Effects of tivozanib: A Synthesis of Findings from 9 Studies

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Original Abstract of the Article

Major Research Findings

A prospective study evaluating the long-term effects of valproic acid treatment on metabolic profiles in newly diagnosed or untreated female epileptic patients found that valproic acid is associated with weight gain and may predispose patients to other health problems such as insulin resistance. 6

Valproic acid has also been shown to affect blood lipid profiles. A meta-analysis revealed that valproic acid therapy in children with epilepsy led to a significant reduction in total cholesterol and low-density lipoprotein cholesterol levels. 9

On the other hand, valproic acid has been found to be effective in preventing seizures during alcohol withdrawal. However, valproic acid can cause side effects such as gastric distress, nausea, and vomiting, making its use a concern. 1

Benefits and Risks

Benefit Summary

Valproic acid may be effective in preventing seizures. 2 It may also be effective in preventing seizures during alcohol withdrawal. 1

Risk Summary

Valproic acid can cause metabolic abnormalities such as weight gain, insulin resistance, and changes in blood lipid profiles. 6 9 It can also cause side effects such as gastric distress, nausea, and vomiting. 1 Therefore, it is important to understand these risks and consult with a doctor before taking valproic acid.

Comparison Between Studies

Commonalities in Studies

Multiple studies have shown that valproic acid is associated with weight gain and metabolic abnormalities. 6 9 It's also known to interact with other medications, so caution is needed when using it concurrently. 5

Differences in Studies

The effects and side effects of valproic acid can vary depending on the patient's age, sex, and type of illness. 6 9

Consistency and Discrepancies in Results

Consistent findings have been observed regarding the impact of valproic acid on metabolism, indicating a potential for weight gain, insulin resistance, and alterations in blood lipid profiles. 6 9 However, the severity of side effects associated with valproic acid can vary among individuals. 1

Precautions for Real-World Applications

Regular monitoring of weight, blood sugar levels, and blood lipids is crucial for individuals taking valproic acid. 6 9 Additionally, as valproic acid can interact with other medications, consulting a physician before taking it is essential. 5

Limitations of Current Research

These studies did not investigate the long-term effects of valproic acid. Furthermore, the sample sizes were limited, making it difficult to generalize the findings to other patients.

Future Research Directions

Further research is needed to examine the long-term effects of valproic acid. Additionally, research on methods to mitigate the metabolic impact of valproic acid is required.

Conclusion

Valproic acid may be an effective treatment for seizures and alcohol withdrawal seizures, but it has the potential to cause metabolic abnormalities such as weight gain, insulin resistance, and changes in blood lipid profiles. 6 9 Therefore, understanding these risks and consulting with a physician before taking valproic acid is crucial.

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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