Influence of mirtazapine on salivary cortisol in depressed patients

Unlike other antidepressants, mirtazapine does not inhibit the
reuptake of norepinephrine or serotonin but acts as an antagonist
at presynaptic alpha(2)-receptors, at postsynaptic 5-HT2 and 5-HT3
receptors, and at histaminergic H1 receptors. Furthermore,
mirtazapine has been shown to acutely inhibit cortisol secretion in
healthy subjects. In the present study, the impact of mirtazapine
treatment on salivary cortisol secretion was investigated in 12
patients (4 men, 8 women) suffering from major depression according
to DSM-IV criteria. Patients were treated with mirtazapine for 3
weeks, receiving 15 mg mirtazapine on day 0, 30 mg on day 1 and 45
mg per day from day 2 up to the end of the study (day 21). Response
to mirtazapine treatment was defined by a reduction of at least 50%
in the Hamilton Rating Scale for Depression after 3 weeks of
therapy. Salivary cortisol concentrations were measured before
treatment (day -1), at the beginning of treatment (day 0), after 1
week (day 7) and after 3 weeks (day 21) of treatment with
mirtazapine. Saliva samples were collected hourly from 08.00 until
20.00 h. The area under the curve values served as parameter for
the salivary cortisol secretion. Following analysis of variance
with a repeated measures design, tests with contrasts revealed a
significant reduction of cortisol concentrations already after 1
day of mirtazapine treatment that was comparable in responders and
nonresponders. In addition to new pharmacological approaches such
as CRH1 receptor antagonists, mirtazapine therefore appears to be
an effective strategy to decrease hypercortisolism and restore HPA
system dysregulation in depression. However, the importance of the
acute inhibitory effects of mirtazapine on cortisol secretion for
its antidepressant efficacy has to be further clarified. Copyright
(C) 2003 S. Karger AG, Basel.