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James L. Levenson, MD

Primary Psychiatry. 2005;12(8):16-18


Dr. Levenson is professor in the Departments of Psychiatry, Medicine, and Surgery, chair of the Division of Consultation-Liaison Psychiatry, and vice chair for clinical affairs in the Department of Psychiatry at Virginia Commonwealth University School of Medicine in Richmond.

Disclosure: Dr. Levenson is on the duloxetine advisory board for Eli Lilly.




Psychosis profoundly impacts the medical care of patients with serious medical illness; patients with chronic psychosis are at increased risk for a number of general medical conditions. This article reviews psychosis, mania, and catatonia in the medically ill; both “primary” and “secondary” conditions, caused by a medical disease or drug, are discussed. For more detailed coverage of this topic, see Masand and colleagues.1


Because schizophrenia and other psychotic disorders occur in 1% to 2% of the general population, the possibility of a primary psychotic disorder should be considered in a medically ill patient manifesting psychotic symptoms before attributing it to medical illness or drugs. Primary psychotic disorders may adversely affect outcomes in the medically ill in a number of different ways. Schizophrenia carries increased risk for obesity and diabetes, and many antipsychotics add to these risks, causing weight gain, glucose intolerance, and hyperlipidemia. Patients with schizophrenia often have poor health habits, such as nonadherence with treatments, inadequate nutrition, physical inactivity, and high rates of smoking and substance abuse,2 as well as problems seeking and accessing health care. Psychosis may also adversely impact the patient’s relationship with healthcare providers.

When psychotic symptoms are observed in a patient who has a concurrent medical illness, the differential diagnosis should include a “primary” psychotic disorder (eg, schizophrenia, bipolar disorder), delirium or dementia, substance intoxication/withdrawal (including medications), or a psychotic disorder due to a general medical condition.

Clinical features differentiate primary from secondary psychotic disorders. In primary psychoses, cognitive function and level of consciousness are relatively normal, focal neurological signs are absent, hallucinations are most often auditory, delusions tend to be complex, thought disorder may be prominent, incontinence is usually absent, and vital  signs are usually normal. In secondary psychoses, cognitive function and level of consciousness are often abnormal, focal neurological signs may be present, hallucinations are most often visual, delusions if present are usually simple, thought disorder is not prominent, incontinence is common, and vital signs may be abnormal. A secondary psychosis is more likely if psychotic symptoms first appear at an older age and if there is no personal or family history of primary psychotic disorders. The temporal pattern of the symptoms may be the most important factor in making the diagnosis. If the course of the psychotic symptoms parallels the course of the medical disorder suspected as cause, a diagnosis of secondary psychosis is more likely.

Medical conditions commonly causing psychotic symptoms are shown in Table 1. Drugs most often causing psychotic symptoms include antidepressants, anticholinergics, antiarrhythmics, antihistamines, ciprofloxacin, antimalarials, antivirals, anticonvulsants, corticosteroids, dopamine agonists, opioids, and sympathomimetics. Delirium and dementia are perhaps the most common causes of psychotic symptoms in the medically ill. Delusions occur in approximately 20% of patients with delirium and 45% of those with dementia.2

When secondary psychosis is suspected, routine testing usually includes a complete blood count, complete metabolic panel, serum levels, thyroid stimulating hormone level, a test for syphilis, urinalysis, pulse oximetry, and a urine toxicology screen. Other commonly indicated tests include a chest radiograph, serum drug levels (eg, theophylline), arterial blood gases, vitamin B12 and folate levels, and testing for human immunodeficiency virus. If intracranial pathology is suspected, a computerized tomography or magnetic resonance imaging scan, and lumbar puncture may also be required. Additional tests may be indicated when particular diagnoses are suspected (eg porphyria).

Regardless of etiology, acutely psychotic medical inpatients may require constant observation, restraints, and/or involuntary treatment. Reassurance and education of the patient and the family about the symptoms and their cause(s), if known, are also helpful.

Unnecessary stimulation of the patient should be avoided (eg, repeated interviews by groups of trainees). All nonessential medications should be discontinued or reduced in dosage if they are possible contributors. To coordinate the patient’s medical care, close collaboration between psychiatric and medical staff is necessary and a joint determination should be made whether inpatients are best treated on a medical unit with psychiatric consultation, or a psychiatric unit with medical consultation.

If the cause cannot be eliminated in medically ill patients with primary or secondary psychosis, antipsychotics are selected, in part, based on potential side effects––some of which may be desired. For short-term use, haloperidol is usually preferred in medically ill patients because of extensive experience with its use, minimal side effects other than extrapyramidal ones, and since it can be administered by mouth, intramuscularly (IM), or intravenously (IV). Typical antipsychotics have the advantage of less extrapyramidal side effects. Some patients may require a particular method of drug administration, ie, as a liquid (eg, haloperidol, risperidone, or ziprasidone) or orally disintegrating tablet (risperidone) in patients who have difficulty swallowing pills.3 While several antipsychotics can be given IM, this route is not practicable if many parenteral doses are required and IV haloperidol should be considered. Most antipsychotics can be used in cardiac patients even after an acute myocardial infarction. While antipsychotics rarely cause adverse hepatic reactions, there is no evidence that liver disease increases their risk of hepatotoxicity. Since all antipsychotics are metabolized in the liver, they should be used more cautiously in patients with hepatic failure. While antipsychotics can lower seizure threshold, their use is not contraindicated in patients who are receiving anticonvulsants, though those with greater liability in this regard (eg, clozapine), should be avoided. In patients with diabetes mellitus or those who at high risk for the condition, antipsychotics are less likely to induce glucose intolerance and are therefore preferred.4


Mania in the Medically Ill

In medical settings, most manic patients have primary bipolar disorder, but secondary causes of mania should often be considered. In Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,5 secondary mania is termed as a mood disorder secondary to a general medical condition. Mania can sometimes be difficult to distinguish from delirium. Both can present abruptly with inattention, agitation, poor sleep, and psychosis. Delirium differs in its waxing and waning course, clouding of consciousness, and visual hallucinations/illusions, whereas mania is characterized by elation, hypersexuality, and pressured speech. A prior history of chronic recurrent mood disturbance points to a diagnosis of primary bipolar illness, whereas patients with secondary mania usually have no prior personal or family history of bipolar disorder. In secondary mania the episode may begin within hours or days of the organic insult, and cognitive dysfunction or focal neurologic signs may be present. The differentiation between primary and secondary mania is based mainly on a temporal correlation between an organic factor and the onset of mania. Age of onset is also a clue, since initial bipolar episodes are uncommon after age 50. One should also consider the possibility that mania is secondary, rather than primary, when it fails to respond to usual treatments. In some cases, there may not be a clear demarcation between primary and secondary mania, since a personal or family history of the former may increase risk of the latter.

Selected causes of secondary mania are listed in Table 2. In most cases of secondary mania, caused by medications or metabolic disturbance, manic symptoms are totally reversible; however, symptoms may persist in patients with mania secondary to diseases in which there is damage to the central nervous system. Patients with suspected secondary mania should have a complete evaluation, which includes a careful history, physical examination,appropriate laboratory tests, and imaging studies selected depending on the likelihood of particular etiologies.

Treatment for secondary manic syndromes has been guided by case reports and clinical experience.6 Ideally, one would first treat the underlying disorder or eliminate the offending agent. This is not always possible (eg, steroid induced mania in a patient with vasculitis), in which case symptomatic treatment is indicated using the same drugs used for primary bipolar disorder; for example, mood stabilizers and antipsychotics can also be used prophylactically to prevent drug-induced mania. For patients with acute secondary mania, particularly when it is expected to be temporary, antipsychotics may be more helpful than lithium or anticonvulsants due to their quicker onset of benefit. Lithium may be contraindicated by the underlying medical disorder (eg, unstable fluid/electrolyte status or renal function). More recently developed anticonvulsants (eg, lamotrigine) may also prove helpful in patients who do not respond to or cannot tolerate first-line drugs.


Catatonia in the Medically Ill

Catatonia may be acute or chronic and is relatively rare––usually thought of as occurring in patients with schizophrenia or severe affective illness. This section focuses primarily on secondary catatonia caused by medical illness or drugs, and the medical complications encountered in chronic catatonia of any cause. The core features of catatonia are stupor, motoric immobility, mutism, negativism, excitement, catalepsy, and posturing.7 Most catatonic patients cannot provide a history or cooperate for a full physical examination, so information must be obtained from collateral sources.

Catatonia has been associated with a number of medical conditions and substances, as listed in Table 3. Neuroleptic malignant syndrome (NMS) may be particularly difficult to distinguish from severe agitated primary catatonia, known as “lethal catatonia.”6 If a patient with catatonia of any cause is treated with a neuroleptic, it can be difficult, if not impossible, to discriminate the original catatonia from neuroleptic-induced catatonia and from NMS. Other disease states may share some signs of catatonia and should be considered in the differential diagnosis when appropriate, including serotonin syndrome, stiff-person syndrome, strychnine poisoning, locked-in syndrome, elective mutism, and hyperkinetic (eg, Tourette’s syndrome) and hypokinetic states (eg, Parkinson’s disease).

Patients with chronic catatonia are often bedridden and undernourished, leading to frequent long-term medical complications, including deep venous thrombosis, pulmonary embolism, cardiovascular deconditioning (especially orthostatic intolerance), aspiration and other complications of enteral feeding, pressure ulcers (decubiti), skeletal muscle deconditioning, flexion contractures, rhabdomyolysis, urinary tract infection, urosepsis, cachexia, and dehydration/hypernatremia.8

If a medical condition or substance is determined to be the cause of catatonia, the underlying condition should be treated or the substance should be discontinued. When this is not possible or the catatonia persists, more direct treatments include benzodiazepines and electroconvulsive therapy (ECT). Benzodiazepines may provide immediate relief of the motor and speech signs of catatonia. ECT is the most effective treatment for catatonia,7 and can be used safely in almost all medically ill patients.9   PP



1. Masand PS, Christopher E, Clary GL, et al. Mania, catatonia, and psychosis in the medically ill. In: Levenson JL, ed. The American Psychiatric Publishing Textbook of Psychosomatic Medicine. Washington, DC: American Psychiatric Publishing, Inc; 2005:235-250.

2. Dixon L. Health, medical comorbidities and diabetes in schizophrenia. Drug Benefit Trends. 2003;4(suppl):6-11.

3. Kelleher JP, Centorrino F, Albert MJ, et al. Advances in atypical antipsychotics for the treatment of schizophrenia: new formulations and new agents. CNS Drugs. 2002;16:249-261.

4. Robinson MJ, Owen JA. Psychopharmacology in the medically ill. In: Levenson JL, ed. The American Psychiatric Publishing Textbook of Psychosomatic Medicine. Washington, DC: American Psychiatric Publishing, Inc; 2005:979-1008.

5.    Diagnostic and Statistics Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.

6. Evans DL, Byerly MJ, Greer RA. Secondary mania: diagnosis and treatment. J Clin Psychiatry. 1995;56:31-37.

7. Caroff SN, Mann SC, Francis A, Fricchione GL, eds. Catatonia: From Psychopathology to Neurobiology. American Psychiatric Publishing, Washington, DC; 2005.

8.    Levenson JL, Pandurangi AK. Catatonia: long-term prognosis, outcome, and medical complications. In: Caroff SN, Mann SC, Francis A, Fricchione GL, eds. Catatonia: From Psychopathology to Neurobiology. American Psychiatric Publishing, Washington, DC; 2005:161-172.

9. Rasmussen KG, Rummans TA, Tsang TSM, Barnes RD. Electroconvulsive therapy. In: Levenson JL, ed. The American Psychiatric Publishing Textbook of Psychosomatic Medicine. Washington, DC: American Psychiatric Publishing, Inc; 2005:957-978.