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Post-traumatic stress disorder (PTSD) is often comorbid with major depressive episodes (MDEs) and both conditions carry a higher rate of suicidal behavior. Hypothalamic–pituitary–adrenal (HPA) axis and serotonin abnormalities are associated with both conditions and suicidal behavior, but their inter-relation is not known. We determined cortisol response to placebo or fenfluramine in MDE, MDE and PTSD (MDE+ PTSD), and healthy volunteers (HVs) and examined the relation of cortisol responses to suicidal behavior. A total of 58 medication-free patients with MDE (13 had MDE+ PTSD) and 24 HVs were studied. They received placebo on the first day and fenfluramine on the second day. Cortisol levels were drawn before challenge and for 5 h thereafter. The MDE+ PTSD group had the lowest plasma cortisol, the MDE group had the highest, and HVs had intermediate levels. There were no group differences in …