Prudent prescribing: Intelligent use of lab tests and other diagnostics
More important than memorizing lists is to understand why and when certain tests are important.
THERAPEUTIC DRUG MONITORING
Therapeutic drug monitoring (TDM) is used to optimize treatment with medications for which therapeutic blood levels for psychiatric disorders have been described.6 These include lithium, valproate, carbamazepine, clozapine, and tricyclic antidepressants.
Keep in mind that “therapeutic” blood levels have been determined in “usual” patients in controlled clinical trials and may not apply to the many “unusual” patients who metabolize drugs differently because of genetic variation, age, and concomitant diseases, diet, or medications.7
Lithium. A therapeutic blood level is typically 0.6 to 1.2 mEq/L, and—although the dosage must be individualized—900 to 1,200 mg/d in divided doses usually maintains this blood level. Lower levels between 0.4 mEq/L and 0.8 mEq/L have been described for the elderly.8
In uncomplicated cases, monitor lithium levels at least every 2 months during maintenance therapy. Draw blood immediately before a scheduled dose—such as 8 to 12 hours after the previous dose—when lithium concentrations are relatively stable.
Consider both clinical signs and serum levels when dosing, as patients unusually sensitive to lithium may exhibit toxic signs at <1.0 mEq/L. Elderly patients often respond to reduced dosages and may exhibit signs of toxicity—such as gastric upset and confusion—at serum levels most younger patients can tolerate.
Valproate. For seizure and bipolar disorders, the therapeutic blood level is 50 to 100 mcg/mL. Potential hematologic complications include thrombocytopenia; indigestion and nausea are common side effects. Typical practice is to obtain levels weekly for the first few weeks and then quarterly thereafter.
Carbamazepine. Plasma carbamazepine concentrations have not been correlated with response in bipolar disorder but are measured to prevent or identify toxicity. Dosages of 600 to 1,200 mg/d usually produce nontoxic levels of 4 to 12 mcg/mL. Carbamazepine interacts with many drugs that affect or are affected by hepatic metabolism. Blood dyscrasias including aplastic anemia are rare side effects.
Clozapine. Consensus is lacking on the optimal clozapine plasma level needed to achieve a therapeutic response. For some patients, it may be 200 to 350 ng/mL, which usually corresponds to 200 to 400 mg/d. Dosing must be individualized, however, because clozapine levels can vary almost 50-fold among patients taking the same dosage.9 Other studies10 and at least one recent textbook11 have reported therapeutic response most associated with clozapine levels >350 ng/mL, although adverse effects may be more likely at this higher dosage.
PROTECTING THE HEART
Before you prescribe any psychotropic with potential cardiotoxic effects, we recommend a baseline ECG for patients with cardiac risk factors, including:
- history of heart disease or ECG abnormalities
- history of syncope
- family history of sudden death before age 40, especially if both parents had sudden death
- history of prolonged QTc interval, such as congenital long QT syndrome.
Cardiotoxic effects such as QTc interval prolongation and torsades de pointes have been associated with thioridazine, mesoridazine, and pimozide. On ECG, a QTc interval >500 msec suggests an increased risk of potentially fatal arrhythmias. Do not prescribe medications associated with QTc interval prolongation to patients with this ECG finding.
Table 3
Screening tests most sources recommend for psychiatric practice
| Blood |
| Complete blood count (CBC) |
| Serum chemistry panel (“CHEM-20,” including liver function tests) |
| Lipid panels |
| Thyroid function tests (TFTs, TSH) |
| Screening tests for HIV, hepatitis C, syphilis |
| Serum B12 |
| Pregnancy tests in women of childbearing age and potential |
| Blood alcohol level in alcohol-intoxicated patient |
| Urine |
| Urine drug toxicology screen for substance abuse |
| Urinalysis |
| Cardiac |
| ECG |
| Imaging |
| Brain CT or MRI (preferred) if clinically indicated* |
| Chest radiography |
| Others |
| Serum medication levels† |
| Erythrocyte sedimentation rate or urine heavy metal screen, as indicated by medical history |
| Erythrocyte uroporphyrinogen-1-synthase |
| Urine uroporphyrins |
| EEG |
| Skull radiography |
| * Such as patient with disorientation, confusion, or abnormal neurologic exam |
| † When therapeutic/toxic blood levels are available for patient’s medications, such as theophylline, tricyclics, digoxin |
ECG is also indicated in patients who experience symptoms associated with a prolonged QT interval—such as dizziness or syncope—while taking antipsychotics. If ziprasidone is prescribed for patients with any of the risk factors described above, we recommend a baseline ECG before treatment begins, with a follow-up ECG if the patient experiences dizziness or syncope.4
Table 4
Screening tests for a patient beginning substance abuse treatment
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WHEN USING CLOZAPINE
Clozapine is the only antipsychotic shown to improve neuroleptic-resistant symptoms12 and reduce suicidality13 in patients with schizophrenia. Unfortunately, clozapine’s potential side effects—including potentially life-threatening agranulocytosis—are legion, but careful monitoring with necessary lab testing can allow its benefits to outweigh the risks.
