Relationship between regional prescriptions of lithium and clozapine and suicide mortality in children and adolescents in France between 2014 and 2019

• Published in: Journal of affective disorders Vol. 389; p. 119738
• Main Authors: Guez, Edouard, Rojas-Chaves, Alejandro, Van Der Waerden, Judith, Melchior, Maria, Pellerin, Hugues, Consoli, Angèle, Cohen, David, Benarous, Xavier
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2025
• Subjects: Adolescent; Antipsychotic Agents - therapeutic use; Bipolar disorder; Child; Child, Preschool; Clozapine - therapeutic use; Cross-Sectional Studies; Drug Prescriptions - statistics & numerical data; Early-onset schizophrenia; Female; France - epidemiology; Healthcare access; Humans; Infant; Lithium - therapeutic use; Male; Psychiatric/Mental Health; Registries; Resistant psychiatric disorders; Self-Injurious Behavior - mortality; Suicide; Suicide - statistics & numerical data; Young Adult; France; Bipolar disorder; Healthcare access; Suicide; Resistant psychiatric disorders; Early-onset schizophrenia
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2025.119738

The protective effect of lithium and clozapine against suicide risk was reported in adults but remains unclear in the pediatric population. This cross-sectional ecological study utilized a combination of health registers to collect information on drug prescriptions (OPENMEDIC national health insurance database), mortality (CepiDC national mortality register), medical demography (CNOM data) and social disadvantage (INSEE data), extracting data on subjects aged 0 to 19 years living in France from 2014 to 2019. The relationships between the regional variabilities in lithium and clozapine dispensations and different death rates: by suicide and self-injury, by mental and behavioral disorders, and all causes. Dispensations of lithium and clozapine varied widely by region. Inter-regional variabilities in lithium and clozapine dispensations were associated with mortality by suicide and self-injury in simple regression models (respectively, β = −0.006, p = .032 and β − 0.0104, p = .009) but not for other causes of mortality. Both dispensations were strongly correlated with social deprivation scores and the density of adult psychiatrists. In robust and multiple regression models, the level of association with suicide and self-injury mortality remained significant for clozapine but not for lithium. Keeping in mind the limitations inherent to spatial study design, these preliminary findings are consistent with a possible antisuicide effect of clozapine in the pediatric population, while the effect of lithium is less clear. Even in the context of the French free-of-charge healthcare system, major spatial inequities exist in access to these medications for youths, partly underlaid by social disparities and medical demography. •Large regional variations in lithium and clozapine dispensations in youths in France•All indexes of social disadvantages negatively correlated with these dispensations.•Relation between regional variations in clozapine dispensations and suicide mortality•The relation was not significant for lithium, when accounting for social indexes.