Managing treatment resistant depression in primary care settings

Scope of problem

Major Depressive Disorder (MDD) is a common, often recurrent or chronic illness associated with significant morbidity. According to the World Health Organization, an estimated 4.4% of the global population suffers from depression. MDD is among the five leading causes of years lived with disability (YLDs) in 2016 ( ). Past-year depression prevalence increased significantly in the United States (U.S.) from 2005 to 2015 ( ). Few studies have estimated the prevalence of treatment-resistant depression (TRD) in primary care. Information is further limited by lack of uniform criteria for defining TRD as detailed in Chapter 1 . Using failure to respond to two antidepressants from different classes as definition for TRD, the InSight study conducted in Canada, found the prevalence of TRD in primary care to be about 22.0% ( ).

Treatment for major depression is often initiated by primary care providers (PCPs) in the form of antidepressants and/or referral to psychotherapy ( ; ; ; ). Only about 20.0%–30.0% of patients in clinical practice respond to initial antidepressant treatment ( ). The large STAR*D trial, which recruited patients from primary care and psychiatric clinics, showed that even with close follow-up and structured treatment, close to 30.0% of patients have TRD ( ).

Various clinical and psychosocial factors contributing to treatment resistance are relevant to primary care practices. Longer duration and severity of current depressive episode, previous failed trials of antidepressants and comorbid anxiety disorders have been associated with increased risk of treatment failure ( ).

Depression comorbid with physical health problems contributes to poor response to depression treatment and poor outcome of physical health problems. The physiological impact of medical illnesses, the presence of other medications, and the burden of physical health problems contributes to lack of response to depression treatment. Also, this relationship is bidirectional with MDD being associated with poor compliance with treatment recommendations for the management of physical health problems, poor self-care, greater functional impairment, and poor quality of life.

Bidirectional relationship between diabetes and depression is well established. A meta-analysis of long-term longitudinal studies found significantly higher risk of incident diabetes in depressed patients ( ). Diabetes patients with depression have poor self-management leading to increased risk of complications and mortality ( ; ). Another meta-analysis found that close top 40% of individuals with TRD met criteria for metabolic syndrome, with men being at significantly higher risk. Of the individuals with TRD, less than a third of patients with hypertension and dyslipidemia were treated for these conditions ( ). Similar to diabetes, prevalence of depression is higher in patients with cardiovascular disease ( ) and is a risk factor for incident cardiovascular illness ( ). Comorbid depression and cardiovascular disease is associated with poor outcomes for both ( ; ). Greater number of comorbid physical health problems has been associated with poor response to depression treatment ( ).

TRD has been consistently associated with high economic burden in the form increased utilization of health services; increased cost of care, poor health-related quality of life, and lost productivity. Compared with non-TRD, patients with TRD had more emergency department visits, more and longer inpatient hospitalizations and higher per person per year health care costs. These patterns have been observed in both government and commercially insured patients ( ). Both general medical and depression care-related costs increase with an increase in the severity of TRD, accounting for close to 30% increase in medical expenditures ( ; ; ; ; ).

Challenges of managing TRD in primary care settings

A major challenge to adequately addressing TRD is the limited number of mental health providers trained to adequately treat the condition. There are too few psychiatrists, advanced practice providers, and therapists to address TRD alone while continuing to treat the myriad other mental health conditions, and primary care providers (PCP) struggle to connect patients with existing mental health providers ( ; ). Thus, supporting PCPs in delivering depression care is the key to expanding their ability to treat TRD. PCPs currently identify and treat the majority of patients with depression, which, combined with their generally long-term relationships with patients, creates natural opportunities for increasing their ability to treat TRD while improving their comfort level in doing so. It also provides opportunities to address comorbid medical conditions that are less likely to be addressed in mental health settings. A number of studies have demonstrated challenges PCPs identify in providing mental health care to patients, including limited time, inadequate knowledge, and lack of resources ( ; ). Thus, it is important to incorporate strategies that help with efficiencies rather than simply adding more demands or requirements.

Collaborative care for management of depression in primary care ( Fig. 36.1 )

Integrating mental health services with general medical services to manage patients with chronic illnesses have been conclusively shown to improve outcomes for chronic physical and mental health problems. Collaborative care is a specific form of integration that provides team-based care including a behavioral health care manager, PCPs, and a psychiatric consultant. Other members, such as a pharmacist and social worker, can also be part of the team to address factors that may be contributing to the maintenance of TRD. Collaborative care teams conduct systematic case and population review using a registry facilitating timely, evidence- and measurement-based recommendations for patients’ PCP ( ; ; ).

The U.S. Preventive Services Task Force (UPSTF) recommends screening for depression in all adults. UPSTF further recommends that positive screens should lead to further assessments, which is often difficult to accomplish in busy primary care practices ( ). A large number of patients referred to mental health services, especially the most vulnerable, do not show up for initial appointment ( ; ). Having a behavioral health care manager available for warm handoffs improves the chances of further evaluation being completed ( ). In the collaborative care model, an initial assessment by the care manager includes the use of rating scales for measuring severity of depression; record of response to past treatment; and screening for comorbid conditions including bipolar disorder and substance use, which are all factors that can complicate treatment of depression. The collaborative care team then provides individualized treatment recommendations to the patient’s PCP. Frequency of monitoring is based on severity of illness, adverse effects, and treatment adherence. The care manager also provides education and support to improve adherence, may use motivational interviewing, and incorporates psychotherapeutic techniques. Routine follow-up allows for early identification of failure or intolerance to pharmacological interventions and treatment is subsequently modified. Structured, manualized cognitive behavior therapy (CBT) can also be integrated in the treatment plan ( ; ).

More than 80 randomized controlled trials have found significantly better response and remission rates for depression with collaborative care compared to usual care. A systematic review of 79 RCTs which included 24,308 participants, showed significantly greater improvement in depression outcomes for adults with depression treated with the collaborative care model in the short-term and medium-term ( ). A meta-analysis of 37 randomized studies that included 12,355 patients with depression in primary care settings showed that depression outcome benefits were maintained for up to 5 years ( ).

In addition, collaborative care programs have been adapted to address both depression and chronic medical conditions. The TEAMCare and subsequent Care Of Mental, Physical, And Substance-use Syndromes (COMPASS) studies delivered collaborative care to patients with depression and comorbid diabetes and/or coronary heart disease. The initial trial found that patients engaged in collaborative care reported greater improvements in depression symptoms; blood sugar, cholesterol, and systolic blood pressure readings; quality of life ratings; and care satisfaction compared to those receiving usual care ( ). Large-scale implementation reported similar, albeit somewhat less robust, results, indicating that such programs can be successfully translated into real-world practice ( ).