Thursday, November 12, 2020

Perampanel potpourri

Santamarina E, Bertol V, Garayoa V, García-Gomara MJ, Garamendi-Ruiz I, Giner P, Aranzábal I, Piera A, Arcos C, Esteve P, Marinas A, García-Escrivá A, Viloria-Alebesque A, Loro FA, de Tienda AP, Olivan JA, Bonet M, Dávila-González P, Sivera R, Molins A, Sansa G, Roche JC, Martínez AB, Monteagudo S, Casadevall T. Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs. Seizure. 2020 Oct 7;83:48-56. doi: 10.1016/j.seizure.2020.09.026. Epub ahead of print. PMID: 33096456.


Purpose: To investigate the efficacy and tolerability of perampanel (PER) when administered as a first add-on therapy to patients with focal epilepsy or idiopathic generalized epilepsy (IGE) taking one other antiseizure drug (ASD).

Methods: This multicentre, retrospective, one-year observational study collected data from patients (≥12 years) who initiated treatment with PER as first add-on therapy. Patients had to be experiencing inadequate seizure control on ASD monotherapy and tried ≤3 ASD monotherapies before initiating PER. Multivariate logistic regression analyses were performed, adjusted for the number and type of previous seizures, duration and aetiology of epilepsy. 

Results: Of the 149 patients included in the study (mean age 41 years; 54.4 % male), 118 (79.2 %) were still receiving PER as first add-on treatment after 12 months. Mean PER dose was 6.2 mg/day. At 12 months, 45.6 % were seizure-free and 84.6 % responders. A significant difference in seizure freedom rate was found between patients with IGE and patients with focal epilepsy, but not in responders. Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs; conversely, increased seizure control was seen when the same dose of PER was combined with enzyme-inhibiting ASDs. The most frequent adverse events were dizziness (15.4 %), irritability (14.1 %) and drowsiness (14.1 %); no differences in tolerance were observed among different combinations. 

Conclusion: PER demonstrated a good efficacy and safety profile when used as a first add-on therapy in patients who did not respond to monotherapy. PER dose adjustments may optimize seizure control when combined with strong enzyme-inducing or enzyme-inhibiting ASDs.

Courtesy of:

Santamarina E, Alpuente A, Maisterra O, Sueiras M, Sarria S, Guzman L, Abraira L, Salas-Puig J, Toledo M. Perampanel: A therapeutic alternative in refractory status epilepticus associated with MELAS syndrome. Epilepsy Behav Case Rep. 2019 Feb 7;11:92-95. doi: 10.1016/j.ebcr.2019.01.008. PMID: 30834194; PMCID: PMC6384302.


To our knowledge, there are no reports of status epilepticus (SE) associated with mitochondrial diseases and treated with perampanel (PER). We present three cases of patients with refractory SE associated with MELAS syndrome who responded favorably to PER. All cases were diagnosed as non-convulsive SE (focal without impairment of level of consciousness). After an initial treatment with other anti-seizure drugs, PER was added in all cases (8, 16 and 12 mg) and cessation of SE was observed within the next 4-8 hours. All the cases involved a stroke-like lesion present on brain MRI. In our patients, PER was an effective option in SE associated with MELAS syndrome. 

Santamarina E, Sueiras M, Lidón RM, Guzmán L, Bañeras J, González M, Toledo M, Salas-Puig X. Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report. Epilepsy Behav Case Rep. 2015 Aug 8;4:56-9. doi: 10.1016/j.ebcr.2015.06.007. PMID: 26286206; PMCID: PMC4536289.


Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status. 

Description: A 51-year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6-8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1. 

Conclusion: This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

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