Lamiae Grimaldi-Bensouda1, Clementine Nordon1, Michel Rossignol2, Vincent Jardon3, Virginie Boss3, Frédérique Warembourg3, Robert Reynolds4, Xavier Kurz5, Frédéric Rouillon6, Lucien Abenhaim1,7. 1. LASER Research, Paris, France. 2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. 3. Service de Psychiatrie, Centre Hospitalier Régional Universitaire de Lille, Lille, France. 4. Pfizer Inc, New York, USA. 5. Inspections & Human Medicines, Monitoring & Incident Management, European Medicines Agency, London, UK. 6. Clinique des Maladies Mentales et de l'Encéphale, Centre Hospitalier Sainte Anne, Université Paris V René Descartes, Paris, France. 7. Department of Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Abstract
PURPOSE: Randomized-controlled trials and claims databases suggest that antiepileptic drug (AED) use may increase the risk of suicide attempts (SA). The present case-control study explores the impact of underlying indications on this potential association. METHODS: Physicians collected the medical history; prior 12-month drug use was obtained from standardized telephone interviews with patients. The association between AED use and SA was explored using multivariate conditional logistic regression. The analyses were replicated after stratification on depression and neurological disorders (epilepsy, migraine, and chronic neuropathic pain). RESULTS: Between 2008 and 2012, 506 adults with an incident SA were recruited in suicide treatment centers from across France and socio-demographically matched to 2829 controls from primary care settings. The association between AED use and odds of SA was not significant overall (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9-2.4). No association was observed for patients with neurological disorders (OR, 1.1; 95%CI, 0.5-2.4) as opposed to patients with depression (OR, 1.6; 95%CI, 1.0-2.5), but unmeasured confounding was suspected. CONCLUSIONS: Our results suggest that the association observed between AED use and increased odds of non-fatal SA in patients with either a lifetime history of depression or no neurological disorder may be explained by the presence of an underlying psychiatric disorder. Accounting for underlying indications is crucial in drug safety studies, as these can cause a reported association (or lack thereof) to be misleading. This may require the prospective collection of medical data at a patient level.
PURPOSE: Randomized-controlled trials and claims databases suggest that antiepileptic drug (AED) use may increase the risk of suicide attempts (SA). The present case-control study explores the impact of underlying indications on this potential association. METHODS: Physicians collected the medical history; prior 12-month drug use was obtained from standardized telephone interviews with patients. The association between AED use and SA was explored using multivariate conditional logistic regression. The analyses were replicated after stratification on depression and neurological disorders (epilepsy, migraine, and chronic neuropathic pain). RESULTS: Between 2008 and 2012, 506 adults with an incident SA were recruited in suicide treatment centers from across France and socio-demographically matched to 2829 controls from primary care settings. The association between AED use and odds of SA was not significant overall (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9-2.4). No association was observed for patients with neurological disorders (OR, 1.1; 95%CI, 0.5-2.4) as opposed to patients with depression (OR, 1.6; 95%CI, 1.0-2.5), but unmeasured confounding was suspected. CONCLUSIONS: Our results suggest that the association observed between AED use and increased odds of non-fatal SA in patients with either a lifetime history of depression or no neurological disorder may be explained by the presence of an underlying psychiatric disorder. Accounting for underlying indications is crucial in drug safety studies, as these can cause a reported association (or lack thereof) to be misleading. This may require the prospective collection of medical data at a patient level.
Authors: Md Motiur Rahman; Yasser Alatawi; Ning Cheng; Jingjing Qian; Annya V Plotkina; Peggy L Peissig; Richard L Berg; David Page; Richard A Hansen Journal: Epilepsy Res Date: 2017-06-13 Impact factor: 3.045
Authors: Hari K Raju Sagiraju; Chen-Pin Wang; Megan E Amuan; Anne C Van Cott; Hamada H Altalib; Mary Jo V Pugh Journal: Neurol Clin Pract Date: 2018-08