133 Cognitive Impairment Following Overdose on Lamotrigine

Abstract

METHODS: Data were pooled from three 6-week trials:KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558). Outcome data were analyzed in the safety population by pooled VBZ doses (40 mg, 80 mg) and PBO. Outcomes of interest included: treatment-emergent adverse events (TEAEs) related to depression or suicidality; mean score change from baseline to Week 6 in the Calgary Depression Scale for Schizophrenia (CDSS, for participants with schizophrenia/schizoaffective disorder) or the Montgomery-Åsberg Depression Rating Scale (MADRS, for participants with mood disorder); and, worsening from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation scores. All outcomes were analyzed descriptively.RESULTS: There were 400 total participants in the pooled safety population; 286 participants had schizophrenia/ schizoaffective disorder (40 mg, n = 82; 80 mg, n = 70; PBO, n = 134) and 114 had a mood disorder (40 mg, n = 28; 80 mg, n = 42; PBO, n = 44). Over one-third of participants had a lifetime history of suicidal ideation or behavior (40 mg, 45%; 80 mg, 39%; PBO, 37%). Few participants had a depression-or suicide-related TEAE, with no apparent differences between VBZ and PBO: suicidal ideation (40 mg, 3.6%; 80 mg, 0.9%; PBO, 2.2%); depression (40 mg, 0%; 80 mg, 1.8%; PBO, 1.1%); depressive symptom (40 mg, 0.9%; 80 mg, 0%; PBO, 0.6%); suicide attempt (40 mg, 0%; 80 mg, 0.9%; PBO, 0%). Mean changes from baseline to Week 6 in depression scale scores were generally small and similar across treatment groups: CDSS total score (40 mg, -0.5; 80 mg, -0.6; PBO, -0.3); MADRS total score (40 mg, -0.2; 80 mg, -1.7; PBO, 0.6). Few participants had a shift from no suicidal ideation at baseline (C-SSRS score = 0) to any suicidal ideation during treatment (C-SSRS score = 1-5): 40 mg, 3.9% (4/103); 80 mg, 0.9% (1/111); PBO, 2.9% (5/174). CONCLUSION:Data from 3 double-blind, placebocontrolled trials indicate that once-daily VBZ treatment was not associated with a worsening in depressionrelated symptoms or an increased risk of suicidal ideation or behavior.