The atypical antipsychotics olanzapine and quetiapine, but not haloperidol, reduce ACTH and cortisol secretion in healthy subjects

Abstract

Therefore, this double-blind, placebo-controlled, randomized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone (ACTH), cortisol, and prolactin levels. Eleven healthy male volunteers were studied during four sessions one week apart, orally receiving placebo, quetiapine (50 mg), olanzapine (5 mg), or haloperidol (3 mg). Blood samples were taken at hourly intervals from 0900 until 1700 hours. For ACTH, cortisol, and prolactin a significant effect of treatment condition (p < or = 0.005; p < or = 0.035; p < or = 0.0001, respectively) for area under the curve (AUC) was found. In comparison to placebo, quetiapine and olanzapine significantly reduced ACTH (p < or = 0.002; p < or = 0.05, respectively) and cortisol (p < or = 0.005; p < or = 0.03, respectively). No effect of haloperidol on AUC of ACTH or cortisol levels was observed. In comparison with placebo, haloperidol (p < or = 0.0001) and olanzapine (p < or = 0.0001) elevated AUC of prolactin plasma levels, whereas no significant effect was observed for quetiapine as a main effect of treatment condition. The atypical antipsychotics' strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals' blockade of serotonergic receptors, but blockade of adrenergic or histaminergic receptors may play a role as well. The observed HPA-axis down-regulation may be clinically important for the atypicals' effects on depressive symptomatology and cognitive functioning.

The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: A double blind study

“…On the other hand, olanzapine treatment did not affect significantly plasma cortisol or PRL levels in healthy controls sampled at a similar time-point (i.e. at 9.00 a.m., Cohrs et al, 2006). This difference in the results between healthy and schizophrenic subjects is presumably due to the abnormal HPA axis in schizophrenia (Tandon et al, 1991;Muck-Seler et al, 1999;Mann et al, 2006).…”

Hair cortisol in drug-naïve first-episode individuals with psychosis

“…Cortisol secretion might be altered by antipsychotics. 34 As a direct result of their pharmacological actions, antipsychotics inhibit HPA axis activity. 34 Moreover, we were also careful to only include patients without other psychiatric comorbidities such as depression and PTSD, which induce abnormalities in HPA axis.…”

“…34 As a direct result of their pharmacological actions, antipsychotics inhibit HPA axis activity. 34 Moreover, we were also careful to only include patients without other psychiatric comorbidities such as depression and PTSD, which induce abnormalities in HPA axis. 3,14,15 Therefore, we were able to demonstrate HPA axis abnormalities in the absence of major confounders, and these findings strengthen the idea that the stress response system is independently involved in the pathophysiology of psychotic illness.…”

Positive Association Between Posterior Subgenual Cingulate and Pituitary Volumes in Psychotic Major Depression

“…Indeed, both antidepressants and atypical antipsychotics are suggested to normalize HPA axis hyperactivity and thus possibly exert a neuroprotective effect on brain structures [10,34,35]. However, the significant correlation between PSCV and PV within the psychotic MDD patients remained significant after controlling for the higher rates of atypical antipsychotic use among these patients.…”