Lifestyle interventions for treatment-resistant depression

Introduction

There are several common circumstances in which treatments outside the traditional Western Allopathic medical tradition can be useful for patients with treatment-resistant depression (TRD). While many patients benefit only partially from maximized medication and psychotherapy and desire additional evidence-based recommendations, a holistic approach has other advantages. First, many patients request alternative and complementary treatments with a goal of avoiding or reducing pharmacological therapies and their side effects. Second, behavioral changes that fall outside the commonly used psychotherapeutic approaches can be addressed via complementary approaches. Finally, patients may come from cultural or personal perspectives that value a mind-body approach which when used adjunctively with traditional treatment can improve engagement and adherence and strengthen the therapeutic alliance. Fortunately, many interventions have sufficient clinical evidence of efficacy and underlying scientific and mechanistic foundation to provide a strong menu of recommendations for mental health professionals. Here we will review diet, exercise, mindfulness, and closely related interventions, including some that cross domains.

Diet and nutrition

Although the idea the diet is an important determinant of health, including mental health, has persisted for thousands of years, there is little high-quality contemporary evidence defining “healthy diet” with respect to specific mental disorders. In general, diets are described by ratios of macronutrients and their subtypes (e.g., saturated vs unsaturated fats), by food type (e.g., legumes, dairy, vegetables), by micronutrient and/or fiber content (e.g., low sodium), or a combination of these ( ). The concept of “health” in turn is defined based on long-term weight, cardiovascular, and metabolic outcomes ( ). Thus, expert consensus defines a “healthy diet” as one with carbohydrate > protein > fat caloric macronutrient content, consisting largely of minimally processed plant-derived foods to ensure sufficient fiber, vitamins, and micronutrients ( ).

Most studies focused on diet with respect to major depressive disorder (MDD) are epidemiological, with some clinical trials of diet education interventions in clinical or population samples using self-reported assessments. Mediterranean diets and those conforming to Food and Drug Administration or European health agency guidelines are the most commonly studied. Overall, these data consistently support that healthier diets, grossly defined, are associated with better mood. At the population level, multiple metrics of diet health are associated with lower current and longitudinal depression symptoms ( ). Similarly, trials of diet education/planning interventions in various clinical populations find small decreases in depression symptoms ( ). One small, low quality clinical trial has been specifically designed to reduce depression in a sample with investigator validated MDD; it found that a Mediterranean diet support program was superior to “social support” control ( ; ). However, three trials in obese depressed adults suggest that diet interventions designed to improve metabolic health and lower weight also improve depression symptoms ( ; ; ). Unfortunately, there are no large, high-quality trials of direct diet interventions and none which recruited subjects who were identified as treatment resistant.

Despite the lack of TRD-specific data, the close relationship between mood and metabolic outcomes means that clinicians can confidently recommend the same diet recommended to the general population to patients. Additional recommendations may apply for those with TRD ( ). Patients should be screened and treated appropriately for eating disorders, particularly binge eating disorder which has a high rate of comorbidity with depression ( ; ). The impact of commonly used adjunctive medications that can increase appetite and weight, as well as directly induce metabolic changes should be considered and minimized ( ). Good quality evidence supports the use of metformin or topiramate for metabolic risk reduction in patients on atypical antipsychotics regardless of indication ( ).