Valproic acid (VPA) and its derivatives. The most important initial monitoring for VPA therapy includes LFTs and CBC. Before initiating VPA treatment, take a medical history, with special attention to hepatic, hematologic, and bleeding abnormalities. Therapeutic blood monitoring can be conducted once steady state is achieved and as clinically necessary thereafter.
VPA can be administered at an initial starting dosage of 20 to 30 mg/kg/d in inpatients. In outpatients it is given in low, divided doses or as once-daily dosing using an extended-release formulation to minimize GI and neurologic toxicity and titrated every few days. Target serum level is 50 to 125 μg/mL.
Side effects of VPA include GI distress (eg, anorexia, nausea, dyspepsia, vomiting, diarrhea), hematologic effects (reversible leukopenia, thrombocytopenia), hair loss, weight gain, tremor, hepatic effects (benign LFT elevations, hepatotoxicity), osteoporosis, and sedation. Patients with prior or current hepatic disease may be at greater risk for hepatotoxicity. There is an association between VPA and polycystic ovarian syndrome. Rare, idiosyncratic, but potentially fatal adverse events with valproate include irreversible hepatic failure, hemorrhagic pancreatitis, and agranulocytosis.
Older monitoring standards indicated taking LFTs and CBC every 6 months and serum VPA level as clinically indicated. According to ISBD guidelines, weight, CBC, LFTs, and menstrual history should be monitored every 3 months for the first year and then annually; blood pressure, bone status (densitometry), fasting glucose, and fasting lipids should be monitored only in patients with related risk factors. Routine ammonia levels are not recommended but might be indicated if a patient has sudden mental status changes or change in condition.2
Carbamazepine and oxcarbazepine. The most important initial monitoring for carbamazepine therapy includes LFTs, renal function, electrolytes, and CBC. Before treatment, take a medical history, with special emphasis on history of blood dyscrasias or liver disease. After initiating carbamazepine, CBC, LFTs, electrolytes, and renal function should be done monthly for 3 months, then repeated annually.
Carbamazepine is a substrate and an inducer of the cytochrome P450 (CYP) system, so it can reduce levels of many other drugs including other antiepileptics, warfarin, and oral contraceptives. Serum level of carbamazepine can be measured at trough after 5 days, with a target level of 4 to 12 μg/mL. Two levels should be drawn, 4 weeks apart, to establish therapeutic dosage secondary to autoinduction of the CYP450 system.2
As many as one-half of patients experience side effects with carbamazepine. The most common side effects include fatigue, nausea, and neurologic symptoms (diplopia, blurred vision, and ataxia). Less frequent side effects include skin rashes, leukopenia, liver enzyme elevations, thrombocytopenia, hyponatremia, and hypo-osmolality. Rare, potentially fatal side effects include agranulocytosis, aplastic anemia, thrombocytopenia, hepatic failure, and exfoliative dermatitis (eg, Stevens-Johnson syndrome).
Patients of Asian descent who are taking carbamazepine should undergo genetic testing for the HLA-B*1502 enzyme because persons with this allele are at higher risk of developing Stevens-Johnson syndrome. Also, patients should be educated about the signs and symptoms of these rare adverse reactions so that medical treatment is not delayed should these adverse events present.
Lamotrigine does not require further laboratory monitoring beyond the initial recommended workup. The most important variables to consider are interactions with other medications (especially other antiepileptics, such as VPA and carbamazepine) and observing for rash. Titration takes several weeks to minimize risk of developing a rash.2 Similar to carbamazepine, the patient should be educated on the signs and symptoms of exfoliative dermatitis (eg, Stevens-Johnson syndrome) so that medical treatment is sought out should this reaction occur.
Atypical antipsychotics. Baseline workup includes the general monitoring parameters described above. Atypical antipsychotics have a lower incidence of extrapyramidal side effects than typical antipsychotics, but are associated with an increased risk of metabolic complications. Other major ADRs to consider are cardiac effects and hyperprolactinemia; clinicians should therefore inquire about a personal or family history of cardiac problems, including congenital long QT syndrome. Patients should be screened for any medications that can prolong the QTc interval or interact with the metabolism of medications known to cause QTc prolongation.
Measure weight monthly for the first 3 months, then every 3 months to monitor for metabolic side effects during ongoing treatment. Obtain blood pressure and fasting glucose every 3 months for the first year, then annually. Repeat a fasting lipid profile 3 months after initiating treatment, then annually. Cardiac effects and prolactin levels can be monitored as needed if clinically indicated.2
You discuss with Ms. W choices of a mood stabilizing agent to treat her bipolar II disorder; she agrees to start lithium. Before initiating treatment, you obtain her weight (and calculate her BMI), blood pressure, CBC, electrolyte levels, BUN and creatinine levels, liver function tests, fasting glucose, fasting lipid profile, and thyroid panel. You also review her medical history, lifestyle factors (cigarette smoking status, alcohol intake), and family history. A urine pregnancy screen is negative. The pharmacist assists in screening for potential drug-drug interactions, including over-the-counter medications that Ms. W occasionally takes as needed. She is counseled on the use of NSAIDS because these drugs can increase the lithium level.