Savvy Psychopharmacology

How should you use the lab to monitor patients taking a mood stabilizer?

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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

CASE CONTINUED
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.

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