From the Guidelines
Starting citalopram while simultaneously increasing valproic acid to 250mg twice daily and decreasing olanzapine should be done with caution and close medical supervision due to potential drug interactions and side effects. When initiating citalopram, it's typically started at a low dose (10-20mg daily) and gradually increased if needed, as noted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. The valproic acid increase to 250mg twice daily should be implemented with regular monitoring of blood levels to ensure therapeutic range (50-125 μg/mL) and avoid toxicity. Olanzapine reduction should be gradual to prevent withdrawal symptoms or rebound effects. Some key considerations for this medication adjustment include:
- Monitoring for serotonin syndrome (agitation, confusion, rapid heart rate, dilated pupils, muscle rigidity) since citalopram combined with other psychotropics can increase this risk 1
- Regular monitoring of liver enzymes, as all three medications can affect liver function
- Patient education on reporting unusual side effects promptly, including increased depression, suicidal thoughts, unusual bleeding, severe dizziness, or significant mood changes during this medication transition period It's essential to weigh the benefits and risks of this medication adjustment and consider the potential for drug interactions, particularly with citalopram, which may interact with drugs that prolong the QT interval 1. Close medical supervision and regular monitoring are crucial to ensure the safe and effective management of these medications.
From the FDA Drug Label
As the valproic acid dosage is titrated upward, concentrations of phenobarbital, carbamazepine, and/or phenytoin may be affected (see ) PRECAUTIONS - Drug Interactions The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response If the total daily dose exceeds 250 mg, it should be given in divided doses
The FDA drug label does not answer the question.
From the Research
Medication Interactions and Changes
- Starting citalopram, increasing valproic acid to 250mg twice daily, and decreasing olanzapine simultaneously may involve several considerations, including potential interactions between these medications 2, 3.
- The combination of olanzapine and valproic acid is commonly prescribed for bipolar or schizoaffective disorders, but valproic acid can reduce olanzapine concentration, particularly in oral formulations 2.
- Studies have shown that valproic acid can increase the risk of insufficient effect of olanzapine, especially in smokers, and may produce different metabolic effects when combined with various antipsychotic drugs 2, 3.
- Monotherapy outcomes for bipolar disorder patients prescribed lithium, valproate, quetiapine, olanzapine, venlafaxine, or citalopram have been compared, with results indicating varying treatment failure rates 4.
- Decision-making about changing medications, including patient and family engagement, is crucial for safe and high-quality medication management, especially across transitions of care 5.
- Interventions to reduce medication errors in adult medical and surgical settings have been systematically reviewed, highlighting the effectiveness of various strategies, including pharmacist-led medication reconciliation and computerised physician order entry 6.
Potential Risks and Considerations
- The potential for medication errors or interactions when starting, increasing, or decreasing medications simultaneously should be carefully evaluated 2, 3, 6.
- Patient and family engagement in decision-making about medication changes can contribute to improved medication management and reduced errors 5.
- The metabolic effects of adjunctive valproic acid with antipsychotic drugs, such as olanzapine, should be considered, as they may vary depending on the specific medication combination 3.