From the FDA Drug Label
The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 μg/mL in females and 135 μg/mL in males. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 μg/mL). Therapeutic valproate serum concentrations for most patients with absence seizures is considered to range from 50 to 100 μg/mL.
The target trough level for Depakote (valproate) is 50 to 100 μg/mL. This range is considered the usually accepted therapeutic range for most patients. However, it's essential to note that some patients may be controlled with lower or higher serum concentrations. The trough level should be monitored to avoid concentrations above 110 μg/mL in females and 135 μg/mL in males, as this increases the risk of thrombocytopenia 1.
From the Research
The target trough level for Depakote (valproate) should be maintained between 50-100 mcg/mL (or 50-100 mg/L) for most indications, with levels between 50-125 mcg/mL potentially targeted for bipolar disorder management, as evidenced by the most recent and highest quality study available 2. When monitoring Depakote therapy, blood samples should be drawn in the morning before the first dose of the day (trough level) to ensure consistent and accurate measurements. Some key points to consider include:
- Therapeutic drug monitoring is essential because valproate has a relatively narrow therapeutic window, and levels above the target range increase the risk of adverse effects such as sedation, tremor, and hepatotoxicity, as noted in various studies 3, 4, 5, 6.
- Levels below the therapeutic range may result in inadequate symptom control.
- Individual dosing should be guided by both clinical response and measured serum levels, with adjustments made gradually to minimize side effects while maximizing therapeutic benefit.
- The appropriate therapeutic serum valproate level in maintenance therapy for bipolar disorder may vary, with one study suggesting levels of 52.2 +/- 20.4 microg/ml in bipolar I and 41.0 +/- 18.3 microg/ml in bipolar II disorder patients 2.
- It is also important to consider that some patients may achieve therapeutic benefits at lower levels, while others may require higher levels for symptom control, as seen in a study where patients with improved seizure control had valproate levels ranging from 111-196 micrograms/ml 6.