Efficacy and Tolerability of Lacosamide in Lennox–Gastaut Syndrome: A Systematic Review and Meta-analysis

Abstract

Purpose Lennox–Gastaut syndrome (LGS) is one of the most difficult to treat childhood-onset epileptic encephalopathies. There is growing evidence that lacosamide is safe and efficacious in patients and adults with refractory epilepsy. However, the evidence regarding the efficacy of lacosamide in LGS is controversial so far. We aimed to evaluate the efficacy and tolerability of lacosamide in patients with LGS. Methods We conducted a systematic review on MEDLINE, EMBASE, COCHRANE CENTRAL, Google Scholar, and Web of Science, collating all available literature till July 31, 2020. The qualitative review included case reports, case series, and both controlled/uncontrolled trials as well as retrospective studies, but for determining pooled estimates, we only included studies with a sample size of 5 or more. The primary outcome was the efficacy of lacosamide in patients with LGS. Clinical variables related to efficacy and adverse events attributed to lacosamide were extracted from each publication. The pooled estimate of variables related to these parameters was performed using a random-effect model. Results Of the 68 items identified by the search, 14 were reviewed as full-text. Eleven articles including two prospective and six retrospective studies fulfilled eligibility criteria and described outcomes in 81 patients (42 adults, 39 children, 60% male, range—1.4–61 years). On average, 35.2%, 27.9%, 7.3%, and 29.4% patients had > 50% reduction, < 50% reduction, no change, and worsening of seizure frequency, respectively. Although 36% of patients had adverse events like somnolence, behavioral abnormalities including irritability, aggressiveness, nausea, tremor, memory problems, dizziness, gastrointestinal discomfort, vomiting, and weight loss, no serious adverse events were noted. Conclusion The evidence available in the current literature is not sufficient to support or refute the use of lacosamide in patients with LGS. Although it is one of the possible therapeutic options worth exploring in patients with LGS, caution is still necessary, as there are reports of worsening of seizure frequency in some patients.

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

“…In line with this, another SLR conducted to assess the impact of LCM on mood in adult patients with epilepsy found that studies either reported a neutral or positive effect, including positive effects on depressive and anxiety symptoms [ 287 ]. A SLR in patients with DRE [ 288 ], and another specifically in patients with LGS [ 289 ], have noted that LCM can be associated with adverse mood and behavioural changes; however, AEs rarely led to discontinuations [ 288 ]. Of note, studies have suggested that LCM is effective and tolerable, with good retention rates in patients with epilepsy and intellectual disability [ 290 , 291 ]; a slower titration in the first 3 months of initiating LCM has been recommended to reduce PBAEs [ 290 ].…”

Effective Modulation by Lacosamide on Cumulative Inhibition of INa during High-Frequency Stimulation and Recovery of INa Block during Conditioning Pulse Train

“…It is commonly administrated in patients with epilepsy and occasionally in patients with trigeminal neuralgia or other neuropathic pain [ 1 , 5 , 7 , 8 , 9 , 10 , 11 , 12 ]. A growing body of evidence demonstrated the effectiveness and tolerability of LCS in patients with epilepsy [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Earlier reports have shown that this compound can decrease the frequency of interictal spikes as well as high-frequency oscillations in mesial temporal lobe epilepsy or refractory focal epilepsy [ 13 , 20 ].…”