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CATEGORY 1
Sponsored by CME LLC Psychiatric Times MAY 2010
Earn 1.5 AMA PRA Category 1 Credits through May 2011.

A Guide to the Judicious Use of Laboratory Tests and Diagnostic Procedures in Psychiatric Practice
by Ilse R. Wiechers, MD, MPP, Felicia A. Smith, MD, and Theodore A. Stern, MD
Dr Wiechers is chief resident, Acute Psychiatry Service of Massachusetts General Hospital and clinical fellow in psychiatry at the Harvard Medical School, Boston; Dr Smith is director of Acute Psychiatry Service of Massachusetts General Hospital and instructor in the department of psychiatry at the Harvard Medical School; and Dr Stern is chief of The Avery D. Weisman, MD, Psychiatry Consultation Service of Massachusetts General Hospital and professor in the department of psychiatry at the Harvard Medical School. Drs Wiechers and Smith report no conflicts of interest concerning the subject matter of this article. Dr Stern reports that he is a speaker on general hospital psychiatry with Reed Elsevier, he receives royalties for books on psychiatry from McGraw-Hill and Mosby Elsevier, and he is an employee of the Academy of Psychosomatic Medicine.

old man with coronary artery disease, diabetes, and dementia. What follows is a discussion about which tests may be considered to be part of routine screening. We consider aspects of the diagnostic workup of specific psychiatric symptoms. We also discuss tests that are necessary for the prudent monitoring of specific medications used to treat psychiatric illness. Finally, we address the implications of abnormal test results and the responsibilities of clinicians to respond with changes in treatment or (when appropriate) to refer the patient for speciality care.

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of CME LLC and Psychiatric Times. CME LLC is accredited by the ACCME to provide continuing medical education for physicians. CME LLC designates this educational activity for a maximum of 1.5 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

sychiatric diagnoses are primarily made by recognizing patterns of symptoms and clinical phenomenology, as outlined in DSM-IV-TR. Thus, the first critical steps in the identification of diagnoses are obtaining a thorough history, conducting a comprehensive mental status examination, and performing a focused physical examination. The results of these endeavors help focus attention on areas that need further diagnostic assessment and identify appropriate laboratory tests and procedures (including blood work, neuroimaging, and tests of electrophysiology) that will aid in assessment. When psychiatric symptoms are of acute onset, atypical in nature, or of late onset, or if there is a history of chronic medical illness, a medical cause (rather than primary psychiatric illness) should be suspected. While routine screening is often done for patients who have new-onset psychiatric symptoms, there is no consensus on what tests should be included in a typical screening battery. In practice, the clinical situation guides the choice of tests. For example, new-onset psychotic symptoms in a healthy 19-year-old man demand a different set of tests and procedures from the set that is warranted when those symptoms occur in an 81-year-

ROUTINE SCREENING The decision to order screening tests during the assessment of new-onset psychiatric illness should take into consideration the ease of administration, the clinical implications of abnormal results, the sensitivity and specificity of the tests, and their cost. Unfortunately, there is no consensus about when to order routine screening tests. However, in clinical practice, such tests often include a complete blood cell (CBC) count; serum chemistry; kidney function tests, such as blood urea nitrogen (BUN) and creatinine; levels of thyroid-stimulating hormone (TSH), vitamin B12, and folate; an erythrocyte sedimentation rate (ESR); levels of substances in the urine and serum (ie, toxicology); and syphilis serologies (Table 1). Liver function tests (LFTs) are also frequently obtained, especially in patients with known liver disease, in those at high risk for liver dysfunction (eg, secondary to alcohol abuse), or in those taking medications that are potentially hepatotoxic. Additional screening tests may be added to the battery listed above on the basis of a patients physical complaints or findings present on physical examination. For example, one should consider obtaining a chest film in a patient with cough and fever, a urinalysis in a patient with dysuria or increased urinary frequency, or a lumbar puncture when a patient presents with an altered mental status associated with fever, headache, photophobia, or meningeal symptoms. An ECG should be considered in a patient with chest pain or discomfort, especially when the patient has a history of cardiac disease or significant cardiac risk factors (Table 2). In addition, women of childbearing age should have a pregnancy test

EDUCATIONAL OBJECTIVES
After reading this article, you should be familiar with:
The appropriate use of routine screening tests Diagnostic workup for specific psychiatric symptoms Which tests are needed for monitoring results of medications When to modify treatments to ensure highquality care and overall well-being for patients

Who will benefit from reading this article?

Psychiatrists, psychologists, primary care physicians, nurse practitioners, and other health care professionals. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing and certification boards.

to help make the diagnosis and plan treatment. Testing for certain infectious diseases (ie, HIV infection and hepatitis) may also be warranted as part of a screening battery when clinical concern is high.

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Mood disorders Depression is primarily a psychiatric illness, but it can be associated with several medical conditions, including thyroid dysfunction, Addison or Cushing disease, pituitary adenoma, neurodegenerative disorders, systemic lupus erythematosus, anemia, and pancreatic cancer. The routine screening battery will assess for thyroid dysfunction and anemia. When a clinical presentation points toward one of these causes, additional tests (eg, an assessment of adrenocorticotropic hormone for Addison disease, a dexamethasone suppression test for Cushing disease, and an antinuclear antibody test for systemic lupus erythematosus) may be ordered. New-onset mania is akin to new-onset psychosis; it warrants a complete medical and neurological evaluation as described above.

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DIAGNOSTIC WORKUP More detailed laboratory tests and procedures may be warranted in the diagnostic workup of a patient with specific new-onset psychiatric illness. Psychosis and delirium New-onset psychotic symptoms or delirium warrants a full medical and neurological assessment. The differential diagnosis for these symptoms is broad and includes a wide variety of often lifethreatening causes, such as infections, CNS lesions, metabolic abnormalities, medication effects, intoxication with or withdrawal from certain substances, trauma, hypoperfusion or hypoxia, and seizures. The initial assessment should be thorough and systematic. It should include a history, a physical examination, mental status examination, and routine screening laboratory tests. Additional studies are warranted when the cause of symptoms is unclear. Further testing should be guided by clinical symptoms (Table 1). An elevated serum ammonia level occurs with hepatic encephalopathy and liver failure, as well as with GI bleeding. A history of high-risk behaviors (eg, unprotected sexual encounters or injection drug use) raises clinical suspicion for HIV infection. Following proper consent, patients with these risk factors should be screened for infection. In a patient who exhibits signs and symptoms of liver disease, uncontrolled movements, and behavioral changes, a ceruloplasmin level should be obtained; low levels are consistent with Wilson disease. Testing for heavy metals (eg, mercury, arsenic, and lead) may also be warranted. An electroencephalogram may help diagnose a seizure disorder or support a diagnosis of toxic or metabolic encephalopathy (Table 2).1 Neuroimaging is strongly encouraged in patients with new-onset psychosis or delirium, especially when a patient exhibits abnormal neurological findings. In patients with acute mental status changes or who need a rapid evaluation, it is appropriate to obtain a CT scan of the head. Further evaluation by brain MRI allows for more detailed assessment of white matter and of small structures (Table 3). Anxiety disorders The list of potential medical causes of anxiety is extensive and includes cardiac disease (eg, myocardial infarction, mitral valve prolapse), respiratory compromise (eg, asthma, pulmonary embolism, chronic obstructive pulmonary disease), endocrine dysfunction (eg, thyroid and parathyroid disorders, hypoglycemia), neurological disorders (eg, seizures, brain injuries), and use or abuse of drugs and other substances. Many of these etiologies are evaluated by the tests discussed in the section Routine screening. A patient who presents with a clinical picture and history suggestive of cardiac disease should have an ECG and have his or her cardiac enzyme values checked. Additional tests (eg, parathyroid hormone level, cardiac ultrasonography, pulmonary function tests) and investigation of rare causes of anxiety (eg, pheochromocytoma, acute intermittent porphyria) should be pursued if warranted by the clinical presentation.

If macrocytic anemia is present, levels of folate and vitamin B12 should be assessed. If chronic liver damage is present, coagulation factors should be checked as well. Drug users (especially those with a history of sharing needles) should have an HIV test and hepatitis serologies completed. An ECG is critical in the assessment of any cocaine abuser with cardiac symptoms.

Dementia A number of possible causes exist for dementia, including vascular (eg, stroke and chronic subdural hemorrhage), infectious (eg, HIV infection, Creutzfeldt-Jakob disease, and neurosyphilis), degenerative (eg, Alzheimer disease, frontotemporal dementia, Parkinson disease), endocrine (eg, hypothyroidism, Cushing syndrome), metabolic (eg, thiamine deficiency, vitamin B12 deficiency), tox-

One should carefully consider the clinical significance of a test result; the appropriate response to a test requires going beyond just noting that a result is outside the range of normal for a given test.
Eating disorders Along with clues from the patients history, several physical findings should raise clinical suspicion of an eating disorder. Cachexia strongly raises concern of anorexia. Dental decay or knuckle lesions (ie, Russell sign) indicate self-induced vomiting of bulimia nervosa. In a patient with an eating disorder, it is essential to assess serum electrolytes and the nutritional status. Albumin levels are decreased with malnutrition, although they are often normal in patients with anorexia. A patient who chronically purges will show evidence of an elevated amylase level as well as hypokalemia and hypochloremia. Long-term laxative use often results in hypocalcemia and hypokalemia. Substance abuse Intoxication and withdrawal from drugs are common causes of many psychiatric symptoms, including anxiety, agitation, psychosis, depression, and confusion. Serum and urine toxicology helps in the assessment of what substances have been used. Substances can usually be detected in the serum for hours to a few days after they are used. In the urine, substances can be detected for days to weeks, depending on the substance being used and whether it has been used long-term (Table 1). While serum levels of alcohol or benzodiazepines may be of clinical benefit, they do not correlate well with the timing of withdrawal symptoms. A patient who presents with a history of alcohol abuse should undergo LFTs and a CBC count.

ins (eg, heavy metals, chronic alcoholism), neoplastic (eg, carcinoma, paraneoplastic syndrome), inflammatory (eg, vasculitis), and hydrocephalus (eg, normal pressure, obstructive hydrocephalus). Identifying the precise cause may be difficult; it requires careful assessment of history from the patient and family as well as ruling out other diagnosesespecially depression and delirium. Laboratory tests should include a CBC count; levels of vitamin B12, folate, serum glucose, and serum electrolytes; an ESR; and tests of liver and thyroid function. Neuroimaging is often useful to assess for stroke, hydrocephalus, tumor, or hematoma (Table 3). Positron emission tomography also helps differentiate between several of the degenerative etiologies of dementia. A lumbar puncture may be indicated if there is concern about normal pressure hydrocephalus on imaging studies or if a patient has a known or suspected cancer or CNS infection. When clinical suspicion is high, additional tests (such as an HIV test, syphilis serologies, antinuclear antibody or rheumatoid factor assessments, and heavy metal screening) may be completed.

MEDICATION MANAGEMENT Patients who take many commonly used medications require routine laboratory monitoring. Monitoring of specific serum drug levels aids in dose titration, helps prevent toxicity, and assesses medication adherence. Drug levels may also be help(Please see Laboratory Tests, page 50)

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Antipsychotics Use of typical and atypical antipsychotics is linked to increased rates of adverse cardiovascular effects.4 Arrhythmias and QTc prolongation can be assessed with a baseline and follow-up ECG. Many typical antipsychotics (eg, chlorpromazine) and several atypical antipsychotics (eg, olanzapine, risperidone, and aripiprazole) have been associated with orthostatic hypotension. When clinically relevant, monitoring of orthostatic vital signs can help guide treatment by identifying a patient who is experiencing this adverse effect. Use of typical antipsychotics as well as some atypical antipsychotics (eg, risperidone, paliperidone) can lead to elevated prolactin levels.5 Monitoring the prolactin level can help assess the role of medications in a patient with clinical evidence of hyperprolactinemia (eg, with sexual dysfunction or galactorrhea). Several antipsychotics, most notably clozapine, phenothiazines, and olanzapine can cause blood dyscrasias (such as agranulocytosis and neutropenia).3 Thus, it is prudent to check a baseline and follow-up CBC count in patients taking these medications. Clozapine is the antipsychotic medication that requires the closest monitoring because the incidence of agranulocytosis may be as high as 1% to 3% in patients taking this medication. For the first 6 months of treatment, weekly monitoring of the CBC count with differential is required. For the second 6 months, monitoring can occur every other week; after 1 year, monitoring can occur monthly. A current and acceptable level is defined as a white blood cell (WBC) count of 3500/L or greater and an absolute neutrophil count (ANC) of 2000/L or greater and no older than 7 days from the dispense date.6 Leukopenia (WBC count less than 2000 to 3000/L) or granulocytopenia (ANC less than 1000 to 2000/L) mandates immediate discontinuation of clozapine and daily checking of the CBC count. Clozapine may be cautiously reinitiated once blood counts normalize. If severe leukopenia (WBC count less than 2000/L) or agranulocytosis (ANC less than 1000/L) occurs, however, clozapine is discontinued for life. Initial enthusiasm for atypical antipsychotics has been tempered by the recognition that they are associated with metabolic effects (ie, weight gain, dyslipidemia, glucose intolerance).7,8 This is not a trivial issue, because patients with serious mental illness have a life expectancy that is reduced by more than 20 years compared with those in the general population.9 In recognition of the urgent need to reduce iatrogenic morbidity and to improve the physical health monitoring of patients treated with atypical antipsychotics, several guidelines have been proffered.10-12 Consensus guidelines of the American Diabetes Association and the American Psychiatric Association recommend obtaining baseline measurements of weight, waist circumference, and blood pressure as well as a fasting serum glucose and lipid panel. The guidelines also recommend assessment of weight monthly for the first 3 months of treatment, and quarterly thereafter; blood pressure, fasting glucose, and a lipid profile should be checked at 3 months; and waist circumference, blood pressure, and fasting glucose should be monitored annually with a follow-up fasting lipid profile assessed every 5 years.

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Continued from page 49

ful in assessing for slow or fast metabolism in patients with an unexpected response (eg, a poor response despite taking a therapeutic dose, development of extreme adverse effects). Monitoring of serum drug levels is also important when considering drug-drug interactions because certain medications result in changes in blood serum levels and subsequently in the efficacy of other medications. For example, carbamazepine is a potent inducer of certain cytochrome P-450 enzymes and leads to decreased levels of other medications metabolized through those enzymes (eg, clozapine, haloperidol). In addition, assessment of routine laboratory test results allows for monitoring the adverse effects (including organ toxicity and metabolic effects) of medication. Table 4 summarizes proposed laboratory monitoring for mood stabilizers, antipsychotics, and antidepressants.2

Mood stabilizers Lithium has the potential for both acute and chronic organ toxicity, whether blood levels are inside or outside of a narrow therapeutic range (usually between 0.5 and 1.2 mEq/L). In acute lithium toxicity, a patient may present with CNS, cardiac, and renal toxicity. Over the long term, lithium can lead to adverse effects on the thyroid, heart, and kidneys. Recommended screening tests before initiation of lithium treatment include measurement of electrolytes, BUN, creatinine, and TSH; CBC count; urinalysis; and electrocardiography. Because of lithiums potential teratogenicity, all women of childbearing age should have a pregnancy test before starting treatment. Serum levels of lithium should be checked once a week as the dosage is titrated; measurement of electrolytes and kidney function tests are needed every 2 months thereafter. TSH should be assessed every 6 months. Recommended baseline laboratory tests for a patient starting treatment with valproic acid include a CBC count, LFTs, and pregnancy test in female patients (because of the association of valproic acid with neural tube defects). Following initiation of valproic acid therapy, check the CBC count, LFT results, and serum drug level weekly until a stable dose (based on a therapeutic serum level between 50 and 100 mEq/L) is achieved. Once a patient is receiving a stable dose, these values can be checked every 6 to 12 months. Baseline laboratory tests for a patient starting treatment with carbamazepine are similar to those obtained before use of valproic acid. Additional screening of serum sodium level (because of the risk of hyponatremia) is needed, as are tests of thyroid and renal function. Follow-up testing of the serum sodium, CBC count, liver function, and serum drug levels is recommended every 1 to 2 weeks while titrating the dosage of carbamazepine (based on a therapeutic serum level between 6 and 12 g/mL). Close monitoring of the CBC count is essential, given the risk of blood dyscrasias; neutropenia develops in approximately 1 in 200 patients taking carbamazepine.3

Antidepressants There are no established guidelines for monitoring antidepressant medications. Tricyclic antidepressants (TCAs) are the most frequently monitored, because adverse effects are often correlated with serum drug levels. Steady-state levels are achieved in 5 days, and a trough level should be measured 10 to 14 hours after the last oral dose.13 Given the risk of cardiac conduction abnormalities, a baseline and subsequent annual follow-up ECG are crucial for any patient taking a TCA who is 35 years or older or who has a history of cardiac problems. While patients taking other classes of antidepressants do not require routine monitoring, there are several clinical situations that may warrant obtaining laboratory tests. For example, an elderly patient taking an SSRI who presents with fatigue, nausea, and a change in mental status should have electrolytes checked for hyponatremia (which has been associated with use of SSRIs and venlafaxine). Checking liver function, BUN, and creatinine may help guide adjustment of doses on the basis of renal and liver function in patients who are medically ill. IMPLICATIONS OF ABNORMAL RESULTS It is a clinicians obligation to review the results of any tests he orders and to respond in a clinically appropriate manner to an abnormal result. One should carefully consider the clinical significance of a test result; the appropriate response to a test requires going beyond just noting that a result is outside the range of normal for a given test. For example, an elevated serum lithium level of 1.7 mEq/L is concerning and requires a dosing change in a healthy, asymptomatic 21-year-old patient; it can represent a medical emergency in a 68-yearold patient with an altered mental status, tremor, and impaired renal function. Some test results require a comparison with a patients baseline studies. For example, an ECG from a patient taking an antipsychotic medication cannot definitively show evidence of medicationassociated QTc prolongation unless it is compared with the baseline QTc obtained before initiation of the treatment. In many cases, when a treatment modification takes place as a consequence of an abnormal test result, a follow-up with repeated tests to assess for a change in findings is prudent. There are several different ways in which one can consider modifying treatment as a result of test outcomes. Certain findings require definitive treatment modifications. For example, findings of agranulocytosis in a patient taking clozapine require the immediate cessation of the medication. A positive result on an HIV test or on syphilis serologies mandates treatment of the infectious disease and/or reporting the result to the department of public health. Other tests (eg, serum drug levels of mood stabilizers or TCAs) require more of a rheostat approach, with modifications of slow, small increases or decreases in drug dose being more appropriate. Still other abnormal test results lead down multiple pathways for treatment modifications, and the decision of which pathway to take requires careful consideration of the options by

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trist to communicate with the patients primary care physician or to make an appropriate referral to specialty care (eg, an endocrinologist). Prompt referral to medical care is also essential when a diagnostic workup reveals findings that are suggestive of an underlying organic cause to the psychiatric symptoms.

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both the clinician and the patient. Finding that dyslipidemia has developed in a patient taking an atypical antipsychotic is one such example. In one patient, the right clinical response may be switching the treatment to a drug with a lower metabolic risk profile or stopping the antipsychotic medication altogether. Another patient, such as one with a severe psychotic illness in whom multiple trials of antipsychotics have failed, may need to remain on the current regimen despite the worsening lipid profile. In such cases, it is crucial that the patient understands the risks and benefits of continuing such treatment. Another consideration may be using adjunctive treatment with additional medications that target the dyslipidemia directly. Certain treatment modifications are outside the practice parameters of most psychiatrists: for example, the use of levothyroxine for lithiuminduced hypothyroidism or the use of metformin for atypical antipsychoticassociated diabetes. In such cases, it is essential for the treating psychiaEditors note: Because of space constraints, the Tables to which the authors refer have been posted to www.psychiatrictimes.com.

CONCLUSION The cornerstone of psychiatric diagnosis is a thorough assessment of a patients history and mental status examination. However, as discussed, the addition of laboratory tests can aid in diagnosis as well as help guide treatment. It is also important for clinicians to be aware of the appropriate use of laboratory monitoring of medications used in treatment of many psychiatric illnesses. Once a given test has been ordered, it is important to follow up results and modify treatment when clinically appropriate.
References
1. Roffman JL, Stern TA. Diagnostic rating scales and laboratory tests. In: Stern TA, Fricchione GL, Cassem NH, et al, eds. Massachusetts General Hospital Handbook of General Hospital Psychiatry. 5th ed. Philadelphia: Mosby; 2004:44. 2. Smith FA. Laboratory test and diagnostic procedures. In: Stern TA, Rosenbaum JF, Fava M, et al, eds. Massachusetts General Hospital

Comprehensive Clinical Psychiatry. Philadelphia: Mosby/Elsevier; 2008. 3. Flanagan RJ, Dunk L. Haematological toxicity of drugs used in psychiatry. Hum Psychopharmacol. 2008;23(suppl 1):27-41. 4. Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death [published correction appears in N Engl J Med. 2009;361:1814]. N Engl J Med. 2009;360:225-235. 5. Bostwick JR, Guthrie SK, Ellingrod VL. Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009;29:64-73. 6. Teva Clozapine Prescribing Reminders. https://www.clozapineregistry. com/AboutClozapine/PrescribingReminders.aspx.Accessed March 29, 2010. 7. Meyer JM. Effects of atypical antipsychotics on weight and serum lipid levels. J Clin Psychiatry. 2001;62(suppl 27):27-34. 8. Newcomer JW.Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry. 2007;68(suppl 4):8-13. 9. Colton CW, Manderscheid RW. Congruencies in increased mortality rates, years of potential life lost, and causes of death among public mental health clients in eight states. Prev Chronic Dis. 2006;3:A42. 10. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004; 27:596-601. 11. Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004;161:13341349. 12. Goff DC, Cather C, Evins AE, et al. Medical morbidity and mortality in schizophrenia: guildelines for psychiatrists. J Clin Psychiatry. 2005; 66:183-194. 13. Rosenbaum JF, Arana GW, Hyman SE, et al. Drugs for the treatment of depression. In: Handbook of Psychiatric Drug Therapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:55-120.

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Category 1 Posttest
1. Which of the following need to be taken into consideration when ordering screening tests for the assessment of new-onset psychiatric illness? A. Ease of administration B. Clinical implications of abnormal results C. The sensitivity and specificity of the tests D. All of the above E. None of the above 5. Checking a drug serum level to assess for slow or fast 2. Once the routine screening tests are completed there is no need for additional tests. A. True B. False 3. Although rare, which of the following may cause anxiety? A. Acute intermittent porphyria B. Addison disease C. Pancreatic cancer D. All of the above E. None of the above metabolism is a good idea in cases of unexpected medication response. A. True B. False 6. Lithium is considered safe and effective in patients with mood disorders; therefore, after baseline screening, very few follow-up laboratory tests are needed. A. True B. False A10001051 8. Patients taking which of the following classes of antidepressants need routine monitoring for adverse effects: A. Monoamine oxidase inhibitors B. SSRIs C. Tricyclic antidepressants D. All of the above E. None of the above 4. Laboratory tests should include which of the following when trying to determine the etiology of dementia: A. Complete blood cell count B. Levels of vitamin B12 and folate C. Tests for liver and thyroid function D. All of the above E. None of the above 7. Antipsychotics are linked to which of the following adverse effects: A. Orthostatic hypotension B. Hyperprolactinemia C. Agranulocytosis D. All of the above E. None of the above

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Table 1
Test/procedure

Common screening tests and procedures during the assessment of new-onset psychiatric illness
When to order Abnormal finding

CBC count Hematocrit WBC count

Routine screening; depression workup Decreased with anemia Increased with lithium use, NMS; decreased with use of phenothiazines, carbamazepine, clozapine Decreased with use of phenothiazines, carbamazepine, clozapine Increased with vitamin B12 or folate deficiency, alcohol use Decreased with certain anemias Routine screening; delirium workup; eating disorder workup; evaluation of SIADH Decreased with use of SSRIs, carbamazepine, anabolic steroids and with hypoadrenalism, myxedema, CHF, diarrhea, polydipsia Increased in hyperkalemia, acidosis, anxiety in cardiac arrhythmia; decreased in cirrhosis, metabolic alkalosis, psychogenic vomiting and with anabolic steroid use, laxative and diuretic abuse, bulimia Increased or decreased with delirium; decreased with agitation, anxiety, depression Increased with psychogenic vomiting, bulimia; decreased with hyperventilation, panic, anabolic steroid use Increased in hyperventilation, panic; decreased in psychogenic vomiting, bulimia Increased in hyperparathyroidism; decreased in hypoparathyroidism, long-term laxative use Increased with panhypopituitarism; decreased with alcohol abuse; associated with agitation, delirium, seizures Decreased with panic, hyperventilation, renal failure, diabetic acidosis, hypoparathyroidism, cirrhosis, hyperparathyroidism, hypokalemia Routine screening; monitoring of renally excreted agents Routine screening; monitoring of renally excreted agents Routine screening; depression workup Routine screening; dementia workup Increased with renal disease, dehydration Increased with renal disease, dehydration Increased in hypothyroidism (lithium use); decreased in hyperthyroidism Decreased in megaloblastic anemia, dementia, psychosis, fatigue, agitation, delirium Decrease associated with fatigue, agitation, dementia, delirium, psychosis, alcohol abuse, phenytoin use Increased with hepatic encephalopathy/failure, GI bleed, severe CHF Decreased with Wilson disease Increased levels of mercury, lead, arsenic

Platelets Mean corpuscular volume Reticulocyte count Serum chemistry

Sodium

Potassium

Glucose

Bicarbonate

Chloride

Calcium

Magnesium

Phosphorus

BUN Creatinine TSH Vitamin B12

Folate

Routine screening; dementia workup

Ammonia Ceruloplasmin Heavy metals LFTs

Delirium workup Psychosis workup Psychosis workup; abnormal movements Routine screening; monitoring of hepatically metabolized agents; acetaminophen toxicity

Alanine transaminase

Increased in hepatitis, cirrhosis, liver metastasis; decreased with pyridoxine (vitamin B6) deficiency Increased with hepatic disease, pancreatitis, alcohol abuse Increased in hepatitis, cirrhosis, biliary obstruction, hemolytic anemia Increased in biliary obstruction Increased with phenothiazine use, hyperparathyroidism, hepatic disease, hepatic metastases, heart failure; decreased with pernicious anemia (vitamin B12 deficiency)

Aspartate transaminase Total bilirubin Direct bilirubin Alkaline phosphatase

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Creatine kinase ESR Toxicology

Delirium workup Routine screening Routine screening; known or suspected substance abuse; delirium workup; psychosis workup

Increased in NMS, seizure, heart attack, myocarditis, brain injury or stroke Increased in infection, inflammation, autoimmune or malignant process Serum: alcohol (1 - 2 days), cocaine (hours to 1 day), benzodiazepines (variable), opiates (variable), THC (n/a); urine: alcohol (1 day), cocaine (2 - 3 days), benzodiazepines (2 - 3 days), opiates (1 - 3 days), THC (30 days or more with long-term use) Increased in pregnancy Positive ELISA screening test to be followed up with confirmatory Western blot in order to make positive diagnosis High titers in syphilis (CNS involvement with tertiary syphilis)

-HCG HIV infection

Routine screening in all women of childbearing age Psychosis workup; delirium workup; dementia workup

Syphilis serologies Urinalysis

Routine screening; dementia workup Delirium workup; patient with fever; dysuria, hematuria, or urinary frequency; elevated WBC count, BUN, or creatinine

Ketones Glucose Blood

Present in poor nutrition/starvation, diabetes Present in diabetes, renal glucosuria Present in trauma, urinary tract infections, kidney stones, malignancy, glomerular disease Present in diabetes Present in urinary tract infections Present in urinary tract infections Present in urinary tract infections Present in urinary tract infections or in asymptomatic bacteriuria Delirium workup; patient with positive pulmonary ROS, fever, or elevated WBC count Patient with mental status changes associated with fever, headache, photophobia, or meningeal symptoms NPH: elevated opening pressure; bacterial meningitis: decreased glucose, elevated protein, greatly elevated cell count (predominantly PMNs), bacteria-positive culture; aseptic meningitis: normal glucose, normal or elevated protein, mildly elevated cell count (predominantly lymphocytes) Infection: antibodies present or cultures positive for various infectious agents; leptomeningeal metastases: malignant cells on cytology Evidence of pneumonia, tuberculosis, pulmonary edema

Protein Leukocyte esterase Nitrite WBCs Bacteria Chest films

Lumbar puncture

Routine CSF studies: opening pressure, appearance, Gram stain, culture, cell counts, protein, glucose

Additonal studies: HSV, Lyme, Cryptococcus antigens, acid-fast staining, cytological examination for leptomeningeal metastases

CBC, complete blood cell; WBC, white blood cell; NMS, neuroleptic malignant syndrome; SIADH, syndrome of inappropriate antidiuretic hormone secretion; CHF, congestive heart failure; BUN, blood urea nitrogen; TSH, thyroid-stimulating hormone; LFT, liver function test; ESR, erythrocyte sedimentation rate; THC, tetrahydrocannabinol; n/a, not applicable; HCG, human chorionic gonadotropin; ELISA, enzyme-linked immunosorbent assay; ROS, review of systems; CSF, cerebrospinal fluid; NPH, normal pressure hydrocephalus; PMNs, polymorphonuclear leukocytes; HSV, herpes simplex virus. Adapted from Smith FA. Massachusetts General Hospital Comprehensive Clinical Psychiatry. 2008.2

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Table 2
Test

Tests of electrophysiology: which to orderand when

When to order Select abnormal findings

Electroencephalography

Concern for seizure activity; delirium; part of polysomnography

Generalized seizure: bilateral, symmetric, synchronous, paroxysmal spike; sharp waves followed by slow waves Absence seizure: 3-Hz spike-wave complexes Complex partial seizure: temporal lobe spikes, polyspikes, and waves Delirium: generalized and activity slowing of the background Alzheimer or vascular dementia: accompanying myoclonic jerks Benzodiazepines and barbiturates: Focal lesions: focal slowing activity Neuroleptics and antidepressants: nonspecific changes

CJD and subacute sclerosing parencephalitis: periodic complexes

Electrocardiography

Monitoring antipsychotic and TCA use and to rule out cardiac disease in patients with anxiety symptoms; consider in geriatric patients

Prolonged QTc (often associated with antipsychotic use); cardiac conduction abnormalities (associated with TCA use)

CJD, Creutzfeldt-Jakob disease; TCA, tricyclic antidepressant. Adapted from Roffman JL, Stern TA. Massachusetts General Hospital Handbook of General Hospital Psychiatry. 2004.1

Table 3
Test When to order

Neuroimaging tests: which to orderand when

Select abnormal findings

Head CT

Acute mental status change; history of head trauma; delirium of unknown etiology; before initial ECT treatment; focal neurological symptoms; subacute and chronic stroke (> 24 h); when MRI is contraindicated; when rapid evaluation is needed; clearance for lumbar puncture

Tumors: mass effect and midline deviation, post-contrast enhancement Skull fracture: linear or depressed Acute hemorrhage/hematoma: hyperdensity in sulci and fissures (subarachnoid); crescent-shaped hyperdensity, does not cross dural reflections (subdural); biconvex hyperdensity, crosses dural reflections, associated with skull fracture (epidural); hyperdensity in ventricles (intraventricular); hyperdensity or heterogeneous appearance (intracerebral) Ischemic stroke: diffuse hypodensity and sulcal effacement, loss of gray/white distinction, hyperdense vessel sign, lentiform nucleus obscuration, mass effect, hemorrhagic transformation Degeneration: diffuse cerebral atrophy, enlarged ventricles, and widened sulci (DAT); caudate atrophy (Huntington disease); frontotemporal atrophy (FTD/Pick disease) Infection: post-contrast enhancement or no abnormal findings (meningitis); hypodense mass with rim enhancement (abscess) NPH: enlarged ventricles

Brain MRI

New-onset psychosis; new-onset dementia; evaluation of white matter lesions and small structures or visualization of posterior fossa; acute stroke (< 24 h)

Ischemic stroke: area of decreased ADC/hyperintensity on DWI, hypointensity on T1, hyperintensity on T2; diffusion-perfusion mismatch Degeneration: temporal and parietal atrophy (DAT); caudate atrophy (Huntington disease); frontotemporal atrophy (FTD/Pick disease); pallor of substantia nigra (DLB); centrum seviovale and periventricular ischemic white matter disease (vascular) Multiple sclerosis: multiple T2 hyperintense white matter lesions, especially periventricular and corpus callosum lesions

PET

Primarily used in research; evaluation of deep seizure foci; differentiating dementia diagnoses

Seizure: ictal changes in glucose metabolism FTD: hypometabolism in frontal and anterior temporal cortices DAT: hypometabolism in posterior cingulate gyrus, hippocampus and parietotemporal cortices, frontal lobes in advanced disease DLB: hypometabolism in parieto-occipital regions

ECT, electroconvulsive therapy; DAT, dementia of Alzheimer type; FTD, frontotemporal dementia; NPH, normal pressure hydrocephalus; ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; DLB, dementia with lewy bodies; PET, positron emission tomography.

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Table 4
Medication

A guide to monitoring patients taking psychotropic medications

Baseline tests Early monitoring Long-term monitoring Serum level Warnings

Mood stabilizers Lithium Electrolytes, BUN/creatinine, CBC, TSH, U/A, ECG (if > 35 years old), pregnancy test Check drug level (8 - 12 hours after last dose) once a week while titrating, then every 2 months Weekly LFTs, CBC, and drug level until stable dose, then monthly for 6 months Na, CBC, LFTs, drug level every 1 - 2 weeks while titrating, then monthly for 4 months Check drug level (8 - 12 hours after last dose) every 2 months with BUN/ creatinine and electrolytes; check TSH every 6 months LFTs, CBC, and drug level every 6 - 12 months 0.5 - 1.2 mEq/L Lithium toxicity, renal insufficiency/failure

Valproic acid

CBC with differential, LFTs, pregnancy test

50 - 100 mEq/L

Hepatotoxicity, teratogenicity, pancreatitis

Carbamazepine

Na, CBC with differential, BUN/creatinine, LFTs, TSH, pregnancy test

Na, CBC, BUN/creatinine, LFTs, TSH, drug level every 6 - 12 months

6 - 12 g/mL

Aplastic anemia, agranulocytosis, neutropenia, seizure, myocarditis

Antipsychotic medications Typical antipsychotics (first-generation) CBC, ECG (including QTc), orthostasis CBC, ECG (including QTc), prolactin level (if clinically indicated), orthostasis Black box warning for increased mortality risk in elderly dementia patients, blood dyscrasias, hyperprolactinemia Black box warning for increased mortality risk in elderly dementia patients

Atypical antipsychotics (second-generation)

Weight, waist circumference, blood pressure, fasting glucose and lipid profile ECG (including QTc), heart rate, orthostasis CBC with differential

Monthly weight for first 3 months, then quarterly; blood pressure, fasting glucose and lipid profile at 3 months

Annual waist circumference, blood pressure, fasting glucose; fasting lipid profile every 5 years ECG (including QTc), heart rate, orthostasis

Aripiprazole Clozapine

Black box warning as above Black box warning as above, agranulocytosis, seizure, myocarditis Black box warning as above, neutropenia Black box warning as above

CBC with differential weekly for 6 months, then every other week for next 6 months

CBC with differential once a month after 12 months of continuous therapy ECG (including QTc), orthostasis, CBC ECG (including QTc), heart rate, orthostasis, prolactin level (if clinically indicated) ECG (including QTc) ECG (including QTc), heart rate, potassium and magnesium

Olanzapine Risperidone and paliperidone

ECG (including QTc), orthostasis, CBC ECG (including QTc), heart rate, orthostasis

Quetiapine Ziprasidone

ECG (including QTc) ECG (including QTc), heart rate, potassium and magnesium

Black box warning as above Black box warning as above

Tricyclic antidepressants Imipramine ECG (including QTc) Level (10 - 14 hours after last dose) symptomdriven by signs of toxicity; annual ECG or more frequently with cardiac disease Level (10 - 14 hours after last dose); annual ECG or more frequently with signs of toxicity Same as imipramine 200 - 250 ng/mL; check level of parent component and its metabolite (desipramine) 50 - 150 ng/mL (therapeutic window)

Nortriptyline

ECG (including QTc)

Desipramine

ECG (including QTc)

Unclear, > 125 ng/mL correlates with favorable response Unclear, possible range 75 - 150 ng/mL; check level of parent component and its metabolite (nortriptyline)

Amitriptyline

ECG (including QTc)

Same as imipramine

BUN, blood urea nitrogen; CBC, complete blood cell; TSH, thyroid-stimulating hormone; U/A, urinalysis; LFTs, liver function tests; Na, sodium. Adapted from Smith FA. Massachusetts General Hospital Comprehensive Clinical Psychiatry. 2008.2