is a Resident Physician in Family Medicine and Psychiatry, UC Davis Health;

is Chief Resident Physician in Internal Medicine, UC Davis Health, Internal Medicine and Psychiatry; and

 is Associate Professor, UC Davis Health, Internal Medicine and Psychiatry.

Sleep disorders are highly prevalent in the older population and frequently encountered in psychiatry and primary care. More than one-half of the elderly have at least one sleep complaint.

 Given the impact of sleep on quality of life, cognitive functioning, and health outcomes, understanding sleep disorders in older adults is vital to their overall care.

The most common sleep disorder both in the general population and in seniors is insomnia. Women tend to have a higher incidence of insomnia than men. Findings indicate that insomnia affects 31% to 38% of adults aged 18 to 64 years but 45% of those aged 65 to 79 years.

 Many factors can contribute to insomnia, including psychiatric or neurological disorders, medical conditions, polypharmacy, medication adverse effects, substance use, environmental changes (home, hospital, care home), decreased sensory input (blindness, deafness), unrealistic expectations of sleep, lifestyle changes (retirement, change in daily structure), and psychosocial stressors.

Related content: Mini Quiz: Sleep Hygiene

In addition to insomnia, several other sleep disorders are more often seen in older adults. Obstructive sleep apnea is especially common and affects 25% to 35% of people aged over 60 years, compared with 2% to 4% of 30- to 60-year-olds.

 Rates of sleep apnea are higher in men than women and are highest among institutionalized elderly adults (33% to 70%), particularly those with dementia.

 REM sleep behavior disorder is characterized by acting out dreams during sleep due to lack of muscle atonia and primarily affects elderly men. Additional disorders include circadian rhythm disorders (shift in the sleep-wake schedule), periodic limb movement disorder (repetitive and stereotyped limb movements during sleep), and restless legs syndrome (uncomfortable urge to move prior to sleep onset).

As our brains age, physiological changes alter the timing and quality of sleep. Older adults frequently report waking up at earlier times, increased sleep-onset latency (taking longer to fall asleep), more nighttime awakenings, and decreased total sleep.

 With aging, progressively more time is spent in light sleep (stages 1 and 2), and less time is spent in deep sleep (stages 3 and 4). In addition, REM sleep is decreased. As sleep becomes more fragmented, there are more frequent shifts between sleep stages and more opportunities for awakenings.

Changes in circadian rhythm can also occur, because of decreased responsiveness of the superchiasmatic nucleus (which controls our internal clock) to external cues (light). Circadian rhythm dysfunction can be exacerbated by the loss of daily structure (or typical work routines), increased daytime napping, or inconsistent exposure to light, such as in nursing homes where day and night blend together. This often leads to advanced sleep phase syndrome, a circadian shift in the sleep-wake cycle where older adults feel tired earlier and earlier each evening, and then wake up earlier and earlier each morning. These changes in sleep architecture can result in less total sleep, decreased sleep efficacy (the proportion of time asleep compared with time in bed), and early morning awakenings.

Medical disorders, substance use disorders, and medications

Older adults often have one or more medical comorbidities that can contribute to difficulty with sleep. Data from an epidemiologic study of 6800 elderly adults over 3 years showed that only 7% of the cases of insomnia were in isolation of common comorbid conditions.

 Heart disease, diabetes, and respiratory disease were all associated with long-term persistence of insomnia at the 3-year follow-up (Table 1).

14 Medical Conditions That Contribute to Insomnia

Finding and treating the underlying cause of the sleep disturbance is critical to effective management. For example, awakenings from sleep to urinate can be triggered by nocturia from benign prostatic hyperplasia, from polyuria with diabetes, from drinking water or alcohol too close to bedtime, or from evening doses of diuretics.

Substance use is often under-reported in older adults and can adversely affect sleep, especially with metabolic changes with age. For example, caffeine can have a stimulant effect for over 8 to 14 hours in older adults, and alcohol can also take longer to metabolize, leading to disrupted sleep and nocturnal awakenings. Nicotine can also interfere with falling asleep and decrease sleep duration. These changes increase sleep fragmentation and can worsen symptoms from other sleep disorders, such as obstructive sleep apnea.

Careful review of pharmaceutical agents is necessary in geriatric patients with sleep disruptions (Table 2). Older adults, especially those with multiple psychiatric or medical comorbidities, are usually excluded from clinical drug trials. Clinicians also must consider reducing usual doses for older adults, as there is increased accumulation of drug due to a larger volume of distribution (the elderly have a higher relative ratio of fat to muscle) and decreased drug clearance (due to age-related decrease in renal or hepatic function). Furthermore, older adults have a higher risk of adverse events related to polypharmacy, so clinicians should consider stopping or decreasing the dose of a current medication before adding a new medication.

Patient education regarding timing of medications is advised, so that stimulating medications are taken in the morning and sedative medications are taken in the evening. Medications intended to treat insomnia, such as antidepressants, benzodiazepines and their agonists, antipsychotics, and antihistamines, can cause excessive daytime sleepiness in older adults, which may lead to delirium, falls, or rebound insomnia, or paradoxically disrupt the sleep-wake cycle.

Psychiatric disorders and risks of antipsychotic use for insomnia

When assessing sleep, screening for psychiatric disorders is vital because many people with depression or anxiety initially present with insomnia or fatigue. In one study, 65% of patients with depression, 61% of patients with panic disorder, and 44% of patients with generalized anxiety disorder reported insomnia.

 Patients with PTSD can also have disrupted sleep with distressing nightmares. These diagnoses may be unrecognized or undertreated in older adults.

Inadequate sleep can also worsen psychiatric disorder symptoms and can contribute to suicidality. In one 10-year study among older adults with poor quality sleep, the risk of death by suicide was increased 1.4-fold.

 Similarly, in a 2-year prospective study, risk of depression recurrence was 5 times more likely in older adults with insomnia, independent of other symptoms of depression, antidepressant use, other medical comorbidities, or socio-demographic factors.

 This model predicted that treating 5 cases of insomnia could prevent one patient from relapsing into depression.

Although second-generation antipsychotics are often used for bipolar spectrum and psychotic disorders in older adults, these medications are frequently prescribed off-label for sleep or sedation. A meta-analysis on the off-label use of second-generation antipsychotics showed that there was a small benefit in using them for psychosis, agitation, and other behavioral symptoms in elderly patients with dementia, but there was not enough evidence to justify their use for insomnia.8 Furthermore, adverse effects, especially cardiovascular symptoms, fatigue, extrapyramidal symptoms, falls, and urinary symptoms were common, and there was a 1.5-fold increase in risk of death.

To effectively manage sleep disorders in older adults, physicians must first screen for symptoms of fatigue or poor sleep. Next, a thorough history that includes symptom severity, chronology, exacerbating/alleviating factors, associated symptoms, sleep-wake patterns, and details about the sleep environment is gathered. A sleep log is a helpful tool for collecting additional data. Medical history, psychiatric history, substance use, and medications should also be reviewed for potential triggers. Then, a physical examination (focusing on the oral cavity, neck, heart, and lungs) and a mental status exam are done. Basic laboratory studies can screen for thyroid disorders, anemia, liver/renal dysfunction, and blood glucose abnormalities. Any signs of untreated medical conditions or sleep disorders (such as obstructive sleep apnea) should be further evaluated. (The Figure illustrates a suggested treatment algorithm.)

The first step in treatment is to optimize management of comorbid medical, psychiatric, or substance use disorders as these often can contribute to insomnia. Without treatment of the underlying etiology, the sleep dysfunction is unlikely to resolve.

Improving sleep hygiene is very effective and low-risk in older adults. Interventions include establishing a consistent bedtime that is late enough to decrease early morning awakenings, finishing meals several hours before going to bed, having a relaxing bedtime routine, minimizing caffeine/alcohol/nicotine intake, managing stress, and increasing morning exercise. Older adults should avoid wake-promoting activities, such as daytime napping, using the bed for activities other than sleep, and looking at the TV/computer before bed, as the light can be stimulating. Instead of lying in bed awake and watching the clock, getting up and doing a soothing, non-stimulating activity can be helpful. The bedroom should be comfortable, cool, dark, and quiet (except for white noise or a fan). Progressive muscle relaxation (thoughtfully recognizing and controlling muscle tension), biofeedback, listening to music, or meditation can also be helpful.

Cognitive behavioral therapy for insomnia (CBT-I) is a recommended first-line treatment, as it “produces reliable, durable benefits in 70% to 80% of patients, may reduce the use of sedatives, and improves time to fall asleep, continuity, restfulness, and duration of sleep.”

 CBT-I was found to be superior to medication use in short- and long-term management of insomnia in older adults. It improved sleep efficiency, reduced sleep latency, and decreased time awake during the night.

Strategies of CBT-I include correcting cognitive distortions about insomnia, improving sleep hygiene, addressing maladaptive behaviors, reducing stimuli that promote wakefulness, and incorporating relaxation training/biofeedback. Patients can receive CBT-I through trained therapists or self-guided modules. Brief behavioral treatment for insomnia (BBTI) is derived from CBT-I but delivered in one session with 2 to 3 brief follow-ups, focusing on sleep consolidation.

When medications are considered for insomnia, shared decision-making with the patient is necessary given that the risks of medications can be severe and include delirium, agitation, falls, and drug-drug interactions (Table 3). Zolpidem has been implicated in more than one-fifth of all emergency department visits for psychotropic adverse drug events in older adults.

 Moreover, data studies that show drug efficacy are limited and often weakened by biases from corporate sponsorship, short follow-up, comparison with placebo only rather than standard treatment, and small sample sizes.

Ideally, medications should not be used alone as the only treatment, and should only be used as short-term adjuncts to behavioral management in cases where benefits of medication outweigh risks. Practical recommendations are to choose a medication with a shorter half-life to minimize daytime drowsiness, and to use the smallest effective dose for the shortest duration of time (3 to 4 weeks only) with intermittent dosing (as needed rather than daily). For older adults, use lower starting doses (half of normal dose), given the increased risk of adverse effects.

Because pharmacotherapy is not intended for long-term use, non-pharmacologic and/or behavioral interventions should always be emphasized concurrently. This can ease rebound insomnia and anxiety associated with discontinuing medications once the short course has ended. Medications are an option of last resort in limited circumstances, and prudent clinical judgment is necessary for cases in which judicious prescribing is warranted.

The authors report no conflicts of interest concerning the subject matter of this article.

 Foley D, Monjan A, Brown S, et al. Sleep complaints among elderly persons: an epidemiological study of three communities. 

Alessi C, Vitiello M. Clinical evidence handbook: primary insomnia in older persons. 

Roepke SK, Ancoli-Israel S. Sleep disorders in the elderly. 

 Foley DJ, Monjan A, Simonsick EM, et al. Incidence and remission of insomnia among elderly adults: an epidemiologic study of 6,800 persons over three years. 

 Ohayon MM, Roth T. What are the contributing factors for insomnia in the general population? 

 Bernert RA, Turvey CL, Conwell Y, Joiner TE Jr. Association of poor subjective sleep quality with risk for death by suicide during a 10-year period: a longitudinal, population-based study of late life. 

Cho HJ, Lavretsky H, Olmstead R, et al. Sleep disturbance and depression recurrence in community-dwelling older adults: a prospective study.

 Maher AR, Maglione M, Bagley S, et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis. 

 Trauer JM, Qian MY, Doyle JS, et al. Cognitive behavioral therapy for chronic insomnia. 

 Buysse DJ, Rush AJ, Reynolds CF. Clinical management of insomnia disorder. 

 Hampton LM, Daubresse M, Chang HY, et al. Emergency department visits by adults for psychiatric medication adverse events. 

Articles

Understanding Sleep Disorders in Older Adults

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To understand the role of stress in the manifestation of depressive symptoms.

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is Professor of Psychiatry, Professor of Medical Education, and Master Teacher, Icahn School of Medicine at Mount Sinai, New York, NY.

Adjustment disorders (ADs) are one of the most frequently diagnosed psychiatric disorders and are a common diagnosis in the military, in children and youth, and in the consultation-liaison psychiatric setting. Their historical evolution, the conundrums of establishing their diagnosis, their relationship with other psychiatric disorders, their treatment, and the potential for a more biological understanding are presented below.

In 1952 the criteria for transient situational personality disturbance were developed for DSM-I. This emanated from a view developed during World War II that psychological symptoms related to combat experiences were normal responses to abnormal situations and transient unless treated in ways that increased secondary gain. A separate diagnostic category was created for these situationally specific phenomena, and combat-related psychopathology: gross stress reaction.

In DSM-II the category was altered to transient situational disorders-adjustment reactions of life: infancy, childhood, adolescence, late life. It was felt that the symptoms are the means by which individuals struggle to adjust to an overwhelming situation. In the presence of good adaptive capacity, symptom remission occurs when the situational stress diminishes. Persistent failure to resolve the stressors or the effects of the stressor indicates a more severe underlying disturbance. It is important to note that the stressor could be regarded as traumatic or non-traumatic.

The nomenclature was again changed in DSM-III to read ADs, with 10 subtypes: depression, anxiety, depression and anxiety, mixed emotional features, disturbance of conduct, mixed disturbance of emotions and conduct, work or academic inhibition, withdrawal, physical complaints, and not otherwise specified. In addition, other criteria were added: an AD was diagnosed when the individual experienced a stressor (traumatic or not) that was significant (undefined) and that the reaction to the stressor was excessive (undefined) considering the culture of the individual. By intention the stressor, the dysfunction, and the distress were not given measurable values so having these 3 essential entities for the diagnosis was based on clinical assessment alone.

Spitzer, one of the chief architects of DSM-III and DSM-III-TR, regarded the ADs diagnosis as a “wild card” in the psychiatric lexicon by design, in order that there would be a placement for patients who had psychological issues that warranted treatment, but who did not reach the threshold for a primary psychiatric diagnosis (eg, MDD, general anxiety disorder). In fact, the ADs diagnosis was not part of the seminal Epidemiological Catchment Area study because it depended on clinical judgment and did not have measurable variables across clinicians or institutions.

 It was acknowledged that the diagnosis had neither reliability nor validity.

In DSM-IV and DSM-IV-TR, ADs remained an independent diagnosis-an orphan entity-in its own “chapter,” but some of the subtypes were eliminated: work or academic inhibition, withdrawal, physical complaints, not otherwise specified. It also remained poorly defined and had no guidelines for the measurement of the diagnostic criteria. The clinician remained the “gold standard” of diagnosis. The term psychosocial stressor was changed to the broader concept of stressor (eg, the Chernobyl reactor incident, cardiac surgery, 9-11 terror attack).

In DSM-5, ADs were combined with a cadre of traumatic disorders in the “Trauma and Stressor-Related Disorders” chapter, which also included PTSD and acute stress disorder (ASD). ADs were no longer an orphan category, and it was anticipated this would not only promote research but upgrade the diagnosis from its historical placement as a sub-threshold entity to a primary psychiatric diagnosis.

The DSM-5 Stress Related Work Group proposed adding 2 additional subtypes, but they were not accepted: AD with PTSD-like symptoms and ASD-like symptoms. This would have allowed a diagnosis for symptom profiles that did not reach threshold for all the required symptoms (ie, not experiencing a traumatic stressor for PTSD and ASD).

Maercker and colleagues2 have provisionally made an important difference in ICD-11 diagnostic features for ADs. The criteria require positive symptoms of preoccupation and failure to adapt (ie, inability to recuperate), and dysfunction and distress are required to make the diagnosis.

 This changes the identifiable criteria for diagnosis of ADs between the 2 major taxonomies for mental disorders and remains a concern for research initiatives.

ADs could appear to be either the prodromal stage of MDD or the state of coming out of major depression as the patient responds to treatment. A refractory AD should make the clinician aware that a more serious depression may be developing. Similarly, AD with anxiety may appear to be a predecessor or successor of an anxiety disorder.

The diagnosis of ADs is subjective and phenomenologically driven, and has no universal biological or genetic markers. In fact, DSM-5 has no measurement standards or check lists for the 4 components essential for diagnosis: the stressor, degree of dysfunction, degree of distress or mood, or alteration of behavior. There is no consensus on reliable and valid measures, algorithms, guidelines, or diagnostic instruments. This makes it difficult to distinguish normal behavior from AD pathology. Phenomenological definitions may be reliable but are not necessarily valid, and this makes the accuracy of the diagnosis difficult.

 has described, there is a need to distinguish normal adaptive responses from recognized disorders. The chasm that separates various diagnostic categories from each other and from normality is called the “zone of rarity.” Using this concept there should be a clear demarcation between those who are ill and those who are not, with few, if any, individuals in the intermediate zone. This is the approach used in general medicine where various diseases are recognized and distinguished from others by their symptoms, etiology, pathophysiology (including biological markers), course, prognosis, and response to treatment.

In psychopathology “zones of rarity” do not exist between various psychiatric conditions, especially the common mental disorders such as MDD, ADs, PTSD, and generalized anxiety.

 The symptoms of one condition are also often found in others, calling into question the validity of many of the syndromes conventionally regarded as discrete psychiatric disorders. The impact of the failure to find “zones of rarity” is that definitive diagnosis is difficult for the clinician. Thus, diagnostic categories are heterogeneous, and symptoms of one condition are present in others. Casey also emphasizes the difficulties with not only the issue of symptom number but the duration criterion. The tendency to falsely diagnose a psychiatric disorder when there is none is referred to as the false-positive dilemma.

According to Casey, this heterogeneity stems from the fact that not all the specified symptoms are required to make the diagnosis and all are regarded as equally important. This is known as the polythetic approach and is the one used by DSM. Individuals with the same diagnosis can present with diverse clinical pictures. One way to address this is to require that certain symptoms be essential to making a diagnosis (the monolithic approach). For example, for PTSD, flashbacks or re-experiencing the trauma would be essential symptoms.

In light of the absence of zones of rarity between different psychiatric disorders and between normality and mental illness, dimensional measures instead of categorical labels have been proposed.

 The dimensions might range from biological measures, to symptom severity scores or measures of social functioning, although little work has been done on these for ADs. Yet for all the problems with the categorical approach, there is no agreement on what dimensions should be measured or to which diagnostic criteria should apply. A dimensional approach would not assist in deciding on the boundary between what a normal reaction to stress is and what is pathological unless the cut-off point is defined by research evidence.

In an attempt to capture the continuum from normality to pathology that is the hallmark of mental illness, DSM-5 incorporates a dimensional as well as categorical approach.

Science depends on measurement and independent validation, and phenomenology of mental illness constitutes a formal description of the subjective experiences of psychiatric patients without any independent confirmation that they are true.

 Psychiatric classifications rely on a mix of hard objective data (eg, an MRI scan), softer objective data (eg, neuropsychological testing), and careful clinical observation (observed behavior, symptoms, and phenomenology).

What has been realized is that good reliability is not enough to make a good diagnosis. Trained assessors can always achieve good reliability, but a highly reliable diagnosis can still be completely invalid. As a consequence, the emphasis on operational criteria as the gold standard of diagnosis is questioned. And this is the situation we have with ADs.

The intent of the RDoC concept is to accelerate new discoveries by fostering research that translates findings from basic science into new treatments addressing fundamental mechanisms that cut across current diagnostic categories. It is important to note that the conceptual framework for RDoC is “explicitly agnostic.” Can ADs be better understood and better diagnosed in the context of the RDoC schema?

As a clinical syndrome, depression is related to abnormal activity in the prefrontal cortex, amygdala, anterior cingulate cortex, nucleus accumbens, and multiple monoamine systems and undoubtedly other central nervous system components. Does this have applicability to AD with depressed mood? Are the physiological correlates of depression (eg, relationship to glucose metabolism, platelet activation, cytokine activity, alterations in cortisone) present in AD with depressive features?8

Findings indicate that ADs are associated with suicide attempts, completed suicide, substance abuse, somatic complaints, other mental disorders, and being a general medical or surgical patient.

 A study of the neurochemical variables of AD of all patients who attempted suicide revealed biological correlates consistent with the more major psychiatric disorders. Suicide attempters had lower platelet monoamine oxidase activity, higher MHPG (3-methoxy-4hydroxphenylglycol oxidase) activity, and higher cortisol levels than controls. An AD may complicate the course of illness by impairing adherence with the medical regimen or increasing the duration of hospital stay. The behaviors of some patients with AD are seriously pernicious and underscore that for the patient at risk, AD is not a sub-threshold diagnosis.

ADs occur in children, adolescents, and the elderly (2% to 8%) in community samples; in acute care general hospital inpatients (12%); in mental health outpatient settings (10% to 30%); and, in special settings (eg, following cardiac surgery, up to 50%).

 In children and adolescents, diagnosed AD may progress to more serious mental disorders over time and into adulthood. (The AD may be an earlier form of a more serious illness that appears later.) The diagnosis of AD may not be used if the symptoms are secondary to the physiologic effects of a general medical illness or its treatment (eg, drugs), nor should it be employed for demoralization.

Psychotherapy is the mainstay of treatment and should be the first line of therapeutic intervention. Often, as the stressor or its effects remit, the illness resolves without intervention. Some stressors are self-imposed; other stressors may have accentuated value that is not warranted. Reality orientation by counseling, psychotherapy, crisis intervention, family therapy, or group treatment may be utilized to encourage the verbalization of fears, anxiety, rage, helplessness, and hopelessness related to the stressors. Enhancement of coping skills and resilience and group support are therapeutic approaches that can be used to reduce the concerns and conflicts that the patient is experiencing. Cognitive behavioral therapy has been used successfully in young military recruits who experience adjustment problems.

Randomized controlled trials rarely focus on ADs. Pharmacotherapy decisions are based on the subtype present: depression or anxiety. First-generation antidepressants have been prescribed for depression and benzodiazepines for anxiety. Tianeptine, alprazolam, and mianserin were found to be equally effective in those with anxiety AD. Pharmacotherapy may be combined with psychotherapy if there is no or minimal improvement in functioning and/or distress.

Regardless of whether psychotherapy or pharmacotherapy is employed singularly or in combination, a significant aspect of treatment of the AD is to remain alert that this initial diagnosis may indicate a patient who is in the early phase of a major mental disorder. Therefore, if a patient continues to worsen, becomes more symptomatic, and does not respond to treatment, it is critical to review the patient’s symptom profile and confirm that the patient does not have an evolving major mental disorder.

Stress-induced alterations in the hypothalamic-pituitary-adrenal (HPA) axis function have been demonstrated in depression, PTSD, and other anxiety disorders.

 Research to determine how the HPA system operates in AD and whether each AD subtype exhibits similar psychobiological alterations needs to be undertaken. Given the great body of research demonstrating stress-related HPA reactions, it would be surprising if at least some of the AD subtypes were not associated with HPA mechanisms.

 reported that telomere length is shortened in patients with depression, anxiety, stress, and ADs. They also observed that the mitochondrial DNA copy number is associated with symptoms of depression, anxiety, stress, and AD.

 Further investigation might reveal that a specific AD subtype has commonality with the primary diagnoses (eg, MDD, general anxiety disorder) or that the subtypes have discrete biological functioning that might separate them from each other.

It is hoped that HPA research and the concept of “allostatic load” (McEwen and Rasgon

) will provide a useful psychobiologic conceptual framework within which to conduct both basic research and clinical trials to enhance our understanding of the relationship among stressor response syndromes: AD, PTSD, and anxiety. This would also provide a theoretical context within which to investigate different therapeutic approaches for the different AD subtypes.

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 Regier DA, Myers JK, Kramer M, et al. The NIMH Epidemiologic Catchment Area Program. Historical context, major objectives, and study population characteristics. Arch Gen Psychiatry. 1984;41:934-941.

 Maercker A, Brewin CR, Bryant RA, et al. Diagnosis and classification of disorders specifically associated with stress: proposals for ICD-11. World Psychiatry. 2013;12:198-206.

 Casey P. Borderline between normal and pathological responses. In: Casey P, Strain JJ, eds. 

. Washington, DC: American Psychiatric Press; 2016:1-22.

 Cooper R. Avoiding false positives: zones of rarity, the threshold problem and the DSM clinical significant criteria. 

 Kendall R, Jablensky A. Distinguishing between the validity and utility of psychiatric diagnosis. 

Tyrer P. Limits to the phenomenological approach to the diagnosis of adjustment disorders. In: Casey, P Strain JJ, eds. 

. Washington, DC: American Psychiatric Press; 2016:23-36.

 Cowles MK, Nemeroff C. Depression as a systemic disease. In: Blumenfield M, Strain JJ, eds. 

. Philadelphia: LLW Publishers; 2006:47-65.

Runeson BS, Beskow J, Waern M. The suicidal process in suicides among young people. 

 Oxman TE, Barrett JE, Freeman DH, et al. Frequency and correlates of AD relates to cardiac surgery in older patients. 

Strain JJ, Friedman M. Adjustment disorders. In: Dale DC, Federman DD, eds. 

Southwick SM, Davis LL, Aikins DE, et al. Neurobiological alterations associated with PTSD. In: Friedman MJ, Keane TM, Resik PA, eds. 

. New York: Guilford Press; 2007:166-189.

 Wang X, Sundquist K, Hedelius A, et al. Leukocyte telomere length and depression, anxiety and stress and ADs in primary health care patients. 

 Wang X, Sundquist K, Rastkhani H, et al. Association of mitochondrial DNA in peripheral blood with depression, anxiety and stress-and adjustment disorders in primary care patients. 

 McEwen BS, Rasgon NL. The brain and body on stress: allostatic load and mechanisms for depression and dementia. In: Strain JJ, Blumenfield M, eds. 

. New York and Oxford: Oxford University Press; 2018:14-36.

What is the role of stress in the manifestation of depressive symptoms?

Adjustment Disorders

is Assistant Professor of Clinical Psychiatry, Indiana University School of Medicine, IU Health Neuroscience Center, Indianapolis, IN;

s a Resident, Department of Psychiatry, Indiana University School of Medicine, IU Health Neuroscience Center;

is Resident, Department of Internal Medicine, Indiana University School of Medicine;

is Associate Professor of Medicine, Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Internal Medicine, Indiana University School of Medicine.

Post-intensive care syndrome (PICS) is a rapidly growing phenomenon in older adults. As survival rates from ICU hospitalizations have increased over the past few decades, the long-term cognitive, psychological, and physical sequelae of the illness have become a major challenge in critical care medicine. More than half of all ICU survivors suffer from at least one PICS-related impairment, and these effects can persist as long as 5 or more years.

PICS has become an increasingly important phenomenon in older adults for several reasons. First, the number of older adults with critical illness is rapidly increasing as the population ages and now accounts for about 50% of ICU admissions.

 Second, more than 70% of older adults hospitalized in the ICU develop delirium, which is a major risk factor for ICU-acquired cognitive impairments.

 Third, cognitive and functional impairment before an ICU hospitalization increases the likelihood of cognitive and functional decline afterward.

Paul, a 76-year-old widower, was found lying on the floor of his home. When the emergency medical technicians arrived, he was having trouble breathing and was not oriented to place or time. In the emergency department, the diagnosis was sepsis secondary to pneumonia. He was intubated and placed on mechanical ventilation. In the ICU he was treated with intravenous fluids, vasopressors, and antibiotics for overwhelming infection and septic shock. After 1 week, he was extubated and transferred to the regular floor. For the first few days on the regular floor, he remained confused and only sometimes recognized his surroundings. Eventually, he improved physically and was fully oriented to person, place, and time upon discharge.

Two months later, Paul’s neighbor brought him to his primary care physician. Paul was having difficulties paying his bills and keeping track of his medication regimen. He was still able to drive a few blocks to the grocery store but became tired if he drove more than 30 minutes. He was also less willing to drive to unfamiliar places because he had difficulty following the GPS. The neighbor noted that Paul was frequently repeating himself and misplacing items. Paul seemed withdrawn and depressed.

ICU-acquired long-term cognitive impairments (LTCIs) affect 30% to 80% of survivors. LTCIs appear to affect multiple domains, including executive functioning, memory, and attention. For many, LTCIs improve within the first year, although they can persist for many years in some people. Risk factors for LTCIs in older adults include neurological dysfunction, infection or severe sepsis, and acute dialysis. Duration of delirium is also a risk factor for LTCIs.

Current theories suggest that LTCIs from delirium may be distinct from Alzheimer disease (AD). While beta-amyloid deposition appears to be a key factor in the development of AD, long-term cognitive impairment from delirium appears to be caused by hypoxia and pro-inflammatory cytokines.

 This theory is consistent with the observation that the onset of LTCIs from delirium may depend on the duration of exposure to the pathophysiologic processes of delirium.

Evidence also suggests that LTCIs from delirium appear to differ from AD in several important ways. First, many patients’ LTCIs improve after the acute hospitalization. This trajectory is quite different from the progressive nature of AD. Second, executive functioning in LTCIs is associated with more severe depression and subsequently worse mental health quality of life.

 Finally, LTCIs may be associated with white matter damage and smaller superior frontal lobes, thalamus, and cerebellar volumes, whereas AD is classically associated with predominant hippocampal atrophy. However, it is interesting to note that smaller hippocampal volumes are also associated with longer duration of delirium.

Depression, anxiety, and PTSD are the best-characterized mental health impairments in PICS. Among adult ICU survivors, the prevalence of depression is 19% to 37%

; the prevalence of anxiety is 32% to 40%

; and the prevalence of PTSD is 19% to 22%.

 Psychiatric comorbidity in ICU survivors is 4 to 6 times more common than in the general population (25% to 33% of ICU survivors versus 6% for the general population).

 Moreover, patients in whom critical illness develops may be more likely to have premorbid psychiatric illness compared with those hospitalized in general wards and the general population.

Paul was referred to an interdisciplinary ICU survivor clinic for further workup and management. He completed the Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS), a 30-minute cognitive screen. His test results showed that he had mild cognitive impairment, multidomain amnestic type, and comorbid moderate depression. The consulting psychiatrist recommended starting venlafaxine to help with his depression and neuropathic pain. He was also referred for additional outpatient physical therapy and to a psychologist for cognitive behavioral therapy for his depression.

There are no multisite randomized, double-blind, placebo-controlled studies that show the efficacy of medications to ameliorate long-term cognitive impairment or mental health symptoms of PICS. Studies are underway to test the efficacy of treatments for PICS. The mobile Critical Care Recovery Program is an ongoing clinical trial studying the efficacy of a home-based multidisciplinary intervention for PICS. The IMPROVE trial is another ongoing clinical trial to test whether combined physical and cognitive training can improve outcomes of long-term cognitive impairment.

Physical and occupational therapy should be utilized to ameliorate functional difficulties. Home health services can be invaluable for the patient who remains in the home independently, while reducing caregiver burden. Added medications during the hospitalizations can result in polypharmacy, which psychiatrists can help reduce.

ICU patients are often discharged on inappropriate medications, and they continue to take these medications for a significant duration. These medications include anticholinergics, opioids, nonbenzodiazepine hypnotics and benzodiazepines, and atypical antipsychotics. Despite the recommendation to minimize use of antipsychotics, close to one-quarter of patients who were given a new antipsychotic during their hospitalization were discharged on an antipsychotic. If clinicians decide to continue psychotropics upon discharge from the ICU, they should carefully weigh the benefits versus risks, such as the FDA black box warning for antipsychotics.

Evidence for the efficacy of psychotropics specific for ICU survivors is limited. It makes sense, however, to deliver evidence-based mental health treatment and for primary care physicians to screen for depression and anxiety using self-report questionnaires such as the Patient Health Questionnaire-9 (PHQ-9) for depression and Generalized Anxiety Disorder-7 (GAD-7) for anxiety. ICU survivors with depression and anxiety should be aggressively treated with antidepressants and depression-focused psychotherapies. Those who have a history of treatment with mental health specialists, have been hospitalized on psychiatric wards, received ECT, or are not responding to first-line treatments should be referred for subspecialty mental health treatment.

Dedicated post-ICU survivor clinics are another important resource. In 2016, the Society of Critical Care Medicine (SCCM) sponsored the creation of a national collaborative network of ICU survivor clinics, known as the Thrive Post-ICU Clinic Peer Collaborative. A small longitudinal study of the Critical Care Recovery Center in Indianapolis found beneficial effects on patients’ cognitive and functional symptoms.

 Future studies will need to further examine the effectiveness of ICU survivor clinic across the US.

There are a number of special challenges with older adults. Although age is not a risk factor for long-term cognitive impairment, older adults are more likely to develop delirium compared with their younger counterparts. Older adults are also more likely to develop functional difficulties post-ICU, since they may already have functional disability before hospitalization.

Studies have found mixed results on whether age increases the risk of mental health symptoms. Nevertheless, older adults frequently encounter additional barriers as they seek mental health treatment. For example, older adults who need psychotropics may be at increased risk for adverse effects of medications and may have to overcome more physical challenges to attend psychotherapy sessions.

Post-intensive care syndrome-family (PICS-F) describes the psychological impact of ICU hospitalization and post-ICU recovery on family members and other caregivers. PICS-F symptoms can start in the ICU and often persist in the post-ICU phase. Interventions for PICS-F include keeping diaries and using educational materials. Diaries are written by the ICU staff and family, and include photos of patients and family members during the ICU stay. Educational materials include pamphlets or brochures about PICS and informational videos available on the hospital TV and social media.

The rapid growth in numbers of older ICU survivors presents the field of medicine and surgery with an unprecedented clinical challenge to care for this population. Psychiatric morbidity in ICU survivors is associated with adverse effects on patients’ quality of life and increased acute care service utilization after discharge from the ICU. However, the role of mental health professionals in these ICU survivorship models has not been well-defined.

Psychiatrists can play a key role in building and leading new health delivery models for PICS. Because clinical practice guidelines for the neuropsychiatric sequelae in ICU survivors do not exist, psychiatrists provide invaluable input on the diagnosis and management of post-ICU cognitive and mental health impairments. Next, psychiatrists need to collaborate with the leadership in the hospital to build system-wide interventions for ICU survivors. These interventions should focus on a proactive assessment of psychiatric comorbidity for both patients and caregivers upon admission. These interventions should create a plan for ongoing management throughout patients’ entire hospitalization and in the outpatient setting. A recovery care coordinator needs to be identified during the ICU hospitalization. This ensures that care coordination starts with patients and caregivers during the ICU hospitalization. The recovery care coordinator can collaborate with the psychiatrist to implement the individual care plans and ensure continuity of care in outpatient settings. Most importantly, the recovery care coordinator continues to work with the patient and family in the outpatient setting until the care plan goals are achieved.

All psychiatrists, including geriatric psychiatrists, can be part of interdisciplinary teams by providing clinical services and leading clinical practice and research innovations. They can provide diagnostic and treatment recommendations via traditional face-to-face visits, electronic/telephone consultation, or videoconferencing. Psychiatrists can also increase their impact by educating trainees in the fields of mental health and medical and surgical subspecialties. Proactive collaboration between psychiatry and medical and surgical fields will raise awareness of cognitive and mental health impairments and decrease the stigma of mental health treatment.

Dr. Wang reports that she received book royalties from American Psychiatric Publishing Inc. Drs. Kheir, Allen, and Khan report no conflicts of interest concerning the subject matter of this article.

-Dr. Wang is supported by NIA 2P30AG010133, NCATS UL1TR001108 (Project Development Team), and DOD AZ160032. Dr. Khan is supported by NIA K23-AG043476, NHLBI R01HL131730, and NIA R01AG055391.

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What are the symptoms and treatment strategies for this rapidly growing phenomenon in older adults?

Post-Intensive Care Syndrome: Recognizing the Critical Need for Psychiatric Care

practices psychiatry in Manhattan, New York. He continues to publish frequently on film, media, and popular culture. For many years, his cinema column appeared in

He has appeared frequently on national and international network and cable television programs including

 Good Morning America, Today, CBS Evening 

PBS, CNN, Showtime, and BBC-TV. Please address communications to Dr. Greenberg at 

Over his long career, Ridley Scott has directed movies in many genres-historical and science-fiction pictures predominating. At times, he has adhered strictly to genre conventions. He’s also radically subverted them (eg, 

[1991] tragi-comic feminist critique of the macho buddy road movie).

 (1979) was Scott’s first genre-blender, melding tropes of horror and science-fiction. Audiences came in droves to see it-and to watch it again. The return phenomenon, so dear to Tinseltown’s 

 formidable cinematic power and its gruesome chest burster sequence. Viewers eager for an even bloodier 

 sequel were disappointed and puzzled by Scott’s next film, 

 (1982), based on Philip K. Dick’s short story, 

 is set in the devastated, yet still functioning Los Angeles of 2018. Dank rain drizzles incessantly from a blemished sky; the opalescent air is breathable, but permanently polluted. The rusted-out mechanisms of this dominion of detritus are not replaced, but “retrofitted,” like the water lines snaking up building exteriors. The entire mise-en-scÃ¨ne has a distinctive “retro” look, conflated with Japanese and-curiously-vaguely Mayan architecture and interiors.

The wealthy live in totemic skyscrapers. Packed grotty streets are reminiscent of an older Tokyo or an Istanbul grand bazaar. Street-people hustle whatever trinkets or grub they can; speak an incomprehensible argot of Japanese, English, whatever. The swirling crowds comprise an omnium-gatherum of races and faces. Clothing comprises a dizzying assortment of high fashionista gear and Salvation Army cast-offs.

Febrile consumerism is ubiquitous in this mercantile dystopia, where global corporations, many Japanese, vie for power (possibly alluding to the escalating economic sway of Japan in the real 1980s). Stupendous fluorescent Coca-Cola signs blaze across building facades. Gaudy blimps hawk the pleasures of life on the “off-world colonies,” where every whim is gratified by obedient androids.

“Replicants”-servants, soldiers, whores-have been genetically engineered by genius entrepreneur, Dr. Eldon Tyrell. Despite an adult appearance, the early models were immature; potentially unstable. So Tyrell provided them with a 4-year life span.

Tyrell’s latest “Nexus” models match or surpass human capabilities. But their dawning sentience is sowing seeds of revolt. Replicants are sporadically killing their masters. A special LA police “Blade Runner” squad has been formed to “retire” them.

Rick Deckard (Harrison Ford), a disillusioned ex-Blade Runner, is unwillingly re-enlisted to execute a particularly vicious replicant hit-squad, led by a super-Nexus warrior, Roy Batty. Deckard is summoned to Tyrell’s corporate flagship to test “a human subject,” his niece Rachel (Sean Young), a ruby-lipped beauty in iconic 1940 Vogue apparel.

Tyrell later reveals to Deckard that, unbeknownst to her, Rachel is actually an “experimental” Nexus, with memory implants to provide “a cushion” against incipient rebellion. Suspecting her true identity, she flees Tyrell’s dubious protection.

Deckard is immediately drawn to her, and dismayed by Tyrell’s latest callous manipulation-“You’re talking about memories!!!” he protests. He goes on to kill Batty’s crew-but only when each attacks him. After Tyrell tells Batty that he cannot give him more life-the hope of that spurred the replicants’ return, Batty crushes his skull like an eggshell, then hunts down the hunter, Deckard.

The chase ends as Batty dangles Deckard over an urban abyss. Suddenly he hauls Deckard to safety, and quietly dies. “I never knew why he saved my life . . . I guess he loved life . . . any life . . . my life,” muses the amazed Deckard. Later, he discovers Rachel has returned to his apartment. The 2 renegades depart, their fate obscure.

The sequel probes the big questions without flinging them in the viewer’s face. How does memory articulate with one’s sense of origin and purpose-and, above all, of death?

Psychiatric Times Vol 35 No 2

Understanding Sleep Disorders in Older Adults

Adjustment Disorders

Post-Intensive Care Syndrome: Recognizing the Critical Need for Psychiatric Care

Blade Runner 2049: Tears in Rain

Functional Connectivity: Probing the Brain’s Astounding Complexity

Cultural Perspectives on Migration and Psychopathology

We Wrote

The Wrong Way on a Long and Winding Road: Suicide in the US

Psychiatry, “Dangerousness,” and the President

ECT for Self-Injurious Behavior in Autism: A New Indication