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In providing medication, practitioners always provide some talking “therapy”—clinical management. This process includes educating the patient about the illness, medication or therapy options, side effects, prognosis, and treatment plan. Adjustments in treatment and adherence are also discussed. This clinical management is essential to optimal treatment (see Chapter 2).
Mental health care practitioners may engage in more formal therapies such as supportive therapy to provide advice, guidance on current problems, reinforcement of the patient’s psychological strengths, and development of social supports. Modification of work schedules, reduction or management of current demands, and resolution of current interpersonal difficulties all are part of supportive therapy, which can take 15 to 50 minutes per session. Supportive psychotherapy has not been studied per se in randomized controlled trials. However, a closely related therapy, interpersonal psychotherapy, has been specifically designed for depressed patients and formally tested. In combination with medication, interpersonal psychotherapy seems both to reduce early termination and to result in better symptom relief and social adjustment than either treatment alone (Weissman, Prusoff, DiMascio, et al., 1979). By logical extension, supportive therapy may be particularly useful in those with complex social difficulties not resolved with medication or in those with adherence problems.
Other formal therapies, such as cognitive therapy and behavioral therapy, have been developed and tested with depressed patients alone or in combination with medication. When used alone, the targets are symptom reduction and restoration of psychosocial function. In combination with medication, the same targets apply; but, in addition, these treatments may be aimed more selectively at psychosocial difficulties, with medication as the mainstay of symptom amelioration. The term combined treatment, thus, refers to the combination of medication and a formal psychotherapy.
Guideline: Combined treatment is a reasonable consideration for initial acute phase treatment if:
For other patients, psychotherapy may be added to acute phase medication once the patient has responded to an optimal medication regimen if significant psychological or interpersonal problems continue following symptom remission. (Strength of Evidence = C.)
It is recommended that medication be added to (or substituted for) acute phase psychotherapy if:
There are few data to guide clinicians in determining when to choose the combination of medication and a formal psychotherapy. While it is common psychiatric practice to use such a combination in the treatment of major depressive disorder, the need for this combination in primary care patients is not well established. Available research does not allow for strong recommendations in this area for several reasons:
On the other hand, some research supports the ideas that:
Guideline: Formal psychotherapy can be used in combination with medication with the objectives of rectifying ongoing psychosocial difficulties that contribute to some depressive symptoms, such as pessimism, low self-esteem, or marital difficulties. (Strength of Evidence = B).
There are no well established predictors of which patients preferentially benefit from combined treatment. The following suggestions are based on logical inference from the few studies that have searched for predictors of who is best served by combined treatment, from the clinical experience of the panel, and from knowledge about the course and complications of major depressive disorder.
Psychotherapy as an adjunct to medication can be useful in addressing associated psychosocial problems, such as marital difficulties (Friedman, 975). The structured psychotherapies also tend to be specific, targeted, and time-limited. Some practitioners believe and some evidence suggests that the therapies are more effective if patients are less severely symptomatic and, therefore, better able to participate in the therapy.
Guideline: The likelihood that adjunctive therapy is indicated may be better gauged once the depressive syndrome has largely resolved with medication, since medication alone improves psychosocial difficulties in many patients. (Strength of Evidence = B.)
Psychosocial difficulties may well improve during the 1 to 3 months following symptomatic improvement in depressed outpatients (Mintz, Mintz, Arruda, et al., 1992). For example, should marital problems persist well past the reduction of the depressive symptoms, marital therapy may be more clearly indicated.
One problem is to decide when the combined treatment should begin. In primary care settings, given the limited time and need to educate the patient (and family, where appropriate) about the treatment and prognosis of major depression, the likely optimal procedure in the treatment of patients who are to receive medication and a formal psychotherapy is to (1) begin medication, (2) provide support and education, (3) optimize adherence, (4) adjust the dosage, and (5) gain symptom relief and resolution of psychosocial problems before starting formal therapy. Once medication has reduced symptoms, a reassessment for continuing psychosocial or chronic interpersonal problems may identify those patients who may benefit by adding psychotherapy to the medication. This approach has the added advantage of allowing the practitioner time to develop a close alliance with the patient and to explore briefly in the course of general clinical management ongoing difficulties that may be exacerbating the depression.
Many practitioners recommend formal psychotherapy combined with medication for depressed patients with personality disorders. In these cases, the therapy is aimed at the personality disorder itself. The diagnosis of a personality disorder is complex, time-consuming, and generally impractical in primary care settings. However, evidence from clinical trials of medication and psychotherapy suggests that patients with personality disorders are more likely to exhibit partial responses to short-term, symptom-reducing therapies or to medication, to have stormy life histories with a variety of smoldering symptoms between episodes, and to terminate treatment prematurely. Treat the major depression first; a partial success or a lack of patient adherence raises the logical possibility of a personality disorder and, therefore, a consultation or referral. Specific considerations in selecting combined treatment and initiating it appropriately are shown in Table 13.
Table 13. Considerations for combined treatment
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Table 14 shows those studies of combined acute phase treatment for which meta-analyses were feasible. Altogether, seven acute phase randomized controlled trials compared the combination of formal psychotherapy and medication to one or the other treatment alone in depressed adult outpatients (six studies) (Beck, Hollon,Young, et al., 1985; Covi and Lipman, 1987; Hersen, Bellack, Himmelhoch, et al., 1984; Murphy, Simons, Wetzel, et al., 1984; Roth, Bielski, Jones, et al., 1982; Rush and Watkins, 1981) or inpatients (one study) (Bowers, 1990). No such geriatric randomized controlled trials were found. Of these seven, five included cognitive therapy plus medication, two included behavioral therapy plus medication, and one included interpersonal psychotherapy plus medication. None included marital therapy or brief dynamic psychotherapy combined with medication.
Table 14. Meta-analysis of combined treatment in outpatients with major depressive disorder
| Combination1 | Combination Efficacy |
Combination vs. Wait List or Placebo |
Combination vs. Therapy2 Alone |
Combination vs. Other Therapy Alone3 |
Combination vs. Drug Alone |
| Behavioral therapy plus medication |
34.6% (10.9)4 [2]5 |
N/A | -7.4% (22.3) [1] |
-2.2% (11.5) [1] |
6.2% (11.4) [1] |
| Brief dynamic psychotherapy plus medication |
N/A | N/A | N/A | N/A | N/A |
| Cognitive psychotherapy plus medication |
53.7% (17.3) [5] |
N/A | 6.4% (15.3) [6] |
35.4% (9.4) [1] |
39.4% (32.9) [2] |
| Interpersonal psychotherapy plus medication |
N/A | N/A | N/A | N/A | N/A |
1Intent-to-treat sample.
2Therapy contrast is that specified in the combination coulmn (e.g., behavioral therapy).
3The combination indicated in the first column was compared to a different form of psychotherapy alone.
4Standard deviation is in parenthesis.
5Number of cells in the meta-analysis is in brackets.
These intent-to-treat analyses lead to an interesting potential conclusion. The efficacy of the combination (column 2, Table 14) is roughly equal to the efficacy of medication alone. The combination versus therapy alone is roughly equal, but the number of studies is small (column 4, Table 14). However, in a study with a primary care and a tertiary care sample (not included in Table 14 because intent to treat could not be calculated) (Blackburn, Bishop, Glen, et al., 1981), the effects of the psychotherapy (cognitive therapy) exceeded those of combined treatment or medication alone (primary care); in contrast, combined treatment was better than either alone in the tertiary care setting. This study and the meta-analyses (column 6, Table 14) are consistent with the idea that some patients—perhaps those with milder, less chronic forms of depression or those who are earlier in the course of what may become a more recurrent illness (Post, 1992 - may not specifically benefit from combined treatment. On the other hand, those with more severe or chronic disease and partial responders to either treatment alone may benefit specifically from the combination.
One difficulty in the literature available is the lack of placebocontrolled, primary care psychotherapy, medication, and combined treatment randomized controlled trials. It is clear from the many available studies that some patients with major depressive disorder respond and some even remit fully with placebo and clinical management. Patients with less severe, less chronic forms of illness seem most responsive to such nonspecific treatment. It is logical to suspect that such patients are more likely to be found in primary care settings. For this reason, a two- to threevisit evaluation may be useful to determine which patients require formal treatment (see Chapter 3). There are no studies in primary care settings of less severely ill patients with major depressive disorder given several sessions of clinical management followed, for those who do not remit, by either psychotherapy, medication, or placebo with clinical management. Such information would provide a firmer basis for recommending treatment options for these less symptomatic, less chronic, and less recurrent forms of major depression.
For these reasons, routine use of the combination of medication and a formal psychotherapy as an initial treatment is not recommended for all patients. Some patients who actually need psychotherapy may be lost to treatment if they find the medication intolerable. For others, medication may be especially useful and therapy unneeded. Thus, initial therapy for less severely ill patients may be either a trial of medication or a trial of time-limited psychotherapy, as long as the outcome (symptom remission) is monitored. Should either trial fail to produce remission, the alternative treatment or a consultation are options.
Guideline: Given the modest advantage for combined treatment and the suggestive evidence that some patients respond better (but others do not) to the combined treatment, clinical judgment remains the basis for deciding when to use combined treatment and which type of psychotherapy to use. (Strength of Evidence = C.)
Current evidence (Table 14) suggests the efficacy of medication combined with either cognitive, interpersonal psychotherapy (Weissman, Prusoff, DiMascio, et al., 1979), or possibly behavioral therapy (Table 14), at least for some patients (Blackburn, Bishop, Glen, et al., 1981). Whether the efficacy of other forms of therapy combined with medication is greater than for either alone has not been studied.
Practically speaking, the type of psychotherapy used will be substantially dictated by the availability of trained and skilled practitioners. When psychotherapy is added to medication to assist patients with psychosocial problems that may be contributing to their symptoms, the selection of therapy should be based on the specific difficulties identified by the patient (e.g., marital or family therapy for such problems, vocational counseling for those with occupational skill deficits, cognitive or interpersonal psychotherapy for low self-esteem/interpersonal difficulties). Since short-term, targeted therapies in combination with medication have been studied to some degree, while longer term therapies have not, logic and parsimony suggest that psychotherapy be limited in focus and duration when used in combination with medication in acute treatment and that its effectiveness be monitored.
Patients in combined treatment may require greater time for each session than do those receiving either medication or psychotherapy alone. The frequency of visits for medication and psychotherapy is dictated by the same forces as if either were being used alone, such as severity of illness, need for determinations of blood levels, and type of psychotherapy. As symptoms improve, the intervals between visits will also increase. When possible, appointments with the physician and therapist should be coordinated to minimize inconvenience, thereby maximizing adherence.
Full therapeutic dosages of medication should be prescribed for patients receiving combined treatment. Dosage adjustments follow suggestions in Chapter 4.
Guideline: If a patient given the combination of medication and formal psychotherapy has not responded at all by week 6 or only partially by week 12, the practitioner is advised to reevaluate the patient’s condition to ensure that an alternative source for symptoms has not been overlooked. (Strength of Evidence = A.)
There is no evidence that changing the form of psychotherapy will alter the course of symptoms. However, changing or augmenting the medication is a strong consideration. For severely depressed patients who are unresponsive to combined treatment, a consultation or referral for alternative medication or ECT may be considered.
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