It is surprisingly easy for physicians to lose track of the psychological impact of severe general medical illness. For example, only recently was post-traumatic stress disorder recognized to be a common sequela of a stay in an intensive care unit.¹ Psychiatrists should assume, for each of their seriously ill patients on the psychiatric unit, that the general medical illness is a life crisis. Exactly how it is experienced of course varies from patient to patient. Factors influencing the impact include the patient’s premorbid personality, the severity and nature of the patient’s psychiatric illness, the patient’s past experience of illness in general and personal or family experience of this sort of illness in particular, his or her knowledge and understanding of the current illness, the quality of the relationship with the doctor treating the illness, the acuity versus chronicity of the illness itself and its prognosis, the presence or absence of pain or other specific symptoms, and the nature of family and social support. Obviously in the case of pregnancy the “crisis” is of a somewhat different sort. Even with pregnancy, however, the “illness” is likely to cause major changes in the patient’s life situation and to require psychological and family-system adaptation.

On the psychiatric unit, the psychiatrist should develop a formulation of the patient’s experience and situation including these and other factors. In almost every case, the psychiatrist should devote a portion of each interview to discussing the patient’s general medical illness and concerns, to allow the patient to bring these concerns into the conversation, and to improve the psychiatrist’s understanding of the problems. “We’re here to talk about your depression, Dr. Smith will be by later to talk about your cancer” is not an adequate approach to the care of the medically ill psychiatric inpatient. Work with the family and on the patient’s discharge plan must include consideration of disability due to illness and the expected change in the patient’s physical condition over time.

Nonpsychiatric physicians are likely to be involved with these patients during the psychiatric hospitalization, and finding ways to work with them collaboratively is another challenge for the psychiatric team. If possible, team meetings should at times include the nonpsychiatric physician (or other members of the medical treatment team), so that all members of the psychiatric team have the opportunity to familiarize themselves with the medical situation and to ask questions or make comments about it and so that the nonpsychiatric physician learns about the psychiatric situation. Nonetheless, often the psychiatrist has to explain general medical issues to nurses and nonmedical psychiatric staff and address their concerns about the illness and its management. The psychiatrist must be closely familiar with the treatment regimen, even if it is prescribed by others, to allow adequate monitoring for treatment-related side effects (including mental side effects) and drug interactions.

Delirium is common in the medically ill.² It is a disturbance of consciousness that has an abrupt onset and is associated with fluctuating abnormalities in cognition, perception, emotions, and behavior. The disturbance often is not recognized by nonpsychiatric clinicians and sometimes missed by psychiatrists. Those suffering delirium are usually inpatients and, in this population, initial management goals are to control agitation and determine treatable medical causes.

Delirium is a sign of serious underlying systemic illness, and frequently, the afflicted patients need emergency treatment. It is often a harbinger of significant morbidity and mortality and frequently leads to increased in-hospital complications and length of stay.³ Some patients with delirium have severe agitation that places them and those involved in their care at risk for physical injury.

Although the discussion focuses on the evaluation and management of delirium after it occurs, the reader should be aware of a growing trend to teach clinicians how to anticipate and prevent delirium. The Yale Delirium Prevention Trial was the first trial to show that delirium can be prevented.⁴ The incidence of delirium was reduced from the expected 15% to just less than 10%. However, the severity and recurrence rate of delirium once it occurred were not affected. Interventions were targeted to specific risk factors, such as reality orientation for cognitive impairment, nonpharmacologic sleep enhancement for sleep deprivation, early mobilization for immobilization, vision and hearing aids, and volume repletion for dehydration.

Delirium most often has an acute onset, but some patients experience a prodrome of severe anxiety and autonomic instability. They may have poor short-term memory, display dependent behavior, or experience illusions; for example, an over-the-bed exercise bar may look like a gun. Later, they may become frankly disoriented and disorganized and have visual hallucinations. In most cases, the disorder lasts 1 to 2 weeks and resolves without residua. However, a few patients develop a chronic course or progress to dementia.

Fragmented sleep, sometimes with a complete reversal of the sleep-wake cycle, is common in delirium. Sundowning refers to deterioration of behavior marked by worsening agitation and disorientation late in the day, sometimes with frightening visual hallucinations and persecutory delusions. The affective, behavioral, and cognitive manifestations of delirium often mimic primary psychiatric disorders, including mood, psychotic, and anxiety syndromes. A major distinguishing feature of delirium is a fluctuating level of consciousness. Fluctuations in behavior often lead to conflicting reports by clinical staff about the status of the patient that, in themselves, are valuable clues to the diagnosis.

Disturbed psychomotor activity—increased or decreased—is also seen in delirium. Hyperactive or agitated patients quickly get the attention of clinicians because they climb out of bed, pull out their catheters and intravenous lines, and wander about the ward. Patients with hypoactive delirium often appear depressed because they are immobile and display a flat affect. However, when fully evaluated, they have the usual disorientation, inattentiveness, and perceptual disturbances diagnostic of delirium. Mortality seems to be higher in the hypoactive subtype relative to normal and hyperactive groups.⁵

Rating scales may aid in identifying delirium, of which in the authors’ view the most promising is the Confusion Assessment Method (CAM).⁶ Other rating scales can also be used as diagnostic aids and to assess response to pharmacologic treatment. The Delirium Rating Scale (DRS) and the Memorial Delirium Assessment Scale (MDAS) are examples.

There are many causes of delirium; often the disorder has multiple etiologies. Some causes of delirium are associated with irreversible central nervous system injury or death if they are not recognized and treated quickly. For example, Wernicke encephalopathy, the diagnosis of which commonly is missed, may lead to permanent memory impairment if not treated promptly with thiamine.⁷ Patients with Wernicke encephalopathy are commonly slowed with flat affect and could be misdiagnosed as depressed if the clinician does not have a high index of suspicion, which should extend not just to alcoholics but to any patient who has had a substantially decreased nutritional intake.

The diagnostic workup of delirium includes the usual complete history and physical examination along with a mental status examination. The cognitive and physical examinations of the psychiatric inpatient are discussed in Chapters 4 and 5. A physical sign of particular importance is asterixis (or its inverse, multifocal myoclonus). As discussed in Chapter 5, finding this abnormality clinches the diagnosis of an organic mental state. A close review of the medication list is essential; prescribed
medicines are the sole cause of delirium in as many as one third of cases, and they contribute to a multifactorial process in others.⁸ Suggested laboratory and special test evaluation include electrolytes, urinalysis, brain imaging, and electroencephalogram (EEG). The EEG typically shows a pattern consistent with diffuse brain dysfunction, with slow wave activity except in nonalcohol withdrawal delirium. Faster β-wave activity is typical of alcohol withdrawal delirium. However, not every patient with delirium has an abnormal EEG, and it does not distinguish dementia from delirium.

According to a case-control study, delirium in psychiatric inpatients occurs significantly more frequently in those who are older, who have a history of cognitive impairment, and who are exposed to in-hospital lithium or anticholinergic medicines.⁹ In this study, antipsychotic medicines were associated with delirium only at relatively high doses, and antidepressants and sedative hypnotics were not associated with delirium. These findings suggest that moderation in using anticholinergic and antipsychotic agents may help prevent delirium in psychiatric inpatients.

Because many psychiatric symptoms occur in delirium, it is generally unwise to diagnose a primary psychiatric disorder, such as major depression, when delirium is present. When the delirium resolves, these associated features may also disappear. Adding antidepressants or anxiolytics may further confuse the clinical picture by adding psychotropic side effects to an already overburdened brain.

Some specific considerations regarding delirium arise among psychiatric inpatients. Neuroleptic malignant syndrome (NMS) is caused by dopamine-blocking drugs (antipsychotic and antinausea agents) or the abrupt discontinuation of dopamine agonists. The syndrome features fever, extrapyramidal signs such as rigidity, and delirium. On the inpatient unit, any patient who becomes delirious while on an antipsychotic is a suspect for NMS. Stopping the neuroleptic and supportive measures—especially careful attention to hydration—are the mainstays of management. Antipsychotic agents should be held in patients who develop delirium while on them pending a diagnosis of the cause of the delirium. Unfortunately, measuring creatine kinase (CK) does not generally provide an answer to whether the delirium is due to NMS because the CK may rise in patients on neuroleptics who become febrile for other reasons.¹⁰ Many clinicians use dopamine agonists, such as bromocriptine, and some use dantrolene, a muscle relaxant, in patients who do not respond to supportive measures and discontinuation of the dopamine blocker.¹¹ The utility of dantrolene is questionable. Electroconvulsive therapy (ECT) appears to be highly effective in the treatment of cases of NMS that do not respond to other measures.¹² NMS is discussed also in Chapter 4.

Serotonin syndrome is marked by tachycardia, fever, diarrhea and hyperactive bowel sounds, shivering, diaphoresis, myoclonus, hyperactive tendon jerks with clonus, and delirium, although not all of these phenomena are present in mild cases.¹³ It is associated with increased serotonin levels and results from combinations of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors, other combinations of serotonergic agents, or the inhibition of hepatic enzymes degrading serotonergic drugs. The offending agents should be stopped, and supportive measures are the initial treatment; the use of the 5-HT_2A antagonist cyproheptadine can be considered.

The management of delirium begins with treatment of the underlying medical illness or removal of the offending toxin. Patients must be monitored closely to ensure safety. Protecting the patient may require restraints, although their use may increase agitation. However, improper use of restraints may lead to serious injuries, even death. Restraint is discussed more fully in Chapter 12.

In the authors’ opinion and that of others,² the medicine of choice for the treatment of agitation in delirium is haloperidol. Numerous uncontrolled case studies show that it is effective in reducing the psychosis, disorganization, and psychomotor agitation. The choice of agent for agitation in general on the psychiatric unit is discussed further in Chapter 3. In general medical settings, intravenous haloperidol is often used, despite the lack of U.S. Food and Drug Administration (FDA) approval for this route of administration. Intravenous haloperidol is associated with cardiac side effects including hypotension, arrhythmias, and prolongation of the corrected QT (QTc) interval. Because it is most safely administered where telemetry is available, the use of intravenous haloperidol is generally inadvisable on the psychiatric unit.¹⁴

Dosing of haloperidol should be individualized based on the level of agitation. In general, a starting dose of 1 to 2 mg orally or intramuscularly every 2 to 4 hours is reasonable. Severely agitated patients may require much higher doses. Patients with cancer or acquired immunodeficiency syndrome (AIDS) may tolerate only lower doses combined with lorazepam. A starting dose of 3 mg of haloperidol followed by 0.5 to 1.0 mg of lorazepam has been recommended in these populations.¹⁵

Depression is the most common psychiatric disorder in patients with coronary artery disease. The point prevalence is estimated at approximately 15% to 20%, yet it is often undiagnosed and untreated. Patients with depression are about twice as likely to develop ischemic heart disease.¹⁶ In those with preexisting coronary artery disease, the risk of death for patients with depression is three to four times higher than in those without depression. The association between depression and general medical illness is discussed further in Chapter 4.

The Sertraline Antidepressant Heart Attack Randomized Trial (SADHART), published in 2002, established the safety of sertraline and its efficacy in recurrent depression in patients with recent myocardial infarction (MI) or unstable angina when there are no other life-threatening medical conditions.¹⁷ Other SSRIs are probably comparably efficacious, although they are likely all rarely cause bradycardia and presyncope as well. Some SSRIs, notably fluoxetine and fluvoxamine, can alter the effect of warfarin, as discussed further in subsequent text. Cognitive behavioral treatment of depression in this setting also is effective, although neither form of treatment can be counted on to reduce cardiac events or mortality.¹⁸

Although tricyclic antidepressants are not absolutely contraindicated in this population, they are often avoided. The Cardiac Arrhythmia Suppression Trial of the late 1980s and early 1990s demonstrated that antiarrhythmic drugs were unexpectedly linked to increased mortality rates in post-MI patients.¹⁹ Tricyclic antidepressants are believed to be similar in effect to these antiarrhythmics because of their quinidine-like properties that have potential proarrhythmic effects. Ever since then, cautionary statements have been made against starting tricyclic antidepressants immediately in patients with ischemic heart disease. They also are associated with orthostatic hypotension and sinus tachycardia, which can increase myocardial oxygen demand.

Hepatitis C virus infects >4 million Americans and is the leading cause of liver failure leading to transplantation. Patients with hepatitis C have high rates of psychiatric disorders even before treatment, including substance abuse, depression, and anxiety. Contrariwise, the rate of hepatitis C infection in the mentally ill, especially in injection drug abusers, is very high.²⁰ As discussed in Chapter 4, testing for hepatitis C should commonly be considered in psychiatric inpatients. The role of hepatitis C infection itself in causing cognitive and psychiatric symptoms is uncertain, but concurrent hepatitis C infection may be factor in aggravating the impairment in patients with AIDS.²¹,²²