Laboratory Tests in Psychiatry
Laboratory testing is an integral part of psychiatric assessment and treatment. Compared to other medical specialists, however, psychiatrists depend more on the clinical examination and observation of signs and symptoms to make the diagnosis than they do on laboratory tests. For example, no test can establish or rule out a diagnosis of schizophrenia or mood disorder. Nevertheless, advances in neuropsychiatry and biological psychiatry have made laboratory tests more and more useful to psychiatrists in the management of emotional illness.
I. Neuroendocrine Tests
A. Thyroid function tests
Include tests for thyroxine (T4) by competitive protein binding (T4D), radioimmunoassay (T4RIA) involving a specific antigen–antibody reaction, free T4 index (FT4I), triiodothyronine uptake, and total serum triiodothyronine measured by radioimmunoassay (T3RIA).
Tests are used to rule out hypothyroidism, which can appear with symptoms of depression.
Up to 10% of patients complaining of depression and associated fatigue have incipient hypothyroid disease. Neonatal hypothyroidism results in mental retardation and is preventable if the diagnosis is made at birth.
Thyrotropin-releasing hormone (TRH) stimulation test indicated in patients whose marginally abnormal thyroid test results suggest subclinical hypothyroidism, which may account for clinical depression.
Procedure
At 8 AM, after an overnight fast, have the patient lie down and warn of a possible urge to urinate after the injection.
Measure baseline levels of thyroid-stimulating hormone, triiodothyronine (T3), thyroxine (T4), and T3 resin uptake.
Inject 500 µg of thyroid-releasing hormone intravenously.
Measure thyroid-stimulating hormone levels at 15, 30, 60, and 90 minutes.
B. Dexamethasone suppression test (DST)
Procedure
Give 1 mg of dexamethasone orally at 11 PM.
Measure plasma cortisol at 4 PM and 11 PM the next day (may also take 8 PM sample).
Any plasma cortisol level above 5 µg/dL is abnormal (although the normal range should be adjusted according to the local assay so that 95% of normals are within the normal range).
Baseline plasma cortisol level may be helpful.
Indications
To help confirm a diagnostic impression of major depressive disorder. Not routinely used because it is unreliable. Abnormal results may confirm need for somatic treatment.
To follow a depressed nonsuppressor through treatment of depression.
To differentiate major depression from minor dysphoria.
Some evidence indicates that depressed nonsuppressors are more likely to respond positively to treatment with electroconvulsive therapy or tricyclic antidepressants.
Proposed utility in predicting outcome of treatment, but DST results may normalize before depression resolves.
Proposed utility in predicting relapse in patients who are persistent nonsuppressors or whose DST results revert to abnormal.
Possible utility in differentiating delusional from nondelusional depression.
Highly abnormal plasma cortisol levels (>10 µg/dL) are more significant than mildly elevated levels.
Reliability. The problems associated with the DST include varying reports of sensitivity or specificity. False-positive and false-negative results are common. The sensitivity of the DST is considered to be 45% in major depressive disorders and 70% in major depressive episodes with psychotic features. The specificity is 90% compared with controls and 77% compared with other psychiatric diagnoses. Some evidence indicates that patients with a positive DST result (especially 10 µg/dL) will have a good response to somatic treatment, such as electroconvulsive therapy or cyclic antidepressant therapy.
C. Catecholamines
Level of serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) is elevated in the urine of patients with carcinoid tumors.
Elevated levels are noted at times in patients who take phenothiazine medication and in those who eat foods high in serotonin (i.e., walnuts, bananas, and avocados).
The amount of 5-HIAA in cerebrospinal fluid (CSF) is low in some people who are in a suicidal depression and in postmortem studies of those who have committed suicide in particularly violent ways.
Low CSF 5-HIAA levels are associated with violence in general.
Norepinephrine and its metabolic products—metanephrine, normetane-phrine, and vanillylmandelic acid—can be measured in urine, blood, and plasma.
Plasma catecholamine levels are markedly elevated in pheochromocytoma, which is associated with anxiety, agitation, and hypertension.
High levels of urinary norepinephrine and epinephrine have been found in some patients with posttraumatic stress disorder (PTSD).
The norepinephrine metabolic 3-methoxy-4-hydroxyphenylglycol level is decreased in patients with severe depressive disorders, especially in those patients who attempt suicide.
Table 5-1 Other Laboratory Testing for Patients Taking Lithium | ||||||||||||||
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D. Other endocrine tests.
In addition to thyroid hormones, these hormones include the anterior pituitary hormone prolactin, growth hormone, somatostatin, gonadotropin-releasing hormone, and the sex steroids—luteinizing hormone, follicle-stimulating hormone, testosterone, and estrogen. Melatonin from the pineal gland has been implicated in seasonal affective disorder (called mood disorder with seasonal pattern in the text revision of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR]).
II. Renal and Hepatic Tests
A. Renal function tests.
Serum blood urea nitrogen (BUN) and creatinine are monitored in patients taking lithium (Eskalith). If the serum BUN or creatinine is abnormal, the patient’s 2-hour creatinine clearance and, ultimately, the 24-hour creatinine clearance are tested. Table 5-1 summarizes other laboratory testing for patients taking lithium.
B. Liver function tests
Total bilirubin and direct bilirubin values are elevated in hepatocellular injury and intrahepatic bile stasis, which can occur with phenothiazine or tricyclic medication and with alcohol and other substance abuse.
Liver damage or disease, which is reflected by abnormal findings in liver function tests (LFTs), may manifest with signs and symptoms of a cognitive disorder, including disorientation and delirium.
LFTs must be monitored routinely when using certain drugs, such as carbamazepine (Tegretol) and valproate (Depakene).
III. Blood Test for Sexually Transmitted Diseases (STDs)
Venereal Disease Research Laboratory (VDRL) test is used as a screening test for syphilis. If positive, the result is confirmed by using the specific fluorescent treponemal antibody-absorption test (FTA-ABS test), in which the spirochete Treponema pallidum is used as the antigen.
A positive HIV test result indicates that a person has been exposed to infection with the virus that causes AIDS.
IV. Tests Related to Psychotropic Drugs
A. Benzodiazepines
B. Antipsychotics
No specific tests are needed, although it is good to obtain baseline values for liver function and a complete blood cell count. Antipsychotics are metabolized primarily in the liver, with metabolites excreted primarily in urine. Many metabolites are active. Peak plasma concentration usually is reached 2 to 3 hours after an oral dose. Elimination half-life is 12 to 30 hours but may be much longer. Steady state requires at least 1 week at a constant dose (months at a constant dose of depot antipsychotics).
With the exception of clozapine (Clozaril), all antipsychotics acutely cause an elevation in serum prolactin (secondary to tuberoinfundibular activity). A normal prolactin level often indicates either noncompliance or nonabsorption. Side effects include leukocytosis, leucopenia, impaired platelet function, mild anemia (both aplastic and hemolytic), and agranulocytosis. Bone marrow and blood element side effects can occur abruptly, even when the dosage has remained constant. Low-potency antipsychotics are most likely to cause agranulocytosis, which is most common bone marrow side effect. These agents may cause hepatocellular injury and intrahepatic biliary stasis (indicated by elevated total and direct bilirubin and elevated transaminases). They also can cause electrocardiographic changes (not as frequently as with tricyclic antidepressants), including a prolonged QT interval; flattened, inverted, or bifid T waves; and U waves. Dose-plasma concentration relations differ widely among patients.
Clozapine. Because of the risk of agranulocytosis (1% to 2%), patients who are being treated with clozapine must have a baseline white blood cell (WBC) and differential count before the initiation of treatment, a WBC count every week throughout treatment, and a WBC count for 4 weeks after the discontinuation of clozapine. Physicians and pharmacists who provide clozapine are required to be registered through Clozaril National Registry (1-800-448-5938).
C. Tricyclic and tetracyclic drugs.
An electrocardiogram (ECG) should be given before starting a regimen of cyclic drugs to assess for conduction delays, which may lead to heart blocks at therapeutic levels. Some clinicians believe that all patients receiving prolonged cyclic drug therapy should have an annual ECG. At therapeutic levels, the drugs suppress arrhythmias through a quinidinelike effect.
Blood levels should be tested routinely when using imipramine (Tofranil), desipramine (Norpramin), or nortriptyline (Pamelor) in the treatment of depressive disorders. Taking blood levels may also be of use in patients for whom there is an urgent need to know whether a therapeutic or toxic plasma level of the drug has been reached. Blood level tests should also include the measurement of active metabolites (e.g., imipramine is
converted to desipramine, amitriptyline [Elavil] to nortriptyline). Some characteristics of tricyclic drug plasma levels are described as follows.
converted to desipramine, amitriptyline [Elavil] to nortriptyline). Some characteristics of tricyclic drug plasma levels are described as follows.
Imipramine (Tofranil). The percentage of favorable responses to imipramine correlates with plasma levels in a linear manner between 200 and 250 ng/mL, but some patients may respond at a lower level. At levels that exceed 250 ng/mL, there is no improved favorable response, and side effects increase.
Nortriptyline (Pamelor). The therapeutic window (the range within which a drug is most effective) of nortriptyline is between 50 and 150 ng/ mL. There is a decreased response rate at levels greater than 150 ng/mL.
Desipramine (Norpramin). Levels of desipramine greater than 125 ng/mL correlate with a higher percentage of favorable responses.
Amitriptyline (Elavil). Different studies have produced conflicting results with regard to blood levels of amitriptyline, but they range from 75 to 175 ng/mL.
Procedure for determining blood concentrations. The blood specimen should be drawn 10 to 14 hours after the last dose, usually in the morning after a bedtime dose. Patients must be receiving stable daily dosage for at least 5 days for the test to be valid. Some patients are unusually poor metabolizers of cyclic drugs and may have levels as high as 2,000 ng/mL while taking normal dosages and before showing a favorable clinical response. Such patients must be monitored closely for cardiac side effects. Patients with levels greater than 1,000 ng/mL are generally at risk for cardiotoxicity.
D. Monamine oxidase inhibitors (MAOIs).
Patients taking MAOIs are instructed to avoid tyramine-containing foods because of the danger of a potential hypertensive crisis. A baseline normal blood pressure (BP) must be recorded, and the BP must be monitored during treatment. MAOIs may also cause orthostatic hypotension as a direct drug side effect unrelated to diet. Other than their potential for causing elevated BP when taken with certain foods, MAOIs are relatively free of other side effects. A test used both in a research setting and in current clinical practice involves correlating the therapeutic response with the degree of platelet MAO inhibition.
E. Lithium.
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