Side Effects of ethosuximide: A Synthesis of Findings from 20 Studies

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Original Abstract of the Article

Main Research Findings

Ethosuximide is a common treatment for childhood absence epilepsy (CAE). 9 While it is often the first-line treatment for CAE, there are still questions surrounding its efficacy and side effects. 9 Some studies suggest that it may be more effective than newer medications. 10 However, even though it is an older drug, there is still a limited amount of information regarding its cognitive effects in children. 7 Ethosuximide has been shown to be effective in animal models, but it's important to further assess its effectiveness and safety in humans. 6 One recent study explored the potential for ethosuximide to be used as a treatment for neuropathic pain, but more clinical studies are necessary. 6

Reasons for Side Effects

The exact mechanisms underlying the side effects of ethosuximide are not fully understood, but it is likely related to its interaction with various neurotransmitter systems in the brain. As a T-type calcium channel blocker, it may affect the activity of different nerve cells beyond those involved in absence seizures. Additionally, it is known to inhibit the aromatase complex, which converts androgens to estrogens, which may cause hormonal imbalances. 18

Common Side Effects

Gastrointestinal

Ethosuximide has been associated with a range of gastrointestinal side effects. These can include nausea, vomiting, abdominal pain, and loss of appetite. 19 Some studies have also noted a possible link between ethosuximide and increased appetite. 18

Central Nervous System

Ethosuximide may also affect the central nervous system. While most studies suggest that it does not have a significant negative impact on cognition, some patients have reported experiences with drowsiness, dizziness, headaches, and decreased attention. 7 In rare cases, ethosuximide may even cause more serious mental health issues, such as mania and suicidal thoughts. 13

Blood

Ethosuximide may also cause side effects in the blood, including leukopenia (low white blood cell count) and thrombocytopenia (low platelet count). 19

Other

Ethosuximide has been linked to a wide variety of other side effects. These can include allergic reactions, weight gain, and hair loss. 19 In extremely rare cases, ethosuximide may also cause macroglossia (enlarged tongue) and oropharyngeal edema (swelling of the throat). 2 In children, it may also affect hormone levels, potentially affecting growth and development. 18

Countermeasures for Side Effects

Gastrointestinal Side Effects

To manage gastrointestinal side effects, ethosuximide can be taken with food or at bedtime. 19 Dietary changes and lifestyle modifications may also be beneficial. 19

Central Nervous System Side Effects

For central nervous system side effects, a gradual increase in dosage is often recommended. 19 If the side effects are severe, consulting with a doctor to reduce the dosage or switch medications may be necessary. 19

Blood Side Effects

Regular blood tests are essential to monitor for blood-related side effects. 19 If test results are abnormal, adjusting the dosage or switching medications may be necessary, which should be discussed with a doctor. 19

Comparison Between Studies

Similarities Between Studies

Several studies have confirmed the effectiveness of ethosuximide in treating absence seizures. 9 However, there is a consistent finding across studies that it can cause side effects, including cognitive impairment. 11 These studies highlight the importance of weighing the benefits against the potential risks of ethosuximide therapy.

Differences Between Studies

There is some variability in the reported effectiveness and side effects of ethosuximide across studies. For instance, one study indicated that ethosuximide is highly effective for treating absence seizures. 16 In contrast, another study suggested that it is likely to cause cognitive impairment. 7 These varying findings suggest that the individual responses to ethosuximide can differ.

Things to Keep in Mind When Applying to Real Life

Ethosuximide is a valuable medication for managing absence seizures, but it's crucial to be aware of its potential side effects. 19 It's essential to follow your doctor's instructions carefully and monitor for any adverse reactions. If you experience any concerning side effects, discuss them with your healthcare provider. 19 Moreover, it's advised to avoid driving or operating machinery while taking ethosuximide due to the possibility of drowsiness or dizziness. 19

Limitations of Current Research

Further research is needed to fully understand the side effects of ethosuximide, particularly its effects on cognitive function. 7 More research on the long-term effects of ethosuximide, especially in children, is also critical.

Future Research Directions

Future research should prioritize a thorough investigation of the cognitive side effects of ethosuximide. 7 Developing new strategies to minimize or manage side effects is also a crucial area for future research. 19 Additionally, more research is needed to explore the potential therapeutic benefits of ethosuximide for conditions other than absence seizures, such as neuropathic pain.

Conclusion

Ethosuximide is an effective treatment option for absence seizures, but it is important to be aware of its potential side effects. Open communication with your doctor regarding any concerns or side effects you experience is crucial. By working closely with your healthcare team, you can make informed decisions about the best treatment approach for you or your child.

Literature analysis of 20 papers
Positive Content
14
Neutral Content
2
Negative Content
4
Article Type
1
1
1
6
19
1.

An evidence based systematic review of remifentanil associated opioid-induced hyperalgesia.

Author: RivosecchiRyan M, RiceMark J, SmithburgerPamela L, BuckleyMitchell S, CoonsJames C, Kane-GillSandra L

Opioid-induced hyperalgesia
Respiratory depression

Opioid-induced hyperalgesia (OIH) is a concerning side effect of therapeutic opioid use. While opioids are known for their effects on bradycardia and respiratory depression, OIH remains an area of active research to better understand its mechanisms and management.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

2.

Ethosuximide induced macroglossia and oropharyngeal edema.

Author: ShangHanqing, GlaunMica, OngkasuwanJulina

Laryngeal edema
Macroglossia

This case report describes a patient who developed a swollen tongue and larynx after starting a medication called ethosuximide. These side effects resolved after the medication was stopped.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Waddling Gait: A complication of valproate therapy and a thought beyond vitamin D deficiency.

Author: SharmaAmit, SinhaSiddhartha, NarangAmit, ChouhanDushyant K, GuptaSumit

Muscle weakness treatment
Muscle weakness

Sodium valproate, an antiepileptic and antipsychotic drug, can cause proximal myopathy, which can be misdiagnosed as vitamin D deficiency. This case report describes a 13-year-old girl who developed proximal myopathy after taking sodium valproate. Her symptoms resolved after the drug was replaced with ethosuximide and she received carnitine supplementation.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

4.

A Practical Guide to Treatment of Childhood Absence Epilepsy.

Author: KesslerSudha Kilaru, McGinnisEmily

CAE treatment

Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome with distinct seizure semiology and electroencephalography (EEG) features. Ethosuximide is the treatment of choice for CAE, while valproic acid and lamotrigine are also effective. Refractory CAE occurs in fewer than half of patients, and treatment strategies are available, though efficacy data are lacking.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

The effects of ethosuximide on aversive instrumental learning in adult rats.

Author: OrczykJohn J, GarraghtyPreston E

Improved learning
Reduced cognitive side effects

Ethosuximide (ETH) treatment did not impair cognitive performance in rats compared to controls in various learning tasks. This suggests ETH is a safe and effective antiepileptic drug for absence seizures, showing better results than valproic acid.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Assessment of the effectiveness and safety of Ethosuximide in the Treatment of non-Diabetic Peripheral Neuropathic Pain: EDONOT-protocol of a randomised, parallel, controlled, double-blinded and multicentre clinical trial.

Author: KerckhoveNicolas, MalletChristophe, PereiraBruno, ChenafChouki, DualeChristian, DubrayClaude, EschalierAlain

Neuropathic pain treatment

Neuropathic pain is often difficult to treat with traditional pain medications. T-type calcium channel blockers, like ethosuximide, have shown promise as potential new treatments for neuropathic pain. Although ethosuximide is already approved for epilepsy, more research is needed to explore its analgesic efficacy specifically in patients with neuropathic pain.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
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

7.

The Cognitive Profile of Ethosuximide in Children.

Author: IJffDominique M, van VeenendaalTamar M, Debeij-van HallMariette H, JansenJacobus F A, de LouwAnton J A, MajoieMarian H J M, AldenkampAlbert P

Attentional dysfunction

This cross-sectional study of 61 patients with epilepsy who were treated with monotherapy ethosuximide found that the drug was effective in the majority of patients. However, the study also found that the drug was associated with impairments in intelligence, visuomotor, and attentional function.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

The anti-absence effect of mGlu5 receptor amplification with VU0360172 is maintained during and after antiepileptogenesis.

Author: D'AmoreValerio, RaaijmakersRenée H L, SantoliniInes, van RijnClementina M, NgombaRichard Teke, NicolettiFerdinando, van LuijtelaarGilles

Anti-absence properties
Cognitive side effects

Ethosuximide (ETX), an anti-absence drug, can alter the sensitivity of VU0360172, a positive allosteric modulator of mGluR5, and may affect cognition during and after chronic treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Cognitive side-effects of antiepileptic drugs in children.

Author: IjffDominique M, AldenkampAlbert P

Cognitive enhancement
Epilepsy treatment
Attention impairment
Cognitive impairment
Language function impairment
Memory impairment

This article explores the impact of antiepileptic drugs (AEDs) on cognitive function in patients with epilepsy. It highlights the varying cognitive effects of different AEDs, emphasizing the importance of selecting appropriate AEDs to minimize cognitive impairment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Ethosuximide-induced mania in a 10-year-old boy.

Author: ChienJoseph

Mania
Psychosis
Suicidal ideation

This case report describes a 10-year-old boy who developed acute mania, psychotic symptoms, and suicidal ideation while taking ethosuximide. This highlights the potential psychiatric complication of mania associated with ethosuximide treatment.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

14.

[Absence epilepsy models in rodents].

Author: EguibarJosé R, CortésM del Carmen

Absence seizures
Animal model

This study explores the use of animal models, specifically GAERS and WAG/Rij rats, in researching absence seizures. These models exhibit characteristic spike wave discharges (SWD) and respond predictably to anti-epileptic drugs. The study also introduces the 'taiep' rat, a myelin mutant model that displays SWD with increased frequency during waking periods. These models provide valuable insights into the neuroanatomical, electrophysiological, and pharmacological aspects of absence seizures.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : Spanish

15.

Effects of L- and T-type Ca²(+) channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis.

Author: LeeJae Ho, AhnHak Jun, LeeSang Jin, GyeMyung Chan, MinChurl K

Male infertility

A study using prepubertal male mice found that chronic exposure to L-type and T-type Ca²(+) channel blockers nifedipine and ethosuximide, respectively, caused a significant reduction in body weight, testis size/weight, and sperm production. This was associated with spermatogenic arrest and a reduction in Leydig cells, serum testosterone, and StAR protein mRNA.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Antiepileptic drug therapy in pregnancy II: fetal and neonatal exposure.

Author: HovingaCollin A, PennellPage B

Antiepileptic drug safety
Lactation safety
AED breast milk concentration

This review discusses the transfer of antiepileptic drugs (AEDs) across the placenta and into breast milk. While most AEDs are safe for breastfeeding with some cautions, phenobarbital and primidone should be avoided.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

19.

Ethosuximide: from bench to bedside.

Author: GörenM Zafer, OnatFiliz

Absence epilepsy treatment
Central nervous system side effects
Gastrointestinal side effects
Hematopoietic adverse effects

Ethosuximide is a drug used to treat absence seizures. It has a narrow therapeutic profile and can cause gastrointestinal and central nervous system side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

20.

[Carbamazepine-induced systemic lupus erythematosus--a case report].

Author: MottaEwa, KazibutowskaZofia, LorekAndrzej, JanuszewskiKrzysztof, GołbaAnna, WianeckaAldona

Systemic lupus erythematosus

A 30-year-old woman with epilepsy was treated with valproic acid (VPA) for 3 years. After 8 months of treatment with carbamazepine (CBZ), she developed painful swelling of all joints and leucopenia. Systemic lupus erythematosus was diagnosed and prednisone therapy was introduced. The increased titer of ANA antibodies persisted for several years, and skin and muscle biopsy revealed inflammatory infiltration and deposits of IgG and IgM in skin and vessel walls. However, after 8 years of observation, the lack of clinical manifestations permitted to exclude a connective tissue disease.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Polish

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