Integrated risk assessment of suicidal ideation and behavior in drug development

•We provide a brief outline of the clinical landscape and present labeling of compounds with suspected drug-induced suicidal intent and behavior (SIB).•The present regulatory recommendations for prospective assessment of SIB are highlighted.•We discuss the importance of target identification for SIB assessment in the preclinical setting.

Treatment-related suicidal ideation and behavior (SIB) adverse events are under increasing public, legal and regulatory scrutiny. Prospective assessment of SIB is emerging as a challenging safety requirement by health authorities for the development of drugs but the underlying risk factors remain ill defined. To help with the understanding of risk factors that trigger a prospective assessment of SIB in clinical trials, we present an industry consensus framework for risk assessment and decision making of SIB during drug development. Application of this strategy is based on chemical and pharmacological similarities of compounds with clinical evidence of suicidal intent, target or indication classes associated with high incidence of SIB, in vitro neuropharmacological activity profile, in vivo ADME properties, patient population of the underlying indication and regulatory precedents.