Treatment With Medication and Formal Psychotherapy (Combined Treatment)
It is often common practice to combine medication and formal psychotherapy at the outset. However, for many patients, the efficacy of this practice is not substantiated by randomized controlled trials. In fact, this combination treatment appears not to add to the symptom-reducing effects obtained by either treatment alone (for meta-analytic findings, see Depression Guideline Panel 1993; Thase et al. 1997b; Wexler and Nelson 1993) in nonchronic, uncomplicated forms of major depressive disorder. On the other hand, even for these less complex forms of depression, the combination may have a broader spectrum of action (e.g., symptom reduction and psychosocial restoration). Clinical impression and recent “mega-analyses” also suggest certain indications for the combined treatment approach. Specifically, more severely or chronically depressed patients may especially benefit from the combination.

Logically, there are three basic paths to combined treatment: 1) initiation of the combination at the outset of treatment; 2) the addition of formal psychotherapy when there is a partial response to medication alone (e.g., residual cognitive, psychological, and/or interpersonal symptoms); or 3) the addition of medication in the context of partial response to psychotherapy alone.

The combination of medication and formal psychotherapy at the outset of acute-phase treatment would be called for if either 1) medications were used for symptom control and formal psychotherapy were aimed at adherence or 2) the targets of each treatment were defined as somewhat distinct and both targets were in need of early remediation (e.g., medication to control symptoms and psychotherapy to address problems in the marriage; or medication to control symptoms and psychotherapy aimed at combating demoralization and the low self-esteem that may be concomitants of a chronic illness). In addition, combination treatment may be preferable to either treatment alone 1) when there is a coexisting Axis II disorder, 2) when there is a chronic or recurrent pattern with incomplete interepisode recovery, or 3) when the patient is discouraged and demoralized as well as clinically depressed (Depression Guideline Panel 1993; Rush and Thase 1999; Thase et al. 1997b).

Strategies and Tactics in the Treatment of Depression Introduction Acute-Phase Treatment -General Issues -Strategic Issues -Tactical Issues -Treatment With Medication and Formal Psychotherapy Continuation-Phase Treatment Maintenance-Phase Treatment Patient Preference Conclusions Antidepressant and Antimanic Medications Depression-Focused Psychotherapies Psychodynamic Psychotherapies Combined Medication and Psychotherapy Electroconvulsive Therapy Light Therapy Treatment-Resistant Mood Disorders Treatment of Mood Disorders in the Medically Ill Patient

A recent study (Keller et al. 2000) was the first to demonstrate the particular utility of combined treatment in outpatients with several forms of chronic major depression. In this large multisite outpatient trial, patients were randomized to nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP) (McCullough 2000), or the combination. CBASP is a time-limited approach specifically designed for the treatment of chronic depression. Response rates were 48% for nefazodone, 48% for CBASP, and 73% for the combination (intent-to-treat sample). Furthermore, the remission rates were 30%, 33%, and 48%, respectively. Thus, the combination of nefazodone and CBASP increased the number of responders and the magnitude of the effect (i.e., increased the number of patients attaining remission). This is the first definitive evidence that clearly recommends the combination of medication and psychotherapy for chronically depressed patients.

In general, especially for patients with little prior treatment, both diagnosis and medication management require time for the patient to collaborate in the optimal use of the medication. Thus, it is often simpler initially to begin with medication and clinical management and then, subsequently, to determine whether formal psychotherapy (either to complete the symptom remission or to address psychosocial problems not relieved by medication) is indicated.

Indications for adding psychotherapy when there is a partial response to medication might include the persistence of cognitive and interpersonal difficulties after remediation by medication of the other criterion symptoms of the mood disorder. When to initiate psychotherapy in conjunction with medication is unclear. Evidence indicates that psychosocial and functional improvements occur weeks to months after symptom responses, whether induced by medication or by psychotherapy (Mintz et al. 1992). Miller et al. (1998), however, found substantial functional improvement within 4 weeks of symptom improvement. Psychotherapy may be added to medication even some months after symptom response to further reduce symptoms and improve functioning, but when to add it is a clinical judgment that depends, in part, on the duration and severity of the psychosocial and functional difficulties, the presence of Axis II disorders, and patient preference. Since psychosocial improvements do follow symptom response to medication, a 4- to 8-week observation period to evaluate the full effects of medication on psychosocial functioning seems logical in many cases. Obviously, the need for psychotherapy to redress psychosocial difficulties becomes clearer if symptom control persists over time while psychosocial problems continue.

Given evidence that switching medication classes appears to be effective, when combined treatment does not produce a full response, a switch of medication classes with continued psychotherapy would logically be the next step.