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Eur Neuropsychopharmacol. 2011 Sep;21(9):691-9. doi: 10.1016/j.euroneuro.2011.03.002. Epub 2011 Apr 1.

Antidepressant use and salivary cortisol in depressive and anxiety disorders.

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Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.


Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic-pituitary-adrenal axis functioning, the alteration of which could be partially responsible for treatment efficacy. The association between antidepressants and cortisol was investigated in 1526 subjects of the Netherlands Study of Depression and Anxiety who were grouped into 'serotonin reuptake inhibitor (SSRI) users' (n=309), 'tricyclic antidepressant (TCA) users' (n=49), 'other antidepressant users' (n=100), and 'non-users' (n=1068). All subjects had a current or past diagnosis of anxiety and/or depression. Subjects provided 7 saliva samples from which 3 cortisol indicators were calculated: cortisol awakening response (CAR), evening cortisol, and cortisol suppression after ingestion of 0.5mg dexamethasone. 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). 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.

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