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Partial Seizures
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Clobazam has been shown to have anticonvulsant activity and is found to be of benefit as adjunctive treatment in drug resistant epilepsy in both open and double-blind studies (38–40). The effect of clobazam as adjunctive treatment in patients with intractable seizures, both generalized and partial, was investigated in an open prospective study (41). Twelve patients with partial seizures were studied over a period of 18 months when clobazam was added to existing drug treatment. Response to treatment is summarized in Figure 1. Sixteen percent of patients achieved complete control and 35% of patients a greater than 50% reduction in seizure frequency over a period of 6 months.
Achieving and Sustaining Precision Effects
Published in Betty Wedman-St Louis, 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.
Pharmacokinetic/Pharmacodynamic Correlations of Anticonvulsants
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Meindert Danhof, Rob A. Voskuyl
The PTZ threshold model has been applied in some other studies with benzodiazepines. One of the applications has been to determine the anticonvulsant potency of the major metabolite of clobazam, N-desmethylclobazam.17 The findings of this study showed that N-desmethylclobazam may contribute significantly to the effects observed following the administration of the parent compound clobazam.
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].
Stiripentol for the treatment of seizures in Dravet syndrome
Published in Expert Review of Clinical Pharmacology, 2019
Krista Eschbach, Kelly G Knupp
This initial efficacy and tolerability study highlighted a potential use for stiripentol in the treatment of children with Dravet syndrome. There were two subsequent pivotal studies in the approval of stiripentol for the treatment of children with Dravet syndrome, STICLO France and STICLO Italy. Both studies were designed as a randomized placebo-controlled trial of add-on stiripentol vs placebo in children with Dravet syndrome receiving treatment concurrently with clobazam and valproic acid. In the first study by Chiron et al., there were 21 patients in the stiripentol group with a responder rate of 71%, compared to only 5% with the addition of placebo [54]. This included nine patients (43%) that became seizure free during the double-blind phase of the study, and five of these children remained seizure free during the open-label portion of the study [54]. Primary adverse effects were sedation and weight loss, the former requiring dose reduction in concomitant clobazam dosing. When clobazam was decreased, the adverse effects disappeared in 12/21 patients. In the subsequent STICLO Italy trial, 23 children participated, and the overall seizure rate was reduced by 70% in the treatment group with stiripentol [65].
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.