Pharmacotherapy

While pharmacotherapeutic strategies for TRD are covered in 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 , there is evidence that the collaborative care model is associated with better implementation of available pharmacotherapy strategies with stepped intensification of care, resulting in a significantly greater number of antidepressant medication trials in patients enrolled in the intervention when compared to those under usual care ( ). Several large-scale collaborative care programs for depression have been implemented in primary care. Compared to those receiving usual care, patients with MDD who engaged in the collaborative care program reported greater medication adherence, quality of care, and improvement depressive symptoms. Importantly, greater improvement in depressive symptoms was observed among patients who required a medication adjustment, suggesting that collaborative care may be most impactful for patients who do not initially respond to treatment ( ). Large single-payer health care systems, such as the Veterans Administration (VA), have implemented collaborative care. The Translating Initiatives in Depression into Effective Solutions (TIDES) found high rates of medication adherence and treatment engagement among veterans enrolled in collaborative care. A significant decrease in depressive symptoms was reported over the course of treatment, which was similar in magnitude to veterans referred to mental health specialty ( ). The Telemedicine Enhanced Antidepressant Management (TEAM) study provided evidence for a telehealth-based collaborative care program delivered in rural VA clinics without on-site psychiatrists. Veterans participating in the program reported greater medication adherence, reductions in depression symptoms, and satisfaction of care compared to those receiving usual care ( ). This study provided preliminary evidence for telehealth-based collaborative care programs as a way to reach rural and underserved populations, which has since been expanded to other health care settings ( ; ).

Psychotherapy

The presence of psychological services in primary care has steadily grown over the past two decades ( ). Behavioral activation (BA) and problem-solving therapy (PST) are the most common psychotherapy interventions employed across primary-care–based collaborative care programs for depression. BA is based on a behavioral model of depression. This model proposes that individuals who develop depression experience low-levels of positive reinforcement due to limited access to, availability of, or ability to engage in pleasant activities, which results in depressed mood and avoidance. The very nature of depressive symptoms, such as loss of interest, lack of motivation, poor energy, and social withdrawal, serve to maintain this negative cycle. Ultimately, this perpetuates the problem and leads to continued low levels of positive reinforcement ( ). BA is a brief, structured psychotherapy that aims to increase engagement in pleasant, masterful, and/or valued activities and decrease avoidance. This is accomplished through a number of different strategies including activity monitoring, activity scheduling, and problem solving ( ). PST is based on a cognitive-behavioral model of depression. This model postulates that individuals with depression exhibit deficits in problem-solving skills ( ) including a negative problem-solving orientation and maladaptive problem-solving style ( ). PST is a brief psychotherapy approach that aims to teach effective problem-solving attitudes and skills. This is achieved through a step-by-step strategy in which the patient identifies the problem, generates potential solutions, selects and implements a solution, and evaluates the outcome with the option to trial another solution if necessary ( ).

The rationale behind selecting these two interventions include their strong evidence-base, short-term structure, and straight-forward theoretical framework and therapeutic techniques. The structure of these therapies aligns well with the population-based model of care practiced in primary care settings. While there are a number of different protocols available, both interventions typically consist of only 6–12 sessions ( ; ). The fact that these therapies are relatively easy to understand conceptually and implement practically enables care managers, often without specialized training in mental health, to deliver these interventions with high treatment fidelity.

While, BA and PST are evidence-based treatments for depression, these have not been extensively studied in patients with TRD. Rather, TRD trials have investigated the use of CBT, which often includes the same strategies used in BA and PST ( ; ).

The efficacy of CBT for TRD has begun to be evaluated in primary care. Only one large-scale psychotherapy trial has been conducted ( ). The Cognitive-Behavioral therapy as an Adjunct to pharmacotherapy for primary care patients with Treatment-resistant depression (CoBAulT) randomized clinical trial was conducted in primary care practices across the United Kingdom. Participants included primary care patients with TRD as operationalized as antidepressant medication adherent, but not responsive, for at least 6 weeks. Participants who engaged in individual CBT were significantly more likely to achieve response and remission at 6 ( ) and 46 months ( ) compared to those receiving treatment as usual. Older participants were found to benefit more from CBT while participants with more severe depressive symptoms at baseline benefited less; however, these differences were relatively small and resulted in the authors ultimately recommending CBT for all patients with TRD ( ). While these results are promising, this trial has not yet been replicated in other primary care settings. Various psychotherapeutic interventions for TRD are further detailed in Chapter 25 .

Collaborative model of care expands access to evidence-based psychotherapy to a larger proportion of the primary care population. Studies have employed a variety of providers as care managers including psychologists ( ; ), nurses ( ; ; ; ; ; ; ), other medical professionals ( ; ), and paraprofessionals ( ). While outcomes differ slightly across studies, collaborative care can be competently delivered by care managers from diverse backgrounds. This model of care can also expand access to mental health specialists such as clinical psychologists, master’s level clinicians, and clinical social workers for patients experiencing more severe or long-lasting depressive symptoms.

Improving capacity of primary care providers

Decision tools to assist PCPs, such as the Texas Medication Algorithm Project and the psychopharmacology algorithm project at the Harvard South Shore Program, have the potential to improve depression outcomes by facilitating systematic decision-making around evidenced-based treatments for TRD ( ; ). However, in studies of improving depression treatment in primary care by using algorithms, decision support, guideline implementation strategies, or education alone for PCPs the improvements have been limited ( ; ; ; ; ).

Project ECHO is a telementoring model of education in which participating clinicians remotely attend lecture and case-based learning sessions hosted by specialists at regular intervals to improve their capacity to manage complex medical conditions. It is intended to improve access to specialty care to communities that would otherwise have difficulty accessing specialty care, such as rural locations. As opposed to traditional telepsychiatry models in which one clinician interacts with one patient at a time, Project ECHO allows for dissemination of specialty expertise to many primary care clinicians simultaneously and incorporates time for practical discussion of cases submitted by participating clinicians. Project ECHO has not specifically been studied for TRD but has demonstrated positive outcomes for a number of behavioral health conditions ( ). Further research is needed to test this model of education and support for TRD.

Another approach to expand the capacity of PCPs to treat TRD is to make informal curbside consultation to psychiatric providers easily accessible ( ). That approach is often a component of collaborative care models, but can also be leveraged in clinics or systems which have not implemented collaborative care. The Massachusetts Child Psychiatry Access Project (MCPAP) is an example of such a program that offers mental health consultation services to enrolled PCPs across Massachusetts, usually by telephone ( ). It has been very well received by PCPs ( ). The model can be replicated on a smaller scale within medical systems or even by contracting with a consulting psychiatrist to provide education and assistance with coordination of care when needed. While not yet studied for TRD, it provides the opportunity to assist PCPs in taking additional steps to treat TRD than they might otherwise take with the guidance of a psychiatrist.

Integrating digital solutions

A variety of digital tools have become available in recent years to treat mental health conditions. Mental health applications have proliferated rapidly, and along with their availability has come claims of their efficacy for a variety of conditions ( ). Although some have been tested in randomized controlled trials and proven efficacious ( ; ), many do not incorporate evidence-based interventions, and even fewer have been studied to evaluate their outcomes ( ; ). There is great promise that, over time, they will be studied in clinical trials and be evaluated specifically for TRD, and there have been some initial efforts to do so. A 2017 Japanese study compared the effectiveness of a smartphone CBT app as an adjunctive treatment for patients who had not responded to initial treatment with at least one antidepressant ( ). While the study population did not meet commonly used definitions for TRD, the intervention group had low dropout rates and those in the treatment arm scored lower on standard measures of depression severity and side effects than the control arm. The accessibility and affordability of smartphone apps make them ideal vehicles for distribution of psychotherapy for patients with TRD treated in primary care, but the ability for them to be produced and marketed without proper evaluation raises concerns about their quality. Further trials are needed to identify those most effective for TRD.

Telemental health, the remote delivery of mental health care through telecommunication technology, has an evidence base dating back several decades and is widely accepted by patients and providers. Studies comparing synchronous telemental health with in person care in primary and specialty care settings have shown similar treatment outcomes and levels of patient satisfaction, adherence, and health care cost ( ; ; ; ). The ubiquity of telemental health renders it able to be delivered to patients in a variety of settings (e.g., home, work, primary care clinic) by clinicians in a range of locations and adds flexibility to how mental health treatment can be incorporated into primary care settings. A growing body of literature is emerging on the value of being deliberate in developing and managing virtual teams to improve their efficacy in delivering telemental health ( ). There is still a need to study telemental health specifically for TRD, but the studies that have shown it to be effective across a range of conditions including depression suggest it can be successful in treatment TRD as well.

Other digital solutions, such as asynchronous telemental health and e-consults, have been identified as ways to expand access to psychiatric care ( ). Similar to other digital modalities they have not been rigorously studied specifically for TRD in primary care. Early literature on asynchronous telemental health is promising, suggesting potential for it to be implemented by the clinical team, maintain patient satisfaction, and improve access to care ( ). Likewise, e-consults have been shown to improve access to care, especially for non-Native English speakers and vulnerable populations, but improvements in other treatment outcomes have not yet been demonstrated ( ; ).