Effects of tolvaptan (kidney disease): A Synthesis of Findings from 9 Studies

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Original Abstract of the Article

Main Research Findings

Valproic acid (VPA) is a drug that is commonly used to treat epilepsy. Research suggests that VPA may have a variety of effects on the body, including effects on the nervous system, metabolism, and the immune system. 5 found that VPA increases the need for rocuronium, a muscle relaxant, in patients undergoing brain surgery. 9 showed that VPA treatment can reduce levels of total cholesterol and LDL cholesterol in children with epilepsy. 4 found that VPA may enhance exposure-based cognitive therapy for anxiety disorders in humans. 3 determined that VPA and lamotrigine, another anti-epileptic drug, have different effects on motorcortical neuronal excitability. 8 investigated the potential cytoprotective effects of a high dose of VPA. 6 prospectively evaluated the long-term impact of VPA on metabolic profiles in women with epilepsy. 7 examined the safety and tolerability of intravenous VPA in healthy subjects. Finally, 2 compared VPA to phenytoin, another anti-epileptic, in patients with newly diagnosed tonic-clonic seizures. 1 studied the effectiveness of VPA in preventing alcohol withdrawal seizures.

Benefits and Risks

Benefit Summary

VPA has shown promise as a treatment for epilepsy. It has been found to be effective in preventing seizures in some patients. 2 VPA also may have the potential to improve cognitive therapy for anxiety disorders. 4 Research suggests that VPA may help lower levels of cholesterol in children with epilepsy. 9

Risk Summary

VPA can have side effects such as nausea, vomiting, and gastric distress. 1 It can also increase the need for rocuronium, a muscle relaxant. 5 VPA is not recommended for use in pregnant or breastfeeding women, or in individuals with liver or kidney disease. 7 It is important to discuss the risks and benefits of VPA with a doctor before starting treatment.

Comparison Across Studies

Commonalities Across Studies

The studies reviewed all focused on different aspects of valproic acid (VPA), a drug commonly used to treat epilepsy. VPA has shown to be an effective treatment for epilepsy, with varying degrees of success. 2

Differences Across Studies

The studies explored a wide range of effects of VPA, including its impact on muscle relaxation, cholesterol levels, cognitive therapy for anxiety, motorcortical neuronal excitability, cytoprotective effects, and metabolic profiles in women with epilepsy, and its effectiveness in preventing alcohol withdrawal seizures. Each study provided unique insights into the multifaceted effects of VPA.

Consistency and Discrepancies in Results

While the studies consistently demonstrate that VPA is effective in treating epilepsy, they also highlight the various side effects associated with its use, such as increased rocuronium requirement, potential metabolic effects, and gastrointestinal discomfort. It is important to note that these side effects can vary depending on the individual and the dosage. 5 , 6 , 1

Considerations for Real-World Applications

VPA has been established as a valuable medication for managing epilepsy, but its use should be carefully considered, taking into account the potential risks and benefits. The studies suggest that VPA may have a range of effects beyond its primary anti-epileptic function, such as potentially affecting muscle relaxant needs and cholesterol levels. It is crucial to consult with a doctor to determine if VPA is the right treatment option and to discuss any potential side effects.

Limitations of Current Research

The studies reviewed each focused on specific aspects of VPA's effects, and further research is needed to gain a more comprehensive understanding of its mechanisms and long-term effects. Some studies were limited in scope or sample size, requiring larger and more comprehensive studies to solidify the findings. 7 , 8

Future Research Directions

Future research on VPA should focus on exploring its long-term effects, particularly its potential impact on various aspects of metabolism and the nervous system. Longitudinal studies are essential to understand the long-term safety and efficacy of VPA. Further research should investigate the optimal dosage for different patients and conditions, as well as develop strategies to mitigate potential side effects. Investigating the use of VPA in combination with other therapies could also lead to more effective treatment strategies. In addition, researchers should delve deeper into VPA's potential to benefit cognitive therapy for anxiety disorders and other mental health conditions. 4

Conclusion

VPA is an important drug for the treatment of epilepsy, and its effects on the body are increasingly understood. However, more research is needed to fully explore the potential risks and benefits of VPA. It is crucial to consult with a doctor to determine if VPA is the right treatment option for you and to discuss any concerns or potential side effects. Further research will continue to enhance our understanding of VPA and its potential role in various medical applications.

Literature analysis of 9 papers
Positive Content
7
Neutral Content
2
Negative Content
0
Article Type
8
1
0
0
9
1.

Prevention of alcohol withdrawal seizures with carbamazepine and valproic acid.

Author: HillbomM, TokolaR, KuuselaV, KärkkäinenP, Källi-LemmaL, PilkeA, KasteM

Prevents alcohol withdrawal
Gastric distress
Nausea and vomiting
Rash
Vertigo

Carbamazepine and sodium valproate were compared to placebo in 138 intoxicated alcoholics for alcohol withdrawal symptom prevention. Sodium valproate induced gastric distress, while carbamazepine caused intolerable side effects in half of the subjects. Both drugs had limited utility due to side effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Comparison of valproic acid and phenytoin in newly diagnosed tonic-clonic seizures.

Author: WilderB J, RamsayR E, MurphyJ V, KarasB J, MarquardtK, HammondE J

Mild side effects
Seizure prevention
Toxic hepatitis

Valproate and phenytoin were both effective in preventing seizure recurrence in newly diagnosed epileptic patients. Valproate was more effective than phenytoin, with similar mild side effects and laboratory abnormalities.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

3.

Lamotrigine and valproic acid have different effects on motorcortical neuronal excitability.

Author: LiXingbao, RicciRaffaella, LargeCharles H, AndersonBerry, NahasZiad, GeorgeMark S

To investigate the different cortical effects of lamotrigine and valproic acid, 30 healthy adult men were randomly and blindly given a single dose of either lamotrigine (325 mg), valproic acid (1,250 mg), or placebo on three separate days (separated by a week). Resting motor threshold (RMT), cortical silent period (CSP), and motor evoked potential recruitment curves (RC) were assessed at baseline and 3 hours after administration. Lamotrigine caused a significant increase in RMT (63.32 vs. 69.25) compared to a non-significant increase with valproic acid (62.50 vs. 63.35) and a decrease with placebo (62.60 vs. 62.36; F (2,26) = 18.58, P < 0.0001). No significant difference in CSP was found between placebo and the drugs (F (2,26) = 0.119, P > 0.05). RCs were significantly suppressed by lamotrigine (t = 2.07, P < 0.05) and enhanced by valproic acid (t = 2.39, P < 0.05). The study demonstrates that lamotrigine and valproic acid have different effects on cortical neuronal excitability, as shown by TMS.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

4.

Effect of D-cycloserine and valproic acid on the extinction of reinstated fear-conditioned responses and habituation of fear conditioning in healthy humans: a randomized controlled trial.

Author: KuriyamaKenichi, HonmaMotoyasu, SoshiTakahiro, FujiiTakeshi, KimYoshiharu

Treats anxiety disorders
None mentioned

A single dose of DCS or VPA might enhance exposure-based cognitive therapy of anxiety disorders by reducing the vulnerability to reinstatement and preventing relapses of fear-conditioned responses.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Effects of valproic acid and magnesium sulphate on rocuronium requirement in patients undergoing craniotomy for cerebrovascular surgery.

Author: KimM-H, HwangJ-W, JeonY-T, DoS-H

Reduced rocuronium requirement

Valproic acid (VPA) increases the rocuronium requirement during surgery, but magnesium sulphate infusion can attenuate this effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

6.

Evaluate the effects of long-term valproic acid treatment on metabolic profiles in newly diagnosed or untreated female epileptic patients: A prospective study.

Author: SidhuHarpreet Singh, SrinivasR, SadhotraAkshay

Insulin resistance
VPA-induced obesity

This study evaluated the long-term impact of sodium valproate (VPA) monotherapy compared with lamotrigine (LTG) monotherapy on anthropometric and metabolic parameters in women with epilepsy. The primary objective was to understand the underlying mechanism responsible for VPA-induced obesity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

7.

Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial.

Author: GeorgoffPatrick E, NikolianVahagn C, BonhamTess, PaiManjunath P, TafatiaCelia, HalaweishIhab, ToKathleen, WatcharotoneKuanwong, ParameswaranAishwarya, LuoRuijuan, SunDuxin, AlamHasan B

Traumatic injury treatment

This trial determined the maximum tolerated single dose of intravenous valproic acid in healthy humans.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

8.

Assessment of the Cytoprotective Effects of High-Dose Valproic Acid Compared to a Clinically Used Lower Dose.

Author: BhattiUmar F, RemmerHenriette, WilliamsAaron M, BiesterveldBen E, RussoRachel, WakamGlenn, KempMichael, TagettRebecca, LiuBaoling, LiYongqing, AlamHasan B

Cytoprotective changes
Improved survival

This study investigated the proteomic changes induced by a single high-dose of valproic acid (VPA) compared to the FDA-approved dose in healthy humans and an injured patient. The researchers found that a high dose of VPA induced changes in protein levels that may be associated with cytoprotective effects.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

9.

Effect of long-term valproic acid therapy on lipid profiles in paediatric patients with epilepsy: a meta-analysis

Author: GuoHong-Li, DongNa, ChenFeng, ZengYuan-Yuan, HuYa-Hui, XiaYing, TianMan, LuXiao-Peng, QiuJin-Chun

Reduced cholesterol

This meta-analysis reviewed the effects of valproic acid (VPA) therapy on lipid profiles in children with epilepsy. VPA therapy was associated with a significant reduction in total cholesterol and low-density lipoprotein cholesterol levels. No significant effects were observed on high-density lipoprotein cholesterol or triglycerides.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

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