Risk of suicide attempt associated with isotretinoin a nationwide cohort and nested case-time-control study

Catherine Droitcourt (1, 2, 3) , Emmanuel Nowak (4) , Caroline Rault (1) , André Happe (1) , Béranger Le Nautout (1) , Sandrine Kerbrat (1) , Frédéric Balusson (1) , Florence Poizeau (1, 2) , David Travers (2) , Jean-Marc Sapori (5) , Emmanuel Lagarde (6, 7) , Grégoire Rey (8) , Bernard Guillot (9) , Emmanuel Oger (1) , Alain Dupuy (1, 2)

1 REPERES - Recherche en Pharmaco-épidémiologie et Recours aux Soins
2 CHU Pontchaillou [Rennes]
3 CIC - Centre d'Investigation Clinique [Rennes]
4 CIC Brest
5 Hôpital Edouard Herriot [CHU - HCL]
6 ISPED - Institut de Santé Publique, d'Epidémiologie et de Développement
7 BPH - Bordeaux population health
8 CépiDc - Centre d'épidémiologie sur les causes médicales de décès
9 CHU - Hôpital Lapeyronie [Montpellier]

Background Isotretinoin is the only effective treatment for severe acne. An isotretinoin-related suicide risk is still debated and under scrutiny by regulatory agencies. Our objectives were: to assess the risk of suicide attempt before, during and after isotretinoin treatment; to detect any potential triggering effect of isotretinoin initiation on suicide attempt. Methods We implemented a cohort and nested case-time-control study of subjects treated with oral isotretinoin (course or initiation) aged 10–50 years, using the Nationwide French Health Insurance data (2009–2016). The main outcome was hospitalized suicide attempt. Standardized incidence ratios for hospitalized suicide attempts were calculated before, during and after isotretinoin treatment. The number of isotretinoin initiations was compared in risk and control periods of 2 months using a case-time-control analysis. Results In all, 443 814 patients (median age 20.0 years; interquartile range 17.0–27.0 years) were exposed to isotretinoin, amounting to 244 154 person-years, with a marked seasonality for treatment initiation. Compared with the French general population, the occurrence of suicide attempts under isotretinoin treatment was markedly lower, with a standardized incidence ratio of 0.6 [95% confidence interval (CI) = 0.53–0.67]; the same applied, to a lesser extent, before and after isotretinoin treatment. In the case-time-control analysis, among cases of suicide attempt, 108 and 127 isotretinoin initiations were observed in the risk and control periods respectively (i.e. 0–2 months and 2–4 months before the date of suicide attempt). The comparison with the 1199 and 1253 initiations observed among matched controls in the same two periods yielded a case-time-control odds ratio of 0.89 (95% CI = 0.68–1.16). A sensitivity analysis using three-month periods and a complementary analysis adding completed suicides for case definition showed consistent results. Conclusion Compared with the general population, a lower risk of suicide attempt was observed among patients exposed to isotretinoin and there was no evidence for a triggering effect of isotretinoin initiation on suicide attempt. A selection of patients at lower risk for suicidal behaviour and appropriate treatment management could explain these findings. Risk management plans should therefore be maintained.

Keywords: Isotretinoin; Suicide attempt; Case-time-control analysis; Acne; Standardized incidence ratio; Suicide; Mental Health

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Santé publique et épidémiologie

Catherine Droitcourt, Emmanuel Nowak, Caroline Rault, André Happe, Béranger Le Nautout, et al.. Risk of suicide attempt associated with isotretinoin a nationwide cohort and nested case-time-control study. International Journal of Epidemiology, 2019, 48 (5), pp.1623-1635. ⟨10.1093/ije/dyz093⟩. ⟨hal-02150353⟩