lacosamide and Mental-Disorders

Background The number of patients with epilepsy receiving perampanel or lacosamide as an add-on treatment following levetiracetam treatment has increased. Although levetiracetam causes psychiatric disorders, it is unclear whether they occur with the combined use of these antiepileptic drugs. Objective To determine the frequency of psychiatric disorders in patients received lacosamide or perampanel in combination with levetiracetam. Setting A single-center retrospective cohort study. Method Patients who received levetiracetam + lacosamide or levetiracetam + perampanel were selected. Medical records from the start of combination therapy contained characteristics of patients and the incidence of psychiatric disorders. Main outcome measure The frequency of psychiatric disorders, the time to onset, dose reduction or discontinuation following psychiatric disorders, and the clinical course following disorder onset. Results Forty-four patients used levetiracetam + lacosamide and 50 used levetiracetam + perampanel. The incidence of psychiatric disorders was significantly lower (p < 0.001) with levetiracetam + lacosamide (6.8%) than with levetiracetam + perampanel (44%). The incidence of affect lability was significantly higher with levetiracetam + perampanel than with levetiracetam + lacosamide (p = 0.018). The time to the onset of psychiatric disorders was within 1 month of dose initiation or increase in one case (33.3%) with levetiracetam + lacosamide and 16 cases (72.7%) with levetiracetam + perampanel. There was no significant difference in clinical characteristics and antiepileptic drug dosages owing to the presence or absence of psychiatric disorders. Conclusion As the frequency of psychiatric disorders was higher with levetiracetam + perampanel therapy, levetiracetam + lacosamide may be preferable. These disorders tended to develop within 1 month of therapy and were not dose-dependent. Antiepileptic drugs should be cautiously prescribed to avoid psychiatric disorders.

Topics: Anticonvulsants; Drug Therapy, Combination; Humans; Lacosamide; Levetiracetam; Mental Disorders; Nitriles; Pyridones; Retrospective Studies; Treatment Outcome

Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 focal-onset seizures, 116 generalized genetic epilepsies [GGEs]) participated in eight prospective, observational audits from 1996 to 2014. These patients were prescribed adjunctive topiramate (n=170), levetiracetam (n=220), pregabalin (n=135), zonisamide (n=203), lacosamide (n=160), eslicarbazepine acetate (n=52), retigabine (n=64), or perampanel (n=54). Doses were titrated according to efficacy and tolerability to optimize zeizure outcomes and reduce side effects. Psychiatric comorbidities were recorded prior to and after the addition of each AED. At baseline, patients with focal-onset seizures (189 of 942; 20.1%) were statistically more likely to have psychiatric diagnoses compared to patients with GGEs (14 of 116, 12.1%; p=0.039). Following adjunctive AED treatment, neuropsychiatric adverse effects led to AED withdrawal in 1.9-16.7% of patients. Patients with a pre-treatment psychiatric history (22 of 209; 10.5%) were statistically more likely to discontinue their new AED due to psychiatric issues compared to patients with no previous psychiatric diagnosis (50 of 849; 5.9%; p=0.017). Patients receiving sodium channel blocking AEDs (4 of 212, 1.9%) were statistically less likely to develop intolerable psychiatric problems, compared to those on AEDs possessing other mechanisms of action (68 of 846, 8.0%; p=0.012). Depression was the commonest problem, leading to discontinuation of AEDs in 2.8% (n=30) patients. Aggression was statistically more common in men (11 of 527, 2.1%) compared to women (1 of 531, 0.2%; p=0.004). Patients with learning disability (12 of 122, 9.8%; p=0.0015) were statistically less likely to have psychiatric issues prior to adjunctive AED treatment compared to other patients (208 of 936, 22.2%), but there were no statistically significant differences once the new AEDs were added (8 of 122 patients with learning disability, 6.6%; 64 of 936 other patients, 6.8%). Awareness of these issues may assist clinicians in avoiding, identifying and treating psychiatric comorbidities in people with epilepsy.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Dibenzazepines; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Fructose; Humans; Lacosamide; Levetiracetam; Male; Medical Audit; Mental Disorders; Middle Aged; Nitriles; Piracetam; Pregabalin; Prospective Studies; Pyridones; Retrospective Studies; Seizures; Sodium Channel Blockers; Topiramate; Young Adult