What the new US FDA guidance in assessing suicidal ideation and behavior in clinical trials means for trial design

Abstract

While antidepressants have been associated with an overall reduction in the rates of suicide in patients with depression [1], case reports of increased suicidal ideation and behavior (SIB) in patients taking antidepressant medications are in long standing [2–6]. However, it is not clear whether the increased SIB seen in patients taking antidepressants is part of the natural disease course of major depressive disorder, or whether antidepressants themselves, independent of the primary disease process, are responsible for the presence of SIB. Regardless of the causal relationship, the general consensus is that patients, especially those experiencing depression, should be carefully monitored for increased SIB when changes in psychotropic medication are made (i.e., stop, start or dosage titration). The US FDA Guidance for Industry: Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials, expands the monitoring of SIB to be included in “all clinical trials involving any drug being developed for any psychiatric indication, as well as for all antiepileptic drugs and other neurologic drugs with central nervous system (CNS) activity, both inpatient and outpatient, including multiple-dose Phase 1 trials involving healthy volunteers” [101].