lacosamide and Intellectual-Disability

Forced normalization (FN) indicates psychotic episodes associated with seizure remission and disappearance of epileptiform activity on EEG. FN is likely to occur when frequent seizures are abruptly terminated by anti-epileptic drugs (AEDs) or epilepsy surgery.. We describe an atypical case of a patient with FN induced by lacosamide (LCM).. A 23-year-old female patient with Lennox-Gastaut syndrome (LGS) was administered AEDs for LGS and hospitalised with weight loss and abnormal behaviour. Her condition fulfilled the FN criteria, which was considered to be induced by LCM. After a reduction in LCM dose, her abnormal behaviour and appetite improved. During LCM use, the patient developed no seizures, and the high amplitude diffuse sharp and slow wave complexes that were frequently observed before LCM disappeared on EEG. The LCM dose was tapered to 150 mg per day, and she became calmer with socially appropriate behaviours, although a few mild focal seizures relapsed.. LCM was effective for treating LGS in this patient and induced FN. Initially, it was difficult to recognise FN in cases of psychiatric disorders, especially in patients with intellectual disability. Patients with FN induced by LCM are rare, and only four patients have been previously reported who were treated by antipsychotic drug for psychosis.

Topics: Adult; Anticonvulsants; Electroencephalography; Female; Humans; Intellectual Disability; Lacosamide; Lennox Gastaut Syndrome; Psychoses, Substance-Induced; Young Adult

Lacosamide (LCM) is an antiepileptic drug (AED) with insufficient clinical experience in patients with intellectual disability (ID). They often have more severe epilepsy with comorbidities. The objective was to evaluate the efficacy and tolerability of lacosamide (LCM) in patients with refractory epilepsy with and without ID in a real-life setting, taking drug monitoring (TDM) data into account therapeutic.. Retrospectively, we identified 344 patients using LCM from the TDM service covering the majority of the country, at the National Center for Epilepsy in Norway (2013-2018). Clinical and TDM data were available for 132 patients.. Forty-four of the 132 patients (33%) had ID. The retention rate was significantly higher in the ID vs the non-ID group after 1 year (84% vs 68%, P < .05). By combining clinical and TDM data, we demonstrated that 37/38 responding patients had serum concentrations above the lower limit of the reference range (>10 µmol/L), and 16/17 with lower concentrations were non-responders. Mean serum concentration/dose ratios were similar in both groups, 0.06 and 0.07 µmol/L/mg. There were no significant differences regarding efficacy and tolerability. The risk of LCM withdrawal was significantly higher when LCM was added to sodium channel blockers, even if the latter was discontinued.. Lacosamide was generally well tolerated in patients with drug-resistant epilepsy, where one third had ID, and in these patients the retention rate was higher. The combination of clinical and TDM data could possibly facilitate LCM therapy in these vulnerable patients.

Topics: Adolescent; Adult; Anticonvulsants; Drug Monitoring; Epilepsy; Female; Humans; Intellectual Disability; Lacosamide; Male; Middle Aged; Sodium Channel Blockers

The objective of this study was to evaluate the tolerability and efficacy of lacosamide (LCM) in residential patients at our epilepsy centre. We assessed retrospectively 80 patients (mean age 36.2 years, range 18-63 years; 29 female) with intellectual disability (ID) and drug-resistant epilepsy using an industry-independent, non-interventional study design based on standardised seizure records. Evaluation, including calculation of retention rate, was carried out for the intervals 3-6, 9-12 and 21-24 months after LCM initiation. The Clinical Global Impression scale (CGI) was used to allow assessment of qualitative changes in seizure severity and clinical status. CGI improved for 61% of the patients. The responder rate was 48%; ten patients (13%) became seizure free. The response was not related to the degree of ID. The retention rates after 12 and 24 months were 71% and 65%, and were significantly lower in patients taking other sodium-channel blockers (SCBs; 76% vs. 55%). The occurrence of adverse events (AEs) was related to the administration of concomitant SCBs (48% with SCBs vs. 26% without). Sedation (15%), ataxia (13%), vertigo (11%), and nausea (9%) were the commonest AEs. While 60% of our patients had concomitant psychiatric diagnosis, we found no relevant effect of this on challenging behaviour. Adjunctive LCM may provide an antiepileptic treatment option for patients with ID with or without additional psychiatric diagnosis. The occurrence of AEs and the LCM retention rate were affected by concomitant SCB use but not by psychiatric comorbidity.

Topics: Adolescent; Adult; Anticonvulsants; Comorbidity; Drug Resistant Epilepsy; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Intellectual Disability; Lacosamide; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Voltage-Gated Sodium Channel Blockers; Young Adult

This study aimed to analyze the retention rate of lacosamide (LCM) in patients with epilepsy and intellectual disabilities (IDs), to identify factors influencing retention rate, and to investigate the LCM retention rate with and without concomitant sodium channel blocker (SCB). We hypothesized that the retention rate of LCM with concomitant SCB would be lower than without SCB.. Using the Kaplan-Meier estimator, we conducted a monocentric, retrospective, observational, open-label study to evaluate LCM retention rates in patients with IDs and drug-resistant epilepsy. In addition, the impact of therapy-related variables on the long-term retention of LCM was evaluated.. One hundred thirty-six subjects with IDs and drug-resistant epilepsy were included (age 2-66 years); most patients had focal epilepsy. Long-term retention rates were 62.0% at 1 year, 43.7% at 2 years, and 29.1% at 3 and 4 years. Reasons for LCM discontinuation included insufficient therapeutic benefits (69%), adverse events (11%), or a combination of both factors (8%). The LCM retention rate was influenced by the number of background antiepileptic drugs (AEDs). An additional and independent influence of concomitant therapy with SCB on retention rate could not be confirmed.. One of the major challenges in medically caring for patients with epilepsy and IDs is the high rate of drug resistance. However, there is a lack of evidence-based information about the efficacy and tolerability of AEDs in this population. It has been shown that concomitant SCB use is a key factor in increasing the risk of LCM failure in children with epilepsy. This finding has not been replicated in our predominantly adult sample of patients with IDs.

Topics: Acetamides; Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Female; Humans; Intellectual Disability; Kaplan-Meier Estimate; Lacosamide; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

We describe the effectiveness of lacosamide as adjunctive therapy in patients with epilepsy and an intellectual disability. This information is relevant, as few data exist pertaining to this population with a high prevalence of (intractable) epilepsy.. We performed a retrospective study in three specialised institutions. Inclusion criteria were (1) focal onset or symptomatic generalized (2) therapy-resistant epilepsy, (3) intellectual disability and (4) residence in a care-facility for people with intellectual disabilities (PWID). The primary outcome variables were the retention rates of lacosamide, estimated through Kaplan-Meier survival analysis. Secondary outcomes were reported seizure control, side effects and clinical factors influencing discontinuation.. One hundred and thirty-two patients were included. The median retention time of lacosamide in our cohort was four years. The estimated one-, two- and three-year retention rates of lacosamide were 64%, 57% and 56% respectively. Severity of intellectual disability and seizure type did not influence whether lacosamide was continued. In 48.5% of patients, a reduction of seizure activity was reported. Side effects were at least part of the reason for discontinuing treatment in 26.5% of all patients. Common side effects were tiredness/somnolence (in 30.3%), aggression/agitation (24.2%), and instable gait (15.2%). Five deaths during follow-up were considered unlikely to be related to the use of lacosamide. One patient died unexpectedly within two months of treatment onset, probably this was a case of SUDEP.. These retention rates of lacosamide in PWID are similar to rates of previously registered anti-epileptic drugs in PWID. Behavioural side effects were noted in a high proportion compared to the general literature on lacosamide. Other side effects were in line with this literature. Lacosamide seems effective and safe for PWID and refractory epilepsy.

Topics: Acetamides; Adolescent; Adult; Aged; Anticonvulsants; Epilepsy; Female; Humans; Intellectual Disability; Kaplan-Meier Estimate; Lacosamide; Longitudinal Studies; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

Lennox-Gastaut syndrome is an intractable epileptic encephalopathy, with most patients experiencing daily seizures despite therapy with multiple antiepileptic drugs. New treatments need to be tested to define their efficacy in this syndrome. Lacosamide is a new antiepileptic drug recently approved for the treatment of partial-onset seizures. We describe three patients with Lennox-Gastaut syndrome resistant to conventional antiepileptic drugs whose seizures were aggravated by lacosamide.

Topics: Acetamides; Adult; Anticonvulsants; Female; Humans; Intellectual Disability; Lacosamide; Lennox Gastaut Syndrome; Male; Spasms, Infantile