Treatment-resistant depression in geriatrics

Introduction

There has been a considerable increase in the number of older individuals in the United States, with those over the age of 85 representing the fastest growing segment of the population ( ). The global population has also seen an increase in the proportion of older individuals, especially among developing countries ( ). We must appreciate this demographic change by recognizing the many biopsychosocial elements unique to this diverse population. As clinicians and researchers, we must always remain vigilant to the ever-changing and specific needs of our patients. This will require particular focus on the complex network of associations and relationships that govern the everyday lives of people. This is crucial when discussing mental health, especially in the older patient population. The mental health of older individuals has profound consequences for not only quality of life but also morbidity and mortality. This is deeply concerning given that many psychiatric disorders are often underdiagnosed and therefore untreated in geriatric patients ( ; ; ; ; ; ; ; ). Even when recognized, some psychiatric disorders have prolonged and tortuous treatment courses. This is often the case for late-life depression (LLD). In general, it has been determined that depression is among one of the leading causes of disability-adjusted life years (DALYs) in the world ( ). It is well known that depression has devastating health consequences in older adults that include but are not limited to social deprivation, decreased quality of life, cognitive decline, and suicide ( ).

The development of psychiatric disorders later in life has significant health consequences for these individuals. There are complex bidirectional interactions that occur between medical and psychiatric diseases that often leads to worse outcomes overall ( ; ; ). As an example, there is significant worsening of cardiovascular outcomes in patients with coronary heart disease and comorbid depression ( ). It has also been determined that patients with depression are at increased risk of diabetic complications due to worse glycemic control ( ). This remains relevant when discussing healthcare outcomes for geriatric patients given their increased burden of medical disease in combination with the historical under recognition of psychiatric disorders ( ; ; ). In addition to the unique health burden assumed by aging populations, there are many psychosocial factors that influence the overall wellbeing of geriatric patients ( ). It has been determined that psychological and social variables such as environmental mastery, sense of purpose, and autonomy were crucial elements related to the diagnosis of major depression in older individuals ( ; ). In addition to unique psychosocial stressors experienced later in life, older individuals are also at increased risk for depression due to age specific biologic changes ( ; ). There is mounting evidence that supports unique pathophysiology for LLD with wide-ranging medical etiologies ( ). This has profound consequences for disease presentation, clinical course, symptom management, treatment response, and prognosis ( ; ). In this chapter, we will focus primarily on LLD with particular emphasis on treatment resistance.

Epidemiology

There are many epidemiological studies that exclude older adults, focusing more on younger populations when investigating psychiatric disorders ( ). This is due to the misconception that psychiatric disorders are rare in older individuals ( ). Although there is epidemiological evidence suggesting an overall lower rate of depression among this population, we must consider how underdiagnosis impacts the validity of these studies. It has been well documented that depression in geriatric patients is often not recognized, underdiagnosed, and inadequately treated ( ; ; ; ; ; ; ; ). There is data to suggest that depression in older adults is not fully assessed due to differences in clinical presentation when compared to younger individuals ( ; ; ). There is a paucity of training leading to poor clinical competency in the area of geriatric depression which has further exacerbated the level of underdiagnosis ( ). In addition, we must also be cognizant of changes in diagnostic criteria or algorithms over time and how this can impact prevalence data ( ; ). Therefore, late-life depression has the potential to be higher than traditionally reported in the geriatric population.

In general, there is a 20% lifetime prevalence for major depressive disorder ( ). In terms of psychiatric disorders presenting later in life, depression remains one of the most frequent diagnoses with the majority of individuals having no previous psychiatric history ( ; ; ). It has been determined that over 50% of elderly patients with depression are experiencing their first episode ( ; ). The overall prevalence of major depression in adults over the age of 65 was roughly 1% with rates of 1.5% in women and 0.5% in men ( ). Depressive symptoms do not preclude the diagnosis of other psychiatric diseases and are not mutually exclusive. There is evidence to suggest that depression occurring later in life increases the risk of developing other psychiatric disorders. This is particularly true when considering alcohol use disorder, which is three to four times more likely to occur in the setting of geriatric depression ( ). These psychiatric comorbidities may contribute to increased treatment resistance in geriatric depression. For example, comorbid anxiety is associated with poorer treatment response ( ). Treatment nonresponse in geriatric depression has also been associated with clinical factors such as higher baseline depressive severity, longer duration, more guilt, and greater functional impairment ( ).

There are many sociodemographic factors to consider when discussing depression ( ; ; ). Some of these risk factors specific to LLD include but are not limited to social isolation, bereavement, low income or educational level, divorced or separated marital status, sleep problems, and prior history of depression ( ; ). Moreover, low level of perceived social support has been shown to be one of the risk factors for poor response to psychotherapy in LLD ( ).

There are studies revealing 50%–60% of patients overall do not achieve adequate response following initial treatment for depression ( ). Other studies revealed that between 29% and 46% of patients with depression did not achieve therapeutic effect from antidepressant medications even after adequate dose and duration ( ). One study had determined that only 19% of elderly individuals with depressive disorders were on antidepressant medications ( ). It was found that treatment resistance was present in roughly 18%–40% of the elderly population ( ). There are some survey data that report even higher rates with nearly 55%–88% of elderly patients with major depression not responding to selective serotonin reuptake inhibitor (SSRI) or SNRI medication ( ).