Research into the efficacy and effectiveness of treatments for depression has grown exponentially during the past several decades. Numerous studies show that disorders like major depression and dysthymia can be treated successfully with antidepressant medication and/or psychotherapy.1 Therapeutic effect sizes from efficacy trials are 18% for antidepressants compared with placebo and 26% for psychotherapy compared with no treatment.2-4 However, when these interventions are administered in real world settings, much lower response rates have been found.5-8
The evidence from these studies indicates that in controlled settings and with highly selected patients, current methods for treating depression are efficacious. However, there are still many people who do not respond to current guideline-based treatment and many segments of the population that have not been included in clinical studies. We briefly review the research and discuss which populations respond to current treatment, which do not, and which require further study.
Definitions of treatment and treatment response
For the purposes of this paper we defined “treatment” as antidepressant medication or psychotherapy. Because the majority of psychotherapy research has focused on cognitive-behavioral and interpersonal therapies, we use psychotherapy as a generic term for these 2 types of treatment. Most depression treatment studies have defined “response” as no longer meeting Diagnostic and Statistical Manual of Mental Disorders criteria for a disorder and exhibiting a statistically significant change on a symptom severity scale (usually a decrement of at least 50%). For the purpose of this paper, we will consider response to mean a significant change in depression severity.
Who responds to treatment?
The authors of several studies have examined patient traits linked to treatment response.9 For the most part, patients who are educated, are experiencing uncomplicated depression, have had 2 or fewer previous episodes of depression, and have faith in their treatment typically respond to guideline-level treatment.10 Depression experts once believed that only patients of this type were likely to show a treatment response and that those who were older, a member of an ethnic minority, or from lower socioeconomic groups were less likely to respond to guideline treatment. Recent research shows that people from low socioeconomic backgrounds can respond to existing treatment, provided they have access to quality care.11,12 Several studies specifically about treating depression in older adults have found positive effects, both in university and primary care settings.4,6 Although research on ethnic minorities is scarce and focused primarily on Latinos and African Americans, the literature indicates that members of these ethnic groups do respond to psychotherapy. With respect to medication treatment, research on the pharmacokinetics of antidepressants in African Americans, Asians, and certain Latino groups indicates that dosages may need to be altered to reduce side effects.13
Current research also indicates that patients with complicated psychiatric presentations can respond to guideline-level treatment. For example, although patients more severe depressive symptoms may not respond to monotherapies as well as patients with milder symptoms,14 they generally respond well to combination treatments.8 The presence of Axis II features and comorbid anxiety or substance abuse does not necessarily have an impact on treatment outcome, although much of the data focus primarily on acute care of depression.14 Finally, even patients with cognitive impairment can respond to both medication and psychotherapy for depression.15
Who does not respond?
Growing evidence suggests that while effective treatments for depression do exist, they are not helpful for everyone. Treatment nonresponders fall into 2 categories: those who are treatment resistant and those who simply resist treatment.
Patients who are treatment resistant have been given an adequate course of either antidepressant medication or psychotherapy and have either no response or a limited response to treatment. Research investigating predictors of treatment failure indicates that several psychiatric and psychosocial variables are related to treatment resistance. Patients with more psychosocial stressors and less social support are more likely to show a limited response to treatment,9 as are patients with a greater number of previous depressive episodes.16 This may be due in part to increased feelings of hopelessness17 or lack of faith in treatment,18 both found to contribute to treatment resistance. Comorbid Axis II features, such as borderline and dependent personality traits tend to predict a decreased treatment response, in part because of the poor psychologic resources these patients have to cope with their symptoms.15 Such patients may benefit from additional interventions to alleviate their symptoms, such as case management, longer courses of psychotherapy, and multiple medications.
Patients who resist treatment include those who despite being identified as depressed and offered treatment, never follow through with the treatment plan. The primary reasons why patients do not adhere to treatment for depression include stigma concerns19 and the belief that depressive symptoms are not significant enough to treat.20 Other factors, such as cognitive impairment, using multiple medications,21 comorbid medical illnesses, sensitivity to side effects,13 cost of mental health services,22 location of mental health services, and cross-cultural issues23 may also have an impact on patient willingness to accept treatment. Once in treatment, psychologic factors such as self-efficacy24 and readiness for change25 can influence whether a patient will adhere to a treatment plan. There is early evidence that educational interventions or treatment management programs may benefit patients with acceptance or adherence issues.26