Psychotropic medication effects on cortisol: Implications for research and mechanisms of drug action

Stress and the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in the etiology of a range psychiatric disorders; abnormalities in cortisol secretion are well documented in mood, anxiety, and psychotic disorders. There is, however, evidence that psychotropic medications affect HPA function, and are often a confound in research on the relation of cortisol secretion with psychiatric symptoms and syndromes. Psychotropic effects are particularly problematic in longitudinal research on individuals at clinical high risk (CHR) for serious mental illness, because they have the potential to obscure neurobiological mechanisms involved in crossing the threshold from CHR states to clinical disorders. This paper reviews the research literature on the relation of cortisol secretion with the three major classes of psychotropic medication that are most often prescribed; antipsychotics, antidepressants, and stimulants. The studies included in this review are those that measured both baseline and post-treatment cortisol. Taken together, most studies of antidepressants find that they are associated with a reduction in both basal and post-dexamethasone-CRH (DEX/CRH) cortisol, although some report no change. Similarly, antipsychotics, both typical and atypical, are found to reduce basal and DEX/CRH cortisol levels in most studies. Psychostimulant medications, in contrast, are associated with an increase in basal cortisol levels or no change. Effects of psychotropics on the cortisol awakening response (CAR) are less consistent. Implications of these effects for clinical research, especially studies of CHR populations, are discussed. Limitations of the research, due to variations in sample demographic and methodologic factors, are noted, and directions for future research are proposed.