The key observation that emerges from a systematic review of the literature is that current evidence examining the effect of psychotherapy as augmentation or substitute therapy for treatment resistant depression is sparse and reveals mixed results. The three good quality studies, one fair quality study, and two poor quality studies all demonstrated that psychotherapy may be beneficial in managing treatment resistant depression whether used as a substitution or augmentation strategy. One fair quality study demonstrated that medications may be better than cognitive therapy. We conclude that although evidence is sparse, psychotherapy appears to be effective and is a reasonable treatment option for treatment resistant depression.
The utility of psychotherapy in treatment resistant depression is further supported by various theoretical and clinical reasons. First, maladaptive cognitions and behaviors endemic to MDD may lead to chronic depressive symptoms. Such cognitions and behaviors may be best modified with psychotherapy techniques such as cognitive restructuring, behavioral activation, or skills training. This is especially true when patients are experiencing acute stressors (e.g., divorce), where psychotherapy may improve patients’ long-term outcomes.13
Second, antidepressants have side effects which may increase in number or severity upon adding another antidepressant. Side effects are known to reduce quality of life and increase the chances of non-adherence, thereby interfering with the treatment of MDD.38
Using psychotherapy can help mitigate the issue of side effects. Third, patients may not respond to antidepressant treatment, may prefer not taking medications, or may become frustrated at the lack of response to treatment regimens. For all these reasons, psychotherapy may be an important treatment option for treatment resistant depression.
Despite these advantages, treatment via psychotherapy continues to face numerous barriers. First, access to psychotherapy can be limited if patients live in underserved areas. This issue is exacerbated by the greater time commitment required to receive traditional psychotherapy, which often requires weekly or biweekly face-to-face contact, typically for an hour each appointment. Second, the relative cost of delivering psychotherapy compared to antidepressants can be a barrier. The short-term costs of psychotherapy are typically higher, especially when delivered by a mental health professional such as a psychologist.39,40
However, psychotherapy may have more favorable cost profiles when mid to long-term outcomes are examined.39,41,42
In addition, psychotherapy may have unique economic advantages in the domains of work absenteeism,43
treatment of medical comorbidities,44
A recent study examining the cost-effectiveness of psychotherapy in treatment resistant depression concluded that adjunctive cognitive therapy was more costly but also was more effective than antidepressants alone.32
Because treatment resistant depression is both common and costly,45
large, high quality, long-term randomized trials are needed to evaluate both the effectiveness and cost-effectiveness of different treatment strategies for patients with treatment resistant depression.
One strategy to increase access and cost-effectiveness of psychotherapy involves collaborative care. Recent research has shown that training non-mental health professionals (e.g., nurses) to provide brief psychotherapeutic interventions are effective in reducing depressive symptoms.46–48
Collaborative care models involving depression care managers have been shown to improve the quality of depression care, symptom severity, patient satisfaction, and functional impairment.8,40
A few of these trials utilized empirically based psychotherapy as a treatment option for treatment resistant depression.47,49
Unfortunately, psychotherapy in these trials was delivered as part of a package of collaborative care and its unique contribution to improved outcomes cannot be assessed. Nevertheless, evidence suggests that training non-mental health professionals to deliver brief psychotherapy may improve outcomes in primary care patients without excessively burdening limited resources.
Several limitations of the current literature emerged upon review. First, few RCTs exist that adequately address the question of treatment resistant depression. Whereas each of the included studies addressed a portion of the research question, none of the studies provided a complete answer nor did an evidence synthesis across the studies provide an entirely satisfactory answer. Most studies appeared to be underpowered to detect moderately large treatment effects. Conclusions are tempered by the heterogeneity in study designs and patient populations, as well as the limited number of good quality trials.
Second, there was significant heterogeneity in the definition of treatment resistant depression as well as the measures used to determine MDD. Measures included clinician-administered scales (e.g., HAM-D), self-report scales (e.g., BDI), diagnostic criteria (DSM-III-R, DSM-IV, ICD-10), and clinical judgment. Third, the majority of trials used cognitive therapy. Traditionally, cognitive therapy requires a minimum of 12-16 sessions and is often delivered by trained experts. As a result, it is questionable whether the psychotherapies reviewed are suitable for use in primary care settings or will be accepted by primary care patients. Brief therapies such as problem-solving therapy have been adapted by non-mental health professionals as first step treatments in primary care settings, with demonstrated effectiveness.40
Newer interventions continue to be adapted for treatment within primary care settings. For example, a recent study examining the cognitive behavioral analysis system of psychotherapy (CBASP) found no effects of psychotherapy in treating treatment resistant depression.50
This study was excluded because of the limited empirical base of CBASP; nonetheless, well-designed trials such as this one are necessary to evaluate the efficacy of using these newer and/or briefer therapies in primary care settings. Fourth and finally, we were unable to comment on the fidelity to psychotherapy protocols from the published studies. Future reports should provide information regarding treatment fidelity to ensure that the real world applicability of the research is accurately represented.
There is a pressing need to examine psychotherapy as a second step treatment in patients who have not responded to initial antidepressants treatment. This may be addressed in two ways: 1) re-analysis of existing data from trials in which patients with treatment resistant depression are recruited, or 2) conducting studies designed to examine this question. As a field, it is important to develop a standardized, operational definition of treatment resistant depression to facilitate comparisons across studies.51
Finally, comparative effectiveness studies that compare the effects of augmentation or substitution of psychotherapy to acceptable treatment options will help elucidate the utility of psychotherapy in the treatment resistant population. Future investigations should also address the cost-effectiveness of different treatment options. Ideally, studies designed for this purpose would involve longer follow-up, as well as measures of direct costs, indirect costs, costs associated with comorbid non-psychiatric conditions, and societal costs. Collectively, these studies will help improve treatment of this important clinical population.