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Mirtazapine Regulates Stress Hormones, Improves Sleep In Depressed Patients: Presented at ISP


By Alison Palkhivala

Special to DG News

QUEBEC CITY, QC -- August 8, 2001 -- Mirtazipine might be the best option for depressed patients with sleep disturbance and irregularities in stress hormone function.

Two new studies, presented in poster sessions at the 32nd Annual Meeting of the International Society of Psychoneuroendocrinology taking place this week in Quebec City, suggest that the drug can correct both these irregularities.

Mirtazapine has a tetracyclic chemical structure that is distinct from selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants and monoamine oxidase (MAO) inhibitors.

Since it has only been on the market a short time, little is known about mirtazapine's effects on the physiologic changes that often accompany depression, including changes in stress hormones and sleep disruption.

"Depression is often accompanied by sleep disturbance -- subjective and objective -- as well as [hypothalamic-pituitary-adrenal] HPA-axis dysregulation," said D. Astrid Schmid. "Mirtazapine is a treatment that [profoundly affects] the HPA-axis within hours and promotes sleep within days."

Dr. Schmid is completing her PhD at the Max-Planck-Institute of Psychiatry, Krapelinstr, in Munich, Germany.

Schmid and colleagues examined the effect that mirtazapine had on eight individuals with major depression or bipolar disorder. Subjects were treated with up to 60 mg of mirtazapine, and measures of endocrine function and sleep quality were taken before treatment, right after treatment, and then regularly for four weeks.

Participants' subjective assessments of sleep quality improved after only a couple of days of mirtazapine treatment.

EEG data revealed that, over time, the drug increased deep sleep while decreasing wake time and light sleep. Most importantly, rapid eye movement (REM) sleep was either unaffected or slightly increased. In comparison, both SSRI and tricyclic antidepressants tend to reduce REM sleep. SSRIs may also disrupt deep sleep.

Endocrine studies revealed trends towards normalization of stress hormone function, including that of cortisol, adrenocorticotropin (ACTH), and corticotropin-releasing hormone (CRH).

More evidence for normalization of the endocrine system comes from research by Gregor Laakmann and Cornelius Schele from the department of psychiatry at the University of Munich.

They tested the 24-hour urinary free cortisol (UFC) levels of 16 healthy men and 20 men and women with major depression. Patients were treated with mirtazapine while controls were treated with either mirtazapine or placebo. In both patients and controls, mirtazipne significantly reduced UFC concentrations, which is often elevated in depressed patients.

According to Schmid, these findings suggest that mirtazapine might be the best therapeutic option for patients with depression who also have sleep disturbance and altered HPA-axis functioning.

Improved regulation of stress hormone functioning could reduce the risk of depressive relapse.





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