What should be assessed first in a patient on Valproate (valproic acid) therapy for bipolar disorder presenting with cognitive slowing and somnolence?

From the Guidelines

When a patient on valproate therapy for bipolar disorder shows signs of cognitive slowing and drowsiness, the first assessment should be to check valproate serum levels, as these symptoms can indicate valproate toxicity, which can occur even within the therapeutic range in some patients 1.

Key Considerations

• A comprehensive metabolic panel should also be ordered to evaluate liver function, as valproate can cause hepatotoxicity, and baseline liver function tests are recommended before initiating valproate therapy 1.
• Ammonia levels should be measured since valproate can cause hyperammonemia, which may present with these neurological symptoms even when serum valproate levels are normal.
• The patient's medication list should be reviewed for potential drug interactions that might increase valproate levels, particularly other CNS depressants, to avoid unnecessary polypharmacy 1.
• It's essential to inquire about recent dosage changes, timing of doses, and adherence patterns, as medication trials should be as systematic as possible, with the duration of trials sufficient to determine the agent's effectiveness 1.

Additional Evaluations

• These symptoms could also represent other medical conditions like hypothyroidism or infection, so a broader workup may be necessary if initial testing is unrevealing.
• Temporary dose reduction might be considered while awaiting laboratory results if symptoms are significant, but this should be done cautiously to avoid destabilizing the patient's bipolar disorder, and the phase of illness is an important consideration when choosing a medication 1.

From the FDA Drug Label

The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. In elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events

The patient's somnolence and cognitive slowing should be assessed first, as these may be signs of adverse reactions to valproate therapy, particularly in elderly patients or those with higher doses.

• Dose reduction or discontinuation of valproate may be necessary to mitigate these adverse effects.
• The patient's valproate serum concentrations should be monitored to determine if they are within the therapeutic range (50 to 100 μg/mL) 2.
• The patient's fluid and nutritional intake should also be monitored, as decreased intake may contribute to somnolence and other adverse events 2.

From the Research

Assessment of Cognitive Slowing and Drowsiness in a Patient on Valproate Therapy

The patient's symptoms of cognitive slowing and drowsiness while on valproate therapy for bipolar disorder should be assessed in the context of potential side effects of the medication.

• The therapeutic serum levels of valproate should be checked to ensure they are within the recommended range, as levels outside of this range may contribute to adverse effects 3.
• Monitoring of serum valproate levels is crucial, as evidenced by a study that found a significant positive correlation between days taken to reach maximum dose and hospital stay 4.
• The patient's response to valproate therapy should be evaluated, considering factors such as the presence of therapeutic serum levels and the potential need for adjunctive therapy with atypical antipsychotics 5.
• It is essential to consider the patient's overall clinical presentation, including the severity of their bipolar disorder symptoms and any potential comorbidities, when assessing the cause of cognitive slowing and drowsiness 6, 7.

Potential Next Steps

• Check the patient's valproate serum levels to determine if they are within the therapeutic range.
• Evaluate the patient's response to valproate therapy and consider adjusting the dose or adding adjunctive therapy if necessary.
• Assess the patient's overall clinical presentation and consider potential comorbidities that may be contributing to their symptoms.
• Consider alternative mood stabilizers, such as lithium, if valproate is not effective or is causing significant side effects 3, 5.