J. Nile Wagley
Mood Disorders
Normal variations exist in mood (emotional state) and affect (outward display of mood). Factors including age, personality development, and genetically predisposed temperament influence how any one person may interpret events, behave, and modulate his or her emotions. Specific criteria exist to separate these normal displays of personality and coping styles from episodes of diagnosable mood disorders that may benefit from treatment. Mood disorders, according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), are defined by mood episodes.1
A major depressive episode describes a condition in which a person has depressed mood or anhedonia (loss of interest or sense of pleasure) and four of the following symptoms: unintended change in weight, sleep disturbance, psychomotor agitation or retardation, fatigue, feelings of worthlessness or guilt, inability to concentrate, and recurrent thoughts of death or thoughts of suicide.
A manic episode is defined by a period of time (at least one week) during which a person’s mood is abnormally elevated, expansive, or irritable in addition to at least three of the following symptoms: inflated self-esteem (grandiosity), decreased need for sleep without fatigue, pressured speech, racing thoughts, distractibility, psychomotor agitation, and excessive involvement in pleasure-seeking activities that may have high risk for undesirable consequences (excessive spending, sexual indiscretions).1
A mixed episode is present when symptoms of both major depressive and manic episodes are present nearly every day for a week or more and these symptoms are not related to a medication effect or substance. Like manic and major depressive episodes, a mixed episode can be diagnosed only when the symptoms cause marked impairment in one’s ability to participate in usual activities and to function at previous expectations.1
A hypomanic episode describes symptoms of a manic episode that are shorter in duration and do not match the severity of a manic episode and thus are not associated with such marked impairment of function. Hypomanic episodes are not debilitating enough to warrant hospitalization or to lead to dangerous consequences.1
By use of the DSM-5 as a guide, diagnosis of a mood disorder includes consideration of psychosocial stressors. A major depressive or mood episode may follow a stressful event or traumatic experience. Often, family members and providers attribute some symptoms as appropriate coping in response to such an event. This bias, however, may delay access to treatment and result in additional complications in medical health, further coping, and overall prognosis. A person’s response to the loss of a loved one is an example of this risk.
Grief and Bereavement
Bereavement is currently not defined in DSM-5. The “V-Code” (which was established in DSM-IV to signify a condition that is the focus of clinical treatment but may not be a mental disorder) no longer exists in DSM-5. DSM-5 does refer to bereavement; it recommends that good clinical judgment be exercised in considering depressive symptoms when the loss of loved ones has occurred. Previously, a “bereavement exclusion” existed that prevented the diagnosis of certain depressive syndromes after the loss of a loved one. This has been removed in DSM-5 in acknowledgement that the loss of a loved one can precede or even precipitate severe depressive symptoms. DSM-5 contains Section III (Emerging Measures and Models), which lists Persistent Complex Bereavement Disorder under Conditions for Further Study but not as an official diagnosis. Although the DSM-5 seems to have carefully balanced its ability to provide standardized language for continuity of care with its desire to have continued usefulness as a billing tool, the underlying principles of bereavement and grief as part of our human experience have not changed. The International Classification of Diseases, Tenth Revision (ICD-10) classifies bereavement as a billable code: Z63.4. Both coding systems categorize grief as a condition that may be the focus of treatment; however, it is not considered a mental illness.1,2 The terms grief and bereavement are used interchangeably in this section. Grief is associated with a wide range of emotions, including sadness, anger, guilt, and despair. Because no one is immune to loss, no age group or culture escapes the potential complications of grief.
According to the 2012 World Health Organization (WHO) data published in 2014, there were 56 million deaths globally, nearly one in nine deaths throughout the world was of a child younger than 5 years.3 It is estimated that each death leaves an average of five people bereaved, resulting in almost 13 million people grieving each year in the United States alone.4
Grieving usually occurs after a person experiences the death of a family member, spouse, child, close friend, or pet. A grief response can also occur with other losses, such as a job or career loss, loss of physical health or abilities, miscarriage, divorce, financial loss, or the diminishing health of a spouse or loved one. The initial painful experience of disbelief, shock, loss, and sadness is often followed by a sense of emptiness, hopelessness, and loss of interest in usual activities, followed by a prolonged phase of restitution and recovery, which for many individuals represents a departure from the state of health and well-being to which they are accustomed.5–7
The length of the grief response varies. Elizabeth Kübler-Ross is credited with defining the five stages of grief that most people experience. She postulated that individuals experience periods of denial, anger, bargaining, depression, and acceptance.8 The process of grieving is ongoing, does not follow a rigid order or time frame, and may vary or even skip stages. Not all of the stages of grief are necessarily obvious. They may be repeated many times and are often not completed before the process of moving through another stage.
Cultures have different ways of expressing and coping with grief. Some cultures expect and encourage expressions of grief, whereas in other cultures these expressions are suppressed. People of a certain heritage may have varying degrees of connection to traditional practices of their culture. The clinician should be cautious and not assume what may be a “normal” expectation of recovery or expression for any patient after a loss. The grieving patients themselves are the best source of information about cultural practices and beliefs around death. Only they can accurately represent how their values, traditions, and beliefs influence their grieving.
Gender and age differences in grief responses have been categorized and described in the literature. It has recently been suggested, however, that characteristics of coping style, preexisting mental health, and ability to provide help to others after the loss are more robust factors associated with recovery (absence of development of persistent depressive or anxiety symptoms).5–9
Physical complaints, which are often vague, are common during the grieving period. Office visits to the health care provider may become more frequent. Sleep and appetite disturbances are often reported. Women have been reported to have more illness and disability than men after the death of a family member.10 If a person has been a caregiver to a loved one recently deceased, that person may have neglected his or her own personal health for months or years. The provider must be careful not to minimize somatic complaints during the period acutely following a loss.
Symptoms commonly associated with grief, such as sadness, low energy, and sleep and appetite disturbances, overlap with the symptoms of a major depressive episode as described earlier. Table 248-1 highlights some differences according to DSM diagnostic criteria for a depressed mood episode and symptom descriptions of grief.
TABLE 248-1
Assessing Symptoms of Grief and a Depressive Mood Episode
| Symptom | Common in Grief | Concerning for Depressive Mood Episode |
| Guilt | Specific to actions or behaviors at the time of death of loved one | Generalized and grandiose, not specific to one person or event |
| Thoughts of death | “Should have died with/instead of” the deceased | Pervasive and persistent with possible planning for self-injury |
| Sense of worthlessness | Helplessness specific to cause or circumstances of death | Pervasive and persistent sense of worthlessness and hopelessness |
| Psychomotor slowing | Limited time; days to weeks | Pervasive and persistent for more than 2 weeks |
| Functional impairment | Episodic; if consistent throughout all areas of function, limited to less than 2 months | Consistently impaired throughout all domains; inability to work, to engage with others, and to maintain basic self-care |
| Hallucinations | Only in relation to the deceased, such as hearing the deceased’s voice or feeling as if the person were nearby | Not related to a specific person or event |
The DSM-5 has proposed criteria for a Persistent Complex Bereavement Disorder with a unique constellation of symptoms. A 2009 paper reviewed the development and validation of symptom criteria, identifying Persistent Complex Bereavement Disorder as a distinct syndrome, separate from any mood or anxiety disorder described elsewhere in the text. The authors also suggested that identification of this disorder within 12 months of a loss has predictive value, citing the relative risk for development of comorbid anxiety and mood disorders or demonstration of marked functional impairment.2
Social support is critical after a loss. Providers should be aware of local resources for caregivers of patients with dementias or cancers, including support groups as well as therapists and social workers available for individual counseling. After a traumatic loss, however, social support may be so powerful as to mediate the effect of the loss and prevent symptoms that may lead to a diagnosis of post-traumatic stress disorder.
Medication is commonly used for short-term symptom relief as indicated but should not be considered a first-line treatment when more effective therapies such as psychotherapy are available. Benzodiazepines (clonazepam, lorazepam, and alprazolam) prescribed in small doses for infrequent use may be helpful for symptoms of anxiety associated with grief, but the benefits gained may not be worth the side effects and inherent risk associated with these medications. Antidepressants may be indicated for some persons after a loss. If there is a previous history of a major depressive episode (before the loss) or additional history of trauma, a person may be more vulnerable to the development of a depressive disorder after the stress of the loss of a loved one. There is no evidence that normal bereavement requires professional intervention.11 When considering treatment for complex bereavement, it has been demonstrated that psychotropic medication and supportive talk therapies have little impact. However, Complicated Grief Treatment (CGT) is a combination of cognitive behavioral interventions such as interpersonal psychotherapy and motivational interviewing that focuses on repeatedly revisiting and coming to terms with the loss while reengaging in life.12 Prescribing practices should follow the guidelines described later in the section on management of depressive disorders.
Evidence is well established for the effectiveness of cognitive behavioral therapy in treating anxiety and depressive symptoms related to bereavement. Analyses continue to best determine who is most likely to benefit from this intensive therapy.13 Primary care providers and family members can support recovery of the bereaved by supporting and encouraging completion of structured cognitive behavioral programs; the evidence suggests that if people are able to complete the program, they significantly benefit.13
Although loss indiscriminately affects people of all ages, ethnicity, and gender, many styles of coping exist. Because of this variation, characteristics of the bereaved are associated with different responses to treatment. Children may fear abandonment or the loss of others they love, and they may feel guilt or responsibility for the loss. They may begin to have behavioral problems at home or school. The loss of a parent in childhood is associated with more behavioral issues and psychosocial problems in adulthood. This may be related to the available coping skills of the child and the ability of remaining caregivers to be healthy supports. When children are included in the treatment of bereavement, such as with a family bereavement program, they have less-problematic symptoms related to the loss.14
Approximately 15% of pregnancies end in miscarriage; mothers and fathers often react differently, but both have high rates of persistent symptoms of bereavement that affect relationships, mood, physical health, and productivity months to years after the loss. Involvement in counseling sessions as a couple (as few as three sessions) can significantly reduce the prevalence of symptoms for both grieving parents.15
Older adults who lose their life partner are more at risk for complications in bereavement, including additional physical health problems and development of mental illnesses such as major depressive disorder (MDD) or PTSD. In a sample of nearly 300 bereaved elder adults, 16% met criteria for PTSD within 3 months of the loss and maintained this diagnosis for at least 18 months after the death of a spouse.16 After a loss, people of all age groups are at higher risk for substance abuse and suicide.
Depressive Disorders
Definition and Epidemiology
Major depressive disorder (referred to as MDD or depression throughout this chapter) is the most common of the depressive disorders and is diagnosed when all criteria are met for at least one major depressive episode, without history of manic or hypomanic behavior. Persistent Depressive Disorder (a consolidation of the DSM-IV–defined diagnoses Dysthymic Disorder and Chronic Major Depressive Disorder) describes a longer-term, persistent presentation of depressed mood accompanied by few or no episodes of positive mood or affect. The symptoms must not be better explained by any other medical or psychiatric condition, must cause marked impairment in function, and must be prominent for more days than not in a 2-week period for a diagnosis of MDD and a 2-year period for Dysthymic Disorder. The diagnosis Depressive Disorder Not Otherwise Specified (NOS) is used to describe patterns of symptoms that do not fit into these categories, yet for which depressed mood remains the predominant symptom.
WHO has developed a method for evaluating disease burden beyond mortality statistics. A report published in 2012, which reviewed statistics for 2014, analyzed causes of death and burden of injury and illness globally, by region, by gender, by age, and by national income. In this publication, WHO identified depression as the leading cause of disability in the world. Depression is already a major contributor to global disease burden. By 2020, it is estimated that depression will be the leading cause of overall disease burden across the globe (combining years of healthy life lost and mortality data), regardless of age, gender, or income.3 In addition to lost work time and impairment in interpersonal and role functioning, people with MDD have been noted to use medical services at an increased rate. For example, a study of Medicaid recipients found that people with MDD receive the majority of their care in the general (primary care) setting. They cost the system more than twice (2.33) as much as someone without a diagnosable mental health problem in areas of general medical care and drug costs. Specialty care (mental health) was less used by those with MDD, and overall costs were surpassed only by those with diagnoses of bipolar disorder and psychotic disorders.17
Information on the epidemiology of MDD comes primarily from four large studies since the publication of the DSM-III in 1980. On the basis of these studies and the WHO data, the prevalence of lifetime depression in adults aged 18 to 65 years is 13% to 16%, with 5.3% to 8.6% of this population currently meeting criteria for the diagnosis.18,19
Women are approximately twice as likely as men to experience MDD in their lifetime. Adults aged 30 to 60 years have the highest rates of MDD, in samples of people younger than 65 years. The first diagnosed depressive episode was noted to occur at approximately 30 years of age, yet clinical reports and guidelines suggest that the first episode of MDD most often occurs at ages 18 to 22 years.1 Of greater concern, treatment is often not sought until approximately 3 years after the onset of symptoms.
The National Comorbidity Survey (Replication) found that people identified as Hispanic or non-Hispanic black were less likely than non-Hispanic whites to have depression.19 This differs greatly from the original reports of the 1980s and data from the original National Comorbidity Survey. Research consistently suggests no differences in prevalence of depression by education, urban versus rural, access to care, or geographic region; however, a disparity still exists in response to treatment, with those of a higher income status having better outcomes. The disparity is hypothesized to be related to the exposure to chronic stress in populations with less resources.20
Two specific populations have been omitted from these large-scale studies: (1) the elderly and (2) children and adolescents. Prevalence rates for these age groups vary widely, perhaps because of the complexity of changing roles, developing personalities, cognitive development or deterioration, and medical comorbidities. Several studies that screened adolescents for subclinical depression found rates as high as 30%.21 Rates of diagnosed MDD are less clear, yet correlates of medical illness and impaired function match those of their adult counterparts. With control for the effects of medical illness, screening positive for probable depressive disorder was associated with poorer functioning in overall role activity and less educational achievement. Clinically, available interventions are offered when subclinical symptoms have been identified, thereby ideally reducing later complications of adult MDD.
In general, the prevalence of MDD has been noted to be slightly lower in older adults (>65 years) than in those 30 to 60 years of age. Although prevalence rates in older adults are 4% to 8%, the incidence (number of new cases in 1 year) has been noted to be as high as 15%.22 Estimates of MDD in older adults vary widely by setting. Healthy older adults living in the community have an estimated prevalence of MDD of 3%. Of those who frequently access primary care services, rates increase to 17% to 37%, and 12% to 30% of those living in long-term care facilities meet diagnostic criteria for MDD.23 Factors such as physical illness, hospitalization, death of a partner, and cognitive decline are more powerful predictors of MDD than is age alone. It is expected that as the retiring generation lives longer (women outliving men), with more medical problems, more hospitalizations, and less income, rates of MDD will continue to trend higher.
Pathophysiology
With technologic advances allowing the evaluation of brain metabolism, neurotransmitter activity, and subtle differences in size of regions of the brain, literature related to the pathophysiology of neurologic disorders is abundant. Several theories have emerged for the biologic genesis of depression. Increased blood flow in the amygdala region and dysfunction in the limbic-prefrontal cortex communication systems have been identified in people with MDD.24,25 Cortisol levels have been evaluated and explored as a potential measure for diagnosis of MDD. Studies have found increased basal levels of cortisol in people with depression as well as a general dysregulation of the stress response function that mediates cortisol. The hypothalamus-pituitary-adrenal axis is responsible for regulating the body’s response to stress and is mediated by cortisol release. In people with MDD, it is slower to recover from stress stimuli.26 Disruption of sleep patterns has been strongly associated with the occurrence of MDD, yet it remains unclear whether this is a risk factor or sequela of the disorder.1
The biologic theory that has the strongest implication for pharmacologic treatment involves the relationship between synaptic levels of neurotransmitters and MDD. Although norepinephrine and dopamine levels are implicated in symptom manifestation, the strongest research associates lower levels of serotonin with the diagnosis of MDD. Other studies suggest that rather than having a central role in the modulation of mood and sleep, serotonin levels may be more closely linked with the regulation of other neurobiologic systems in the brain designed to respond to stressful or emotional stimuli. Much of the research on serotonergic activity has been driven by the pharmaceutical companies and is therefore difficult to interpret at times. Advanced technology is now being used to explore the role of glutamate and melatonin and will have remarkable implications for predicting risk and future pharmaceutical interventions.27
Depression has a strong familial association; MDD is 1.5 to 3 times more common in first-degree biologic relatives of those with the disorder compared with the general population.1 Environmental factors and personality development are closely linked with coping styles. Psychodynamic theories of the manifestation of mental illness include the need for mastery of developmental tasks, the healthy interpretation of events, and successful interpersonal interactions. Logically, children of parents with depressive symptoms are more inclined to develop difficulties with role functioning, including behavioral problems, substance abuse, and depressed mood.1 Although some twin studies suggested a genetic predisposition, genetic variations have not been shown to increase the risk for depression.28
Clinical Presentation
The majority of people with depressive disorders are seen by their health care providers for initial treatment, yet they may not identify the depressive symptoms as their chief complaint. Many patients may focus on vague somatic concerns rather than identifying or sharing emotions such as sadness or hopelessness. Family members or a provider who has established rapport with the patient may notice increased irritability. Irritability is likely to be the predominant symptom in children, whereas depressed mood and hopelessness are more apparent in adults, and somatic concerns dominate older adults’ presentation. Loss of interest or pleasure in previously enjoyable events and social withdrawal are almost always present. Appetite is usually less than normal, and insomnia is prevalent yet may be missed because the person with depression may complain of fatigue or anergia without significant physical stimuli. Preoccupations with perceived personal deficits along with an exaggerated sense of guilt or worthlessness are also common. Impaired concentration, difficulty with decision-making, and mild memory impairment are possible and must not be confused with cognitive changes associated with dementia. Thoughts of death vary from “the world would be better off without me” to engaging in dangerous behaviors without concern for personal safety and to having specific plans for suicide.1
Depression is often a chronic condition. Depressive episodes may be separated by periods of partial or full recovery of varying lengths of time. Of people who have experienced one depressive episode, 60% are likely to have another; 70% of those who have had two depressive episodes are likely to have a third, and 90% of those who have had three episodes will have more. Five percent to 10% of people who have a depressive episode may later have a manic episode. Factors such as incomplete recovery, comorbid substance use, and personality disorders may have some predictive value in estimating the course of the illness, with these factors associated with more frequent episodes and increased severity of impairment.29
The presentation, communication, and interpretation of symptoms related to depressive disorders can be complicated by culture because research shows that the cultural background of the provider affects how those symptoms are interpreted. In the broadest of definitions, culture refers to the context in which one was raised and the norms with which one identifies. Family patterns, religious beliefs, societal and generational norms, and past experience all influence how symptoms of mental health problems are disclosed. A strong patient-provider relationship enhances the ability to detect and effectively manage mental health problems, regardless of cultural expectations or differences in subtle presentations of symptoms.
Physical Examination
During a clinical visit, the provider can elicit risk factors for depression through careful interview. Psychosocial stressors, sleep patterns, nutritional habits, and physical activity can be important indicators of a depressive disorder because many of these realms are often impaired when depression is present. Many people may come to the health care provider with vague somatic concerns. Even when depression is suspected, all other medical and psychiatric diagnoses must be explored through comprehensive history and physical examination. Many medical conditions and medications are associated with symptoms of depression, and complications of common medical conditions (including mortality) are greater in people who have also been diagnosed with MDD.17,22
Diagnostics
Currently, no laboratory tests or imaging studies can definitively diagnose MDD, in spite of the progress made in the exploration of biologic correlates of mental illness. Blood tests to evaluate nutritional, endocrine, and thyroid function are critical in ruling out medical, reversible causes for presenting symptoms. Imaging of the head and cardiac stress tests may also be helpful in considering ischemic disease, emboli, and traumatic injury as complicating factors.
MDD is diagnosed by interview, when criteria are met for a depressive episode and there is no history of manic or hypomanic behavior. A depressive episode is present when five of the following symptoms occur, more days than not, in a 2-week period and cause significant impairment in any realm of functioning: depressed mood, loss of interest or pleasure, significant unintended change in weight or appetite, significant change in sleep pattern, change in psychomotor activity (increased restlessness or psychomotor retardation), fatigue or loss of energy, feelings of worthlessness or guilt, impaired concentration or decision-making ability, and recurrent thoughts of death or suicide. At least one of the symptoms must be depressed mood (subjective or observed) or anhedonia (loss of pleasure), and symptoms must not be better explained by another medical or psychiatric disorder.1
Several structured interviews are available for the diagnosis of depressive disorders. The Structured Clinical Interview for DSM Disorders can be separated into modules for specific disorders. The Hamilton Depression Scale and the Beck Depression Inventory involve self-report of symptoms and do not require interviewer time. The Geriatric Depression Scale offers the ability to better assess the presence of depression that may be complicated by multiple physical conditions or medication effects common in the older population. The Primary Care Evaluation of Mental Disorders (PRIME-MD) is a tool designed for the use of health care providers in their daily practice, considering the pressures of time in the outpatient clinical setting.
Specifiers that further describe the characteristics of the disorder may be included but are more commonly diagnosed by a mental health provider. These include depression with the following characteristics:
• With or without psychotic features
• c: With melancholic features
• p: That is a single episode or recurrent
The diagnostic criteria for MDD must be initially met, and the specifiers are used only to describe the pattern of onset or predominant symptom presentation.1
A diagnosis of Persistent Depressive Disorder (formerly know as Dysthymic Disorder) requires the presence of depressed mood (subjectively or reported by others) for more days than not during a 2-year period accompanied by two of the following: poor appetite or overeating, insomnia or hypersomnia, low energy, low self-esteem, poor concentration, and feelings of hopelessness. The presence of any specific mood episode must be excluded, and the symptoms must not be better accounted for by another medical or psychiatric diagnosis. Persistent Depressive Disorder is less common than MDD and often has an earlier onset. Children are more commonly seen with irritability rather than reporting depressed mood. The prevalence of Dysthymic Disorder is lower than that of MDD, with a lifetime community prevalence of 6%; however, Dysthymic Disorder may precede MDD. In these cases, the likelihood of full remission between episodes is decreased.1
Depressive Disorder NOS includes some symptoms of other depressive disorders, although full criteria for another diagnosis are not met because of duration of symptoms or severity of functional impairment. This category is also often used when medical or other psychiatric complications have not yet been fully explored, yet all symptoms for a major depressive episode are met.1
Differential Diagnosis
Patients with the following conditions may have sad mood, anhedonia, fatigue, and change in appetite: viral infection, hypothyroidism, hypoparathyroidism, hypoadrenocorticism, leukemia, lymphoma, cancer (pancreatic and others), cerebrovascular disease (transient ischemic attacks, stroke, vascular dementia), myocardial infarction, vitamin B12 deficiency, malnutrition, and concussion. When onset and intensity of depressive symptoms parallel the pattern of the medical illness yet persist in the context of optimum treatment for the medical condition, mood disorder resulting from a general medical condition with depressive features can be diagnosed.1 Treatment options mirror those of MDD, and optimum treatment of depressive symptoms is associated with better overall prognosis.
Many medications cause side effects similar to depressive symptoms. Cardiovascular drugs such as clonidine and beta blockers may cause sedation and fatigue. Antiparkinsonian drugs such as levodopa and amantadine may be associated with psychomotor slowing. Antianxiety or sedative medications such as benzodiazepines may not be metabolized in the older person as quickly as expected, and accumulated metabolites may lead to general central nervous system depressive effects. Anti-inflammatory and antibiotic medications, stimulants, hormones, and antihistamines all may have an additional impact on the older adult. These potential medication effects must be considered and offending medications eliminated, when possible, to evaluate for a new diagnosis of MDD.
Management
Management begins with a therapeutic alliance and thorough assessment. Included in this assessment must be an evaluation of the patient’s safety (see the section on suicide). Once symptoms have been assessed and other medical causes excluded or treated, the provider needs to consider the most appropriate setting for treatment. In the primary care setting, the provider must be able to follow indicators of recovery, the functional status of the patient with and without treatment, and the degree to which treatment is effective, as well as provide ongoing patient and family education. When the patient is referred elsewhere for psychiatric services, the primary care provider remains the central figure in managing and coordinating treatment.
Several classes of medications have emerged for the treatment of depression. Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) were the standard of care until the first selective serotonin reuptake inhibitor (SSRI) was approved for use in the late 1980s. This was closely followed by the emergence of serotonin-norepinephrine reuptake inhibitors (SNRIs). Although these agents are relatively equal in efficacy of reducing symptoms of MDD alone, SSRIs and SNRIs offer a gentler side effect profile, have fewer drug interactions, and are less likely to be lethal in overdose.30 MAOIs increase the level of tyramine, making it necessary for patients taking these drugs to restrict ingestion of tyramine-containing foods to avoid dangerous cardiotoxic effects. TCAs carry a risk of arrhythmia, are highly anticholinergic, and are lethal in overdose.30 The newer, atypical agents (SNRIs) alter levels of norepinephrine in addition to serotonin with consistent efficacy in the management of depressive symptoms; however, they have some additional variations in side effect profile compared with the SSRIs.
Given equal efficacy among the general classes of medications, specific agents should be chosen on the basis of individual considerations of predominant symptoms, potential side effects, risk for interactions, and comorbid conditions.30 Table 248-2 lists some of the adverse reactions to be considered in selection of an antidepressant. For example, an older adult woman with insomnia and decreased appetite may benefit from mirtazapine because it is likely to cause somnolence and to stimulate appetite. In this case, the individual or her caregivers must also be aware of the risk for hypotension with mirtazapine because it may increase her risk for injury related to dizziness or falls. Box 248-1 includes basic tips for prescribing antidepressant medications.
