The following is provided for informational purposes only. It is not to be used as a means to establish
a diagnosis. The Handbook of Psychiatric Emergencies (Paperback) by Andrew E. Slaby, states that about 80% of all those who
present to a hospital Emergency Room with a Psychiatric problem have an underlying medical condition accounting for their
symptoms. We encourage all who seek treatment to see their Physician to rule out General Medical Conditions.
Psychiatric Presentation of Medical Illness-
Mental Disorders Secondary to General Medical Conditions
Updated: April 13, 2006 Rate this Article
AUTHOR INFORMATION Section 1 of 10
Introduction Neurologic Disorders Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin
Deficiency States Exogenous Toxins Author: Linda Chuang, MD, Clinical Instructor, Department of Psychiatry, Division of Consultation-Liaison,
Bellevue Hospital, New York University
Coauthor(s): Nancy Forman, MD, Associate Director, Department of Psychiatry,
Division of Consultation-Liaison Psychiatry, Bellevue Hospital Center, New York University
MD, is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine,
American Psychiatric Association, Medical Society of the State of New York, and Phi Beta Kappa
D Schmetzer, MD, Professor and Vice-Chair for Education, Director of Residency Training, Department of Psychiatry, Indiana
University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Iqbal Ahmed, MD, Program
Director, General and Geriatric Psychiatry Residency Programs, Vice Chair for Education, Professor, Department of Psychiatry,
John A Burns School of Medicine, University of Hawaii; Harold H Harsch, MD, Program Director of Geropsychiatry, Department
of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry, Assistant Professor, Department of Medicine, Froedtert
Hospital, Medical College of Wisconsin; and Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty,
Metropolitan College of Boston University, Boston, MA
INTRODUCTION Section 2 of 10
Introduction Neurologic Disorders Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin
Deficiency States Exogenous Toxins
Evaluation of patients who present to hospitals or physicians with altered
behavior and/or mentation can be time-consuming and difficult and may lead to symptoms being quickly and prematurely dismissed
as psychiatric in nature. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM), the psychiatric presentation
of a medical illness is classified as a "mental disorder due to a general medical condition." These disorders are
characterized by the presence of mental symptoms that are the direct consequences of an underlying medical condition. Therefore,
understanding common psychiatric symptoms and the medical diseases that may cause or mimic them is of utmost importance. Failure
to identify these underlying causal medical conditions can be potentially dangerous because serious and frequently reversible
conditions can be overlooked. Proper diagnosis of a psychiatric illness necessitates investigation of all appropriate medical
causes of the symptoms.
The following features suggest a medical origin to psychiatric symptoms:
Late onset of initial presentation
Known underlying medical condition
Atypical presentation of a
specific psychiatric diagnosis
Absence of personal and family history of psychiatric illnesses
Treatment resistance or unusual response to treatment
onset of mental symptoms
Abnormal vital signs
Waxing and waning mental status
secondary causes of mental disorders exist, as shown in the Table, this article discusses only the most common causes.
Medical Disorders That Can Induce Psychiatric Symptoms*
Medical and Toxic Effects CNS Infectious Metabolic/Endocrine
acid diethylamide (LSD)
Normal pressure hydrocephalus
Urinary tract infection
Congestive heart failure
Systemic lupus erythematosus
*(Adapted from Williams E, Shepherd S. Medical clearance of psychiatric patients.
Emerg Med Clin North Am. May 2000; 18:2; 193.)
NEUROLOGIC DISORDERS Section 3 of 10
Introduction Neurologic Disorders Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin
Deficiency States Exogenous Toxins
Epilepsy is one of the most common chronic
neurologic diseases, affecting approximately 1% of the US population. Approximately 30-50% of patients with a seizure disorder
have psychiatric symptoms sometime during the course of their illness. Psychiatric symptoms can be viewed in the context of
their time relationship with the seizures as preictal, ictal, postictal, and interictal. Two major categories of seizures
are partial and generalized. Increased psychopathology has been associated with different features (eg, seizure phenomenology,
brain pathology, antiepileptic drug use, psychosocial factors). Characteristics of the seizures and their presenting psychiatric
symptoms deserve further attention.
Generalized seizures simultaneously involve both cerebral hemispheres, with
classic symptoms of loss of consciousness, tonic-clonic movements or limbs, tongue biting, and incontinence. While the diagnosis
is relatively straightforward, the postictal state is characterized by a gradual clearing of delirium lasting a few minutes
to many hours.
Partial seizures have focal signs and symptoms resulting from electrical discharge in a limited
site in one brain hemisphere. Simple partial seizures occur without any impairment of consciousness and usually stem from
primary motor, sensory, or visual cortical regions. Complex partial seizures are associated with impairment of consciousness
and usually originate from a focus in the temporal lobe. In such seizures, psychiatric signs abound, with memory dysfunction,
affective auras, perceptual changes (eg, hallucinations), and depersonalization.
In temporal lobe epilepsy, the
most common psychiatric abnormality is personality change. Hyperreligiosity, hypergraphia, and hyposexuality are reportedly
more commonly associated with temporal lobe epilepsy. Development of psychosis is also described in temporal lobe epilepsy.
An estimated 4-27% (average, ~10%) of patients with complex partial epilepsy have psychotic symptoms such as paranoid
ideation, thought disorder, and hallucinations. Mood disorder symptoms occur most often with foci in the temporal lobe. Statistically,
30% of patients with epilepsy have a history of suicide attempts, which attests to the importance of diagnosing depression
in these patients. Fear and anxiety are the most common ictal affective states.
disease (PD) is a disorder characterized by movement abnormalities caused by degeneration of the neurons in the substantia
nigra. Currently, PD affects approximately 1% of the population older than 50 years and up to 2.5% of the population older
than 70 years (Marsh, 2000). PD affects all races about equally; men are more often affected than women.
clinical signs of the motor triad include (1) tremor, usually a rest tremor involving the hands, described as pill rolling;
(2) rigidity; and (3) bradykinesia/akinesia. The classic motor signs may not be obvious early in the disease, and patients
may initially present with only clinical signs of depression (Gonera, 1997). Thus, PD may be misdiagnosed as a primary depressive
illness, and concomitant depression may remain undiagnosed in a patient with PD. Similarities in the symptoms common to major
depression and PD include impaired memory/concentration, slowed psychomotor activity, restricted affect, and fatigue or decreased
The prevalence of major depression in patients with PD is estimated to be 40%, with prevalence rates of
4-70% (Mayeux, 1992). Considerable evidence indicates that depression can precede development of motor symptoms, suggesting
that the depression itself may be a neurologic sign of PD. In addition to mood disturbances, patients with PD commonly present
with symptoms of anxiety, including general anxiety disorder, social phobia, and panic disorder, with a prevalence rate of
25% (Fukunishi, 1991).
The anxiety syndromes in PD are apparently related to an underlying brain disease, with
evidence implicating noradrenergic dysfunction. In several studies, anxiety syndromes developed before or after the onset
of motor symptoms (Stein, 1990).
Hallucinations and delusions can also occur in as many as 40% of patients with
PD (Goetz, 1993). The psychosis can develop spontaneously or in association with mood disturbance but usually develops either
late in the disease process (when significant cognitive impairment is also evident) or with use of dopaminergically active
medication (Olanow, 1998).
Most treatments are aimed at patients' specific symptoms. PD must be considered
in the differential diagnosis of an elderly person presenting with first-time depression/anxiety symptoms, especially when
the patient appears depressed but denies experiencing a depressed mood. In addition, treatment of symptoms can be complicated
in patients with PD because antiparkinsonian drugs may exacerbate psychiatric symptoms and vice versa. Consultation with both
neurologists and psychiatrists can be helpful when treating these patients.
and cerebrovascular disease are important causes of psychiatric symptoms and patients with these diseases can present with
virtually any symptom. A complete clinical history and neurologic examination are essential in diagnosing either condition.
Given the nature of the onset and presentation of a cerebrovascular event, it is rarely misdiagnosed as a mental disorder.
However, up to 50% of patients with brain tumors reportedly have manifestations of a psychiatric nature (Galasko, 1988).
In general, meningiomas are likely to cause focal symptoms because they compress a limited region in the cortex, whereas
gliomas can cause more diffuse symptoms. Delirium is most often secondary to a large, fast-growing, or metastatic tumor. The
specific psychiatric symptoms largely depend on the location of the tumor within the brain and the structures affected by
direct invasion or pressure.
Frontal lobe tumors, which are responsible for approximately 88% of the patients
with psychiatric symptoms, can elicit presenting signs such as cognitive impairment, personality change, or motor and language
dysfunction (Skuster, 1992). Patients also frequently have bowel or bladder incontinence.
Patients with dominant
temporal lesions can present with memory and speech abnormalities. Nondominant tumors can cause auditory agnosia. Bilateral
lesions can lead to Korsakoff amnesia. Occipital lesions can cause visual hallucinations, agnosia, and Anton syndrome (denial
of blindness). The visual pathways all cross in the temporal, parietal, and occipital lobes; therefore, visual hallucinations
can occur with lesions in any of these locations. Auditory hallucinations can also occur with temporal lesions but are apparently
Limbic and hypothalamic tumors can cause affective symptoms such as rage, mania, emotional lability,
and altered sexual behavior (Cummings, 1985). They can also produce delusions involving complicated plots.
which are often considered the hallmarks of psychiatric illness, can be caused by focal neurologic pathology.
diagnostic procedure of choice is brain imaging with contrast head CT scan or an MRI. In many clinical cases, when a CNS tumor
is considered likely, initial CT scan findings may be normal, and MRI may be required to confirm the diagnosis.
Multiple sclerosis (MS) is a demyelinating disorder characterized by multiple episodes of
symptoms of a neuropsychiatric nature related to multifocal lesions in the white matter of the CNS. Prevalence is estimated
to be approximately 50 cases per 100,000 people. MS is more frequent in colder and temperate climates than in tropical locales,
which may suggest a viral etiology. MS is more common in women than in men and usually manifests in persons aged 20-40 years.
This disorder is a highly variable illness, with differences among patients and changes within a patient over time.
Symptoms can be categorized as cognitive and psychiatric. Recent reviews of neuropsychological performance in patients with
MS indicate that 30-50% have cognitive deficits (Fennell, 1990). Of the cognitive deficits, memory loss is the most common
and affects approximately 40-60% of patients (Grafman, 1990). Abstract reasoning, planning, and organizational skills are
some of the functions also affected by MS. Dementia may eventually ensue.
Behavioral symptoms in MS include personality
changes and feelings of euphoria and/or depression. Approximately 25% of patients experience euphoria that is different from
hypomania and is characterized by an unusually cheerful mood. One study showed a 2-fold increase in the lifetime risk of bipolar
disease in MS patients (Mahler, 1992). Major depression is very common in individuals with MS; indeed, 25-50% of patients
experience major depression after the onset of MS. Suicide attempts are common in patients with MS who are depressed. Personality
changes and emotional dyscontrol can also occur. Patients sometimes laugh without cause or weep suddenly. Such emotional lability
can be disturbing for patients and their families and can make assessment of psychiatric symptoms more difficult in patients
MS. INFECTIOUS DISEASES Section 4 of 10
Author Information Introduction Neurologic Disorders
Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin Deficiency States Exogenous Toxins
Neurosyphilis, once a common cause of admission to mental institutions, has become
rare as a result of the invention of penicillin. However, AIDS has reintroduced the infection in certain urban settings. The
infection is caused by the organism Treponema pallidum, which invades the parenchyma of the brain.
is usually clinically apparent as a part of tertiary syphilis, which includes two other types: late benign (gummatous) syphilis
and cardiovascular syphilis. Neurosyphilis is now the predominant form of tertiary syphilis and occurs only after a latent
period of 10-20 years after the primary infection, although infection with HIV negates this general rule (Gliatto and Caroff,
2001). Neurosyphilis primarily affects the frontal lobes, which can result in personality changes, irritability, decreased
self-care, mania, and progressive dementia. Delusions of grandeur occur in 10-20% of patients. Early evidence of neurosyphilis
includes tremors, dysarthria, and Argyll Robertson pupils.
The diagnosis is confirmed using serologic tests. Cerebrospinal
fluid (CSF) analysis always shows abnormal results and reveals primary lymphocytosis and increased protein level. Always consider
neurosyphilis in patients who may have an underlying immunodeficiency disease and present with mental status changes and a
progressive dementia incongruent with advanced age.
Acute bacterial, fungal, and viral
meningitis can be associated with a psychiatric presentation with or without abnormal vital signs. Patients who are immunocompromised
(eg, those with AIDS, individuals in oncology units) are particularly susceptible. Those with indwelling ventriculoperitoneal
shunts are also at high risk for developing the infection. Patients usually present with acute confusion, headaches, memory
impairments, and fever with possible neck stiffness. Because bacterial meningitis is a life-threatening emergency, persons
at high risk who have a sudden onset of mental status changes should always undergo a workup that includes a diagnostic lumbar
More recently, the Haemophilus influenzae type b and the pneumococcal conjugate vaccines have greatly
reduced cases of meningitis caused by these agents (Whitney, 2003). Penicillin resistance has emerged in Streptococcus pneumoniae
Herpes simplex encephalitis
Herpes simplex virus (HSV) is one of the most common and devastating
causes of sporadic and severe focal encephalitis. Infection with HSV can occur in any person—age, sex, and demographic
region are irrelevant. HSV reaches the brain from the bloodstream or peripheral nerves by cell-to-cell spread along the branches
in the trigeminal nerve, which then innervates the meninges or the anterior and middle fossae. Thus, infection is characteristically
localized to the temporal and frontal lobes.
Patients with HSV encephalitis commonly present with bizarre, inconsistent
behavior and a waxing and waning mental status. Symptoms often include seizures, anosmia, olfactory and gustatory hallucinations,
personality changes, and psychosis. Consider this diagnosis when the patient has a prodrome of 1-7 days of upper respiratory
tract infection with headache, fever, and subsequent bizarre psychiatric symptoms.
Lumbar puncture, serology studies,
neuroimaging, and EEG are helpful in confirming the diagnosis.
Treatment consists of intravenous acyclovir, but
if the condition is not diagnosed and treated quickly, long-term psychiatric and neurologic sequelae are likely.
An estimated 42 million people were estimated to be living with HIV worldwide (CDC, 2001).
The number of infected people continues to increase, especially among poor and socially disadvantaged persons in the United
States, although the rate of increase has declined over the years. Thus, recognition and proper treatment of AIDS-related
complications involving the CNS and its behavioral and neurologic manifestations is one of the most common challenges faced
While patients with AIDS have psychiatric and neurologic symptoms from lesions (eg, primary CNS
lymphoma) or opportunistic infections, HIV itself can cause a subacute encephalitis and dementing complex. Clinically, HIV
encephalopathy manifests as a progressive subcortical dementia with nonspecific CSF abnormalities and cerebral atrophy with
ventricular dilation. In the early stages, signs of encephalopathy include difficulty concentrating, subtle mood changes,
disorientation, withdrawal, or lethargy. Motor signs, such as psychomotor slowing, hyperreflexia, and spastic or ataxic gait,
may also be present. Later, psychiatric episodes may become clinically apparent as delirium, mania, or psychosis (Pajeau,
1992). Although HIV encephalopathy has become one of the leading causes of dementia in persons younger than 60 years (McArthur,
1993), it has become less frequent since the introduction of highly active antiretroviral therapy (HAART).
the possibility of HIV encephalopathy in the evaluation of any patient with a psychiatric disorder who has HIV. Carefully
investigate with lumbar puncture and brain imaging to exclude other causes (eg, meningitis, malignancy). Conversely, any patient
presenting with first-time psychiatric symptoms and without a positive psychiatric history should undergo HIV testing. In
addition, being aware of the neuropsychiatric effects of medications used frequently in HIV infection is helpful.
Early therapy with antiretrovirals, particularly azidothymidine (AZT), is recommended because retrovirals may have a protective
effect in delaying or reversing some of the psychiatric and neurologic manifestations of HIV infection (Pajeau, 1992). Otherwise,
symptomatic treatment with psychopharmacologic medications is an important aspect in the treatment of these patients. Because
patients with HIV can be more susceptible to the adverse effects of psychotropic drugs, and because many of these medications
may lower seizure thresholds, use care when prescribing them. In addition, lower doses of the drugs are recommended (at least
for initial treatment), and the maxim “start low and go slow” should be followed.
DISORDERS Section 5 of 10
Dysfunction of the parathyroid glands results
in abnormalities in the regulation of electrolytes, especially calcium. Excessive excretion of parathyroid hormone results
in a state of hypercalcemia. Such hyperparathyroidism usually occurs in the third to fifth decade of life and is more common
in women than in men. Annual incidence is in the 0.1% range and affects up to 0.2% of the population older than 60 years (Cryer,
Hyperparathyroidism is frequently associated with significant psychiatric symptoms, which are caused by
the resultant hypercalcemia and can precede other somatic manifestations of the illness. Patients can experience delirium,
sudden dementia, depression, anxiety, psychosis, apathy, stupor, and coma.
Hypomagnesemia also occurs in association
with hyperparathyroidism, usually after surgical removal of a parathyroid adenoma. Delirium with psychosis is a common presentation
of patients with severe hypomagnesemia. Visual hallucinations and paranoid delusional psychosis are also observed in those
with a magnesium deficiency.
In hypoparathyroidism, expect to find low serum levels of calcium and magnesium.
Patients most commonly experience delirium but may also experience psychosis, depression, or anxiety. Because imbalances of
calcium and magnesium can cause psychiatric symptoms, serum levels of both electrolytes must be ascertained for diagnostic
evaluation of any psychiatric presentation. While patients with hypercalcemia should have parathyroid hormone levels checked,
they should also be evaluated for other causes of hypercalcemia.
is a common clinical condition caused by excess thyroid hormone. Because this disorder is so common, a high index of clinical
awareness for thyroid disease and its complications is needed in any patient who presents with psychiatric symptoms. Always
include evaluations of thyroid-stimulating hormone (TSH [thyrotropin]) and free thyroxine (T4) levels in the medical workup
of patients presenting with psychiatric symptoms for the first time. Graves disease is the most common cause in the population.
Some evidence indicates that stress can precipitate Graves disease and aggravate treated disease (Fukao, 2003). Toxic nodular
goiter is most prevalent in the elderly population.
Patients can present in various ways but commonly present
with symptoms of anxiety, confusion, and agitated depression. Patients can also present with hypomania and frank psychosis.
When hyperthyroidism is suggested, standard clinical symptoms may be present, including heat intolerance, diaphoresis, weight
loss despite increased appetite, palpitations, tachycardia, exophthalmos, and hyperactive tendon reflexes (Hutto, 1998).
In most patients who present with depression or anxiety associated with hyperthyroidism without other psychiatric
history, psychiatric symptoms usually resolve with treatment of the hyperthyroidism.
Unless hypothyroidism stems
from a primary pituitary disorder, it is usually caused by a lack of T4, which results in an elevated TSH level.
Similar to patients with hyperthyroidism, those with hypothyroidism often present with depression and anxiety. The usual
clinical features include apathy, psychomotor retardation, depression, and poor memory. However, when hypothyroidism develops
rapidly, the psychiatric features are usually delirium and psychosis, which has also been termed myxedema madness. Physical
signs and symptoms, including cold intolerance, weight gain, thin and dry hair, facial puffiness, constipation, menorrhagia,
muscle cramps, and slowed and decreased deep tendon reflexes, suggest this diagnosis.
can have either mild or no symptoms of thyroid hormone deficiency. It is fairly common and affects 5-10% of the population,
mainly women, and occurs in 15-20% of women older than 45 years.
T4 replacement in these patients usually reverses
the psychiatric symptoms, although it may not necessarily reverse the cognitive deficits that occur because of changes in
metabolic activity in the CNS.
Adrenal disorders cause changes in the normal secretion
of hormones from the adrenal cortex and may produce significant psychiatric symptoms. Few studies have been performed on psychiatric
symptoms of patients with Addison disease or adrenocortical insufficiency. This condition may result from fungal or, more
commonly, tuberculous infection of the adrenals. Patients with this condition can exhibit symptoms such as apathy, fatigue,
depression, and irritability. Psychosis and confusion can also develop. Steroid hormone replacement is used to treat patients
with this condition; however, cortisol is psychogenic in nature and may produce mania and psychosis.
of moderate-to-severe depression in up to 50% of patients with Cushing syndrome is well documented, with symptoms sometimes
severe enough to lead to suicide. Decreased concentration and memory deficits may also be present. Some patients present with
psychotic or schizophreniclike symptoms. Maintain a high index of clinical awareness for this disorder in patients who have
additional clinical signs such as central obesity, hypertension, striae, easy bruising, buffalo hump, diabetes, and osteoporosis.
In patients with depression believed to be etiologically related to hypercortisolemia, initiate antidepressant treatment while
awaiting surgical or medical therapy for Cushing syndrome. Psychiatric symptoms usually resolve when the cortisol excess is
The most common pancreatic disorders that can have psychiatric presentations
include diabetes mellitus with resulting glycemic dysregulation and pancreatic tumors. Either excessive exogenous insulin
administration or endogenous production of insulin can cause hypoglycemia. However, hypoglycemic-induced mental status changes
usually occur in persons with diabetes who are insulin dependent. Persons who engage in factitious use of hypoglycemic agents
are an exception. Initial symptoms of the hypoglycemic state usually include nausea, sweating, tachycardia, hunger, and apprehension.
With progression, patients may become disoriented and confused and may hallucinate. Eventually, stupor and coma ensue. Persistent
cognitive impairment can be a serious sequela to frequently occurring hypoglycemic states.
begins with weakness, fatigability, polyuria, and polydipsia. Symptoms of clinical worsening include hyperventilation, headache,
nausea, and vomiting. With ketoacidosis, disorientation and confusion can occur, and this state can be fatal if not properly
identified and urgently treated.
Pancreatic tumors, although uncommon, can manifest solely in depression. Despite
a broad differential diagnosis, seriously consider this diagnosis in elderly patients with new-onset depression in the setting
of back pain.
RHEUMATOLOGIC DISORDER Section 6 of 10
Systemic lupus erythematosus
lupus erythematosus (SLE) is an autoimmune disease of sterile inflammation involving multiple organs and multiple autoantibodies.
Approximately 90% of cases are in women, usually of childbearing age. The incidence is 2.4 cases per 100,000 across genders
and race, 92 cases per 100,000 for black women, and 3.5 cases per 100,000 for white women. Asians are also more often more
affected than whites. The diagnosis of SLE requires that patients have at least 4 of 11 criteria set by the American Rheumatism
Association. Remember that the diagnosis usually cannot be confirmed in a single encounter. The myriad of symptoms and serologic
abnormalities often occur over time; therefore, diagnosis involves compiling a thorough history. Organ involvement of the
synovium and skin usually prompts rheumatologists and dermatologists to consider the diagnosis. However, the neuropsychiatric
manifestations of lupus can occur any time during the disease, and most appear in the first few years or before diagnosis
of theillness. Thus, patients with undiagnosed lupus may initially present in psychiatric clinics, neurologic clinics, or
Neuropsychiatric manifestations of patients with lupus have a prevalence of up to 75-90% (Ainiala,
2001). Major psychiatric symptoms include depression, emotional lability, delirium, and psychosis. The presence of severe
depression or psychosis is associated with anti-P antibodies in the serum, which suggests an autoimmune mechanism for inducing
Treatment is with high-dose steroids, which can precipitate or exacerbate psychiatric symptoms.
However, most instances of psychosis in patients with lupus who are on steroid therapy are secondary to lupus cerebritis,
and many improve with an increase in dosage. When patients are on steroid therapy, remembering to exclude infectious causes
of possible brain dysfunction is always important because steroids may mask fever, resulting in an atypical presentation of
Because of the multiple organ systems involved and the complexities of this illness, it behooves the
clinician to consult rheumatologists, neurologists, and psychiatrists as appropriate.
Section 7 of 10
Hyponatremia occurs in various conditions. This condition is usually
observed in postoperative patients and in patients with severe vomiting and diarrhea, syndrome of inappropriate secretion
of antidiuretic hormone (SIADH), extensive burns, cirrhosis, or endocrine abnormalities (eg, myxedema, Addison disease). Consider
hyponatremic disorders in patients experiencing acute mental status changes. Classic symptoms of hyponatremia include nausea,
anorexia, and muscle weakness. As the serum sodium level continues to drop, patients may become irritable, confused, depressed,
and intensely anxious (Lishman, 1998). Delusions and hallucinations can also occur at this stage. Without proper treatment,
seizures, stupor, and coma ultimately ensue. Treatment consists of correcting the serum sodium level at a slow but adequate
rate. Overly rapid correction of hyponatremia can lead to central pontine myelinolysis.
results from inadequate ingestion of water or from the inability of the kidneys to conserve water. The elderly population
is particularly sensitive to dehydration, and elderly persons can have acute mental status changes. As with hyponatremia,
the rate of correction of hypernatremia is important. Overly rapid correction can lead to cerebral edema. Always consider
cerebral edema if the patient has worsened mental status when hypernatremia has been corrected.
Hepatic encephalopathy is a complex neuropsychiatric syndrome that complicates advanced liver
disease. In acute hepatic encephalopathy, fulminant hepatic failure is usually present. Cerebral edema plays an important
etiologic role in this setting. Chronic hepatic encephalopathy usually occurs in patients with chronic liver disease, and
it manifests as subtle neuropsychiatric disturbances. The clinical picture of this form of encephalopathy varies and is characterized
by acute exacerbations and remissions accompanied by neurologic abnormalities. The clinical manifestations of stages of hepatic
encephalopathy are listed below (Andreoli, 1993).
Reversal of sleep rhythm
Beginning of mood swings
Beginning of behavioral disinhibition
Short episodes of psychiatric symptoms
Stage IV - Coma (responsive only to pain)
acute exacerbations, impairment of consciousness is prominent. Rapid changes in consciousness can be accompanied by hallucinations,
mainly visual. Hypersomnia also occurs early in the course of illness. Prior to the development of coma, patients can also
experience abrupt mood swings and behavioral disinhibition. Patients may also experience short episodes of depression, hypomania,
anxiety, and obsessive-compulsive symptoms. At this stage, patients usually have neurologic signs, which may include asterixis,
myoclonus, constructional apraxia, and/or hyperreflexia.
The etiology of such changes is unclear; however, the
pathogenesis of hepatic encephalopathy is believed to involve inadequate hepatic removal of mostly nitrogenous compounds or
other toxins formed in the GI tract. Inadequate removal of these toxins results from both impaired hepatocyte function and
shunting of portal blood into the systemic circulation. Treatment involves identification of precipitating factors, dietary
protein restrictions, and removal of ammonia from the bowel.
from impairment in kidney functioning. Initially, patients feel nonspecifically and generally unwell and often describe a
sense of fatigue. They may have difficulty with concentration and may experience some memory impairment. As uremia progresses,
memory worsens. Depression, apathy, and social withdrawal become clinically apparent. In advanced uremia, patients may experience
impaired mentation, lethargy, myoclonus, asterixis, and other neuropsychiatric symptoms similar to those in hepatic encephalopathy.
Psychosis can also occur.
The differential diagnosis of psychiatric symptoms in persons with chronic renal failure
is quite broad and should include hypercalcemia, hypophosphatemia, hypernatremia/hyponatremia, hyperglycemia/hypoglycemia,
hypertensive encephalopathy, and cerebrovascular disease, among many others. Adequate dialysis can reverse some of the psychiatric
and mental abnormalities, but some subtle deficits in mentation may remain.
Dialysis dementia is a specific syndrome
characterized by encephalopathy, dysarthria, dysphasia, poor memory, depression, paranoia, myoclonic jerking, and seizures
(Lishman,1998). Worsening of dialysis dementia can lead to death within a year of diagnosis. High aluminum levels were found
during autopsy in the brain tissue of patients who died with this clinical syndrome. The etiology was believed to be the aluminum
content of the water used in making the dialysate. In the United States, the incidence of dialysis dementia has diminished
because of proper water treatments.
Psychopharmacologic treatment of uremic encephalopathy should target the individual
symptoms but with a lower starting dosage of medication and with small, cautious dosage adjustments.
Porphyria is a disorder of heme biosynthesis that leads to buildup of excessive porphyrins. In the classic
form, patients have a triad of symptoms, including colicky abdominal pain, motor polyneuropathy, and psychosis. Acute intermittent
porphyria is an autosomal dominant disorder, and onset usually occurs in persons aged 20-50 years. Some studies have shown
that 0.2-0.5% of psychiatric patients have undiagnosed porphyrias. Barbiturates precipitate attacks of acute porphyria and
are therefore absolutely contraindicated.
VITAMIN DEFICIENCY STATES Section 8 of 10
When discussing the appropriate differential diagnosis of new-onset psychiatric symptoms, consideration of vitamin
deficiencies is necessary, especially deficiencies of the B vitamins. Chronic and severe deficiency of vitamin B-1 (thiamine)
leads to pellagra, with neuropsychiatric symptoms of asthenia, fatigue, weakness, and depressed mood. Much more commonly today,
thiamine deficiency manifests as Wernicke encephalopathy, often, but not exclusively, in individuals with heavy and prolonged
alcohol use. The classic triad of gait ataxia, global confusion, and ophthalmoplegia, most often involving the sixth cranial
nerve, leads to the inability to abduct the eyes.
Immediate treatment with parenteral thiamine reveals that this
syndrome is at least partly reversible because the ocular palsy often resolves within hours. As the confusion improves, impaired
cognitive functioning (amnesia) consistent with Korsakoff syndrome often becomes evident. Long-term treatment with thiamine
may result in ongoing improvement over a period of months.
Although this is a clinical diagnosis, brain pathology
is evident on imaging studies and at autopsy. Symmetric lesions of the mamillary bodies, the third and fourth ventricles,
and the periaqueductal areas are present.
Deficiency of vitamin B-12 (cobalamin) is the
cause of pernicious anemia. When a patient presents with megaloblastic anemia and neurologic symptoms from subacute combined
spinal cord degeneration, and a low serum vitamin B-12 level is found on evaluation, the diagnosis is relatively straightforward.
Although the direct cause and effect of concomitant psychiatric symptoms is not always clear, depression, fatigue,
psychosis, and progressive cognitive impairment can accompany neurologic symptoms (Hutto, 1997).
symptoms can predate the neurologic symptoms by months to years and may be present in the absence of anemia or macrocytosis.
When suggested, even if screening vitamin B-12 levels are not revealing, measurements of serum methylmalonic acid and total
homocysteine may be more helpful diagnostically (Lindenbaum, 1988).
As with vitamin B-12 deficiency,
interest has been shown in the relationship between folate deficiency and psychiatric symptoms. Causality is not always clear,
but evidence suggests that folate deficiency states are observed in patients with depressive syndromes and with dementing
syndromes; it appears that folate deficiency is not rare and can cause or exacerbate psychiatric symptoms (Botez, 1977).
Since replacing folate in patients with B-12 deficiency can aggravate the progression of neurologic symptoms, it is
important to search for and correct vitamin B-12 deficiency either prior to or concurrent with folate replacement.
EXOGENOUS TOXINS Section 9 of 10
The role of exogenous toxins is a very broad subject; however, because of the
limited space and scope of this article, only a brief overview is presented. Toxins can include medications, drugs of abuse,
solvents, pesticides, and heavy metals. Some of the most common medications associated with induction of a psychoactive state
are listed below (Rundell, 1999).
Histamine 2 blockers
Idiopathic major depression is
very common, as is the use of medication, alcohol, and/or illicit drugs. Separating causal factors is not always easy. A high
index of clinical awareness is helpful in considering underlying causes of conditions that can appear as primary idiopathic
psychiatric illness. Knowledge of the time course can also be helpful, ie, comparing the onset of symptoms to the initiation
of or change in dosage of the putative offending agent.
Although volumes have been written
concerning the pathologic changes in patients who use alcohol for short and long periods, a brief review is appropriate because
patients in alcohol withdrawal can present with numerous psychiatric symptoms that can be fatal if not identified and treated
Withdrawal symptoms can emerge, particularly in the absence of a measurable blood alcohol level. Florid
delirium tremens (DT) is the most serious and potentially fatal alcohol withdrawal syndrome. The clinical picture includes
hallucinations (most commonly auditory and/or visual), gross confusion and disorientation, and autonomic hyperactivity (eg,
tachycardia, fever, sweating, hypertension). These patients are often agitated and paranoid and may not readily allow physical
examination. The temptation to view an agitated, paranoid, overtly hallucinating patient as in need of nothing further than
admission to a psychiatric unit may be a grave mistake because untreated DT is potentially fatal.
also present with hallucinations in a clear sensorium (differentiating it from DT), usually in the setting of recent cessation
of or significant decrease in the amount of alcohol used. Known as alcoholic hallucinosis, the hallucinations (most frequently
auditory) may be relatively brief, usually resolving within approximately 30 days, but they may persist. Recurrences are likely
with continued alcohol use.
Differentiating this syndrome from schizophrenia can be difficult. The hallucinations
are frequently threatening and persecutory in nature, and patients may act in response to these, leading to a potentially
dangerous situation that may require involuntary psychiatric hospitalization (Cassem, 1997).
Alcohol is a CNS
depressant, and chronic abuse can be associated with significant depression that may, by symptoms alone, be indistinguishable
from idiopathic major depression. However, of patients with depressive disorder from alcohol dependence who are monitored
for 2-4 weeks without alcohol, more than 50% have full remission of symptoms without additional intervention for the depressive
symptoms (O'Sullivan, 1984). A minority of patients, usually those with more severe symptoms, have a continued depressive
syndrome despite sobriety and require additional treatment.
Cocaine and amphetamines
Cocaine is a
powerful stimulant initially causing euphoria and increased alertness and energy. As the high wears off, the user may develop
symptoms of anxiety and depression, often with drug craving. With continued regular use, symptoms of psychosis develop with
hallucinations and frank paranoid delusions. The psychiatric presentation can appear similar to that observed in patients
with chronic amphetamine abuse.
Amphetamines are also CNS stimulants and initially cause feelings of increased
well-being, energy, and concentration. However, amphetamine abuse can cause development of psychotic symptoms.
testing with toxicologic screening of blood and urine can assist with or confirm the diagnosis. Knowing exactly what drugs
are screened for at any individual facility is important because different routine screens include different drugs. Depending
on the clinical presentation, testing for additional individual drugs may need to be specified. For example, patients with
phencyclidine (PCP) intoxication may present with psychosis and with particularly agitated and violent behavior; however,
most routine drug screens do not test for PCP, which can nevertheless be measured when specified.
A brief mention must be made of lysergic acid diethylamide (LSD), a potent hallucinogen that causes intense and
vivid hallucinations in a clear sensorium. LSD-elicited hallucinations are usually of relatively short duration, but flashbacks
of varying intensity may occur in a small number of users. Hallucinogenic mushrooms containing psilocybin and psilocin can
have similar effects.
Ecstasy (3,4-methylenedioxymethamphetamine [MDMA]), a designer drug
synthetically derived from amphetamine, is often used in the context of large and energetic parties (raves) and at nightclubs.
Initially, it causes mild euphoria, increased energy, and increased libido. Tolerance develops rapidly. Depression, anxiety,
and psychosis have also been described with regular use, and some of the symptoms persist for months after cessation of use
Solvent abuse or huffing involves the inhalation of organic solvents for
their euphoriant effects. Inhaled solvents include glues, paints, cleaning fluids, nail-polish removers, lighter fluids, aerosol
propellants, and gasolines. Long-term and heavy use can lead to hallucinations, cognitive impairment, personality change,
and neurologic impairment, particularly cerebellar findings.
Lead, mercury, manganese,
arsenic, organophosphorous compounds, and others can cause psychiatric symptoms. Exposure is usually industrial or environmental
and should be considered in the appropriate settings. Often, CNS or peripheral nervous system signs and symptoms are present.
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