Impaired hypothalamic-pituitary-adrenocortical (HPA) system is related to severity of benzodiazepine withdrawal in patients with depression

Benzodiazepines suppress the activation of the HPA system. The risk of relapse into depression increases with an impaired HPA system. We investigated whether a dysregulation of the HPA system is related to severity of benzodiazepine withdrawal in patients with depression.

14 depressed patients who responded to the antidepressive treatment underwent the combined dexamethasone/CRH test before benzodiazepine discontinuation. The Clinical Institute Withdrawal Assessment-Benzodiazepines (CIWA-B) was used to asses severity of withdrawal, HDRS, MADRS and BDI to monitor depressive symptoms. Patients with a more severe benzodiazepine withdrawal (CIWA-B-increase>14 pts.; n=7) showed a significant higher cortisol and ACTH response in the dexamethasone/CRH test than patients displaying less severe withdrawal symptoms (CIWA-B-increase<14 pts.; n=7) (ANCOVA, p<0.05).

In view of the GABAergic inhibition of in particular limbic CRH type 1 receptors and the anxiogenic effect of CRH the observed withdrawal symptoms in patients with a dysregulation of the HPA system were interpreted as disinhibition phenomenon during discontinuation of benzodiazepines.