From the Guidelines
For a 77-year-old woman with dementia showing aggressive behavior and confusion despite increased olanzapine (5mg twice daily) and valproic acid (125mg bid), I strongly recommend reducing the olanzapine dose to minimize the risk of increased mortality and worsening confusion, as highlighted in the guidelines for managing Alzheimer's disease 1.
Medication Adjustment
- Consider reducing the olanzapine dose to 2.5mg twice daily, as antipsychotics in elderly dementia patients carry black box warnings for increased mortality risk and can worsen confusion, as noted in the treatment guidelines for Alzheimer's disease 1.
- The valproic acid dose is relatively low and could be titrated up gradually to 250-500mg bid with regular monitoring of blood levels (target 50-100 μg/mL), as suggested in the guidelines for managing behavior and mood disorders in Alzheimer's disease 1.
- Adding a selective serotonin reuptake inhibitor (SSRI) like citalopram 10mg daily might help manage agitation with fewer risks than antipsychotics, as recommended in the guidelines for managing Alzheimer's disease 1.
Non-Pharmacological Interventions
- Non-pharmacological approaches are essential and should include:
- Establishing consistent daily routines
- Creating a calm environment
- Identifying and addressing triggers for agitation
- Using redirection techniques, as emphasized in the guidelines for managing Alzheimer's disease 1.
- Medical evaluation for underlying causes such as pain, infection, medication side effects, or metabolic disturbances is crucial, as these often trigger behavioral symptoms in dementia, as noted in the guidelines for managing Alzheimer's disease 1.
Monitoring and Adjustments
- Regular monitoring of cognitive function, behavior patterns, and medication side effects should be implemented, with adjustments made accordingly, as recommended in the guidelines for managing Alzheimer's disease 1.
- This balanced approach addresses both symptom management and patient safety while recognizing that behavioral symptoms in dementia often require multimodal treatment rather than medication escalation alone, as highlighted in the guidelines for managing Alzheimer's disease 1.
From the FDA Drug Label
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications Anyone considering prescribing valproic acid or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. In elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence
The patient is a 77-year-old woman with dementia, exhibiting aggressive behavior and confusion, who continues to show symptoms despite recent increases in olanzapine to 5mg twice daily and initiation of valproic acid 125mg bid.
- The valproic acid dose was increased relatively quickly, which may not be suitable for elderly patients.
- The patient's symptoms have not improved, and the current treatment regimen may need to be reassessed.
- Consider dose reductions or discontinuation of valproate if the patient experiences adverse events such as somnolence, dehydration, or decreased food and fluid intake.
- Monitor the patient closely for signs of suicidal thoughts or behavior, as well as other adverse effects associated with valproic acid treatment 2.
- Consider alternative treatment options or adjustments to the current regimen to better manage the patient's symptoms.
From the Research
Patient Assessment
The patient is a 77-year-old woman with dementia, exhibiting aggressive behavior and confusion, who has been taking olanzapine and valproic acid. Despite recent increases in olanzapine to 5mg twice daily and initiation of valproic acid 125mg bid, she continues to show symptoms.
Medication Interaction
- The combination of olanzapine and valproic acid may lead to a decrease in olanzapine plasma concentrations, as shown in a study published in 2009 3.
- Another study published in 2014 found that valproic acid may interact with olanzapine, leading to a possible increase in adverse drug reactions 4.
- A study published in 2019 found that valproic acid had no effect on olanzapine dose-adjusted concentrations in patients using long-acting injectable formulation, but decreased dose-adjusted olanzapine concentration in patients using oral olanzapine 5.
- A review of human clinical data on interactions between antiepileptic and antipsychotic drugs found that valproic acid may decrease olanzapine concentrations, and that carbamazepine decreases olanzapine concentrations 6.
Recommendations
- Monitor the patient's symptoms and adjust the medication regimen as needed.
- Consider therapeutic drug monitoring to assess the interaction between valproic acid and olanzapine 4, 5.
- Be aware of the potential for decreased olanzapine concentrations when using valproic acid, particularly in patients using oral olanzapine 5.
- Consider alternative treatment options if the patient's symptoms do not improve with the current medication regimen.
Medication Adherence
- Ensure that the patient is taking her medications as prescribed, as non-adherence can lead to decreased treatment efficacy and increased risk of adverse reactions 7.