Pharmacological treatment of focal epilepsy in adults: an evidence based approach

Mula, Marco

doi:10.1080/14656566.2020.1829594

Cited by 14 publications

(13 citation statements)

References 58 publications

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“…The next most frequently tested ASM in our case series was LTG with 727 samples, followed by ESM, PB, PHT, TPM, and LCS. Some studies have indicated LTG as a first-choice option for focal and generalized seizures, and this ASM is very popular, especially in the UK [ 17 , 18 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center

Biso,

Carli,

Kolachalam

et al. 2023

Pharmaceuticals

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Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is subtherapeutic ASMs plasma concentration (C(p)) due to improper drug adherence, interindividual pharmacokinetic differences, or metabolic interactions among different drugs. For these reasons, therapeutic drug monitoring (TDM) by measuring ASMs C(p) is an effective tool that improves pharmacological therapies in clinical practice. Based on these premises, in the present real-world study, we analyzed the C(p) of the most used ASMs in diverse medical conditions, which were assayed during the years 2018–2022 at the University Hospital of Pisa, including about 24,000 samples. This population was largely heterogeneous, and our database did not contain clinical information about the patients. The most used ASMs were Valproate (VPA: 54.5%) and Levetiracetam (LEV: 18.6%), followed by Oxcarbazepine (OxCBZ: 8.3%) and Carbamazepine (CBZ: 7.2%), whereas the associations LEV/VPA, Ethosuximide (ESM)/VPA, and CBZ/VPA were the most frequently proposed. In about 2/3 of assays, ASMs C(p) was in range, except for VPA, which was underdosed in almost half of the samples. Importantly, toxic levels of ASMs C(p) were found very rarely. For VPA, there was a decrease of mean C(p) across ages, from adolescents to older patients, while the C(p) of LEV, CBZ, OxCBZ, and Topiramate (TPM) showed a slight tendency to increase. When we compared females and males, we found that for VPA, the average age was higher for females, whereas women taking Lamotrigine (LTG) and OxCBZ were younger than men. Then, comparing ASMs used in neurologic and psychiatric disorders, based on the request form, it emerged that the mean C(p) of CBZ, OxCBZ, and LTG on samples collected in the Psychiatric Unit was lower compared to the Neurology and Child Neuropsychiatry Units. Finally, the ASMs subjected to multiple dosing starting from an initial subtherapeutic C(p) increased their level at different time points within a year, reaching the reference range for some of them. In conclusion, the present study suggests that TDM is widely applied to monitor ASMs C(p), finding many of them within the reference range, as a demonstration of its utility in clinical practice.

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Section: Discussionmentioning

confidence: 99%

A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center

Biso,

Carli,

Kolachalam

et al. 2023

Pharmaceuticals

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“…of patients with epilepsy are unable to achieve seizure control with currently available anti-epilepsy drugs (AEDs), and the introduction of multiple new drugs over the last two decades has done little to change this (Mula 2020). All current AEDs only suppress seizures, with none confirmed to stop or reverse the process that converts a healthy brain into an epileptic brain, that is, epileptogenesis (Löscher and Brandt 2010).…”

Section: Other Biomarkers In Epilepsymentioning

confidence: 99%

The role of Rho/ROCK in epileptic seizure-related neuronal damage

2022

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Epilepsy is one of the most severe neurological disorders characterized by spontaneous recurrent seizures. Although more than two-thirds of patients can be cured with anti-epileptic drugs (AEDs), the rest one-third of epilepsy patients are resistant to AEDs. A series of studies have demonstrated Rho/Rho-associated kinase (ROCK) pathway might be involved in the pathogenesis of epilepsy in the recent twenty years. Several related pathway inhibitors of Rho/ROCK have been used in the treatment of epilepsy. We searched PubMed from Jan 1, 2000 to Dec 31, 2020, using the terms "epilepsy AND Rho AND ROCK" and "seizure AND Rho AND ROCK". We selected articles that characterized Rho/ROCK in animal models of epilepsy and patients. We then chose the most relevant research studies including in-vitro, in-vivo and clinical trials. The expression of Rho/ROCK could be a potential non-invasive biomarker to apply in treatment for patients with epilepsy. RhoA and ROCK show significant upregulation in the acute and chronic stage of epilepsy. ROCK inhibitors can reduce the epilepsy, epileptic seizure-related neuronal death and comorbidities. These findings demonstrate the novel development for diagnosis and treatment for patients with epilepsy. Rho/ROCK signaling pathway inhibitors may show more promising effects in epilepsy and related neurological diseases.

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“…Hence, testing novel herbal-based candidates is encouraged to overcome these obstacles. Overall, evidence on specific drug combinations remains rare and a combination of routine antiseizure medications with novel candidates such as herbal-based extracts such as cannabidiol (CBD) deserves further investigation ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

The effect of cannabidiol on seizure features and quality of life in drug-resistant frontal lobe epilepsy patients: a triple-blind controlled trial

Ebadi,

Saleki,

Adl Parvar

et al. 2023

Front. Neurol.

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BackgroundTreatment-resistant epileptic seizures are associated with reduced quality of life (QoL). As polypharmacy with routine antiseizure medications has many side effects, novel add-on treatments are necessary. Recent research showed the efficacy of add-on therapy by cannabidiol (CBD) on refractory epilepsy. We attempted to extend data on the efficacy and safety profile of CBD in patients with frontal lobe treatment-resistant epilepsy.MethodsA total of 27 patients were recruited into two CBD (n = 12) and placebo (n = 15) groups. The CBD group received a highly purified liposomal preparation of the drug in addition to routine antiseizure medications. The placebo group only received antiseizure medications. This experiment followed a triple-blinding protocol. Outcome measures were seizure frequency, the Chalfont seizure severity scale (CSSS), and the quality of life questionnaire score (QOLIE-31) assessed at baseline, 4 weeks, and 8 weeks.ResultsAt 4 weeks, results indicated that a higher fraction of patients in the CBD group (66.67%) showed improvement in seizure, compared to the placebo group (20.00%). Before–after comparison revealed that CBD, unlike routine ADEs, was effective in reducing the occurrence of seizures at the study's final timepoint [mean difference 45.58, 95% CI (8.987 to 82.18), p = 0.009]. Seizure severity was not affected by study groups or time intervals (repeated-measures ANOVA p > 0.05). Post-hoc tests found that the QoLI-31 score was improved at 8 weeks compared to baseline [mean diff. −5.031, 95% CI (−9.729 to −0.3328), p = 0.032]. The difference in cases who experienced enhanced QoL was meaningful between the CBD and placebo groups at 8 weeks [RR: 2.160, 95% CI (1.148 to 4.741), p = 0.018] but not at 4 weeks (p = 0.653). A positive finding for QoL improvement was associated with a positive finding for seizure frequency reduction [r = 0.638, 95% CI (0.296 to 0.835), p = 0.001]. Interestingly, limiting the correlation analysis to cases receiving CBD indicated that QoL improvement was not linked with seizure parameters such as severity and frequency (p > 0.05).ConclusionThe present study suggests the benefit of a purified and highly efficient preparation of CBD for seizure frequency reduction and improvement of QoL in refractory frontal lobe epilepsy. Further study with longer follow-ups and larger sample size is advised.Clinical trial registrationhttps://www.irct.ir/trial/56790, identifier: IRCT20210608051515N1.

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Pharmacological treatment of focal epilepsy in adults: an evidence based approach

Cited by 14 publications

References 58 publications

A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center

A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center

The role of Rho/ROCK in epileptic seizure-related neuronal damage

The effect of cannabidiol on seizure features and quality of life in drug-resistant frontal lobe epilepsy patients: a triple-blind controlled trial

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