2 Guideline: Aims of Treatment Guideline: 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. (Strength of Evidence = A.) Acute treatment refers to formally defined procedures used to reduce symptoms and restore psychosocial function. All treatments are administered in the context of clinical management, which refers to the education of and discussion with patients (and families, when appropriate) about the nature of depression, its course, and the relative costs and benefits of treatment options. Clinical management is distinct from supportive therapy, which itself is a "formal" therapy or which can be combined with medication. Supportive therapy goes beyond clinical management and focuses on the management and resolution of current difficulties and life decisions through the use of the patient's strengths and available resources. In some milder, less chronic, nonrecurrent, nonpsychotic cases, an extended evaluation (one or two additional visits), when clinically safe, may help to differentiate those with major depression that requires formal treatment from those with depressive symptoms (not major depression) that may resolve with only time, support, explanation, and reassurance. The certainty of treatment response is weighed against the likelihood and severity of potential adverse treatment effects. Treatment selection is based on an evaluation of the potential benefits and harms of each alternative. Second- and third-line treatments are considered if first-line treatments are contraindicated, ineffective, or inappropriate in particular cases. The optimal treatment is highly acceptable to patients, predictably effective, and associated with minimal adverse effects. It results in the complete removal of symptoms and the restoration of psychosocial and occupational functioning. Potential adverse effects include: ■ Side effects. ■ Medical complications. ■ Exacerbation of the underlying condition. ■ Extraordinary monetary cost in relation to benefit. Excessive time requirement (inconvenience) at the expense of social, occupational, and family responsibilities in relation to benefit. Effective treatment results in symptom remission; improved interpersonal, marital, and occupational functioning (DiMascio, Weissman, Prusoff, et al., 1979; Wells, 1985); reduced potential for suicide; reduction in excess health care utilization and cost (McDonnell-Douglas, 1989, 1990); as well as reduced disability from concurrent general medical conditions and improved long-term outcome (von Korff, Ormel, Katon, et al., 1992). Benefits and Harms of Treatment Formal treatments for major depressive disorder fall into four broad domains: medication, psychotherapy, the combination of medication and psychotherapy, and ECT. (Light therapy is also a treatment option for mild to moderate seasonal depressions.) Each domain has benefits and risks that must be weighed carefully in the selection of a treatment option for a given patient. Medications Medications have several clear benefits. They are easy to administer; are effective in mild, moderate, and severe forms of major depressive disorder; and require little patient time. Medications also have some disadvantages: ■Need for repeated medical visits to monitor response and adjust dosage. ■ Unwanted side effects. More severe (but infrequent) medical reactions, such as allergic reactions. ■ Potential use in suicide attempts. ■Failure of many patients (10 to 30 percent) to complete treatment. ■Need for continuation phase treatment (see Chapter 9). Side effects from antidepressants range from relatively minor, annoying, but fairly frequent, problems (e.g., dry mouth or constipation) to more significant, but less frequent, side effects (e.g., orthostatic hypotension) to substantial side effects (e.g., cardiovascular conduction abnormalities with classic tricyclic antidepressants [TCAS]). Most side effects are dose-dependent, requiring dosage adjustments in many cases. For most patients, the benefits of treatment far outweigh the risks. Psychotherapy The advantages of psychotherapy are: ■Lack of physiologic side effects, such as those found with medication or ECT. ■Logical possibility (not empirically documented) that psychotherapy is effective for some patients for whom medications are not effective. ■ Theoretical possibility (with some empirical, but as yet inconclusive, evidence) that psychotherapy may make the depression less likely to recur once treatment stops because patients learn to cope with or avoid factors contributing to recurrence (Hollon, Shelton, and Loosen, 1991). Although psychotherapy does not have the physiologic side effects found with medications, unrecognized disadvantages may occur when psychotherapy is chosen as the sole therapy: ■ Psychotherapy has rarely been tested in patients with severe or psychotic depressions. ■ Many patients (10 to 40 percent) fail to follow through with the full treatment (Persons, Burns, and Perloff, 1988). ■ Many time-limited forms of psychotherapy, as well as all forms of longer term psychotherapy, have not been tested for efficacy in randomized controlled trials. The efficacy of the psychotherapies tested is defined with less certainty, since few studies have used a placebo or nonspecific therapy contrast group. Those on the wait-list commonly constitute the contrast group, and the more severely ill may refuse placement on the wait-list. ■ Psychotherapy is not effective for all patients with major depressive disorder. ■ Some therapies may differ from others in overall efficacy or in specific effects. For example, marital therapy may be more likely than therapy not focused on the marriage to improve marital function (Friedman, 1975). The quality of the therapy affects outcome, suggesting that the availability of trained therapists is pivotal (Shaw, Elkin, Vallis, et al., unpublished manuscript, 1993; Shaw and Olmsted, 1989; Woody, Luborsky, McLellan, et al., 1983). ■ While psychotherapy, in theory, should reduce the likelihood of recurrence, available data do not support this idea for already established recurrent depressions (Frank, Kupfer, Perel, et al., 1990; Shea, Elkin, Imber, et al., 1992). ■ Therapy sessions are time-consuming and may be inconvenient. ■ Some patients and therapists are reluctant to consider somatic treatment alternatives (e.g., medication, ECT) when the psychotherapy has been ineffective after a reasonable time. ■ Psychotherapy may be expensive, depending on the type of therapy and the provider. ■ Treatment effect is usually measurable later (6 to 8 weeks) than with medication (4 to 6 weeks). Combination of Medication and Psychotherapy Although the routine use of both medication and a formal psychotherapy is not recommended as the initial treatment for most patients, panel consensus, logic, and some research suggest that combined treatment may be specifically useful in the following instances: ■ Either treatment alone, optimally given, is only partially effective. The clinical circumstances suggest two discrete targets of therapy (e.g., symptom reduction addressed by medication and psychological/social/ occupational problems addressed by psychotherapy). ■ The prior course of illness is chronic (episodic with poor interepisode recovery or prolonged current episode greater than 2 years [Weissman, Jarrett, and Rush, 1987]). In these cases, the advantages of combined treatment may include a higher probability of response, a greater degree of response for individual patients, or a lower attrition rate from treatment. The disadvantages of combined treatment include the disadvantages of each alone. Those patients with milder, transient depressions may not require, respond to, or be able to tolerate medication. Those whose illness would have remitted with medication plus clinical management would have spent unnecessary time and money for a formal psychotherapy. Moreover, if the depression recurs, both treatments may again be indicated, since it will be unclear whether one alone would have been sufficient. There is no evidence, however, that the combination of medications and psychotherapy has a worse outcome than either treatment alone (see Depression Guideline Panel, forthcoming). Electroconvulsive Therapy Because of its proven efficacy in severely symptomatic patients who have failed to respond to one or more medication trials, ECT has an important role in the treatment of major depressive disorder. Electroconvulsive therapy is appropriate for patients with severe and/or psychotic depressions who have not responded to other forms of treatment or who have serious general medical conditions and severe depression for which ECT may be safer than medication. Although hospitalization is indicated for acutely suicidal or dangerously delusional patients, some practitioners believe that ECT results in more rapid resolution of these lifethreatening features than does medication. However, ECT should be considered cautiously and used only after consultation with a psychiatrist, because ECT: ■ Has not been tested in milder forms of illness. ■ Is costly when it entails hospitalization. ■ Has specific and significant side effects (e.g., short-term retrograde and anterograde amnesia). Includes the risks of general anesthesia. ■ Carries substantial social stigma. Can be contraindicated when certain other medical conditions are present. ■Usually requires prophylaxis with antidepressant medication, even if a complete, acute phase response to ECT is attained. Clinical Management Treatment for major depressive disorder may include three phases: acute, continuation, and maintenance. The overall aim of all three phases is the attainment of a stable, fully asymptomatic state and full restoration of psychosocial function (a remission). Acute treatment aims at removing all depressive symptoms. If the patient improves with treatment, a response is declared. A remission may occur either spontaneously or with treatment. 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 aims at preventing this relapse. Once the patient is asymptomatic for at least 6 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 aims at preventing a recurrence. Recurrences are expected in 50 percent of cases within 2 years after continuation treatment (NIMH, 1985). For well established, recurrent depressions, the rate may approach 75 percent (Frank, Kupfer, Perel, et al., 1990). Figure 4 illustrates the phases of treatment and the possible course of a depressive episode (Kupfer, 1991). The initially symptomatic patient begins to develop symptoms that ultimately (in days, weeks, or months) increase in number and severity until the full syndrome of major depressive disorder is present. It is useful to conceptualize treatment as having three phases (Frank, Prien, Jarrett, et al., 1991) because: A patient's full treatment plan must be based on his or her history of illness. The simple attainment of remission following acute treatment may be followed by relapse if continuation treatment is not provided. Not all, but a selected subgroup of patients, will require maintenance treatment to prevent recurrences. It is reasonably well established that patients who have only a partial response to acute treatment will have more symptoms during continuation treatment. Furthermore, those with poor symptom control during continuation treatment have a higher chance of earlier relapse, as well as recurrence once treatment is discontinued (Prien and Kupfer, 1986). Figure 5 offers a schematic overview of treatment for depression. |