35.

DELIRIUM
I S . KoGayashi, M.D
1. Why should the psychiatrist be concerned ahout the recognition of delirium? Delirium is frequently misdiagnosed by physicians, is common among the medically ill, and often is either iatrogenic or the initial presentation of a major medical disorder. Although rarely treated as such, delirium is a medical emergency, and patients with delirium have greater morbidity and mortality than other patients. The delirious patient typically is referred to a psychiatrist because of presenting psychiatric symptomatology, but misdiagnosis may result in delay of appropriate medical intervention. 2. Give an example of a situation in which delirium was detected. A 58-year-old man was brought to the emergency department because of the sudden onset of irritable, labile mood, paranoia, agitation, and auditory hallucinations. The prominence of psychiatric symptoms led to a request for a psychiatric consultation. The psychiatrist also noted tachypnea, diaphoresis, and disorientation to place and date. A call to the patients daughter revealed no prior history of psychiatric disorder, no recent change in mental functioning, and no history of substance abuse. Medical history of recent evaluation for breathing difficulties also was obtained from the family. An arterial blood gas showed severe hypoxemia. A diagnosis of delirium due to severe respiratory compromise was made, and treatment of his respiratory condition was initiated.

3. What common presenting clinical symptoms are immediate clues that a patient may be delirious? Intermittent disorientation to time or place Easy distractibility by irrelevant stimuli Mumbling or muttering (dysarthric speech) Hyper- or hypoactivity (agitation or hypersomnolence) Sundowning (increased confusion in the early evening), or a subjective feeling of confusion Illusions and misperceptions or a predominance of visual hallucinations Extreme emotional lability Sudden inability to remember the events of the previous day Transient difficulties in word-finding, or disorganized speech

4. How can these clinical phenomena be easily differentiated from other psychiatric symptoms?
The disorientation and confusion of delirium fluctuates over the day. Manic flight of ideas usually has some thread of coherence, in contrast to simple distractibility. Neologisms (newly created words) or idiosyncratic speech (new meanings or usage) are not simply mispronounced or poorly articulated words, as in dysarthric speech. Manic hyperactivity rarely, if ever, suddenly lapses into somnolence as a delirium can; and a depressive stupor is more stable than a lapsing consciousness. Illusions are misperceptions or misinterpretations of a real stimulus (such as thinking a loud noise is gunfire), whereas hallucinations are devoid of a reality-based stimulus. Histrionic emotionality usually demonstrates less frequent and less acute switches in mood (e.g., from laughing to crying). Acute problems with memory or word-finding are not the profound deficits of expressive aphasia or global amnesia.
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5. How is the clinical presentation of the psychotic patient different from the delirious patient? Chronically psychotic individuals are rarely disoriented; do not customarily identify themselves as confused; may demonstrate nonsensical speech rather than incoherence; hallucinate more than misperceive; and tend to substitute the unfamiliar for the familiar (such as thinking the nurse is a relative) rather than the familiar for the unfamiliar (as in Capgras syndrome, believing someone else has taken on the identity of a family member).
6. What are the formal criteria for diagnosing delirium? There are four primary elements in the diagnosis of a delirium: time course, disturbance of consciousness,change of cognition, and evidence of medical cause. Change in mental status usually occurs over a period of hours to days, and tends to fluctuate during the day. Disturbance in consciousness (i.e., reduced clarity or awareness of the environment) is a core dysfunction, along with reduced ability to focus, sustain, or shift attention. Changes in cognition (e.g., memory deficit, disorientation, language disturbance), disorganized thought process, or perceptual disturbance should not be attributable solely to dementia, and the history, physical examination, or laboratory findings should provide evidence that symptoms are caused by the direct physiologic consequences of a general medical condition. Presumptive causes are among the changes in the DSM-IV categorization of delirium. Substance-induced delirium, for example, includes intoxication and withdrawal syndromes from substances of abuse, as well as medication toxicity.

7. What factors predispose a patient to delirium? Patients with dementia, head injury, cerebrovascular or other disorders of the central nervous system tend to be more easily precipitated into a delirious state. Other risk factors include age over 65 years, with or without prior psychiatric history; history of significant substance abuse; and major medical illness or recent major surgery.
8. What are important elements in a good history for the evaluation of a possible delirium? In addition to identifying predisposing risk factors, the history should include: exposure to medications, substances, or toxins; premorbid level of function; psychiatric and medical history; time course, including acuity of onset and fluctuating symptoms; recent medical procedures or treatments (such as fluid or electrolyte changes); current medical symptomatology.

9. Which medications can cause delirium?

Any psychoactive medication can cause delirium, particularly in high-risk patients, even at therapeutic levels. Toxic levels can cause delirium in any patient. Medications that are well tolerated orally may cause delirium on intravenous administration, and vice versa.
Common Phurmacologic Causes of Delirium

Narcotics Barbiturates Benzodiazepines Antic holinergics Medications with anticholinergic side effects (e.g., amitriptyline,thioridazine, some antihistamines) Steroids Sympathomimetics Anticonvulsants Antihypertensives Antiarrhythmics Antidepressants Antineoplastics (e.g.,5-fluorouracil)

Beta blockers Cimetidine Clonidine Digitalis Pressors (lidocaine) Theophylline derivatives Bromides Antibiotics (cephalosporins,aminoglycosides) (less common) Antifungals (amphotericin B) (less common) Over-the-counter agents (e.g., antitussives and sedatives)

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10. What common medical disorders may be associated with delirium? In addition to causation by medications, substances, and toxins (e.g., heavy metals), delirium can be caused by infection, hypoxia or hypoglycemia, metabolic or fluid and electrolyte disturbance, trauma, vitamin deficiencies, endocrinopathies, cerebrovascular events (strokes, hemorrhage), seizures, and other CNS pathology (e.g., tumors, infections or abscesses, cerebritis, acute hypertensive crisis, hydrocephalus). Finally, a summation effect, in which subclinical factors combine to cause delirium may occur, particularly in predisposed patients. For example, such factors as sleep deprivation, dehydration, anemia, or stress may precipitate delirium in conjunction with a clinical condition, such as a low-grade infection in an elderly patient. 11. What is the differential diagnosis of delirium in psychiatric patients? Substance intoxication or substance withdrawal are differentiated from substance intoxication delirium and substance withdrawal delirium if the symptoms of the delirium are in excess of those usually associated with the intoxication or withdrawal syndrome and are sufficiently severe to warrant independent clinical attention (DSM-IV). If hallucinations and/or delusions are present, consider all psychotic disorders, including brief psychotic disorder, schizophrenia, schizoaffective disorder, and mood disorders with psychotic features. Dementia may predispose the elderly individual to delirium, or may confound the diagnosis.
12. How can the psychiatrist differentiate delirium from other psychiatric diagnoses? Systematic review of risk factors, history, acuity of onset, course, associated symptoms, and possible medical etiologies may determine the diagnosis. Serial mental status examinations can be useful in demonstrating a fluctuating course. Careful clinical observation facilitates the differentiation of illusions from hallucinations, cognitive distractibility from manic flight of ideas, dysarthric from idiosyncratic speech, word-finding difficulties from expressive aphasia, and emotional lability from mood disorder. In schizophrenia, age of onset is rarely after the fifth decade, auditory hallucinations are more common than visual, memory is fundamentally intact, speech is not dysarthric, disorientation is rare, and symptoms do not tend to worsen or fluctuate significantly over the course of the day. The deterioration of ability to function is more gradual and prolonged, and there are more prominent deficit symptoms, such as marked social isolation or withdrawal. Mood disorders with psychotic symptoms manifest a persistent rather than labile disorder of mood, with gradual onset, sometimes with prior similar episodes. Although there may be a manic delirium in a very agitated state, cognitive performance is not routinely impaired (and sometimes it is heightened); flight of ideas may be differentiated from cognitive distractibility by a thread of coherence; and disorientation is unusual. The pseudodementia of depression rarely fluctuates over the day, and patients experience more anhedonia than confusion. A brief reactive psychosis is associated with an acute major emotional precipitant. Patients usually are not disoriented, and memory is intact. There may be emotional lability and some fluctuation of symptoms. Patients with dementia are susceptible to a comorbid delirium but usually experience a gradual decline in memory and other higher cortical functions such as abstract reasoning, judgment, or language prior to manifesting paranoid delusions or hallucinations. In late stages or with significant deterioration, there may be overlapping symptoms such as dysarthric speech, emotional lability, and disorientation. In the past, delirium sometimes was contrasted with dementia as being reversible, but the secondary dementias associated with various medical conditions such as hypothyroidism, B 12 deficiency, porphyria, and nutritional deficiencies are reversible.

13. In which medical conditions may mood disturbances-instead of or in conjunction with cognitive dysfunction-be a prominent manifestationof delirium? Steroid toxicity, hypocalcemia and hypercalcemia, exacerbations of thyroid disease, and tertiary syphilis may result in prominent disturbance of mood.

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14. Why should the diagnostic category of delirium replace terms such as: toxic psychosis, ICU psychosis, acute confusional state, organic psychosis, organic mental syndrome, organic brain syndrome, encephalopathy?
The formal DSM-IV diagnosis of delirium should replace these historic terms because they are simply descriptive or reflective of the presumed causes of the confusional state. Psychoses caused by identifiable biologic factors were historically termed organic to differentiate them from the functional psychoses such as schizophrenia, but this distinction is no longer useful. The term organic may be useful as a descriptive term encompassing a variety of biologic etiologies (physiologic, metabolic, structural) causing changes in mental status, but is less precise than the diagnoses of delirium and dementia.

15. What is the pathophysiology of delirium? There are many differing hypotheses, based primarily on animal research. They involve neurotransmitter abnormalities; inflammatory response with increased cytokines; intraneuronal signal transduction or chemical messenger systems; increased activity of the hypothalamic-pituitaryadrenal axis; or changes in blood-brain barrier permeability.
16. What treatment and clinical management should be provided for the delirious patient? First, identify and treat the underlying disorder. When this is not possible, or there is not a rapid reversal of symptoms, environmental or pharmacologic treatments may be useful. Environmental interventions should make the immediate environment, such as the hospital room, seem more familiar. Methods include having friends and relatives visit frequently, placing familiar objects like photographs nearby, and maintaining a routine. Orientation can be enhanced by the use of calendars, nightlights, and clocks, and by making an effort to orient the patient with each encounter. Confusion can be minimized by structuring activities; maintaining a daily schedule in the same location; keeping directions and discussions simple and brief; minimizing changes in personnel and procedures; and writing down instructions. Rarely, behavioral restraints may be required for the safety of the individual in an acutely agitated state. Pharmacologieagents that are useful in decreasing psychotic symptoms, confusion, and agitation include: (1) Low-dose high-potency antipsychotic medication in divided doses, such as haloperidol (0.5 mg-4 mg/day), trifluoperazine (1-4 mg/day), or possibly risperidone (0.5-4 mg/day); antipsychotics of the butyrophenone class usually are recommended as superior. (2) Benzodiazepines such as lorazepam (0.5-6 mg/day) alone or in combination with antipsychotic medication may be useful for physical agitation or sleep disturbance, as well as for alcohol and sedative withdrawal, but there is risk of further confusion. (3) Psychostimulants (methylphenidate 2.5 mg-20 mg) may be useful in patients with dementia and chronic delirium for increasing ability to focus attention. During treatment, remember that the family of the patient also requires support, and education about the delirium can be helpful to them. 17. What psychotherapeutic issues should be considered in delirious patients? As with any patient, the clinician must be aware of specific countertransference to delirious patients, who may range from passive and unresponsive to agitated and alarming. It also is helpful (but often not done) for a clinician to process the experience of the delirious episode with the patient for four reasons: 1 . Delirious states, known to the Greeks as the waking dream, often produce material that may be helpful for a patient to understand with a clearer consciousness at a later time. 2. It helps to allay patients fears, which otherwise may remain unaddressed, that they are going crazy or losing their minds. 3. The experience may be followed by posttraumatic sequelae, and patient education as well as support and monitoring may be useful, particularly if the causes are iatrogenic. 4. If factors predispose to another episode of delirium, intervention or patient education may be appropriate as soon as the initial episode has resolved.

Psychosis with NeurologidSystemic Disorders

BIBLIOGRAPHY
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Flacker JM, Marcantonio ER: Delirium in the elderly. Drugs and Aging 12(2):1 19-1 30, 1998. Inouye SK: Delirium in hospitalized older patients. Clin in Geriatric Med 14(4):745-764, 1998. Jacobson SA: Delirium in the elderly. Psych Clin North Am 20(1):91-110, 1997. Jacobson S, Schreibman B: Behavioral and pharmacologic treatment of delirium. Am Fam Phys 56(8):20052012, 1997. Mcartnery JR, Boland RJ: Anxiety and delirium in the intensive care unit. Crit Care Clin 10:673-680, 1994. Trzepaca PT: Delirium. Advances in diagnosis, pathophysiology, and treatment. Psych Clin North Am 19(3):429-448, 1996. van der Mast RC: Pathophysiology of delirium. Jnl Geriatric Psych & Neuro 11(3):138-145, 1998. Wise MJ: Delirium. In Hales RE, Yudofsky SC (eds): Textbook of Neuropsychiatry, 2nd ed. Washington, DC, American Psychiatric Press, 1992. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC, American Psychiatric Association, 1994.

36. PSYCHOSIS WITH NEUROLOGIC/SYSTEMIC DISORDERS

C. Munro Cullurn, Ph.D., and Myron F. Weiner, M.D.

1. What is psychosis? Psychosis is an impairment of reality testing manifested by delusions, hallucinations, and/or disordered thought processes. Psychotic symptoms define mental illnesses such as schizophrenia and delusional disorder, but also occur in neurologic disease or CNS dysfunction due to systemic disorders. It is important to differentiate between the mental illnesses and other forms of CNS dysfunction that cause psychotic symptoms because of the differences in treatment and prognosis, but in the acute phase, schizophrenia or mania may be indistinguishable from psychosis secondary to neurologic/systemic disease (see Question 3).

2. What are some of the more common symptoms of psychosis?

Delusions (false ideas, e.g., paranoid, bizarre, grandiose, somatic) Hallucinations (false perceptions) Aberrant, bizarre, and disorganized thinking Incoherent speech (as occurs with extreme, pressured speech in mania) Neologistic speech (coining new words) Bizarre, disorganized behavior Psychotic symptoms, much like fever, are not diagnostic of a particular condition but are indicative of an underlying disorder. The development of psychotic symptoms de novo in a previously normal person clearly requires prompt attention, because it may be related to any of numerous neuromedical factors. Metabolic, medication, and illicit drug effects must be considered early in the diagnostic process so that appropriate (and possibly life-saving) interventions can be instituted.

3. Give the differential diagnosis of conditions associated with psychosis.

Psychotic symptoms associated with neurologic o r systemic disease often differ from symptoms of primary psychiatric disorders.