PMID- 32091535 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20210224 IS - 2168-6157 (Electronic) IS - 2168-6149 (Print) IS - 2168-6149 (Linking) VI - 77 IP - 5 DP - 2020 May 1 TI - Tolerability of Antiseizure Medications in Individuals With Newly Diagnosed Epilepsy. PG - 574-581 LID - 10.1001/jamaneurol.2020.0032 [doi] AB - IMPORTANCE: Tolerability is a key determinant of the effectiveness of epilepsy treatment. It is important to evaluate whether the overall tolerability has improved. OBJECTIVE: To identify factors associated with poor tolerability of antiseizure medications (ASMs) and examine temporal changes in tolerability. DESIGN, SETTING, AND PARTICIPANTS: This was a longitudinal cohort study at a specialist clinic in Glasgow, Scotland. Patients with newly diagnosed and treated epilepsy between July 1982 and October 2012 were included from 2282 eligible individuals. They were followed up until April 2016 or death. Data analysis was completed in August 2019. EXPOSURES: Antiseizure medications. MAIN OUTCOMES AND MEASURES: Univariable and multivariable survival analyses were performed to examine associations between potential risk factors and development of intolerable adverse effects (AEs). Intolerable AE rates of the ASMs as the initial monotherapy were compared between 3 epochs (July 1982-June 1992, July 1992-June 2002, and July 2002-April 2016). RESULTS: Of 1795 patients, 969 (54.0%) were male, and the median (interquartile range) age was 33 (21-50) years. A total of 3241 ASMs were prescribed during the period, of which 504 (15.6%) were discontinued within 6 months owing to intolerable AEs. Children younger than 18 years had lower intolerable AE rates than adults (vs aged 18-64 years: adjusted hazard ratio [aHR], 1.58; 95% CI, 1.07-2.32; vs aged >/=65 years: aHR, 1.90; 95% CI, 1.19-3.02) while female individuals (aHR, 1.60; 95% CI, 1.30-1.96) and those who had more than 5 pretreatment seizures (aHR, 1.24; 95% CI, 1.03-1.49) were associated with having higher risk. For each ASM trial, the risk of intolerable AEs increased with the number of previous drug withdrawals due to AEs (aHR, 1.18; 95% CI, 1.09-1.28) and the number of concomitant ASMs (aHR, 1.31; 95% CI, 1.04-1.64). The proportion of second-generation ASMs prescribed as the initial monotherapy increased from 22.3% (33 of 148) in the first epoch to 68.7% (645 of 939) in the last (P < .001). Although differences in intolerable AE rates and types of AEs were found between the ASMs, there was no difference in the overall intolerable AEs rates to the initial monotherapy across the 3 epochs (first: 10.1% [15 of 148]; second: 13.8% [98 of 708]; third: 14.0% [131 of 939]; P = .41). CONCLUSIONS AND RELEVANCE: In this cohort study, the increased use of the second-generation ASMs had not improved overall treatment tolerability. Greater effort to improve tolerability in ASM development is needed. FAU - Alsfouk, Bshra Ali A AU - Alsfouk BAA AD - University of Glasgow, Glasgow, Scotland. AD - College of Pharmacy, Department of Pharmaceutical Sciences, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. FAU - Brodie, Martin J AU - Brodie MJ AD - University of Glasgow, Glasgow, Scotland. AD - Epilepsy Unit, Scottish Epilepsy Initiative, Glasgow, Scotland. FAU - Walters, Matthew AU - Walters M AD - University of Glasgow, Glasgow, Scotland. FAU - Kwan, Patrick AU - Kwan P AD - Central Clinical School, Department of Neuroscience, Monash University, Melbourne, Victoria, Australia. AD - Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia. FAU - Chen, Zhibin AU - Chen Z AD - Central Clinical School, Department of Neuroscience, Monash University, Melbourne, Victoria, Australia. AD - Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia. AD - School of Public Health and Preventive Medicine, Clinical Epidemiology, Monash University, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PL - United States TA - JAMA Neurol JT - JAMA neurology JID - 101589536 RN - 0 (Anticonvulsants) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Anticonvulsants/*adverse effects MH - Child MH - Cohort Studies MH - Epilepsy/*drug therapy MH - Female MH - Humans MH - Longitudinal Studies MH - Male MH - Middle Aged MH - Scotland MH - Young Adult PMC - PMC7042855 COIS- Conflict of Interest Disclosures: Dr Brodie serves on the scientific advisory boards of Eisai, UCB Pharma, GlaxoSmithKline, Lundbeck, Bial, GW Pharmaceuticals, and Takeda; is on the speakers' bureau for Eisai, UCB Pharma, GlaxoSmithKline, Lundbeck, Sanofi Aventis, and Abbott Laboratories; and has accepted travel grants for scientific meetings from Eisai, UCB Pharma, and Lundbeck. Dr Kwan reports grants from the National Health and Medical Research Council of Australia, the Australian Research Council, the US National Institutes of Health, Hong Kong Research Grants Council, Innovation and Technology Fund, Health and Medical Research Fund, Biscayne Pharmaceuticals, Eisai, GW Pharmaceuticals, LivaNova, Novartis, UCB Pharma, and Zynerba outside the submitted work; speaker fees from Eisai, LivaNova, and UCB Pharma outside the submitted work; and is supported by the Medical Research Future Fund Practitioner Fellowship (MRF1136427). Dr Chen reports grants from UCB Pharma outside the submitted work; is supported by the National Health and Medical Research Council of Australia Early Career Fellowship (GNT1156444); and has received research grants from University of Melbourne Early Career Researcher Grant Scheme. No other disclosures were reported. EDAT- 2020/02/25 06:00 MHDA- 2021/02/17 06:00 PMCR- 2021/02/24 CRDT- 2020/02/25 06:00 PHST- 2020/02/25 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2020/02/25 06:00 [entrez] PHST- 2021/02/24 00:00 [pmc-release] AID - 2761856 [pii] AID - noi200002 [pii] AID - 10.1001/jamaneurol.2020.0032 [doi] PST - ppublish SO - JAMA Neurol. 2020 May 1;77(5):574-581. doi: 10.1001/jamaneurol.2020.0032.