Luigi R. Cardella and Luis A. Giuffra
OVERVIEW
· Psychiatric disorders include a heterogeneous collection of conditions related to behavior, mood, interpersonal interactions, cognition, and personal identity. All cause impairment in personal well-being and meaningful function.
· Internists are integral in the care of patients with mental illness. Primary care physicians provide the sole mental health care for 60% to 70% of patients in the US with psychiatric disorders.1
· Denial or the fear of social stigma induces many patients with psychiatric symptoms to seek help from a primary care physician rather than a psychiatrist. Alternatively, such patients may present with somatic or nonspecific complaints.
Epidemiology
· Approximately one in four American adults suffers from a diagnosable mental disorder annually. Mental illness is widespread across the population, and approximately 6% suffer from serious mental illness. Psychiatric disorders are the leading causes of disability for ages 15 to 44 in the US and Canada.
· Nearly half of patients with mental illness suffer from two or more psychiatric disorders at a single time. Symptoms may also overlap between several conditions. Disease severity sharply increases for coexisting mental illnesses.
Associated Conditions
· Several neurogenetic syndromes (e.g., Turner syndrome, Down syndrome, fragile X syndrome, Prader-Willi syndrome) and medical diseases have associated psychiatric manifestations.
· Socioeconomic, environmental, and cultural stressors contribute to the pathogenesis and definition of psychiatric diseases. The effective treatment and management of mental disorders therefore requires a biopsychosocial approach.
Relationships between Psychiatric and Medical Illnesses
· Psychiatric illnesses are intimately intertwined with medical illnesses. Underlying medical ailments (including endocrine disorders, cardiovascular disease, and respiratory conditions) are associated with increased rates of mental health disorders. Conversely, patients with significant psychiatric conditions have an increased risk for many medical disease categories.
· The severity of psychiatric illness is directly correlated to poor disease control and morbidity in conditions, such as diabetes and heart failure. For example, depression predicts an increased incidence of stroke in hypertensive patients.
· Studies suggest that successful treatment of psychiatric symptoms is associated with significant improvement in physical health and medical outcomes, including mortality.
· Medical illness is a risk factor for the development or exacerbation of depression, and depression is itself a risk factor for medical illness.2
Evaluation
· Patients with one psychiatric disorder should be screened for other coexisting psychiatric disorders.
· Patients should also undergo a thorough mental status examination, with objective evaluation of the following3:
o Appearance and general behavior (e.g., dress, grooming, hygiene, level of distress, degree of eye contact, attitude toward the interviewer [including evaluation of cooperativity])
o Motor activity (e.g., psychomotor agitation, tremors, dyskinesias, akathisia, mannerisms, tics, catatonic posturing, echopraxia, apparent responses to hallucinations, gait/neurologic defects)
o Speech characteristics including rate, rhythm, volume, amount, latency, tone, inflection, and articulation
o Mood (internal/subjective emotional state) and affect (the range, stability, and appropriateness of emotional expression)
o Flow of thought (e.g., logicality, sequentiality, goal directedness)
o Thought content including ideas of reference, overvalued ideas, ruminations, obsessions, compulsions, phobias, and delusions (e.g., erotomania, delusions of persecution, infidelity, infestation, somatic illness, guilt, worthlessness, thought insertion, thought withdrawal, thought broadcasting)
o Thoughts or impulses of harm to self or others (e.g., intensity, specificity of plans, when they occur, what prevents the patient from acting on them)
o Perceptual disturbances including hallucinations (a perception in the absence of a stimulus), illusions (an erroneous perception in the presence of a stimulus), and depersonalization (feeling detached from oneself)
o Sensorium/cognition (e.g., level of consciousness, orientation, attention, concentration, memory)
o Insight (e.g., understanding of current problems, motivation to change health risk behaviors)
o Judgment (i.e., appropriate decision-making abilities)
DEPRESSION
GENERAL PRINCIPLES
Classification
· Mood disorders form a phenotypic spectrum of abnormally altered emotional state.
· Mood disorders are subdivided into those with
o Only abnormally low mood (unipolar depression syndromes)
o Cycling between abnormally elevated and abnormally depressed moods (bipolar syndromes)
o Simultaneous depression and mania (mixed mood syndromes)4
· Mood disorders present with a heterogeneous range of symptom severity and functional impairment.
· Given the complexity of the diagnosis and management of bipolar disorder, a discussion of this illness is beyond the scope of this chapter. If you suspect your patient to have bipolar illness, referral to a psychiatrist is indicated. If your patient is exhibiting signs of mania (see “Clinical Presentation” ), psychiatric hospitalization may be indicated and the patient should be referred to the nearest emergency department.
Epidemiology
· Depression is extremely common worldwide. Nearly 10% of American adults suffer from a mood disorder annually, and the lifetime prevalence of depressive illness is approximately 17% in the US.
· The median age of onset for mood disorders is 25 to 35 years of age.
· Depressive disorders are more common in women, especially postmenopausal women.5
Etiology/Pathophysiology
· Mood disorders stem from incompletely understood interactions between psychophysiologic stressors and alterations in neurohormonal pathways. Multiple different pathophysiologic changes can cause similar phenotypes.
· Serotonin- and norepinephrine-dependent pathways in the limbic system may play a key role in depression. Glutamate and gamma-aminobutyric acid (GABA) levels in the prefrontal cortex have also been shown to have a role in depression.6 Additional changes in the hypothalamus-pituitary-adrenal axis are also likely involved.7
· Major depression exhibits complex inheritance patterns, likely involving multiple genes. Genetic predisposition is stronger in bipolar disorders and in recurrent depression.7
Risk Factors
· Depression syndromes are more likely in those with a history of depression, anxiety, and/or substance abuse; chronic medical illness; family history of major depression; domestic abuse/violence; stressful life events (e.g., death of a loved one, divorce, job change, motor vehicle accident); recent myocardial infarction or stroke; or recent pregnancy.8
· Patients should be evaluated for depression if they exhibit work or relationship dysfunction, changes in interpersonal relationships, worsening performance in activities of daily living, poor follow-through with prior treatment recommendations, multiple unexplained symptoms or frequent medical visits, dampened affect, unintended weight gain or loss, sleep disturbances or chronic fatigue, dementia or memory impairment, irritable bowel syndrome, or fibromyalgia syndrome, and if they volunteer complaints of stress or mood disturbances.8,9
Associated Conditions
· Anxiety disorders and substance abuse frequently co-occur with depressive disorders.5
· Significant medical, psychological, or environmental stressors precipitate the first episode of major depression in 40% to 60% of patients.8
Depression and Medical Illnesses
· Depression has a complex interdependent relationship with medical illness. Medical illnesses may
o Be a direct biologic cause of depression (e.g., thyroid disorder, stroke)
o Contribute to psychological stressors
o Predispose to depression though changes in neurohormonal signaling
o Mimic signs and symptoms of depression (e.g., anemia)10,11
· Overwhelming evidence suggests that depression is associated with worse outcomes, impaired control, and increased risk of complications in diseases such as diabetes mellitus, stroke, myocardial infarction, and congestive heart failure.10
· Poor control of medical illnesses may also contribute to worsened outcomes in depression.
· Treatment of associated medical illnesses may improve depression and vice versa, though data are limited.
DIAGNOSIS
Clinical Presentation
· Compared with nonpathologic normal sadness, depression exhibits a greater intensity, a longer duration, associated neurovegetative symptoms, and a significant impact on patients’ function.
· Major depression is characterized by at least 2 weeks of persistently decreased mood and/or anhedonia (a significant loss of interest in previously interesting activities). Patients also exhibit associated psychophysiologic changes in sleep, appetite, thought patterns, motivation, and overall function.4 The Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) and DSM-5 criteria are minimally different.4,12
· Subsyndromal depression patients meet two to three symptom criteria, rather than the three or more necessary to diagnose major depression.
· In bipolar depression, patients present with episodes similar to major depression but also have a history of manic or hypomanic episodes (abnormally and persistently elevated/expansive/irritable mood with distractibility, insomnia, grandiosity, flight of ideas/feelings, racing thoughts, agitation/increased goal-directed activity, increased/pressured speech, and/or risk taking/hedonism).
· Mixed mood syndromes manifest symptoms of both mania and depression during the same episode.4
· The Two-Question Screen is sensitive but not specific for depression9,13:
o Over the past month, have you been bothered by little interest or pleasure in doing things?
o Over the past month, have you been bothered by feeling down, depressed, or hopeless?
o If the patient answers yes to either screening question, evaluation should be performed using a quantitative standardized instrument (e.g., the PHQ-9, Beck Depression Inventory, or Hamilton Depression Rating Scale).8
· Initial evaluation should also include the following:
o Screening for suicidality or self-harm (see “Deliberate Self-Harm and Suicidality” section)
o Assessment of depression severity
o Evaluation for bipolar and mixed mood disorders
o Screening for concurrent psychiatric issues including substance abuse
Differential Diagnosis
· A great many medical conditions are strongly associated with or contribute to mood disorders including cardiac, endocrine, infectious, metabolic, neoplastic, and neurologic disorders as well as effects due to medications, toxins, and illicit substances.
· Depression must be distinguished from other psychiatric conditions (Table 42-1).4,14
· Appropriate laboratory and radiographic testing should be performed to evaluate for medical conditions contributing to the patient’s depression.
TABLE 42-1 Psychiatric Differential Diagnosis for Major Depression5,8
TREATMENT
· Depression treatment consists of three phases15,16:
o Acute therapy (usually 6 to 12 weeks)
o Continuation (4 to 9 months), which targets prevention of relapse
o Maintenance (6 months to years), which targets prevention of a new distinct episode of major depression
· Bipolar and mixed mood syndromes require mood stabilizers (e.g., atypical antipsychotics, anticonvulsants, lithium) before antidepressant treatment to prevent triggering mania.
· Bipolar disorder eventually manifests in up to 10% of patients initially thought to have unipolar depression.
· Strongly consider treatment of patients with low mood who do not strictly meet criteria for depression but exhibit significant functional impairment.
Acute Therapy
· Patients and family members should be educated that
o Depression is a medical illness, not a sign of weak character.
o Depression can be effectively treated.
o Patients improve with treatment.
o Depression can recur, and patients should seek treatment early if symptoms return.8
· Acute therapy should target symptom remission and not merely improvement.8,11,16 Response to treatment is defined as a ≥50% reduction in symptomatology.8
· Depression-specific psychotherapies and antidepressant medications have similar response rates for mild depression. Both are acceptable initial approaches.
· Antidepressants should be started in patients with moderate or severe major depression. Adjuvant psychotherapy may improve response, especially in severe, recurrent, or chronic depression.8,11,16–20
· Depression with psychotic features should be treated with a combination of an antidepressant and an antipsychotic medication and/or electroconvulsive therapy (ECT).2
· Patients may require ≥6 weeks to achieve full symptom remission after treatment begins.8,21
· If a patient experiences a symptom reduction of ≥25% 4 to 6 weeks after treatment initiation but is not yet in remission, continue current therapy with medication uptitration if tolerated.8
· If there is <25% reduction of symptoms after 6 weeks of appropriate therapy, either adding or switching to another treatment are both effective.8
· Patients who do not respond to an initial selective serotonin reuptake inhibitor (SSRI) have a modestly better chance of response, if changed to a non-SSRI rather than a different SSRI.8,11,21
· Augmentation may include the addition of serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), bupropion, mirtazapine, and/or adjuvant nonpharmacologic interventions. Other strategies may require the assistance of a psychiatrist.
· Figure 42-1 provides a recommended schema for acute treatment with antidepressant medications. Other well-validated algorithms can be used, including the algorithms used in the STAR-D study for depression and the STEP-BD study for bipolar disorder.22–24
· Medications should be tapered when discontinued or added, with vigilance for drug-drug interactions, overlapping side effect profiles, and withdrawal phenomena.
· Patients should be routinely monitored for suicide risk throughout therapy.
Figure 42-1 Suggested schema for acute therapy with antidepressant medications. SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Duration of Treatment
· Treatment should be continued for at least 4 to 9 months after remission of symptoms (the continuation phase).25 Recurrent episodes imply the need for longer medication maintenance.
o First episode: continue medication for 6 to 12 months, withdraw gradually.
o Second episode: continue medication for 3 years, withdraw gradually.
o Three episodes or more: continue medication indefinitely.
· When antidepressants are discontinued, it is commonly recommended that the medications be tapered over 2 to 4 weeks to minimize withdrawal.8
Medications
· Data suggest minimal difference in efficacy among antidepressants for the acute treatment of depression.26,27
· While data are limited, it appears that most medications are also equally effective in preventing relapse. Side effect profiles and cost considerations should guide treatment choices (see Table 42-2).
· Adherence to medication, even after symptom improvement, is key. Premature discontinuation of antidepressant treatment is associated with a 77% increase in the risk of relapse or symptom recurrence.8
· Risks for premature self-discontinuation include younger age, lower educational status, and higher self-perceived mental health.21
· SSRIs and SNRIs are considered first-line agents given their side effect profiles. There appears to be minimal within-class differences in efficacy.
· TCAs are effective but should be used cautiously given cardiac side effects and risk for lethal overdose. Higher doses of TCAs may be more effective in those who partially respond to lower doses.
· Monoamine oxidase inhibitors (MAOIs) should be restricted to patients unresponsive to other medications because of their potential for drug interactions, serious side effects, and the necessity of dietary restrictions.Psychiatric consultation is strongly recommended if an MAOI is considered.
· Psychostimulants (e.g., dextroamphetamine, methylphenidate, and methylamphetamine) are useful adjuvant treatments for depression but have not been adequately studied for use as monotherapy. Psychiatric consultation is strongly recommended if stimulants are considered.
· St. John’s wort and S-adenosyl methionine (SAM-e) are sometimes self-prescribed as natural antidepressants. Studies show mixed results regarding efficacy of these as antidepressants and serious drug-drug interactions as well as the heterogeneity of commercially available preparations argue against use.8,18,28 Other herbals and dietary supplements, such as kava-kava, omega-3 fatty acid (docosahexaenoic acid), and valerian root, have not been proven effective for the treatment of depression.8,28
TABLE 42-2 Antidepressant Medications
Contraind., contraindicated; CYP, cytochrome-P450; DM, diabetes mellitus; HTN, hypertension; immed., immediate; inhib., inhibition; LDL, low density lipoprotein; metabol., metabolized; MI, myocardial infarction; Rx-Rx interact., drug-drug interaction; signif., significant; SFx, side effects; QTc, corrected QT interval; - -, rare; +, seldom; ++, common; +++, frequent.
Modified from Clinical Pharmacology. 2014. http://www.clinicalpharmacology-ip.com. Last accessed 2/1/15. Depression Guideline Panel. U.S. Department of Health and Human Services. Agency for Health Care Policy and Research. Depression in Primary Care: Treatment of Major Depression. AHCPR Publication No. 93-0551. Rockville, MD: AHCPR; 1993; Gartlehner G, Hansen RA, Thieda P, et al.; U.S. Department of Health and Human Services. Agency for Healthcare Research and Quality. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. AHRQ Publication No. 07-EHC007-EF. Bethesda, MD: AHRQ; 2007.
Other Nonpharmacologic Therapies
· Several psychotherapy modalities are effective in the treatment of depression.19 Such interventions should be performed by therapists specifically trained in these techniques.
· Combined therapy using both pharmacologic and psychological therapy may be more effective than either intervention alone.8,19
· ECT may benefit patients with refractory depression, depression with psychotic features, and geriatric patients.
· Other neuromodulation techniques (e.g., repetitive transcranial magnetic stimulation, deep brain stimulation, and vagus nerve stimulation) have shown some promise in treating resistant depression but require psychiatric evaluation.
· Depression that is worse in winter (i.e., seasonality) often improves with phototherapy using broad-spectrum bright light (typically 10,000 lux).29 Such therapy should be initiated only by clinicians trained in prescribing phototherapy.
· Aerobic exercise may be of adjuvant benefit in reducing depressive symptoms.8,18,30 Patients should aim for 30 minutes of moderate-intensity exercise, 3 to 5 days per week.
REFERRAL
· Multiple trials demonstrate the benefit of a collaborative care model with the close integration of physicians, mental health professionals, and case managers.8 While both general medicine and psychiatric specialty settings yield good initial outcomes, therapeutic alliance with mental health specialists should be strongly considered.21
· Psychotherapy should be administered by a skilled therapist. Data suggest that the success of psychotherapy may be linked to the experience level of practitioners.
· Strongly consider psychiatrist or mental health specialist referral if there is intolerance or minimal benefit with first-line agents; signs of psychosis or suicidal ideation; severe symptoms or functional impairment; comorbid medical, psychiatric, or substance abuse disorders; symptoms or history suggestive of mania/bipolar disease or seasonal affective disorder; plans for psychotherapy; need for frequent or close follow-up; and/or patient requests for specialist treatment.
· Consider hospitalization if the patient poses a serious risk for harm to self or others (involuntary hospitalization may be necessary), is severely ill and lacks adequate social supports, has not responded adequately to outpatient treatment, or has significant comorbid psychiatric or medical conditions.16
MONITORING/FOLLOW-UP
Expert opinion recommends patients should be
· Seen within 2 weeks after starting any medications to evaluate for tolerability, effectiveness, and appropriate dosage
· Followed at least every 2 weeks until significant symptom improvement
· Followed at least every 3 months after symptom remission.25
OUTCOME/PROGNOSIS
· Depression is a heterogeneous disorder with a highly variable course.7
· In most patients, major depression is a relapsing-remitting illness with a >40% risk of recurrence within 2 years after the first depressive episode.14
· Repetitive episodes increase the risk of future recurrence.
· Relapse prevention with pharmacologic and nonpharmacologic modalities diminishes but does not completely prevent relapse.19 Clinicians should be mindful to monitor for depression recurrence.
DELIBERATE SELF-HARM AND SUICIDALITY
GENERAL PRINCIPLES
· Deliberate self-harm commonly involves self-cutting, self-poisoning, or intentional medication overdose.31
· Suicide is an act of self-harm with a fatal outcome, consciously initiated and performed with the expectation of death.31
· Individual self-harm acts vary in their associated suicidal intent, degree of planning (e.g., meticulous vs. impulsive, precautions against rescue), and lethality of method (e.g., violent vs. passive).
Epidemiology
· About 3% to 5% of the population has made an attempt at deliberate self-harm at some time during their lives.31
· Approximately one quarter of those with one self-harm attempt will reattempt self-harm within 4 years, with a long-term suicide risk of 3% to 7%.5
· The median mortality from suicide after an act of deliberate self-harm is 1.8% within the first year, 3.0% within 1 to 4 years, 3.4% within 5 to 10 years, and 6.7% within 9 years or longer.31
· Younger adults are more likely to attempt nonfatal self-harm, whereas older adults are more likely to complete suicide.
· Women attempt suicide two to three times as often as men, but men are four times as likely to die by suicide.5
· The highest suicide rates in the United States are found in white men >85 years of age.5
· >90% of those who commit suicide suffered from a mental illness, most commonly a mood or a substance abuse disorder.5
Etiology/Pathophysiology
· Evidence suggests that genetic predisposition, biologic changes, and psychosocial factors all contribute to deliberate self-harm.31
· Reduced serotonin function and lowered cerebrospinal 5-hydroxyindoleacetic acid levels in the central nervous system may underpin the pathophysiologic changes of self-harm.
· Patients who deliberately self-harm also show personality traits of impulsiveness, aggression, inflexibility, and impaired judgment.
Risk Factors
· A large number of risk factors have been associated with suicide attempts including the following8,31,32:
o Suicidal thoughts, past attempts, specific/lethal plans, access to firearms
o Psychiatric illness (depression, bipolar disorder, schizophrenia, substance abuse)
o Psychological features (shame, low self-esteem, impulsiveness, aggression, hopelessness, severe anxiety)
o Significant burden of medical illness
o Socioeconomic factors (lack of support, unemployment, recent stressful events)
o Demographics (women/younger more likely to attempt; men/older more likely to succeed; widowed/divorced/single)
· Studies have not found racial predispositions for attempting suicide.8,14
· Factors with a protective effect include positive social support, children at home, responsibility to family, pregnancy (in the absence of peripartum depression), religious beliefs, life satisfaction, and good judgment/problem-solving skills/coping skills.32
· Antidepressants, including SSRIs and TCAs, may increase risk of suicidality during the initial treatment of psychiatric illness when compared with placebo. The U.S. Food and Drug Administration issued a warning about the risks of suicidal thinking and behavior in adults aged 18 to 24 years during the first 1 to 2 months of treatment for major depression.33
DIAGNOSIS
· At-risk patients should be assessed for thoughts of causing deliberate harm to themselves or others.8,32
· Useful questions include the following:
o Do you feel that life is worth living?
o Do you wish you were dead?
o Have you thought about hurting yourself or ending your life?
§ If so, how often have those thoughts occurred?
§ Have you gone so far as to think about how you would do so?
§ Do you have access to a way to carry out your plan?
· What keeps you from harming yourself?
· Do you feel that others are responsible for your problems? If so, have you thought about harming or punishing them?
TREATMENT
· Immediate hospitalization with close observation should strongly be considered for patients who are deemed high risk for harm to self or others; evidence psychosis or command hallucinations; have current impulsive behavior, severe agitation, or poor judgment; have a specific suicide plan with persistent intent/ideation; have made precautions against discovery or rescue; have previously attempted suicide using means with high lethality; have significant comorbid psychiatric illness (including depression or substance abuse); and are male and >45 years of age.32
· Causes of suicidality or homicidality (e.g., substance withdrawal or intoxication, psychiatric illness, depression) should be identified and treated appropriately.
· Pharmacologic and psychotherapeutic interventions may be beneficial for the treatment of those without underlying reversible causes, though data are limited and inconsistent.
Medications
· Antidepressant medications (e.g., SSRIs, SNRIs, TCAs) should be used to treat depressed patients with suicidal ideation (see Table 42-2).32
· Lithium reduces the risk of both suicide and suicide attempts when used as long-term maintenance for recurring bipolar disorder and major depressive disorder.
· Anticonvulsant agents used as mood stabilizers (e.g., valproate, carbamazepine, lamotrigine) have not been shown to reduce risk of suicidal behavior.
· Benzodiazepines may ameliorate the suicide risk in an agitated patient because of anxiolytic effects but should be used cautiously as they also disinhibit behavior and enhance impulsivity, particularly in patients with borderline personality disorder.
· No pharmaceutical treatments have clearly shown usefulness for reducing recurrent self-harm not associated with underlying psychiatric illness.31
Other Nonpharmacologic Therapies
· Clinical consensus suggests skilled psychosocial interventions and specific psychotherapeutic techniques (e.g., cognitive behavioral therapy [CBT] and dialectical behavior therapy) be used in preventing recurrent self-harm.31,32
· ECT may provide short-term reduction in suicidal ideation, especially in cases of severe depression.32,34
· While recommended, intensive follow-up plus outreach, nurse-led management, emergency contact cards, and hospital admission have not consistently been shown to reduce recurrent self-harm compared with usual care.31,34
REFERRAL
Patients with recurrent or persistent suicidal ideation or self-harm attempts should be cared for in collaboration with psychiatrists and other mental health professionals.
FOLLOW-UP
· Patients who have attempted deliberate self-harm are at risk for future attempts. Repetition is more likely in patients aged 25 to 49 years; unemployed or socioeconomically disadvantaged; divorced, living alone, or with unstable living situations; who have a criminal record; who have a history of stressful traumatic life events or come from a so-called broken home; who have a history of substance abuse, depression, or personality disorder; and who have recurrent feelings of hopelessness or powerlessness.31
· Patients should be routinely monitored by clinicians and family members for evidence of suicidal ideation or recurrent self-harm behaviors. Repeat or long-term hospitalization may be necessary if the patients are persistently a threat to themselves or others.
ANXIETY DISORDERS
· Anxiety disorders are the most common mental health illnesses, affecting nearly one in five American adults.3 The disorders are typified by increased agitation, nervousness, and autonomic tone that disrupt general well-being and function.
· Anxiety disorders include panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder (GAD), and phobias (see Table 42-3).4,14
· Anxiety disorders frequently coexist with depressive disorders or substance abuse. In addition, most people with one anxiety disorder also have another anxiety disorder.5
· Medical issues such as hypoglycemia, hyperthyroidism, respiratory disease, gastrointestinal disease, and medication side effects all predispose to anxiety disorders. Improvement in these conditions may improve psychiatric issues.
TABLE 42-3 Characteristics of Common Anxiety Disorders5,8
Generalized Anxiety Disorder
GENERAL PRINCIPLES
GAD is characterized by unreasonably excessive concern about common issues, such as finances, family, or work. In GAD, worries become so exaggerated that there is difficulty in performing day-to-day tasks. Other anxiety disorders should be ruled out. DSM-IV-TR and DSM-5 criteria are essentially the same.4,12
Epidemiology
· About 3% of American adults suffer from GAD.3 However, studies suggest that GAD may be more prevalent in primary care settings, and suggest that GAD is the anxiety disorder most often seen by general internists.35
· GAD develops gradually and may present at any age, though the median age of onset is about 30 years.
· Similar to other anxiety disorders, GAD is more common in women than in men.5
Etiology/Pathophysiology
· GAD develops from a combination of biologic and psychosocial factors.
· Multiple neurotransmitter and endocrine pathways, including the hypothalamic-pituitary-adrenal axis, have been implicated.36 Medical disorders such as chronic pain, endocrine diseases, and pulmonary conditions may predispose to generalized anxiety.
· Social and environmental stressors, including recent unfavorable events, also likely contribute to GAD.37
· Maladaptive cognitive strategies play a prominent role in GAD. Worry subjectively increases preparedness for feared events but also causes distress over them. GAD patients subconsciously overvalue the worry process and, over time, develop a cycle of worry proneness.35
· Predisposition to GAD appears modestly inheritable but incompletely understood.36,37
Associated Conditions
· Patients with GAD may exhibit worsening job performance, changes in interpersonal relationships, multiple unexplained symptoms or frequent medical visits, concentration difficulties, sleep disturbances or chronic fatigue, and increasing alcohol/tobacco use.
· Patients with GAD are at high risk for developing another anxiety disorder or major depression.37,38
· More than one-third of GAD patients abuse alcohol or illicit drugs.35
· GAD is a chronic condition but can be improved or controlled with treatment. Twenty-five percent of adults with GAD will be in full remission after 2 years, and 38% will have a remission after 5 years.37
· However, nearly one-third of patients in full remission will have a clinically significant relapse within 5 years; the rate is even higher for those with only partial remission.37
DIAGNOSIS
Clinical Presentation
· The hallmark of GAD is excessive and difficult-to-control worry about multiple issues, often despite insight that the anxiety is more intense than warranted.36
· Unlike other anxiety disorders, worry in GAD is not limited to a specific trigger or social situation (e.g., phobias). GAD patients may experience discrete panic attacks but their anxiousness is persistent, pervasive, and focused on multiple components of normal daily living.
· In addition to excessive worry, patients may exhibit other nonspecific signs including irritability or fatigue, difficulty concentrating, increased startle responses, and/or sleep disturbances including insomnia.38
· Patients with GAD frequently have associated somatic symptoms including headaches, muscle tension and myalgias, difficulty swallowing (i.e., globus hystericus), nausea, tremor or tics, sweating, lightheadedness or dyspnea, frequent urination, and/or hot flashes.35,36,38
· Symptom severity fluctuates over time and is often worse during periods of increased stress.36
· GAD patients often seek medical care for their somatic symptoms, but do not necessarily volunteer concerns about their psychological ones.35,36
· Screening can be performed using the 7-item Anxiety Scale (GAD-7), which has reasonable reliability, sensitivity, and specificity.39
· Further assessment should be made through a validated quantitative measure such as the Generalized Anxiety Disorder Questionnaire IV (GAD-Q-IV).40
· Initial evaluation should include the following:
o Screening for suicidality or self-harm
o Assessment of anxiety severity and impact
o Screening for concurrent psychiatric issues including depression and substance abuse
· Appropriate laboratory and radiographic testing should be performed if there are potentially treatable medical conditions contributing to the patient’s symptomatology.
Differential Diagnosis
· Many medical conditions are associated with or contribute to anxiety disorders including cardiac, endocrine, infectious, metabolic, neoplastic, and neurologic disorders as well as effects due to medications, diet, toxins, and illicit substances.
· GAD must be distinguished from other psychiatric conditions (Table 42-3).4,14
TREATMENT
· Both medications and nonpharmacologic treatments benefit GAD, but it is uncertain which is more effective. At least one study involving a pediatric population has shown that sertraline in combination with CBT is more effective than either treatment alone.41
· Strongly consider psychiatrist or mental health specialist referral if there are severe symptoms or functional impairment; signs of psychosis or suicidal ideation; comorbid medical, psychiatric, or substance abuse disorders; plans for psychotherapy; need for frequent or close follow-up; and/or patient requests for specialist treatment.38
Medications
· The SSRIs and SNRIs have all shown benefit over placebo in treating GAD and should be considered first-line agents (Table 42-3).35,37,42
o Although data are limited, there appears to be minimal efficacy and tolerability differences amongst these medications.37
o Patients typically require at least 4 to 6 weeks of therapy with SSRIs before symptoms improve.
· Imipramine has demonstrated benefit for GAD; other TCAs are less well studied.35,37,42 However, the side effect profile of imipramine suggests that it should be considered a second-line agent.
· Benzodiazepines have proven utility in the temporary mitigation of GAD (Table 42-4).37,43
o Short-term adjuvant therapy with long-acting benzodiazepines may benefit some patients during the initial phase of treatment with SSRIs or SNRIs.
o Trials have not shown benefit over other agents when used for long-term anxiety control. The prolonged use of benzodiazepines in GAD also increases risk for dependence, sedation, and traffic accidents.37
o These agents should be limited to use for breakthrough anxiety.
o There does not appear to be significant within-class efficacy differences among the long-acting benzodiazepines.37
· Hydroxyzine (a first-generation antihistamine) has been successfully used as an anxiolytic in GAD.37 Data regarding its efficacy have been mixed, however, and sedating side effects may limit its usefulness.
TABLE 42-4 Frequently Used Benzodiazepines
Short, <6 hours; interm., 6–20 hours; long, >20 hours; bid, twice daily; tid, three times daily; qid, four times daily; hs, at bedtime.
Higher relative potency designates more potent agents (i.e., inverse of dose equivalents). All benzodiazepines have longer-lasting and more potent effects in patients with hepatic impairment. CYP-450 interactions change the metabolism of many benzodiazepines. Patients with panic disorder may need higher total doses than those with GAD for symptom relief.
Modified from Sadock BJ, Sadock VA. Concise Textbook of Clinical Psychiatry, 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008.
Other Nonpharmacologic Therapies
· Psychotherapy is an effective treatment for GAD.44
· CBT focused on insight, education, and coping strategies reduces anxiety symptoms and is beneficial as both short- and long-term treatment.35,36,39
o CBT is more effective than other psychological therapies.45
o CBT should be administered by a skilled therapist. Data suggest that the success of psychotherapy is linked to the experience level of practitioners, though some patients may benefit from nonspecialist delivered supportive psychotherapy alone.35
· Relaxation training had historically been used in treating GAD but has not been well studied in clinical trials.35 Related methods such as applied relaxation and mindful meditation appear to have some efficacy.37
· Aerobic exercise and exercise training likely have general anxiety-lowering benefits but have not been well-studied in the treatment of GAD.30
Panic Disorder and Agoraphobia
GENERAL PRINCIPLES
· Panic attacks are discrete sudden periods of intensive apprehension or terror, often accompanied by physiologic symptoms (e.g., palpitations, chest pain, shortness of breath, dizziness) and feelings of impending doom DSM-IV-TR and DSM-5 criteria are essentially the same.4,12
· Panic disorder is diagnosed, however, only when recurrent unpredictable panic attacks are followed by at least 1 month of persistent concern about having another panic attack or significant behavioral changes related to the attacks.4,14
· Agoraphobia (an irrational fear of public places, crowds, or being outside the home) may also develop in the setting of recurrent panic attacks.
Epidemiology
· Approximately 3% of American adults have panic disorder; of these, one in three develops agoraphobia. Panic disorder is twice as common in women, and moderately heritable.5,46
· Panic disorder typically first manifests in late adolescence or early adulthood, but the age of onset extends throughout adulthood.5,38,46
Etiology/Pathophysiology
· The underpinnings of panic disorder and agoraphobia are multifactorial and incompletely understood. Dysfunction of serotonin-, norepinephrine-, and GABA-mediated central nervous system pathways may be implicated. In addition, patients may have idiosyncratic changes in autonomic system regulation.
· Panic disorder also appears to have an important cognitive-behavioral aspect, and its onset is often preceded by stressful life events.35,38,46
Associated Conditions
· Patients with panic disorder may exhibit worsening job performance, changes in interpersonal relationships, multiple unexplained symptoms or frequent medical visits, concentration difficulties, sleep disturbances or chronic fatigue, and/or increasing alcohol/tobacco use.
· Patients with panic disorder are at high risk for developing another anxiety disorder, depression, or substance abuse.
· The risk of suicide and attempted suicide is markedly higher in patients with panic disorder.46
· Panic disorder is an independent risk factor for coronary heart disease.35
· If untreated, panic disorder chronically recurs with an unpredictable waxing and waning course. Patients may experience residual symptoms, including agoraphobia and somatization, even during periods when actual panic attacks are quiescent.
DIAGNOSIS
Clinical Presentation
· Not all patients who experience panic attacks will develop panic disorder.38 The impact of panic disorder stems mainly from worry about future panic attacks or the possible implications of physical symptoms.
· Panic attacks may feel truly life threatening. Patients are often consumed by recurrent “what if?” worries related to the perceived dangerousness of panic attacks and may persistently seek medical consultations despite reassurance.
· Patients with panic disorder typically first present to emergency or primary care settings with unexplained symptoms rather than direct concerns about panic attacks. Complaints commonly include the following: noncardiac chest pain, palpitations, unexplained faintness, unexplained vertigo and dizziness, irritable bowel symptoms, dyspnea or tachypnea, feelings of impending doom or depersonalization, and nocturnal awakenings from panic attacks.35,38
· Agoraphobia sufferers typically have more severe impairment and panic symptomatology but are more likely to seek treatment than other panic disorder patients.35
· Screening with two questions from the Anxiety and Depression Detector yields a high sensitivity and moderate specificity for panic disorder35,47:
o In the past 3 months, did you ever have a spell or an attack when all of a sudden you felt frightened, anxious, or very uneasy?
o In the past 3 months, would you say that you have been bothered by nerves or feeling anxious or on edge?
o If the patient answers “yes” to either screening question, further evaluation should be performed using a quantitative standardized instrument.
· Initial evaluation should include the following:
o Screening for suicidality or self-harm
o Assessment of panic disorder severity
o Screening for concurrent psychiatric issues including substance abuse
· Appropriate laboratory and radiographic testing should be performed if there are potentially treatable medical conditions (e.g., hyperglycemia, hyperthyroidism, or a pheochromocytoma) contributing to the patient’s symptomatology.
Differential Diagnosis
· As noted, many medical conditions are associated with or contribute to anxiety disorders.
· Panic disorder must be distinguished from other psychiatric conditions (Table 42-4).4,14
TREATMENT
· Panic disorder is highly treatable and the majority of patients receive benefit with appropriate therapy.38
· Strongly consider psychiatrist or mental health specialist referral if there are severe symptoms or functional impairment; agoraphobia; recurrent panic attacks despite treatment; signs of psychosis or suicidal ideation; comorbid medical, psychiatric, or substance abuse disorders; plans for psychotherapy; need for frequent or close follow-up; and/or patient requests for specialist treatment.38
Medications
· Medications improve anxiety and decrease the frequency of panic attacks.35,38,46
· SSRIs are considered the drugs of choice in treating panic disorder (Table 42-3). Efficacy appears similar among the SSRIs. Data also suggest comparable efficacy for venlafaxine.35,46
· Benzodiazepines are beneficial in acutely reducing the symptoms of panic attacks but have a high potential for abuse, dependence, and tolerance (Table 42-4).35,38,46 Short-term adjuvant therapy with long-acting benzodiazepines may benefit some patients during the initial phase of other therapies.
· Bupropion has not been adequately studied to support its use for panic disorder, especially as many patients report that its activating effects actually worsen panic symptoms.35
· β-blockers may help some patients control physical symptoms, though they have not shown effectiveness for panic disorder in controlled trials.35,38
· Gabapentin may exhibit anxiolytic benefit in panic disorder, though data are mixed.48
· Side effects that mimic panic attack symptoms may occur during either initiation or discontinuation of medications. Antidepressants should be started at half the usual initial dose and gradually titrated when increased or withdrawn. Frequent reassurance may aid patient compliance.
Nonpharmacologic Therapies
· CBT is effective for treating panic disorder and is supported by robust clinical trial data.
o It is unclear whether CBT is superior to pharmacotherapy but some data suggest that the benefits of CBT may be long lasting.35,46
o Combined treatment with CBT and antidepressants may be more beneficial than with either modality alone for short-term symptom reduction.46
o More than one-third of patients with panic disorder either cannot tolerate or do not respond to appropriate SSRI or venlafaxine therapy. Many patients who do not respond to medication will, however, respond to CBT.
o CBT should be administered by a skilled therapist. Data suggest that the success of psychotherapy is linked to the experience level of practitioners.
· Aerobic exercise, breathing techniques, and relaxation/biofeedback exercises may indirectly improve panic disorder through lowering hyperreactivity to bodily sensations, though few studies have evaluated their use.30,35,46Similarly, yoga and meditation have theoretical benefit but have been formally evaluated only on a limited basis.49
PSYCHOSIS AND SCHIZOPHRENIA
GENERAL PRINCIPLES
· Psychosis denotes a disturbed perception of reality including hallucination, delusion, or thought disorganization.
· Psychotic states are associated with increased agitation, aggression, impulsivity, and behavioral dysfunction.
· Psychosis may be due to
o Underlying psychiatric illness (e.g., schizophrenia, mania)
o Substance abuse (e.g., cocaine intoxication, alcohol withdrawal)
o Medication side effects (e.g., corticosteroids)
o Medical illnesses (e.g., delirium, encephalitis)
· Patients have variable insight into their psychosis and may or may not recognize the derangements in their thought processes.14,50
Epidemiology
· Approximately 1% of the American adult population has schizophrenia and it is equally frequent in men and women.
· Schizophrenia typically first manifests in men during their late teens or early 20s; women usually exhibit symptoms in their 20s or early 30s.5
· Schizoaffective and mood disorder-associated psychosis may be more common in women.
· Approximately 80% of untreated manic patients develop psychotic symptoms. Psychotic symptoms in the context of mania or depression are often, but not always, congruent with mood (e.g., grandiose delusions).
Etiology/Pathophysiology
· The pathophysiology of schizophrenia is poorly understood. Some studies demonstrate abnormally elevated dopaminergic activity, altered neural network activation patterns, and anatomic atrophy in the central nervous system of patients with schizophrenia.51,52
· These changes likely result from complex interactions between multiple genes and environmental factors.51
Associated Conditions
· A total of 40% to 50% of patients with schizophrenia suffer from substance abuse issues with tobacco, alcohol, or illicit drugs.8
· Schizophrenic patients are also predisposed to be victims of violence and are at higher risk of suicide, depression, homelessness, and unemployment.
DIAGNOSIS
Clinical Presentation
· Types of psychotic symptoms include the following:
o Hallucinations are false perceptions in one of the sensory modalities (e.g., auditory, visual, tactile, olfactory, gustatory). Auditory hallucinations are more common in psychoses due to a primary psychiatric disorder such as schizophrenia. While present in primary psychotic disorders, visual hallucinations should be treated as organic until proven otherwise.
o Delusions are false beliefs that are firmly held despite obvious evidence to the contrary. Delusions are distinct from ideas typical of the patient’s background cultural, religious, or familial belief system. Common delusions include thoughts of persecution, thoughts of grandiosity or superhuman abilities, and thoughts of hyperreligiosity. Delusions are characterized as bizarre or nonbizarre on the basis of their degree of plausibility.
o Delusions of reference are a common type of delusion in which a patient believes that neutral information refers specifically to him or her. Patients may believe in the receipt of special messages transmitted from the television, radio, newspaper, or psychic communications.
o Illogical thought processes are evidenced by nonsensical speech and loose associations, with accompanying functional impairment, bizarre behaviors, and agitation or aggression.
o Agitation can manifest as both heightened emotional arousal and increased motor activity. Agitation is not exclusive to psychosis but frequently accompanies it.
· Schizophrenia is a severe, chronic disorder characterized by periods of active psychosis and an insidious deterioration of social, occupational, and personal functioning. Symptoms are typically subcategorized as follows:
o Positive symptoms, including psychosis with hallucinations, delusions, and thought disorganization
o Negative symptoms, including blunted affect, loss of social interest, decreased motivation, anhedonia, and decreased verbal communication
o Cognitive symptoms, including deficits in memory, attention, verbal processing, and executive function
o Affective symptoms, such as bizarre or inappropriate affect and predisposition for major depression
· Psychotic patients should undergo a complete mental status examination.
· Patients should be specifically questioned about hearing voices; seeing things others do not see; sensations of things touching or crawling on the skin; experiencing odd smells or tastes; fears that others are following, spying on, or wish to cause them harm; thought reading; special messages from television or radio; unusual religious experiences; and special powers or abilities.
Diagnostic Criteria/Differential Diagnosis
· Schizophrenia is characterized by abnormalities of thought (e.g., delusion, hallucinations, and language disorganization) for at least 6 months. These abnormalities significantly affect social functioning. The DSM-5 criteria are essentially the same as the prior DSM-IV-TR criteria.4,12
· Schizophrenia must be distinguished from other psychotic conditions (Table 42-5).4,14
· Many medical illnesses and certain drug intoxications are associated with psychotic symptoms.
TABLE 42-5 Psychiatric Differential Diagnosis of Psychosis5,8
TREATMENT
· The treatment of psychosis and schizophrenia is complex and should be done in conjunction with a psychiatrist or similarly qualified healthcare professional.
· Treatment for psychosis should be voluntary whenever possible but the nature of the illness may lead patients to fear or avoid treatment. Such patients may benefit from involuntary treatment, especially if they exhibit a high risk for harm to self or others.
· Symptomatic treatment of psychosis is appropriate, even if diagnostic evaluation is still in progress.
· Goals for the acute treatment of schizophrenia include the following50,52,53:
o Preventing self-harm
o Controlling disturbed behavior
o Reducing the severity of psychosis and associated symptoms (e.g., agitation, aggression, negative symptoms, affective symptoms)
o Addressing factors that precipitated the acute psychotic episode
o Connecting the patient and family with appropriate support
· Assess the patient for risk factors for suicide or self-harm including prior self-harm attempts, depressed mood, hopelessness, anxiety, suicidal ideation, presence of command hallucinations, extrapyramidal side effects, and alcohol or other substance use.
· When compared with the general population, schizophrenic patients have a significantly higher prevalence of diseases including diabetes mellitus, metabolic syndrome, coronary heart disease, and chronic obstructive pulmonary disease.54 Both antipsychotic medication side effects and sequelae of the primary disease seem to contribute. Such patients should undergo routine screening for such illnesses, with emphasis on early interventions and preventative measures.
Medications
· In schizophrenia, antipsychotic medications are primarily effective for control of positive symptoms. Negative symptoms show a modest response to antipsychotics, affective symptoms respond in about half of patients, and cognitive symptoms respond minimally.50,52,53
· Antipsychotic medications are often classified as first generation (i.e., conventional, typical) or second generation (i.e., atypical). The nonspecific effect on agitation begins early; antipsychotic effect may take longer.Common antipsychotics are presented in Table 42-6.50
· Atypical antipsychotics are a heterogeneous group of medications with respect to efficacy and side effect profile (Table 42-7).50,53,55–57
o Atypical agents may be less likely to induce extrapyramidal side effects than high-potency conventional medications but have an increased risk for other adverse effects including weight gain.55
o Atypical antipsychotics are no more beneficial for the control of symptoms than first-generation agents with the exception of clozapine, which was demonstrated in the CATIE trial.58
o Clozapine decreases the rate of suicide and self-harm attempts in schizophrenia.59
· Antipsychotic medications should be chosen based on side effect profile and patient comorbidities.
· Expert opinion recommends low-dose risperidone, quetiapine, olanzapine, or aripiprazole for psychosis in elderly patients.60
· Adverse effects from antipsychotic medications include the following:
o Hyperprolactinemia (galactorrhea, amenorrhea, loss of libido)
o Weight gain, dyslipidemia, hyperglycemia
o QTc prolongation (arrhythmia, sudden cardiac death)
o Acute dystonia (acute muscular rigidity, laryngospasm)
o Parkinsonism (masked facies, stooped posture, tremor, rigidity)
o Akathisia (intense restlessness)
o Tardive dyskinesia (involuntary movements)
o Neuroleptic malignant syndrome (rigidity, tremor, autonomic instability, mental status changes, potential for death)
· Diphenhydramine or benztropine are helpful in treating extrapyramidal effects (i.e., dystonia, akathisia, parkinsonism).53 Propranolol or other β-blockers may be helpful in treating akathisia.
· A sizable minority of schizophrenic patients do not achieve complete symptom remission despite appropriate antipsychotic medications. Adjuvant treatments including lamotrigine, lithium, carbamazepine, benzodiazepines, β-blockers, valproate, and ECT have been used in schizophrenics whose psychoses did not respond to traditional therapy.61,62
TABLE 42-6 Commonly Used Antipsychotic Medications
Data from American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004;161:1–56; Clinical Pharmacology. 2014. http://www.clinicalpharmacology-ip.com. Last accessed 2/1/15.
TABLE 42-7 Qualitative Frequency of Antipsychotic Side Effects
EPS, extrapyramidal side effects (akathisia, parkinsonism, dystonia); −−, rare; +, seldom; ++, common; +++, frequent.
Data from Lehman AF, Lieberman JA, Dixon LB, et al.; American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004;161:1–56; Dixon L, Perkins D, Calmes C; American Psychiatric Association. Guideline Watch (September 2009): Practice Guideline for the Treatment of Patients with Schizophrenia. American Psychiatric Association; 2009; Drugs for psychotic disorders. Treat Guidel Med Lett 2010;8:61–64.
Other Nonpharmacologic Therapies
· ECT may be useful for the treatment of psychosis refractory to antipsychotic medications, those with prominent catatonic features, or those with comorbid depression or suicidality.50,52,53
· Psychological therapy techniques may be effective adjuvants for psychosis, though data are limited.
· Multiple psychosocial interventions, including vocational training programs and case managers, seem to be beneficial in assisting those with schizophrenia.50,53
OUTCOME/PROGNOSIS
· Schizophrenic patients have a chronic illness with a fluctuating course.
· More than 70% of first-episode patients achieve a full remission of psychotic signs and symptoms within 3 to 4 months and >80% achieve stable remission at the end of 1 year.50
· Predictors of poor treatment response include male gender, pre- or perinatal injury, severe hallucinations and delusions, attentional impairments, poor premorbid function, longer duration of untreated psychosis, and distressing emotional climate (e.g., hostile and critical attitudes and overprotection by others in one’s living situation or high levels of expressed emotion).50
· There is significant unexplained heterogeneity in the long-term outcomes of schizophrenic patients. Poor outcome occurs in <50% of patients, but, frustratingly, good outcome also occurs in <50% of patients.52 Importantly, 20% to 40% attempt suicide and 7% will die of it.50
SPECIAL CONSIDERATIONS IN GERIATRIC PATIENTS
GENERAL PRINCIPLES
· Depression and anxiety are not part of the normal aging process. These illnesses have considerable negative influence on elderly patients’ quality of life.
· Older adults who require recurrent hospitalizations or long-term nursing home care have increased rates of mental health illnesses compared with their peers.
· Some psychiatric disorders in geriatric patients seem to derive from pathophysiology dissimilar to younger adults and may involve subacute neurologic degeneration or ischemia.2,5,20,63
· Underlying medical conditions (such as advanced cardiac, pulmonary, or neurologic illness) predispose to depression and anxiety. The causality of such associations is complex and likely involves both physiologic changes as well as psychosocial stressors.
· Medical diseases common in the geriatric population may present with psychiatric symptoms. Older adults with psychiatric symptoms should be screened for conditions including thyroid and adrenal dysfunction; diabetes mellitus; cardiac arrhythmia or ischemia; nutritional deficiencies; malignancy, including pancreatic cancer; stroke, Parkinson disease, or neurologic disorders; chronic pain; sleep disorders; occult infections; and medication side effects.
· Elderly patients with mental health disorders often present atypically, emphasizing somatic manifestations of their illness rather than psychiatric ones. Practitioners should exercise high levels of vigilance when evaluating older patients and avoid the mistake of simply treating symptoms without addressing possible underlying mental health issues.
· Geriatric patients are prone to medication side effects and drug-drug interactions. Medications should be initiated at lower doses than in younger patients and titrated slowly. Medical comorbidities should be considered when selecting therapeutic modalities and medications.
· Referral to a psychiatrist or other mental health professional should be considered for all elderly adults with mental health disorders given the complexity of care in this population.
DEPRESSION IN OLDER ADULTS
· Depression can be subtle in older adults. Rather than endorsing sadness or feeling depressed, older patients will often manifest depression as47,64:
o Apathy or decreased interest in previous hobbies
o Feelings of ill health with vague somatic symptoms
o Lack of energy
o Psychomotor slowing or agitation
o Worsening control of comorbid medical illnesses and medical noncompliance
o Sleep disturbances or early morning awakenings
o Cognitive impairment including memory deficits and slowed information/visuospatial processing
o Delusions of guilt and worthlessness
o Auditory/visual hallucinations
· Geriatric patients are at increased risk for completed suicide compared with younger adults.5
· Patients with symptoms of depression or a positive Two Question Screen should be evaluated using a geriatric-specific metric, such as the Geriatric Depression Scale.65,66
· Even subsyndromal depression is associated with worsened function, increased mortality, and increased risk of suicide in older adults. Treatment should strongly be considered in such cases given the favorable response rate and benefit of intervention.
· Antidepressant medications should be considered for all geriatric patients with depression.2
· Skilled psychotherapy augments rates of response to medications and may alone be sufficient in mild depression if pharmacologic therapy is contraindicated.11,63,67,68
· Data support the efficacy and tolerance of multiple classes of antidepressants in the elderly.2,11,67 SSRIs or nonselective serotonin agonists (e.g., mirtazapine, bupropion, and SNRIs) should be used as first-line agents for geriatric depression given a more benign side effect profile compared with TCAs (Table 42-3).2,11,20,67 However, these agents may cause falls, sleep disturbances, anorexia, sinus bradycardia, and hyponatremia in the elderly.
· Highly anticholinergic mediations, including amitriptyline and imipramine, are relatively contraindicated in older adults because of risk of arrhythmia, narrow angle glaucoma, urinary retention, delirium, and orthostasis. Older adults also have an increased risk for cardiovascular complications from TCAs and antipsychotics.64
· ECT is generally safe in geriatric patients and may be especially useful for those with severe symptoms including suicidality, catatonia, and psychosis.2,64,69
· Remission of depression progresses more slowly in the elderly. More than half of geriatric patients treated with antidepressants eventually experience treatment response within 2 months.2,67 If symptoms persist after 6 to 8 weeks, additional or alternative treatment options should be considered.
· Assessing therapeutic response should include evaluation of overall quality of life, performance of activities of daily living, and control of comorbid illnesses.68
· Maintenance treatment with antidepressants or ECT should continue for at least 12 months in older adults with moderate or severe depression to reduce the risk of recurrence. Continuance for even longer durations may be worthwhile in such patients.2,70,71 Skilled psychotherapy is a helpful adjuvant in preventing recurrence of moderate or severe geriatric depression but should not be used alone.67,70,71
ANXIETY IN OLDER ADULTS
· Anxiety problems, including GAD, are common in geriatric populations.67,72,73
· Practitioners must differentiate whether an older patient’s symptoms are due to a primary anxiety disorder or secondary to other causes. Cardiac diseases, respiratory illnesses, and medication side effects disproportionately affect older adults and are significantly anxiogenic if not well controlled.
· Agitation (the physical manifestations of hyperactivity) subtly differs from anxiety but should be distinguished as it may require alternate treatment. Elderly adults with agitation do not typically experience the sense of dread or impending doom characteristic of anxiety. Agitation without clear anxiety is also frequent in patients with dementia or delirium.
· Rather than endorsing worry, geriatric patients with anxiety disorders are more likely to present with nonspecific complaints including the following72,73:
o Concentration or memory difficulties
o Restlessness or irritability
o Muscle tension
o Vague visceral discomfort
o Recurrent cardiovascular or gastrointestinal symptoms without clear medical explanations
o Continued medical complaints despite negative workup
o Fatigue
o Decreased physical activity and functional independence
o Low mood or depression
o Increased feelings of loneliness
o Avoidance of certain situations, tasks, or locations
· Anxiety prominently affects sleep in older adults; data suggest that 90% of older adults with GAD report dissatisfaction with sleep.74
· Anxiety disorders are frequently associated with depression in older populations.72,73 The co-occurrence of both disorders increases the risk for suicidality and substance abuse.
· It is unclear which metrics are best to screen older adults for anxiety disorders. The Generalized Anxiety Disorder Severity Scale (GADSS) may help in evaluating for either GAD or panic disorder in elderly patients.75,76
· Despite the prevalence of anxiety disorders in geriatric populations, few potential treatment options have been rigorously studied.67,72,73
· SSRIs appear useful for treating geriatric anxiety disorders (Table 42-3). Both citalopram and escitalopram have shown benefit in the treatment of GAD and panic disorder in small trials.77,78 Minor side effects are relatively frequent in older patients using SSRIs for anxiety and include fatigue, sleep disturbances, and urinary symptoms. More serious adverse reactions, including hyponatremia, may also occur.
· Venlafaxine may also be used to treat older adults with GAD, with an efficacy, safety, and tolerability similar to that in younger patients.79
· Benzodiazepines are the most frequently prescribed anxiolytics for older patients (Table 42-6).67,72,80 Compared with placebo, these medicines seem to decrease anxiety symptoms.72 However, benzodiazepines increase the risk for falls and cognitive impairment in the elderly and should be used cautiously. Geriatric patients have decreased rates of drug metabolism and may tolerate intermediate-acting agents better than long-acting ones. Trials have not yet directly compared benzodiazepines with other treatments for geriatric anxiety.
· CBT has consistently shown promise for the management of geriatric anxiety disorders.67,72,81,82 The benign side effects of CBT suggest that it should be considered in all elderly anxiety patients. Other psychological techniques may also be effective but have not yet been adequately evaluated.67,72,81
PSYCHOSIS IN OLDER ADULTS
· Psychotic symptoms are widespread in the elderly, with prevalence estimates ranging from approximately 1% to 5% in community-based cohorts to as high as 10% to 63% in nursing home populations.69
· Psychosis in elderly patients may be due to schizophrenia/schizoaffective disorder, mood disorders (e.g., depression or mania), dementia (e.g., Alzheimer disease, Lewy body dementia), delirium, delusional disorders, substance-induced disorders, Parkinson disease, and medication side effects.
· The most statistically frequent causes of geriatric psychosis are Alzheimer dementia, depression, and delirium; these conditions should be considered when evaluating any geriatric patient with psychosis.69 Treatment choices should be based on the etiology of the patient’s psychosis.
· Up to 40% of hospitalized geriatric patients with depression manifest psychosis.69 All elderly adults with psychosis should be assessed for depression. Hallucinations and delusions in patients with depression or mania are often (but not necessarily) mood congruent.
· Both ECT and antipsychotics appear to be useful adjuvants for treating depression with psychotic features in older adults who do not respond to antidepressant medications alone.2,60,64,69
· Consensus statements support multidisciplinary psychosocial interventions for both older patients with chronic psychotic illnesses and their families.67 Useful interventions include vocational/social skills training and community support programs.
· Expert opinion, consensus statements, and the few available studies all concur that antipsychotic medications are effective for psychosis or schizophrenia in older patients.60,67,69 Atypical antipsychotics are generally preferredfor most geriatric psychotic disorders and typically used at lower doses than in younger patients.60 Commonly used antipsychotics are presented in Table 42-6.
· Pharmacologic treatment of psychosis in the elderly should be managed in conjunction with a psychiatrist or similarly qualified mental health specialist. Special attention should be given to patients’ age-related issues including pharmacokinetics, comorbid illnesses, and polypharmacy.
· Older patients are particularly susceptible to adverse reactions from antipsychotic medications including (Table 42-7) parkinsonism (i.e., bradykinesia, tremor, cogwheeling rigidity, masked facies), dystonia (involuntary muscle spasms that may be painful), akathisia (feelings of increased agitation and restlessness), Tardive dyskinesia (repetitive purposeless, involuntary movements), weight gain, dyslipidemia, hyperglycemia, cardiac arrhythmias, QTc prolongation, and sudden death.53,56,57,67,69
· In younger patients, extrapyramidal side effects (including parkinsonism, dystonia, and akathisia) are often treated with diphenhydramine or benztropine. However, these anticholinergic agents frequently cause problems, such as cognitive impairment, constipation, and orthostasis in the elderly and must be used with caution.
· The development of extrapyramidal symptoms or Tardive dyskinesia in the elderly is more frequent with use of conventional antipsychotics (e.g., haloperidol) than atypical ones.76
· Antipsychotic medication therapy has been associated with an increased mortality in geriatric patients with dementia, especially from cardiovascular or infectious etiologies. As such, atypical antipsychotic medicines carry an FDA boxed warning regarding their use in dementia-related psychosis. Mortality risk in the elderly may be higher with conventional antipsychotic agents compared with atypical antipsychotics.69
ADDITIONAL RESOURCES
· MedLine Plus. Mental health. http://www.nlm.nih.gov/medlineplus/mentalhealth.html. Last accessed: 2/1/15.
· National Institutes of Mental Health. Mental health topics. http://www.nimh.nih.gov/health/topics/index.shtml. Last accessed: 2/1/15.
· PsychCentral. Mental health & psychology resources online. http://psychcentral.com/resources/. Last accessed: 2/1/15.
REFERENCES
1.Stiebel V, Schwartz CE. Physicians at the medicine/psychiatric interface: what do internist/psychiatrists do? Psychosomatics 2001;42:377–381.
2.Shanmugham B, Karp J, Drayer R, et al. Evidence-based pharmacologic interventions for geriatric depression. Psychiatr Clin North Am 2005;28:821–835.
3.American Psychiatric Association. Psychiatric evaluation of adults, second edition. Am J Psychiatry 2006;163:3–36.
4.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Text Revision, 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2000.
5.National Institute of Mental Health. The numbers count: mental disorders in America. http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml. Last accessed 2/1/15.
6.Hasler G, van der Veen JW, Tumonis T, et al. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry2007;64:193–200.
7.Belmaker RH, Agam G. Major depressive disorder. N Engl J Med 2008;358:55–68.
8.Institute for Clinical Systems Improvement (ICSI). Major Depression in Adults in Primary Care. Bloomington, MN: ICSI; 2008.
9.U.S. Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med 2002;136:760–764.
10.Egede LE. Disease-focused or integrated treatment: diabetes and depression. Med Clin North Am 2006;90:627–646.
11.Fochtmann IJ, Gelenberg AJ. Guideline Watch: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 2nd ed. Arlington, VA: American Psychiatric Association; 2005.
12.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2013.
13.Whooley MA, Avins AL, Miranda J, et al. Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med 1997;12:439–445.
14.First MB, Frances A, Pincus HA. DSM-IV-TR Handbook of Differential Diagnosis. Arlington, VA: American Psychiatric Publishing, Inc.; 2002.
15.American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000;157:1–45.
16.American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd ed. Arlington, VA: American Psychiatric Association; 2010. Available at: http://psychiatryonline.org/guidelines.aspx. Last accessed 2/1/15.
17.King V, Robinson S, Bianco T, et al.; U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality. Choosing Antidepressants for Adults. AHRQ Pub. No. 07-EHC007-3. Rockville, MD: Agency for Healthcare Research and Quality; 2007.
18.Barbui C, Butler R, Cipriani A, et al. Depression in adults (drug and other physical treatments). BMJ Clin Evid 2007;06:1003.
19.Butler R, Hatcher S, Price J, et al. Depression in adults: psychological treatments and care pathways. BMJ Clin Evid 2007;08:1016.
20.Lawhorne L. Depression in the older adult. Prim Care 2005;32:777–792.
21.Cain RA. Navigating the sequenced treatment alternatives to relieve depression (STAR*D) study: practical outcomes and implications for depression treatment in primary care. Prim Care 2007;34:505–519.
22.Rush AJ, Trivedi M, Fava M. Depression, IV: STAR*D treatment trial for depression. Am J Psychiatry 2003;160:237.
23.Simon NM, Otto MW, Weiss RD, et al. Pharmacotherapy for bipolar disorder and comorbid conditions: baseline data from STEP-BD. J Clin Psychopharmacol 2004;24:512–520.
24.Perlis RH, Ostacher MJ, Patel JK, et al. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2006;163:217–224.
25.Qaseem A, Snow V, Denberg TD, et al. Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2008;149:725–733.
26.Schatzberg AF, Cole JO, DeBattista C. Manual of Clinical Psychopharmacology, 6th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2007.
27.Gartlehner G, Hansen RA, Thieda P, et al.; U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. AHRQ Publication No. 07-EHC007-EF. Bethesda, MD: Agency for Healthcare Research and Quality; 2007.
28.Crone CC, Gabriel G. Herbal and nonherbal supplements in medical-psychiatric patient populations. Psychiatr Clin North Am 2002;25:211–230.
29.Terman M, Terman JS, Ross DC. A controlled trial of timed bright light and negative air ionization for treatment of winter depression. Arch Gen Psychiatry 1998;55: 875–882.
30.Ströhle A. Physical activity, exercise, depression and anxiety disorders. J Neural Transm 2009;116:777–784.
31.Soomro GM. Deliberate self-harm (and attempted suicide). BMJ Clin Evid 2008;12:1012.
32.American Psychiatric Association. Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry 2003;160:1–60.
33.U.S. Food and Drug Administration. Antidepressant use in children, adolescents, and adults. http://www.fda.gov/cder/drug/antidepressants/default.htm. Last accessed 2/1/15.
34.Hawton K, Townsend E, Arensman E, et al. Psychosocial and pharmacological treatments for deliberate self harm. Cochrane Database Syst Rev 2000;(2):CD001764.
35.Shearer SL. Recent advances in the understanding and treatment of anxiety disorders. Prim Care 2007;34:475–504.
36.National Institute of Mental Health, U.S. Department of Health and Human Services. Anxiety Disorders. NIH Publication No. 07-4677. Bethesda, MD: National Institute of Mental Health; 2007.
37.Gale C, Millichamp J. Generalised anxiety disorder. BMJ Clin Evid 2007;11:1002.
38.National Institute of Mental Health. U.S. Department of Health and Human Services. Anxiety Disorders. NIH Publication No. 09-3879. Bethesda, MD: National Institute of Mental Health; 2009.
39.Spitzer RL, Kroenke K, Williams JB, et al. A brief measure for assessing generalized anxiety disorder: the gad-7. Arch Intern Med 2006;166:1092–1097.
40.Newman MG, Zuellig AR, Kachin KE, et al. Preliminary reliability and validity of the Generalized Anxiety Disorder Questionnaire-IV: a revised self-report diagnostic measure of generalized anxiety disorder. Behav Ther2002;33:215–233.
41.Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med 2008;359:2753–2766.
42.Kapczinski F, Lima MS, Souza JS, et al. Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev 2003;(2):CD003592.
43.Martin JL, Sainz-Pardo M, Furukawa TA, et al. Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials. J Psychopharmacol 2007;21:774–782.
44.Hunot V, Churchill R, Silva de Lima M, et al. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev 2007;(1):CD001848.
45.Leichsenring F, Salzer S, Jaeger U, et al. Short-term psychodynamic psychotherapy and cognitive-behavioral therapy in generalized anxiety disorder: a randomized, controlled trial. Am J Psychiatry 2009;166:875–881.
46.Kumar S, Malone D. Panic disorder. BMJ Clin Evid 2008;12:1010.
47.Means-Christensen AJ, Sherbourne CD, Roy-Byrne PP, et al. Using five questions to screen for five common mental disorders in primary care: diagnostic accuracy of the anxiety and depression detector. Gen Hosp Psychiatry2006;28:108–118.
48.Mula M, Pini S, Cassano G. The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J Clin Psychopharmacol 2007;3:263–272.
49.Krisanaprakornkit T, Sriraj W, Piyavhatkul N, et al. Meditation therapy for anxiety disorders. Cochrane Database Syst Rev 2006;(1):CD004998.
50.American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004;161:1–56.
51.Jindal RD, Keshavan MS. Neurobiology of the early course of schizophrenia. Expert Rev Neurother 2008;8:1093–1100.
52.van Os J, Kapur S. Schizophrenia. Lancet 2009;374:635–645.
53.Lehman AF, Buchanan RW, Dickerson FB, et al. Evidence-based treatment for schizophrenia. Psychiatr Clin North Am 2003;26:939–954.
54.Oud MJ, Meyboom-de Jong B. Somatic diseases in patients with schizophrenia in general practice: their prevalence and health care. BMC Fam Pract 2009;10:32.
55.Leucht S, Corves C, Arbter D, et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009;373:31–41.
56.Lehman AF, Lieberman JA, Dixon LB, et al.; American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004;161:1–56.
57.Dixon L, Perkins D, Calmes C; American Psychiatric Association. Guideline Watch (September 2009): Practice Guideline for the Treatment of Patients with Schizophrenia. American Psychiatric Association; 2009. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizophrenia-watch.pdf. Last accessed January 30, 2015.
58.McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006;163:600–610.
59.Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003;60:82–91.
60.Alexopoulos GS, Streim J, Carpenter D, et al. Using antipsychotic agents in older patients. J Clin Psychiatry 2004;65:5–99.
61.Schwarz C, Volz A, Li C, et al. Valproate for schizophrenia. Cochrane Database Syst Rev 2008;(3):CD004028.
62.Dold M, Li C, Tardy M, et al. Benzodiazepines for schizophrenia. Cochrane Database Syst Rev 2012;(11):CD006391.
63.Wilson KC, Mottram PG, Vassilas CA. Psychotherapeutic treatments for older depressed people. Cochrane Database Syst Rev 2008;CD004853.
64.Stek ML, Van der Wurff FB, Hoogendijk WL, et al. Electroconvulsive therapy for the depressed elderly. Cochrane Database Syst Rev 2003;(2):CD003593.
65.Holroyd S, Clayton AH. Measuring depression in the elderly: which scale is best? MedGenMed 2000;2. http://www.medscape.com/viewarticle/430554. Last accessed 2/1/18.
66.Sheikh JI, Yesavage JA. Geriatric depression scale (GDS): recent evidence and development of a shorter version. In: Brink TL, ed. Clinical Gerontology: A Guide to Assessment and Intervention. New York, NY: The Haworth Press; 1986:165–173.
67.Bartels SJ, Dums AR, Oxman TE, et al. Evidence-based practices in geriatric mental health care: an overview of systematic reviews and meta-analyses. Psychiatr Clin North Am 2003;26:971–990.
68.Mackin RS, Arean PA. Evidence-based psychotherapeutic interventions for geriatric depression. Psychiatr Clin North Am 2005;28:805–820.
69.Broadway J, Mintzer J. The many faces of psychosis in the elderly. Curr Opin Psychiatry 2007;20:551–558.
70.Reynolds CF, Frank E, Perel JM, et al. Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients >59 years. JAMA 1999;281:39–45.
71.Reynolds CF, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med 2006;354:1130–1138.
72.Wetherell JL, Lenze EJ, Stanley MA. Evidence-based treatment of geriatric anxiety disorders. Psychiatr Clin North Am 2005;28:871–896.
73.Blazer DG, Steffens DC. The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2009.
74.Brenes GA, Miller ME, Stanley MA, et al. Insomnia in older adults with generalized anxiety disorder. Am J Geriatr Psychiatry 2009;17:465–472.
75.Weiss BJ, Calleo J, Rhoades HM, et al. The utility of the Generalized Anxiety Disorder Severity Scale (GADSS) with older adults in primary care. Depress Anxiety 2009;26:E10–E15.
76.Andreescu C, Belnap BH, Rollman BL, et al. Generalized Anxiety Disorder Severity Scale validation in older adults. Am J Geriatr Psychiatry 2008;16:813–818.
77.Blank S, Lenze EJ, Mulsant BH, et al. Outcomes of late-life anxiety disorders during 32 weeks of citalopram treatment. J Clin Psychiatry 2006;67:468–472.
78.Lenze EJ, Rollman BL, Shear MK, et al. Escitalopram for older adults with generalized anxiety disorder: a randomized controlled trial. JAMA 2009;301:295–303.
79.Katz IR, Reynolds CF III, Alexopoulos GS, et al. Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials. J Am Geriatr Soc2002;50:18–25.
80.Benitez CI, Smith K, Vasile RG, et al. Use of benzodiazepines and selective serotonin reuptake inhibitors in middle-aged and older adults with anxiety disorders: a longitudinal and prospective study. Am J Geriatr Psychiatry2008;16:5–13.
81.Ayers CR, Sorrell JT, Thorp SR, et al. Evidence-based psychological treatments for late-life anxiety. Psychol Aging 2007;22:8–17.
82.Stanley MA, Wilson NL, Novy DM, et al. Cognitive behavior therapy for generalized anxiety disorder among older adults in primary care: a randomized clinical trial. JAMA 2009;301:1460–1467.