LEARNING OBJECTIVES: Recognize the diagnostic criteria for major depressive disorder (MDD) according to the DSM-5-TR. Understand the demographic disparities in the diagnosis of major depressive disorder. Identify the primary structures and functions of the central nervous system that underscore the etiology of major depressive disorder. Identify medical and pharmacological management for people with major depressive disorder. Describe the impact that major depressive disorder has on occupational performance and participation.

CASE STUDY: Gail Fredrick is a 41-year-old female referred to the Valley View Therapy outpatient mental health clinic by her family physician for evaluation and treatment of depressed mood. Despite having been treated with mirtazapine for the last three months, she continues to feel down and sad, with crying spells, trouble sleeping, increased eating, impaired concentration, and fatigue. She has not been able to work in over two months. She’s feeling like she can’t handle this anymore. Read more about Gail by following this link to her EHR.

Depressive disorders (clinical depression) is a group of common mental health conditions characterized by “persistently low or depressed mood, anhedonia or decreased interest in pleasurable activities, feelings of guilt or worthlessness, lack of energy, poor concentration, appetite changes, psychomotor retardation or agitation, sleep disturbances, or suicidal thoughts” (Bains & Abdijadid, 2023, Introduction). Depressive disorders are different from regular mood changes and feelings, such as sadness and grief, that one might experience due to adverse events in everyday life (World Health Organization, 2023). Sadness and grief are situational; depression may or may not be situational.

• Sadness is “an emotional pain characterized by a lacking or longing sensation … that does not significantly hinder [one’s] ability to function in day-to-day life for an extended period of time” (BrainsWay, n.d., Depression vs. sadness and grief).
• Grief is “an emotional destabilization process that happens during bereavement [that] centers around a feeling of emptiness due to the loss of a loved one, ability, object, or even an idea” (BrainsWay, n.d., Depression vs. sadness and grief).

According to the Diagnostic and Statistical Manual of Mental Disorders (5th ed. Text Revision; DSM-5-TR; American Psychiatric Association [APA], 2022), depressive disorders include disruptive mood dysregulation disorder, major depressive disorder, persistent depressive disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, other specified depressive disorder, unspecified depressive disorder, and unspecified mood disorder. What distinguishes between these conditions is duration, timing, and etiology (APA, 2022). Here, we will focus exclusively on major depressive disorder (MDD) since it is the most commonly encountered of the depressive disorders in occupational therapy practice.

To gain a better understanding of major depressive disorder and how it impacts the occupational functioning of individuals, this section explores 1) the global, national, and local contexts for MDD, 2) signs and symptoms of MDD across the life course, 3) etiology of MDD, including structures and functions of the central nervous system, 4) common medical interventions for MDD; and 5) common sequelae associated with MDD and their impact on occupational performance.

Epidemiology

Estimates on the prevalence of depressive disorders in the United States range from 5.5% (Our World in Data, n.d.a.) to 7% (APA, 2022), with higher rates of incidence among non-Hispanic White women, ages 18 to 29 years (APA, 2022). Furthermore, the lifetime prevalence in the U.S. is estimated to be approximately 12% of the population (Bains & Abdijadid, 2023). Depression is also more common among people with less social support and among people who have psychiatric or medical comorbidities (Bains & Abdijadid, 2023).

Compared to their urban counterparts, rural communities report the following, which can contribute to higher rates of depression (Probst et al., 2006):

• poorer health status
• more frequent and greater activity limitations
• greater number and severity of comorbidities of chronic diseases such as diabetes, hypertension, and asthma
• higher rates of obesity
• lower educational attainment
• lower socioeconomic status
• higher levels of unemployment
• fewer personal resources
• higher rates of stressful life events

Global Burden of Disease

Depressive disorders come at high medical and social costs. According to Greensberg et al. (2023), the total costs attributed to the treatment of depressive disorders in the U.S. in 2019 was $33.7 billion ($16,854 per individual). Direct costs (including pharmaceuticals and inpatient and outpatient services was $127.3 billion (an estimated $6429 per individual). Indirect costs attributed to unemployment, absenteeism, lost productivity, and disability were $126.3 billion. Indirect costs attributed to unpaid caregiving was $80.1 billion.

Clinical Presentation of Major Depressive Disorder

The DSM-5-TR (APA, 2022) lists five diagnostic criteria for Major Depressive Disorder.

1. Five or more of the following symptoms have been present during the same two-week period and at least one of the symptoms must be either of the first two items:
• Depressed mood most of the day, nearly every day
• Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
• Significant weight loss (when not dieting) or weight gain (change >5% in a month)
• Insomnia or hypersomnia nearly every day
• Psychomotor agitation or retardation nearly every day
• Fatigue or loss of energy nearly every day
• Feelings of worthlessness or excessive guilt nearly every day
• Diminished ability to think or concentrate, or indecisiveness, nearly every day
• Recurrent thoughts of death (including recurrent suicidal ideation without a specific plan, a suicide attempt, or a specific plan for committing suicide)
2. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
3. The episode is not attributable to the physiological effects of a substance or other medical condition.
4. At least one major depressive episode is not better explained by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder,delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.
5. There has never been a manic episode or hypomanic episode.

In a survey of people with Major Depressive Disorder, the most common symptoms experienced were feelings of low energy, sleep disturbances, loss of interest in things (anhedonia), appetite changes, and depressed mood (Our World in Data, n.d.c.).

Major depressive disorder can occur anywhere throughout the life course, but as mentioned earlier, there is greater prevalence among teens and young adults. Symptoms may generally vary among different age groups. Here, we’ll explore three different populations who are more vulnerable: children, teens, and older adults (BrainsWay, n.d.).

• Depression among children: Because their communication skills and capacity for introspection are still developing, children may have a difficult time understanding and expressing their feelings. Signs that children might be depressed include unusually high levels of irritability, clinginess, physical complaints, emotional outbursts, running away from home, refusal to go to school, and academic underperformance.
• Depression among teens: Adolescence is generally a difficult time for everyone, with a shift toward greater independence, exploration and development of roles and responsibilities, and changing bodies. Teens who may have depression may have unusually high rates of feeling misunderstood, increased irritability, poor attendance or underperformance at school, significant weight changes, exhibiting self-harm behavior, take greater risks, experimentation with illicit drugs or harmful substances, and social withdrawal. There is also strong evidence that the use of social media, especially by teens and young adults, has negative ramifications that include depression, anxiety, social isolation, body image dissatisfaction, and sleep health (Zylstra et al., 2020).
• Depression among older adults: With child rearing and career development in the past, many older adults in retirement face their own unique challenges. Changing health status, decreased opportunities for socialization, and changing occupational roles and habits are all contributors for depression among this population. Similarly, depression may be manifested as impaired memory, personality changes, loss of appetite, chronic fatigue, physical aches and pains, and suicide attempts.

FOCUS ON CLINICAL APPLICATION: The use of the Patient Health Questionnaire – 9 (PHQ-9) is frequently used in primary care settings to screen clients suspected of having a depressive disorder. It consists of nine questions that are asked of the client, related to their perceptions of themselves over the past two weeks. Each question is scored on a Likert scale (0=not at all; 1=several days; 2=more than half the days; 3=nearly every day) that measures the severity of symptoms. Little interest or pleasure in doing things. Feeling down, depressed, or hopeless. Trouble falling or staying asleep, or sleeping too much. Feeling tired or having little energy. Poor appetite or overeating. Feeling bad about yourself or that you are a failure or have let yourself or your family down. Trouble concentrating on things, such as reading the newspaper or watching television. Moving or speaking so slowly that other people could have noticed. Or the opposite: being so fidgety or restless that you have been moving around a lot more than usual. Thoughts that you would be better off dead or of hurting yourself in some way. Scores range from 0 to 27, indicating none to severe depression. 0-4: minimal or no depression 5-9: mild depression 10-14: moderate depression 15-19 moderately severe depression 20-27: severe depression To download the PHQ-9, follow this link.

Neuropathophysiology

Early research on major depressive disorder focused primarily on the roles that neurotransmitters and central nervous system (CNS) structures play in its manifestation (Bains & Abdijadid, 2023; Kaltenboeck & Harmer, 2018; Pandva et al., 2012). A review of Section 8.1 of this Course Manual is highly recommended.

• Serotonin: normally regulates behavior, mood, and memory; serotonin is the mood neurotransmitter. Lower levels of serotonin in people with MDD results in depressed mood.
• Noradrenaline: normally regulates the sympathetic nervous system (increases levels of alertness, promotes vigilance, focuses attention, enhances formation and retrieval of memory). Lower levels of noradrenaline in people with MDD results in difficulty concentrating and feelings of low energy.
• Dopamine: normally regulates associative learning (stimulus-response and motivation-reward); dopamine is the pleasure neurotransmitter. Lower levels of dopamine in people with MDD is associated with loss of interest and anhedonia.
• Prefrontal cortex: normally manages and coordinates executive functioning (including decision-making, problem solving, emotional regulation), attention, concentration, memory, and social cognition. A smaller volume of and diminished metabolism in the prefrontal cortex in people with MDD results in dulled thinking processes and difficulty concentrating.
• Basal ganglia: normally regulates movement patterns and executive and emotional functions. Basal ganglia function is responsible for motivation, drive, and reward. A smaller volume of and diminished metabolism in the basal ganglia in people with MDD results in psychomotor agitation (excessive restlessness) or psychomotor retardation (slowed thinking and movements).
• Limbic system, especially the amygdala: normally processes and regulates emotions and regulates appetite. A smaller volume of and diminished metabolism in the limbic system in people with MDD results in depressed mood, emotional lability, and appetite changes.

More recent studies state that the causes of major depressive disorder are likely multifactorial, including biological, genetic, environmental (social and physical), and psychosocial. Additionally, there is increasing evidence of the influence of other neurotransmitters and hormones on depression (Bains & Abdijadid, 2023; Kaltenboeck & Harmer, 2018; Pandva et al., 2012).

• Gamma aminobutyric acid (GABA): normally regulates mood, anxiety, and sleep; it is an inhibitory (calming) neurotransmitter. Lower levels of GABA in people with MDD results in depressed mood and disturbances in sleep.
• Glutamate: normally regulates short-term memory and encoding to long-term memory. Lower levels of glutamate in people with MDD results in low energy and difficulty concentrating.
• Cortisol: A hormone produced by the adrenal glands and regulated by the hypothalamus, cortisol controls the body’s response to stress. In times of high stress, the adrenal glands produce more cortisol. Chronic exposure to high levels of cortisol results in sleep disturbances, weight changes, and fatigue.

Medical Management & Pharmacology

A number of pharmacologic agents are frequently used in combination with psychotherapy in the treatment of major depressive disorder (Bains & Abdijadid, 2023):

• Selective serotonin reuptake inhibitors (SSRIs): block the reuptake of serotonin in the presynaptic membranes. As a result, there is more serotonin in the synaptic cleft to be taken up by the post-synaptic neuron’s serotonin receptors. Common SSRIs include Prozac (fluoxetine), Celexa (citalopram), and Zoloft (sertraline).
• Serotonin norepinephrine reuptake inhibitors (SNRIs): block the reuptake of serotonin and norepinephrine in the presynaptic membranes. As a result, there is more serotonin and norepinephrine in the synaptic cleft to be taken up by the post-synaptic neuron’s serotonin receptors. Common SNRIs include Cymbalta (duloxetine), Effexor (venlafaxine), and Meridia (sibutramine).
• Norepinephrine dopamine reuptake inhibitors (NDRIs): block the reuptake of norepinephrine and dopamine in the presynaptic membranes. As a result, there is more norepinephrine dopamine in the synaptic cleft to be taken up by the post-synaptic neuron’s dopamine receptors. Common NDRIs include Wellbutrin (bupropion) and Ritalin (methylphenidate).
• Serotonin modulator and stimulators (SMSs): block the reuptake of serotonin in the presynaptic membranes and facilitate uptake by the post-synaptic neuron’s serotonin receptors. Common SMSs include Trazodone D (trazodone) and Serzone (nefazodone).
• Tricyclic (TCA) and tetracyclic (TeCAs) antidepressants: work similar to SNRIs by blocking the reuptake of serotonin and norepinephrine in the presynaptic membranes, although it has more unwanted side effects. As a result, there is more serotonin and norepinephrine in the synaptic cleft to be taken up by the post-synaptic neuron’s serotonin receptors. They are still used to treat MDD when SNRIs are not effective. Common TCAs and TeCAs include Elavil (amytryptyline), Ascendin (amoxapine), and Remeron (mirtazipine).
• Monoamine oxidase inhibitors (MAOIs): block monoamine oxidase, and enzyme that is responsible for breaking down norepinephrine, serotonin, and dopamine in the synaptic cleft. As a result, there is more norepinephrine, serotonin, and dopamine in the synaptic cleft to be taken up by the post-synaptic neuron’s receptors. These are the oldest class of antidepressants and they generally have more unwanted side effects. They are still used to treat MDD when SSRIs and SNRIs are not effective. Common MAOIs include Marplan (isocarboxazid) and Nardil (phenelzine).

In conjunction with pharmacologic agents, the use of psychotherapy approaches such as cognitive behavioral therapy (CBT) are highly effective.

Impact on Occupational Performance

Depending on the severity and frequency of symptoms experience by people with major depressive disorder, nearly every occupation may be affected. Here, we’ll explore the many ways that clinical depression may impact a person’s health and well-being.

• Activities of Daily Living (ADLs): Many areas of occupations related to self-care can be negatively impacted in people with major depressive disorder, especially bathing/showering, grooming/hygiene, and sexual activity (Precin, 2024). Symptoms of avolition (decreased ability and interest to initiate and sustain goal-directed activities) and anhedonia (decreased interest in pleasurable or enjoyable activities that were once so) can decrease motivation to engage in ADLs. Additionally, many medications used to stabilize moods may reduce sexual drive or performance (Precin, 2024).
• Instrumental Activities of Daily Living (IADLs): Many people with major depressive disorder struggle with engaging in activities that support daily life in the home and community. These may include the care of others (including pets), driving, financial management, meal preparation and cleanup, home management, and shopping (Precin, 2024).
• Health Management: For someone with major depressive disorder, engaging in activities related to developing, managing, and maintaining health and wellness routines may be especially challenging. These include symptom and condition management, medication management, and physical activity and exercise (Precin, 2024).
• Rest and Sleep: Sleep routines and sleep patterns are often disturbed in people with major depressive disorder. Individuals may experience insomnia, hypersomnia, or have poor sleep quality (Precin, 2024). Sleep schedules may be erratic and change on a daily basis, disrupting the circadian rhythm (Nutt et al., 2008).
• Education: Children and adolescents with major depressive disorder may experience disruptions in school performance, including lower scores during testing, social withdrawal, diminished peer interactions, and disruptive behavior (Precin, 2024). Young adults with major depressive disorder are more likely than their peers to drop out of college, especially if they engage in substance use (Arria et al., 2013).
• Work, Play, & Leisure: Individuals with major depressive disorder are less likely to work outside the home, either full-time or part-time and those who do work outside the home generally have lower productivity and higher absenteeism (Mojtabai et al., 2015). Involvement in healthy leisure activities is usually limited as well due to avolition and anhedonia (Precin, 2024).
• Social Participation: Those who experience recurring depressive episodes, limited success with treatment, or have a limited social support network typically encounter greater decline in overall functioning (Precin, 2024). Individuals with major depressive disorder are more likely to withdraw from social interactions, preferring to participate in more solitary activities.

Summary

Major depressive disorder is a serious and pervasive mental condition that can have a profoundly negative impact on an individual’s occupational performance and participation. Key clinical features of major depressive disorder include a persistent depressed mood, diminished interest or pleasure in activities, changes in sleep patterns and habits, general feelings of fatigue, and a sense of diminished self-worth. These symptoms significantly impair occupational performance in nearly all areas of functioning. Occupational therapists possess the knowledge and skills to address the symptoms of depression by helping clients to identify goals and develop strategies to build structure in their lives and acquire a sense of agency in their lives.

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