Antiepileptic Drugs
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Clonazepam is used for the treatment of myoclonic seizures and absence of seizures in children. Intranasal spray of clonazepam is used as an orphan drug for recurrent acute repetitive seizures. Lorazepam and diazepam are efficacious in the treatment of status epilepticus. The latter is more frequently used because of less lipid solubility, more effectively confined to the vascular compartment, and has a longer effective half-life after a single dose (Porter et al., 2018). Clorazepate is effective in the treatment of focal seizures in combination with other antiepileptics. Clorazepate should be avoided in children less than 9 years of age (Porter et al., 2018). Clobazam is used in a variety of seizure phenotypes and is FDA approved for the treatment of Lennox–Gastaut syndrome in patients of age 2 years or more (Misty et al., 2018). Midazolam is used as an orphan drug for intermittent treatment of episodes of increased seizure activity in refractory epilepsy patients who are otherwise stable on other AEDs. More recently, midazolam was granted orphan drug designation in 2009 as a rescue agent for patients with intermittent bouts of increased seizure activity (i.e., acute repetitive seizure clusters), in 2012 for the treatment of nerve agent-induced seizures, and in 2016 for the treatment of status epilepticus and seizures induced by organophosphorus poisoning (Misty et al., 2018).
Achieving and Sustaining Precision Effects
Betty Wedman-St Louis in Cannabis as Medicine, 2019
Chemotype-III strains with no or only trace amounts of THC are generally considered safe for humans, including for chronic use and in high doses up to 1,500 mg/day.21 However, some studies suggest that all chemotypes of cannabis including a chemotype III may interfere with certain pharmaceutical drugs. For instance, the concomitant use of clobazam (a pharmaceutical drug to treat seizures) with CBD makes the pharma drug more potent, leading to a possible increase in its adverse-effect potential such as drowsiness, ataxia, or irritability.22 However, these adverse effects can be anticipated and avoided by lowering either clobazam or CBD amounts. The same concern applies to all other pharmaceutical drugs that are metabolized (broken down) by the enzymes belonging to the family cytochrome P450. This is due to the fact that CBD inhibits the break-down enzymes.
Anticonvulsvant Drugs and Cognitive Functions in Elderly Patients with Epilepsy
José León-Carrión, Margaret J. Giannini in Behavioral Neurology in the Elderly, 2001
The sedative action of some AEDs, such as phenobarbital, primidone, and the benzodiazepines, can contribute to impaired cognitive function. In particular, phenobarbital and primidone have been found to induce memory impairment, especially in the areas of short-term memory and attention. The effects of phenytoin on cognitive function have been under investigation for some time, and a “Dilantin dementia” was described by Rosen in 1966,19 but it appears that the syndrome is associated with higher plasma drug concentrations.20 In a single blind, randomized study designed to compare the impact of phenytoin and valproic acid on cognitive function in elderly people,21 the authors were able to show only slight effects of the AEDs and only very trivial differences between the two drugs. Other anticonvulsants, such as ethosuximide, clobazam, and carbamazepine, appear to cause insignificant neuropsychological side effects. In a placebo-controlled study in elderly patients taking carbamazepine, valproate, or phenytoin as monotherapy, no cognitive impairment developed when the dose was modestly increased within the target range for each drug.22
Pharmacological treatment of anxiety disorders in adults with epilepsy
Published in Expert Opinion on Pharmacotherapy, 2018
The lack of any evidence-based data for the treatment of anxiety disorders in epilepsy is quite striking. There are no published controlled trials and there is a single open study on the use of a homeopathic remedy [62] but no other studies. For this reason the Internal League Against Epilepsy has suggested a number of recommendations based on current guidelines adopted outside epilepsy [63,64]. Considering that pregabalin is an already licensed AED for the treatment of focal epilepsies, given the existing evidence in GAD and SAD, it seems reasonable to consider this compound first-line treatment in patients with epilepsy and GAD or SAD. Clobazam is also a well-known agent for the treatment of both epilepsy and anxiety [65]. However, data on anxiety are not as robust as for PGB and, as already mentioned in the previous section, BDZ are burdened by a number of limitations and should be carefully used. Regarding other medications, buspirone is of particular interest. The US National Institute of Neurological Disorders and Stroke has sponsored a randomized, double-blind, placebo-controlled, cross-over Phase II study of buspirone for the adjunctive treatment of seizures in people with focal epilepsy (NCT01496612). Results are not currently available. The rational for the use of buspirone in epilepsy is based on data from animal models and human positron emission tomography (PET) imaging studies showing a role for 5HT1A receptors in the pathophysiology of epilepsy [66]. It is clearly evident that further studies on this compound would be of great interest.
Emerging drugs for the treatment of Dravet syndrome
Published in Expert Opinion on Emerging Drugs, 2018
Francesco Brigo, Pasquale Striano, Ganna Balagura, Vincenzo Belcastro
DS is a complex epileptic and developmental encephalopathy, with poor prognosis for long-term seizure control and cognitive outcome. The evidence base for pharmacological treatment of DS is limited and the clinical expression of DS may change with time. Hitherto, the following recommendations and practical advice are the authors’ expert opinion, based on the available evidence, summarized in the present article and based on a narrative review of the literature, and their clinical experience. Sodium valproate, which has never been specifically licensed for use in DS, is the first drug prescribed in most patients presenting generalized or multiple seizure types, due to its broad spectrum and highly unlikely to lead to aggravation of seizures (expert opinion). Oral benzodiazepines, in particular, clobazam is especially useful in the treatment of ‘critical phases’, such as the occurrence of cluster seizures and prolonged absences (expert opinion). Consequently, due to the risk of tolerance, these drug class should generally be considered for use on an intermittent basis and parents should be aware of the possibility of habituation. Moreover, important considerations in the chronic intake of benzodiazepines are the association with a range of cognitive and behavioral effects.
Quality improvement in the management of people with epilepsy and intellectual disability: the development of clinical guidance
Published in Expert Opinion on Pharmacotherapy, 2020
Lance Watkins, Máire O’Dwyer, Michael Kerr, Mark Scheepers, Ken Courtenay, Rohit Shankar
Benzodiazepines, e.g. buccal (oromucosal) midazolam, are widely used as emergency rescue medication and there is good supporting evidence for their use. The prescription of buccal midazolam should be accompanied by specific strict guidelines on how and when to administer and be reviewed regularly. Midazolam is specifically used to help halt seizures in the community and is especially useful due to its buccal administration [31]. Clobazam is a useful adjunct for short periods to manage clusters of seizures [32]. Best practice guidelines for the treatment of prolonged/clusters of epileptic seizures in the community have been published by ESNA (Epilepsy Nurses Association) in association with the ILAE and RCPsych and should be followed. There are several cautions to consider when prescribing benzodiazepines for epilepsy including the potential negative effects on cognition, potential for sedation, and possible tolerance to the drugs [33].