background Antidepressants are an effective treatment for depressive and anxiety disorders. These disorders are frequently accompanied by heightened cortisol levels. Antidepressants might affect hypothalamic-pituitary-adrenal (hpa) axis functioning, the alteration of which may be partially responsible for treatment efficacy.
aim To assess the effects of antidepressants on the hypothalamic-pituitary-adrenal (hpa) axis.
methods The association between antidepressants and cortisol was investigated in 1526 subjects of the Netherlands Study of Depression and Anxiety (nesda) which were grouped into ‘selective serotonin reuptake inhibitor (ssri) users’ (n = 309), ‘tricyclic antidepressant (tca) users’ (n = 49), ‘other antidepressant users’ (n = 100), and ‘nonusers’ (n = 1068).
Subjects provided seven saliva samples from which three cortisol indicators were calculated: cortisol awakening response (car), evening cortisol, and cortisol suppression after ingestion of 0.5 mg dexamethasone.
results As compared to non-users, tca users had a flattened car (effect size: Cohen’s d =
0.34); ssri users had higher evening cortisol levels (d = 0.04), and ssri users showed decreased cortisol suppression after dexamethasone ingestion (d = 0.03).
conclusion These findings suggest that antidepressant subtypes are associated with distinct alterations of the hpa axis. tca users, who showed a flattened car, displayed the strongest alterations of salivary cortisol.