy for uncomplicated, nonpsychotic cases in primary care since effective treatments that are less invasive and less expensive are available (Electroconvulsive Therapy, 1991).
Some patients may refuse any formal treatment. For those who are not severely depressed, psychotic, or suicidal, selected therapeutically oriented reading materials may be more effective than no treatment at all in reducing symptoms (Scogin, lamison, and Davis, 1989; Scogin, Jamison, and Gochneaur, 1989). Furthermore, such information may help those who are in need of treatment to accept it. For those who are suicidal or psychotic, or who pose a substantial danger to themselves or others, involuntary commitment procedures may be necessary.
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