After increasing the Depakote (valproate) dose from 500mg to 715mg twice a day, and considering the patient's recent behavior of stealing medication, should the dose be decreased or should we wait for the blood draw results to assess potential toxicity?

Immediate Dose Adjustment Without Waiting for Blood Draw

Do not decrease the Depakote dose immediately; wait for the blood draw to guide your decision, but ensure the blood draw is obtained urgently (within 24-48 hours) to assess for potential toxicity. The patient's behavior of stealing medication raises serious concerns about either inadequate dosing leading to breakthrough symptoms or potential toxicity causing behavioral changes, and only a valproate level can distinguish between these scenarios 1.

Rationale for Waiting for Blood Draw

The blood level is essential because valproate has a well-established therapeutic range (50-100 μg/mL), and clinical decisions should be guided by objective data rather than behavioral observations alone 1. The FDA labeling explicitly states that "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" 1.

• Behavioral changes can indicate either under-dosing or toxicity, making empiric dose adjustments potentially dangerous 2, 3
• The recent dose increase from 500mg to 715mg twice daily represents a 43% increase, which is substantial and warrants monitoring 1
• Valproate reaches steady-state in approximately 2-4 days, so if the dose was recently increased, levels may still be rising 2

Urgent Safety Assessment Required

While waiting for the blood draw, immediately assess for signs of valproate toxicity:

• Encephalopathy symptoms: confusion, lethargy, somnolence, or altered mental status 2
• Tremor (dose-related and common at higher levels) 2
• Gastrointestinal symptoms: nausea, vomiting, or abdominal pain 2
• Ataxia or coordination problems 3

If any signs of acute toxicity are present, hold the next dose and obtain stat valproate level, liver function tests, ammonia level, and complete blood count 1, 2.

Interpretation of "Stealing Medication"

This behavior requires immediate clarification:

• Is the patient taking extra doses (suggesting perceived inadequate symptom control or drug-seeking)? 4
• Is the patient hoarding medication (suggesting paranoia, psychosis, or fear of running out)? 4
• Is the patient selling/diverting medication (less likely with valproate but possible)? 4

The context matters significantly for your next steps 4.

Blood Draw Timing Considerations

If the patient takes Depakote twice daily, obtain a trough level immediately before the morning dose 1, 5. This provides the most interpretable result against the established therapeutic range of 50-100 μg/mL 1.

• Trough levels are standard for twice-daily dosing and most accurately reflect steady-state exposure 5
• Toxicity risk increases significantly at levels >110 μg/mL in females and >135 μg/mL in males 1

Decision Algorithm Based on Blood Level Results

Once you have the valproate level:

If Level is Subtherapeutic (<50 μg/mL):

• The "stealing" behavior may represent pseudoaddiction or therapeutic dependence due to inadequate seizure/mood control 4
• Increase dose by 5-10 mg/kg/week as tolerated, up to maximum 60 mg/kg/day 1
• Recheck level in 3-5 days after dose adjustment 1

If Level is Therapeutic (50-100 μg/mL):

• The behavior is likely not medication-related
• Maintain current dose and address behavioral issues through psychiatric evaluation 4
• Consider whether the patient has adequate medication supply and understands the dosing regimen 6, 7

If Level is Supratherapeutic (>100 μg/mL) but <110 μg/mL (females) or <135 μg/mL (males):

• Reduce dose by 25-50% immediately 4
• Monitor closely for resolution of behavioral symptoms 4
• Recheck level in 3-5 days 1

If Level is Toxic (>110 μg/mL in females or >135 μg/mL in males):

• Hold medication immediately and consider hospitalization 1, 4
• Monitor for encephalopathy, hyperammonemia, and thrombocytopenia 1, 2
• Resume at reduced dose only after level decreases and symptoms resolve 4

Critical Safety Considerations

Never abruptly discontinue valproate without a clear plan, as this can precipitate status epilepticus if used for seizures 1. However, if the patient is exhibiting signs of severe toxicity, holding doses temporarily is appropriate while arranging urgent medical evaluation 4, 1.

• Document the medication theft incident thoroughly, including exact amounts and timeline 6, 7
• Assess for other drug-related problems including medication errors in dispensing or patient misunderstanding of instructions 6, 7
• Consider whether the patient has access to multiple prescribers or pharmacies 4

Monitoring Plan Going Forward

After resolving the acute situation, implement closer monitoring:

• Check valproate levels every 3-6 months at minimum 4, 1
• Monitor liver function tests, complete blood count, and ammonia if clinically indicated 1, 2
• Consider pill counts at each visit if diversion or non-adherence is suspected 4
• Evaluate for psychiatric comorbidities that may be driving the medication-seeking behavior 4

The key principle is that objective data (the blood level) must guide dose adjustments in this situation, not behavioral observations alone 4, 1. Premature dose reduction could worsen the underlying condition, while maintaining a toxic dose could cause serious harm 4, 1, 2.