Main Research Findings

Valproic acid (VPA) is a widely used antiepileptic drug for treating epilepsy in children. While some studies suggest VPA might contribute to weight gain, its impact on lipid profiles remains unclear. A meta-analysis 9 found VPA treatment significantly reduced total cholesterol and low-density lipoprotein cholesterol levels in children with epilepsy. However, no significant effects were observed in high-density lipoprotein cholesterol and triglyceride levels. Long-term VPA treatment may affect metabolic profiles in women with epilepsy, potentially increasing the risk of health issues like insulin resistance. 6 This study found VPA monotherapy, compared to lamotrigine monotherapy, was associated with increased weight gain, body fat, and insulin resistance. These findings highlight the importance of monitoring metabolic profiles during VPA treatment. VPA might have similar effects to D-cycloserine (DCS) in promoting the extinction of fear-conditioned memories and the habituation of fear conditioning. 4 VPA might enhance exposure-based cognitive therapy for anxiety disorders by promoting extinction and habituation of fear conditioning, and reducing vulnerability to reinstatement of fear-conditioned responses. VPA could potentially be a treatment for preventing alcohol withdrawal seizures, but side effects are a concern. 1 VPA can be an effective treatment for preventing alcohol withdrawal seizures, but it has been reported to cause gastrointestinal side effects. Carbamazepine can be effective in preventing alcohol withdrawal seizures, but intolerable side effects such as dizziness, nausea, vomiting, double vision, and rash may occur, requiring discontinuation of treatment. 1 VPA has been found to be effective and well-tolerated compared to phenytoin in treating newly diagnosed tonic-clonic seizures. 2 VPA may exhibit cytoprotective effects at higher doses (140mg/kg) than the FDA-approved dose (30mg/kg). 8 VPA might have beneficial effects in treating cancer, neurological diseases, and traumatic injuries. 7 VPA may increase rocuronium requirements in patients undergoing craniotomy for cerebrovascular surgery. 5 While VPA can increase rocuronium requirements, magnesium sulfate can reduce this increase. 5 Lamotrigine and VPA might have different effects on motorcortical neuronal excitability. 3 Lamotrigine may suppress motorcortical neuronal excitability, as shown by TMS, while VPA might enhance neuronal excitability.

Benefits and Risks

Benefits Summary

VPA is an effective drug for treating epilepsy in children. Several studies have reported VPA to be effective and well-tolerated compared to phenytoin in treating newly diagnosed tonic-clonic seizures. 2 VPA might have similar effects to D-cycloserine (DCS) in promoting the extinction of fear-conditioned memories and the habituation of fear conditioning. 4 VPA might enhance exposure-based cognitive therapy for anxiety disorders by promoting extinction and habituation of fear conditioning, and reducing vulnerability to reinstatement of fear-conditioned responses. VPA might have beneficial effects in treating cancer, neurological diseases, and traumatic injuries. 7 VPA may exhibit cytoprotective effects at higher doses (140mg/kg) than the FDA-approved dose (30mg/kg). 8

Risks Summary

VPA can lead to side effects like gastrointestinal problems, weight gain, and insulin resistance. 6 VPA can be an effective treatment for preventing alcohol withdrawal seizures, but it has been reported to cause gastrointestinal side effects. 1 Carbamazepine can be effective in preventing alcohol withdrawal seizures, but intolerable side effects such as dizziness, nausea, vomiting, double vision, and rash may occur, requiring discontinuation of treatment. 1 VPA may increase rocuronium requirements in patients undergoing craniotomy for cerebrovascular surgery. 5 While VPA can increase rocuronium requirements, magnesium sulfate can reduce this increase. 5 Lamotrigine may suppress motorcortical neuronal excitability, as shown by TMS, while VPA might enhance neuronal excitability. 3

Comparison Between Studies

Commonalities

Several studies indicate VPA is an effective treatment, but also acknowledge the potential for various side effects. These studies emphasize the importance of careful patient monitoring during VPA treatment.

Differences

These studies demonstrate VPA's potential to affect various parameters in patients, including lipid profiles, weight, metabolic profiles, and neuronal excitability. These investigations reveal that VPA is a multifaceted and complex drug with diverse modes of action.

Consistency and Discrepancies in Findings

There are both consistent and discrepant findings regarding VPA's effects. For example, a meta-analysis 9 found VPA significantly lowered total cholesterol and low-density lipoprotein cholesterol in children with epilepsy, while other studies suggest VPA could contribute to weight gain. 6 These inconsistencies suggest VPA's effects may be influenced by various factors like patient age, gender, epilepsy type, and VPA dosage.

Practical Implications and Considerations

VPA is an effective drug for treating epilepsy in children, but it can have side effects like weight gain and metabolic profile changes. 6 Patients on VPA should maintain a healthy weight through diet and exercise. VPA can potentially be a treatment for preventing alcohol withdrawal seizures, but it has been reported to cause gastrointestinal side effects. 1 Patients taking VPA should carefully follow their doctor's instructions.

Limitations of Current Studies

Most of these studies are relatively small and require larger-scale investigations. Furthermore, these studies have not adequately considered the impact of various factors such as VPA dosage, patient age, gender, and epilepsy type. Additionally, research on VPA's effects primarily involves short-term studies, necessitating long-term studies.

Future Research Directions

Future research on VPA's effects requires larger-scale investigations, long-term studies, and consideration of diverse patient factors. Research exploring VPA's mechanisms of action is also crucial.

Conclusion

VPA is an effective drug for treating epilepsy in children, but it can have side effects like weight gain and metabolic profile changes. 6 Patients taking VPA should carefully follow their doctor's instructions. The findings of these studies highlight the need for further research into VPA's effects.