Psychiatry for Neurologists - part 8 potx

As with any workup, the clinician should use his or her best judgment in the workup for fatigue, ordering appropriate laboratory tests and specialized testing when indicated. THERAPY FOR FATIGUE A management algorithm for fatigue is shown in Fig. 1. The clinician should first seek to elimi- nate or reduce factors that may contribute to fatigue, including mood disturbance, sleep disruption, and medications that may produce fatigue as a side effect. If fatigue persists, more specific interven- tions must be considered. These may include nonpharmacological and pharmacological interventions, or a combination of both. Nonpharmacological Approaches to the Treatment of Fatigue Nonpharmacological interventions to improve fatigue in MS include education and reassurance, exercise programs, nutritional improvements, and energy-conservation strategies. Each has at least some empirical support, but all share common sense features that make them palatable to patients who might be reluctant to add another medication to their regimen. Education Fatigue in chronic illness differs from the fatigue that healthy individuals experience on occasion. The fatigue experienced by persons with post-polio syndrome, PD, or MS differs from that of friends 300 Christodoulou et al. Table 2 Medical Conditions Commonly Associated With Fatigue Anemia Anxiety disorder B 12 deficiency Cancer Cerebrovascular disease Chemotherapy Chronic fatigue syndrome Chronic obstructive pulmonary disease Cushings syndrome Deconditioning Diabetes Dysthymia Fibromyalgia HIV infection Hypothyroidism Lyme disease Major depression Mixed connective tissue disease Multiple sclerosis Myasthenis gravis Obstructive sleep apnea and other sleep disorders Parkinson’s disease Postoperative states Post-polio syndrome Pregnancy Rheumatoid arthritis Somatization disorder Systematic lupus erythematosus Viral illness Fatigue 301 Table 3 Medications That Can Produce Fatigue as an Adverse Event Drug Used for Examples Analgesics Pain control Butalbital, hydrocodone (Vicodin ® ), oxycodone (Oxycontin ® ) Interferon therapies Reducing MS exacerbations IFN β-1a (Avonex ® , Rebif ® ); IFN β-1b (Betaseron ® ) Muscle relaxants Spasticity, muscle strain, Tizanidine (Zanaflex ® ), baclofen (oral or through anxiety disorders an intrathecal pump); carisoprodal (Soma ® ) Sedatives/antihypnotics Sleep aids, anxiety, muscle Alprazolam (Xanax ® ), relaxation clonazepam (Klonopin ® ); diazepam (Valium ® ); zolpidem (Ambien ® ) Anticonvulsants Seizure control; pain Carbamazepine (Tegretol ® ); divalproex (Depakote ® ); control; depression or gabapentin (Neurontin ® ) anxiety Antidepressants Depression and anxiety Clomipramine (Anafranil ® ); nefazodone (Serzone ® ); disorders sertraline (Zoloft ® ) Antihistamines Allergies, hay fever Diphenhydramine (Benadryl ® or other over-the- counter allergy medicines); cetirizine (Zyrtec ® ) Antipsychotics Schizophrenia, psychoses Clozapine (Clozaril ® ); risperidone (Risperdal ® ) Hormone therapies Hormone replacement, Medroxyprogesterone (Depo-Provera ® ) contraception MS, multiple sclerosis; IFN, interferon. (Adapted from ref. 6.) Table 4 Laboratory Tests That Are Useful in the Fatigue Workup Laboratory test Assesses for Serial temperatures Infection, malignancy Complete blood count with differential Infection, malignancy Erythrocyte sedimentation rate Abscesses, osteomyelitis, endocarditis, cancer, tuberculosis, mycosis, collagen-vascular disease Electrolytes Adrenal insufficiency, tuberculosis Glucose Diabetes mellitus Blood urea nitrogen/ Creatinine Renal failure Calcium Hyperparathroidism, cancer, sarcoidosis Total bilirubin Hepatitis, hemolysis Serum glutamic oxalocetic transaminase Hepatocellular disease Serum glutamic pyruvic transaminase Hepatocellular disease Alkaline phosphatase Obstructive liver disease Creatine phosphokinase Muscle disease Urinalysis Renal disease, proteinuria Posteroanterior lateral chest radiograph Cardiopulmonary disease Antinuclear antibodies Systemic lupus erythematosus, other collagen-vascular disease Thyroid stimulating hormone Hypothyroidism HIV antibody test HIV/AIDS Purified protein derivative Tuberculosis Hepatitis screen Hepatitis Lyme serologies Lyme disease/post-Lyme syndrome 302 Christodoulou et al. Fig. 1. An approach to fatigue management that incorporates both nonpharmacological and medication strate- gies for fatigue. Addressing other disease symptoms and remaining vigilant to the possibility of depression of co-existent depression or psychological distress are all features critical for successful management. of families. Fatigue is sometimes wrongly attributed to a lack of effort or laziness. Both patient and family need to be educated that the fatigue is an intrinsic part of the disease process. Exercise Programs An exercise regimen developed in accordance with a patient’s level of physical ability can be of clear benefit in terms of overall effects on aerobic functioning and strength. An exercise plan can be incorporated into an overall wellness plan for the majority of neurological , medical, and psychiatric disorders associated with fatigue. Even individuals with advanced illness, such as cancer patients under hospice care, can benefit from exercise programs. Exercise can help reduce fatigue, as well as increase quality of life, endurance, and aerobic capac- ity in a variety of disorders, including MS, cancer, and COPD. Exercise may also help upregulate cor- tisol levels, which are implicated in fatigue pathophysiology, and may be chronically low in states of deconditioning. Psychological Interventions Several randomized, controlled trials have evaluated cognitive-behavioral therapy (CBT) in CFS populations, showing various degrees of long-term benefit. For example, CBT was more likely than relaxation therapy improve fatigue in individuals with CFS following participating in a clinical trial. Both “behavioral therapies,” and graded exercise therapy, are the main therapies to benefit individu- als with CFS. Diet There is no specific diet that will combat fatigue, however, developing a healthy nutrition program can be of some benefit for patients with significant fatigue. For example, it has been recommended that such patients should avoid foods that contain refined sugars, as erratic blood glucose levels can contribute to fatigue. Adequate hydration is also essential, and patients should avoid caffeine and alco- hol. Eating smaller meals throughout the day, rather than three large meals can also be helpful. The meals should be balanced, being high in vitamins, minerals, protein, and complex carbohydrates Energy Conservation A few studies to date have shown empirical support for the use of energy-conservation techniques to reduce fatigue in patients with MS. One study, for example, assessed the effectiveness of a 2-hour per week energy course, led by occupational therapists. This intervention resulted in reductions in fatigue, as well as improvements in quality of life and perceived self-efficacy. Smaller investigations have found similar results. Although these results are preliminary at this point and require replication, they do suggest that referrals to an occupational therapist with expertise in this area may be helpful. Medications There are a several potential pharmacological approaches to the problem of fatigue in various dis- eases. Some treatments are quite specific. For fatigue caused by anemia, iron supplementation and exogenous erythropoietin have been found to be effective in both improving hemoglobin levels and lessening fatigue. Other pharmacological agents are used in a more general fashion to reduce fatigue, including dopaminergic medications, psychostimulants, wake-promoting agents, and antidepressants and antianxiety agents. Much of the work with pharmacological therapy has been performed in the field of MS. However, positive results in treating fatigue and/or hypersomnolence with pharmacological therapies have also been demonstrated in other disorders, such as post-polio syndrome (bromocrip- tine and amantadine), sleep disorders (modafinil), cancer (methylphenidate), and HIV disease (testos- terone replacement, methylphenidate, and pemoline). Table 5 lists the pharmacological agents most often used for fatigue. One potentially effective agent is amantadine, an antiviral agent and medication used in PD that is believed to act along dopaminergic Fatigue 303 pathways. It has shown benefits in fatigue therapy for about one-third of patients with MS. Given its favorable safety profile and the fact that it is inexpensive, it is a worthwhile medication to try in the individual with fatigue. In the case of MS, some but not all experts have suggested that amantadine be considered as first-line therapy for mild fatigue, whereas other agents are used for severe fatigue. Another potentially effective medication to treat fatigue is modafil, which has a favorable side-effect profile. It has been approved for the treatment of excessive daytime sleepiness associated with nar- colepsy. Modafinil is not a stimulant. It is believed to be a unique “wake-promoting” medication that exerts effects through pathways of “normal wakefulness.” It has been shown to reduce fatigue scores on several different fatigue scales in a range of neurological disorders including MS, and hypersom- nolence states in PD, depression, and OSA. There are a number of CNS stimulants, including pemoline and methylphenidate, that are gener- ally approved for use in the treatment of attention deficit hyperactivity disorder. These medications act to produce wakefulness along the mesocorticolimbic pathways (the pathways involved in the vigi- lance, or “fight or flight” response). Pemoline has been best studied with regard to fatigue treatment, and has been assessed in several trials of MS patients. Results of these trials have been mixed, with higher doses (>75.5 mg per day) tending to show a limited degree of benefit. However, adverse events such as irritability may limit use. Given the documented association between fatigue, depression, and anxiety, use of antidepres- sant and and/or antianxiety agents may be advantageous in the treatment of fatigue. Antidepressants may also help stimulate the appetite in persons who are not meeting their nutritional needs. Antianxiety agents may help conserve energy otherwise being dissipated by maladaptive energy- 304 Christodoulou et al. Table 5 Medications Used to Treat Fatigue (Adult Doses) Usual Usual maintentance maintenance Drug Starting dose dose dose Side effects Amantadine 100 mg per day 100 mg twice 300 mg per day Insomnia, vivid (Symmetrel ® ) in the morning per day dreams, livedo reticularis Modafinil 100 mg per day 200 mg per day 200 mg per day Headache, insomnia (Provigil ® ) in the morning in the morning, or (some people 100 mg in the might respond morning and 100 mg to higher doses) at lunchtime Pemoline (Cylert ® ) 18.75 mg per day 18.75–56.25 mg 93.75 mg per day Irritability, in the morning per day restlessness, insomnia, potential liver problems Bupropion, 150 mg per day 150 mg twice 200 mg twice Agitation, anxiety sustained release in the morning per day per day insomnia, seizures (Wellbutrin SR ® ) Fluoxetine 20 mg per day 20–80 mg per day 80 mg per day Weakness, nausea (Prozac ® ) in the morning insomnia Venlafaxine 75 mg per day 140–180 mg 225 mg per day Weakness, nausea, (Effexor-XR ® ) in the morning per day dizziness Adapted from ref. 16. consuming affective states. However, some antianxiety agents may be sedating and therefore must be used cautiously. SUMMARY Fatigue is a significant factor in the lives of many patients. In many disease states it is among the most commonly reported symptoms. Fatigue is an important symptom to consider as it can disrupt patient’s social lives, occupations, and activities of daily living. Efforts to predict fatigue have been mixed, but it is often related to overall quality of life and mood. From a pathophysiological per- spective, fatigue is multifactorial and complex, involving, changes in the nervous system related to the disease process, neuroendocrine and neurotransmitter changes, dysregulation of the immune system as well as other factors, such as physical deconditioning, sleep disturbance, pain, and medi- cation side effects. Various attempts to assess fatigue have been made, and now many measures are available for use in clinical practice and research. In clinical practice, measures will help guide treat- ment considerations. Recent research has provided valuable strategies to ameliorate fatigue and, many patients receive substantial relief. Nonpharmacological approaches are considered the first step in treatment. These include education and reassurance, exercise programs, dietary considerations, and energy-conservation strategies. For patients who continue to experience significant fatigue, several medications, although not specifically approved for use in the reduction of fatigue, appear to be efficacious. First-line agents include amantadine and modafinil. Second-line agents include pemoline and antidepressant medica- tions. Other pharmacological agents have also shown some promise. ACKNOWLEDGMENTS The authors wish to thank Andrew Sobel for his editorial and technical assistance. REFERENCES 1. Piper BF, Dibble SL, Dodd MJ, Weiss MC, Slaughter RE, Paul SM. The revised Piper Fatigue Scale: psychometric evalu- ation in women with breast cancer. Oncol Nurs Forum 1998;25:677–684. 2. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989;46:1121–1123. 3. Schwartz JE, Jandorf L, Krupp LB. The measurement of fatigue: a new instrument. J Psychosom Res 1993;37:753–762. 4. Chalder T, Berelowitz G, Pawlikowska T, et al. Development of a fatigue scale. J Psychosom Res 1993;37:147–153. 5. Vercoulen JH, Bazelmans E, Swanink CM, et al. Physical activity in chronic fatigue syndrome: assessment and its role in fatigue. J Psychiatric Res 1997;31:661–673. 6. Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and multiple sclerosis: evidence-based management strategies for fatigue in multiple sclerosis. Washington DC: Paralyzed Veterans of America; 1998. 7. Kittiwatanapaisan W, Gauthier DK, Williams AM, Oh SJ. Fatigue in Myasthenia Gravis patients. J Neurosci Nurs 2003;35: 87–93,106. 8. Belza BL. Comparison of self-reported fatigue in rheumatoid arthritis and controls. J Rheumatol 1995;22:639–643. 9. Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995;39:315–325. 10. Stein KD, Martin SC, Hann DM, Jacobsen PB. A multidimensional measure of fatigue for use with cancer patients. Cancer Pract 1998;6:143–152. 11. Iriarte J, Katsamakis G, de Castro P. The Fatigue Descriptive Scale (FDS): a useful tool to evaluate fatigue in multiple sclerosis. Mult Scler 1999;5:10–16. 12. Hann DM, Denniston MM, Baker F. Measurement of fatigue in cancer patients: further validation of the Fatigue Symptom Inventory. Qual Life Res 2000;9:847–854. 13. Hartz A, Bentler S, Watson D. Measuring fatigue severity in primary care patients. J Psychosom Res 2003;54:515–521. 14. Hockenberry MJ, Hinds PS. Barrera P, et al. Three instruments to assess fatigue in children with cancer: the child, parent and staff perspectives. J Pain Symptom Manage 2003;25:319–328. 15. Christodoulou C. The assessment and measurement of fatigue. In: DeLuca J, ed. Fatigue as a Window to the Brain. New York: MIT Press. In press. Fatigue 305 16. Krupp LB. Fatigue in Multiple Sclerosis: A Guide to Diagnosis and Management. New York: Demos Medical Publishing Inc; 2004. SUGGESTED READINGS Adinolfi A. Assessment and treatment of HIV-related fatigue. J Assoc Nurses AIDS Care 2001;12(Suppl):29–34. Bakshi R. Fatigue associated with multiple sclerosis: diagnosis, impact and management. Mult Scler 2003;9:219–227. Bartley SH, Chute E. Fatigue and Impairment in Man. New York: McGraw-Hill; 1947. Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet 2004;363:978–988. Deale A, Husain K, Chalder T, Wessely S. Long-term outcome of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study. Am J Psychiatry 2001;158:2038–2042. DeLuca J. (Ed.) Fatigue as a window to the brain. New York: MIT Press. In press. Dimeo FC. Effects of exercise on cancer-related fatigue. Cancer 2001;92:1689–1693. Dittner AJ, Wessely SC, Brown RG. The assessment of fatigue: a practical guide for clinicians and researchers. J Psychosom Res 2004;56:157–170. Friedman JH, Chou KL. Sleep and fatigue in Parkinson’s disease. Parkinsonism Relat Disord 2004;10(Suppl 1):S27–S35. Krupp LB. Fatigue. Philadelphia, PA: Elsevier Science; 2003. Roelcke U, Kappos L, Lechner-Scott J, et al. Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 1997;48:1566–1571. Stasi R, Abriani L, Beccaglia P, Terzoli E, Amadori S. Cancer-related fatigue: evolving concepts in evaluation and treatment. Cancer 2003;98:1786–1801. Wessely S, Hotopf M, Sharpe D. Chronic Fatigue and its Syndromes. New York: Oxford University Press; 1998. 306 Christodoulou et al. 307 23 Delirium John C. M. Brust DEFINITIONS Consciousness requires both arousal and attentiveness; one is conscious of something. Arousal is mediated by the reticular activating system of the brainstem and diencephalon. Attentiveness depends on the cerebral cortex, especially polymodal association areas. Different states of arousal—lethargy, obtundation, stupor, coma—are defined clinically in terms of response to stimuli. Coma is lack of response to any stimulus, including pain. (An exception to this definition would be someone alert but receiving total neuromuscular blockade.) The cardinal feature of delirium, on the other hand, is impaired attentiveness. Delirium is a syndrome, less easily defined than stupor or coma. A number of terms have been used to describe the symptoms and signs of delirium, including clouding of consciousness, acute brain syn- drome, acute confusional state, acute encephalopathy, metabolic encephalopathy, and toxic psychosis. The essential features of delirium are listed in the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM) of Mental Disorders (Table 1). SYMPTOMS AND SIGNS Delirium evolves rapidly, over hours or days, rarely longer, and it fluctuates in severity from minute to minute or hour to hour. There may be brief periods of lucidity. Either over- or under-stimulation can exacerbate symptoms, which tend to worsen at night. Mild inattentiveness may consist of dis- tractibility and difficulty focusing, maintaining, or shifting attention. Severe inattentiveness may pre- clude any meaningful interaction with the environment, including verbal and nonverbal exchange with the examiner. The term confusion (which carries a number of different clinical connotations) in the context of delirium refers to disorganized thinking; intruding thoughts seem to compete with one another, and an inability to express thoughts in a directed, coherent fashion. Speech is tangential, ram- bling, and punctuated by stops, starts, and perseverations. Alterations in arousal usually accompany delirium. The stereotypic delirious patient has increased psychomotor activity or agitation, yet lethargy and decreased arousal are actually more common. Many patients fluctuate between hypo- and hyper-alertness. In either state they do not fully register the events occurring around them, and they substitute perceptual misrepresentations of their own. Hyper-alert patients are likelier to have illusions or hallucinations, usually visual and three-dimensionally formed (e.g., animals or people). Such perceptual disturbances are usually unpleasant, but auditory halluci- nations as encountered with psychosis (e.g., accusing voices) are unusual. Some patients, although not frankly hallucinating, misperceive their surroundings, for example, declaring that they are at home From: Current Clinical Neurology: Psychiatry for Neurologists Edited by: D.V. Jeste and J.H. Friedman © Humana Press Inc., Totowa, NJ despite obvious visual evidence to the contrary. The sleep–wake cycle is often disturbed, with lethargy during the day and agitation at night (“sundowning”), and it is possible that some hallucinations repre- sent dream-like phenomena intruding into wakefulness. To the extent that they can be tested, delirious patients display an array of cognitive abnormalities, including disorientation to time and place and abnormal ordering of events in time. Inability to regis- ter information limits testing of recent memory by standard means (e.g., repeating three unrelated words and then recalling or recognizing them after a few minutes). The same limitations apply to language and spatial testing, which are often abnormal. Delusions, paranoid or otherwise, tend to be fleeting, not fixed as in psychosis, and they are often strikingly triggered by sensory input. Emotional swings and depression are common. PREVALENCE Delirium is common, especially among patients on general medical/surgical services, in surgical intensive care units, and in coronary care units. Up to one-fourth of hospitalized patients aged 65 or older have delirium on admission, and one-third more develop delirium during hospitalization. HISTORY AND EXAMINATION History-taking often depends on the observations of others. Pre-existing dementia is present in nearly half of all patients hospitalized with delirium, and pre-existing milder cognitive disturbance is present in many more. Delirium and dementia have different time courses, but in already demented patients it may be difficult for family members to pinpoint the earliest symptoms of delirium. Cognitive or behav- ioral performance in dementia can vary from day to day, and greater-than-usual difficulty in perfor- mance might be interpreted as progression of the dementing process. Other early easy-to-misinterpret symptoms include insomnia and frightening dreams. In addition to pre-existing cognitive disturbance, risk factors for delirium include advanced age, systemic illness (especially metabolic, multiple, or severe), infection, malnutrition, medication (especially sedative, analgesic, or anticholinergic), ethanol or drug abuse, sensory impairment (especially visual), sensory overstimulation (e.g., “ICU psychosis”), fever, hypothermia, dehydration, and depression (which can itself produce symptoms that overlap with those of “quiet delirium”). Patients undergoing surgery, especially cardiac, orthopedic, ophthalmo- logical, and urological, are also at risk for delirium. A DSM criterion for delirium is that the condition is caused by “a general medical condition.” That term would include primary disorders of the central nervous system (CNS), and physical/neurological examination must be comprehensively directed at identifying such a condition. Funduscopy might suggest increased intracranial pressure (ICP) or hypertensive encephalopathy. Meningismus might sug- gest CNS or subarachnoid hemorrhage. Focal neurological signs might suggest structural lesions such as stroke, neoplasm, or abscess. Asterixis plus myoclonus is seen with uremia; asterixis without 308 Brust Table 1 Criteria for Delirium in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition 1. Disturbance of consciousness (i.e., reduced clarity of awareness of the environment with reduced ability to focus, sustain, or shift attention). 2. A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by pre-existing, established, or evolving dementia. 3. The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day. 4. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition. Delirium 309 myoclonus is seen with hepatic encephalopathy. Intermittent focal twitching (e.g., of the fingers or the corner of the mouth) might reflect nonconvulsive seizures. Tetany suggests hypocalcemia or hypo- magnesemia. Limitation of eye movement might signify thiamine deficiency and Wernicke encepha- lopathy. Extreme hyperthermia might reflect heat stroke, neuroleptic malignant syndrome, thyrotoxic crisis, or cocaine intoxication. Hypothermia suggests exposure, sepsis, hypotension, myxedema, ethanol or other intoxication, or hypoglycemia. Fever, dry skin, and dilated unreactive pupils suggest anticholinergic poisoning (including tricyclic antidepressants). Tremor is a feature of a number of drug intoxications (including lithium, psychostimulants, and valproate) as well as drug withdrawal syn- dromes (including ethanol and sedatives). Intermittent “burst” nystagmus is seen with phencyclidine (“angel dust”) poisoning. Cerebellar ataxia is a feature of ethanol or sedative intoxication. Asymmetric cranial neuropathy and radiculopathy might reflect meningeal carcinomatosis. In patients capable of cooperating, specific tests for attentiveness include digit-span recitation (normal five to seven), reverse recitation of serial digits (normal four to five), counting backward from 20, reciting the months backward, or spelling backward a word such as world. The ability to follow sequential tasks might include the “palm-side-fist” maneuver or folding a piece of paper in a partic- ular way and then putting in a particular place. Abnormalities on these tasks might reflect impairment of working memory rather than attentiveness per se. Inattentiveness is usually identified during the course of history-taking and general examination; its presence may be especially evident during visual field or proprioceptive testing. LABORATORY STUDIES Laboratory evaluation is individualized. Medications and their side effects are identified; blood or urine toxicological studies (including the identification of illicit drugs) are based on index of suspi- cion. Psychoactive medications are discontinued. A search for infection includes chest radiograph, urinalysis, and appropriate cultures. Complete blood count, serum electrolytes, blood urea nitrogen, creatine, glucose, calcium, phosphate, liver enzymes, arterial blood gases, and electrocardiography are indicated in most patients. If a cause is not readily identified, a spinal tap (preferably preceded by brain imaging) is necessary to exclude meningitis/encephalitis. Brain computed tomography or mag- netic resonance imaging is performed in patients with neurological focal signs, history or evidence of trauma, or signs of increased ICP. Although pharmacotherapy is best avoided in delirium, it may be necessary when brain imaging is performed. Additional laboratory tests include serum levels of cobal- amin, ammonia, and magnesium, and thyroid function tests. The electroencephalogram (EEG) in delirium demonstrates slowing and disorganization (reflect- ing the pathophysiological kinship of delirium to stupor and coma). Its principal usefulness is in diag- nosing occult seizures and in identifying nondelirious psychiatric disorders (normal EEG). Many delirious patients, especially the elderly, have more than one causal disorder. Among the elderly the commonest causes of delirium are metabolic disease, infection, stroke, and drugs, espe- cially sedative, analgesic, and anticholinergic medications. Among younger patients the commonest causes are drug intoxication and withdrawal. DELIRIUM TREMENS A special case is delirium tremens, most often identified with alcohol withdrawal but also sometimes caused by withdrawal from other sedatives, especially barbiturates. Within the first 2 or 3 days, ethanol withdrawal produces tremor, seizures, or hallucinations, but the sensorium is usually clear. By contrast, delirium tremens usually emerges after several days of abstinence, and tremor and hallucinations are accompanied by delirium (usually agitated) and autonomic instability (tachycardia, fever, blood pres- sure swings, profuse sweating). Fluid loss can be marked, and mortality is as high as 15%. The treat- ment of delirium tremens includes sedation with benzodiazepines (often in huge titrated doses), cardiac and respiratory monitoring, and careful attention to fluid and electrolyte balance in an intensive care unit. [...]... 2000; 18: 231 6-2 326 33 Goeb JL, Cailleau A, Laine P, et al Acute delirium, delusion, and depression during INF-beta-1a therapy for multiple sclerosis: a case report Clin Neuropharmacol 2003;26:5–7 34 Browning CH Nonsteroidal anti-inflammatory drugs and severe psychiatric side effects Int J Psychiatry Med 1996;26: 25–34 35 Clunie M, Crone L, Klassen L,Yip R Psychiatric side effects of indomethacin in parturients... 2003;50: 586 – 588 3 28 Dolder and Luna 36 Saint-Cyr JA, Taylor AE, Lang AE Neuropsychological and psychiatric side effects in the treatment of Parkinson’s disease Neurology 1993;43(Suppl 6):S47–S52 37 Juethner SN, Seyfried W, Aberg JA Tolerance of efavirenz-induced central nervous system side effects in HIV-infected individuals with a history of substance abuse HIV Clin Trials 2003;4:145–149 38 Marzolini... 24 hours of ECT: a 4 8- year-old male died from a myocardial infarction and a 50-year-old female had a cause of death listed as a cardiac arrythmia secondary to interstitial fibrosis of the conducting system No information was provided on pre-ECT workups, cardiac consultations, or pretreatment pharmacological interventions Another brief report from the Texas databank examining 49,0 48 treatments over 5... 2000; 48: 560–566 8 APA Task Force on Electroconvulsive Therapy A Task Force Report of the American Psychiatric Association: The Practice of Electroconvulsive Therapy Recommendations for Treatment, Training, and Privileging Washington DC: American Psychiatric Association; 2001 9 Janicak PG, Davis JM, Gibbons RD, Ericksen S, Chang S, Gallagher P Efficacy of ECT: a meta-analysis Am J Psychiatry 1 985 ;142:297–302... risk J ECT 2000;16: 189 –197 27 Kohler CG, Burock M ECT for psychotic depression associated with a brain tumor Am J Psychiatry 2001;1 58: 2 089 28 Salaris S, Szuba MP, Traber K ECT and intracranial vascular masses J ECT 2000;16:1 98 203 29 Saad DA, Black JL, Krahn LE, Rummans TA ECT post eye surgery: two cases and a review of literature J ECT 2000;16: 409–414 30 Madan S, Anderson K ECT for a patient with... dyskinesia and tardive dystonia J Clin Psychiatry 2000;61(Suppl 4):39–44 18 Hasan S, Buckley P Novel antipsychotics and the neuroleptics malignant syndrome: a review and critique Am J Psychiatry 19 98; 155:113–1116 19 Fann JR Neurological effects of psychopharmacological agents Semin Clin Neuropsychiatry 2002;7:196–205 20 Masand PS, Gupta S Long-term side effects of newer-generation antidepressants: SSRIs,... The incidence was reported to be 1.3, 6, and 18. 4% in patients receiving prednisone doses of 40 mg or less per day, 41 mg to 80 mg per day, and 80 mg or more per day, respectively (29) Smaller studies have reported mania in up to 26% of patients taking 80 mg of prednisone per day for 5 days ( 28) Brown and colleagues described significant mood changes, particularly symptoms of mania, in asthma patients... can predict treatment failure and central nervous system side effects in HIV-1-infected patients AIDS 2001;15:71–75 39 Wright JM, Sachdev PS, Perkins RJ, Rodriguez P Zidovudine-related mania Med J Aust 1 989 ;150:339–341 40 Maxwell S, Scheftner WA, Kessler HA, Busch K Manic syndrome associated with zidovudine treatment JAMA 1 988 ;259: 3406–3407 25 Electroconvulsive Therapy Eric J Christopher and Warren... INDICATIONS FOR ELECTROCONVULSIVE THERAPY The second edition of the American Psychiatric Associations (APA) recommendations for ECT (8) outlines the indications for this therapy (Table 1) It is important to recognize that current recommendations identify no absolute contraindications to ECT, although there are certainly patients who are at increased risk for adverse events and so require a more intensive pre-ECT... and non-ketotic hyperosmolar coma for atypical antipsychotics Forty-two percent of cases presented with diabetic ketoacidosis and 84 % presented with glucose intolerance within 6 months of initiating antipsychotic therapy Whereas the majority of patients were overweight, 50% of patients had not experienced any weight gain while prescribed the offending medication Despite the relative rarity of new-onset . difficult for family members to pinpoint the earliest symptoms of delirium. Cognitive or behav- ioral performance in dementia can vary from day to day, and greater-than-usual difficulty in perfor- mance. cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study. Am J Psychiatry 2001;1 58: 20 38 2042. DeLuca J. (Ed.) Fatigue as a window to the brain Neurology 1997; 48: 1566–1571. Stasi R, Abriani L, Beccaglia P, Terzoli E, Amadori S. Cancer-related fatigue: evolving concepts in evaluation and treatment. Cancer 2003; 98: 1 786 – 180 1. Wessely S,