From the Guidelines
Depakote (valproic acid/divalproex sodium) is not recommended as a first-line treatment for delirium due to its limited efficacy and significant risks, including hepatotoxicity, thrombocytopenia, and drug interactions, as noted in various studies 1. The provided evidence does not support the use of valproate as a primary treatment for delirium. Instead, it highlights the importance of addressing underlying causes and implementing non-pharmacological approaches such as reorientation, maintaining sleep-wake cycles, and promoting early mobility. When medication is necessary, antipsychotics like haloperidol (0.5-1mg orally or parenterally, titrated as needed) are preferred due to their faster onset of action and more established efficacy in managing delirium symptoms, as suggested by studies 1. Key considerations in delirium management include:
- Identifying and treating underlying causes
- Implementing non-pharmacological interventions
- Using antipsychotics at the lowest effective dose for the shortest duration
- Monitoring for potential side effects and interactions It is essential to prioritize the patient's safety and well-being, and to consult with a pharmacist and/or pharmacy references when prescribing medications for delirium management, as noted in 1. The lack of strong evidence supporting the use of valproate in delirium treatment, combined with its potential risks, makes it a less desirable option compared to antipsychotics like haloperidol, as discussed in 1.
From the Research
Efficacy of Valproate in Treating Delirium
- The efficacy of Valproate (Depakote) in treating delirium is supported by several studies 2, 3.
- Valproic acid (VPA) has multiple mechanisms of action, including effects on neurotransmitter modulation, neuroinflammation, oxidative stress, and transcription, all of which are implicated in the pathophysiology of delirium 2.
- A review of current literature suggests that VPA can be an effective and well-tolerated treatment option for the management of hyperactive and mixed type delirium 2.
- A systematic review of 10 studies (252 patients) found that delirium improved in 19/22 patients in case series and in retrospective studies at day 3 compared to day 1 3.
- The most common side effects of VPA were hyperammonemia (12-19%) and thrombocytopenia (9-13%) 3.
Comparison with Other Treatments
- Antipsychotics, such as haloperidol, are often considered the first-line pharmacological treatment of delirium, but their use may be limited by lack of efficacy, existing contraindications, or resulting side effects 4, 5.
- Atypical antipsychotics, such as risperidone and olanzapine, have been found to be effective in treating delirium, with response rates of 80-85% and 70-76%, respectively 4.
- Cholinesterase inhibitors, such as rivastigmine, have been studied as a potential treatment for delirium, but the evidence is limited and inconclusive 6.
Limitations of Current Evidence
- There is a lack of randomized controlled trials (RCTs) evaluating the effect of VPA in delirium compared to other alternatives and placebo 2, 3.
- The current evidence is limited to retrospective studies and case series, which have methodological limitations 3.
- Further studies are needed to establish the efficacy and safety of VPA in the treatment of delirium 2, 3.