Antidepressants may ease insomnia in some patients

Researchers endorse treatment shift from improving sleep to reducing anxiety around the clock.

By Victoria Stagg Elliott, amednews staff. Sept. 10, 2001.

Chronic insomnia is increasingly being seen as a problem caused by patients' hyperarousal all day and night rather than a matter of sleep loss. As a result, a new school of thought is emerging in which the disorder may be treated with antidepressants instead of hypnotics, according to sleep disorder experts.

A study in last month's Journal of Clinical Endocrinology & Metabolism found that cortisol and adrenocorticotropic hormone, both of which are associated with increased arousal in animals, were elevated in insomniacs.

The chemistry of insomnia
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"People who secrete the most hormones experience the greatest amount of sleep disturbance," said Alexandros N. Vgontzas, MD, lead author of the study and a professor in the Dept. of Psychiatry at the Pennsylvania State University Medical School in Hershey. "This means that insomniacs are experiencing hormonal changes in their bodies which prevent them from sleeping."

Researchers say this finding is particularly important because of the link between increased levels of the hormones and conditions such as hypertension, depression and obesity.

"We always knew insomnia could be a risk factor for depression, but this data shows furthermore that insomnia is a risk factor for medical morbidity," Dr. Vgontzas said.

Experts praised the study for exploring the chemical basis of a disease that is poorly understood and often treated with a patchwork of behavior modification and hypnotics until something works. Antidepressants are increasingly being used and have been shown to be effective for some, although there is not a lot of scientific evidence that they work.

"Fighting insomnia is a tough battle," said Joyce Walsleben, PhD, director of the New York University Sleep Center. "Each one of these studies adds important sources of understanding, and then treatment options improve."

This study should now increase the shift to antidepressants and change the focus of treatment, according to researchers.

"This information could help doctors who are treating insomniacs refocus their therapeutic goals," said Dr. Vgontzas. "Instead of aiming to simply improve nighttime sleep, doctors may now work to decrease the levels of physiologic arousal."

Experts stress, however, that insomnia is a complicated issue with many causes. It's unlikely that one approach would be appropriate for all.

"Not all insomniacs are the same, but we need clearer ways to differentiate them," Dr. Walsleben said.

The issue is complicated further by the fact that a patient's sleeplessness may be the result of sleep apnea, restless leg syndrome and myriad other conditions, including depression or an anxiety disorder, which could explain why antidepressants sometimes work in people considered to have insomnia.

"When someone comes in and says they don't sleep, they don't know why and they really need to be evaluated," said John Herman, PhD, associate professor in the Dept. of Psychiatry at the University of Texas Southwestern Medical Center in Dallas.

"If you give them a sleep agent, it can be counterproductive if they have sleep apnea or not helpful at all if they have restless leg syndrome," Dr. Herman said. "It might be harmful if they have depression. A differential diagnosis of why they have insomnia is a really important factor."

Researchers say that their study will allow for more accurate diagnosis of this disorder if measuring the hormones results in a possible blood test for insomnia.

"Objective measures of sleep can be potentially useful to predict severity and, therefore, the urgency for treatment," Dr. Vgontzas said. "For now, the only way to diagnose insomnia is the patient complaint, which is subjective. If our data are replicated in other studies, a physician may have an objective measure."

More study required

The study, however, is far from conclusive. The study was small, involving only 11 insomniacs and 13 healthy controls. It is also not clear whether the hormonal elevations are the cause of the insomnia or the result.

"It could be that being awake could cause you to secrete more cortisol as opposed to the other way around," Dr. Herman said. "There's no evidence one way or the other, and I don't think this paper really proves anything."

But experts say the biggest barrier to effectively treating insomnia is not always the condition itself but often the society that surrounds the patient.

"We've come to accept a level of sleeplessness as part of life," Dr. Herman said. "And insomnia is not viewed as a serious medical problem."

Dr. Vgontzas is researching the effects of antidepressants on the overall functioning of insomniacs.

"Most of us -- including myself -- empirically administer antidepressants, but there is a huge lack of studies assessing their effectiveness," he said. "And we need to understand the association between insomnia and depression."

ADDITIONAL INFORMATION:

The chemistry of insomnia

Objective: To examine patterns of secretion of adrenocorticotropic hormone and cortisol in insomniacs.
Participants: Eleven young insomniacs and 13 healthy control subjects.
Method: Subjects snoozed in a sleep laboratory for four nights. Researchers monitored the amount and quality of their sleep. On the fourth day, participants had their blood sampled every 30 minutes for 24 hours.
Results: ACTH and cortisol secretions were significantly higher at all times in insomniacs compared with control subjects, but the stronger elevation levels were observed in the afternoon and late evening.
Conclusion: Chronic persistent insomnia is associated with the hypersecretion of ACTH and cortisol. Medications that down-regulate the activity of the hypothalamic-pituitary-adrenal axis, such as antidepressants, may be a promising pharmacologic approach.

Source: The Journal of Clinical Endocrinology & Metabolism, August

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American Academy of Sleep Medicine (http://www.aasmnet.org/)

Abstract, "Chronic Insomnia Is Associated with Nyctohemeral Activation of the Hypothalamic-Pituitary-Adrenal Axis: Clinical Implications," Journal of Clinical Endocrinology & Metabolism, August (vol. 86, issue 8) (http://jcem.endojournals.org/cgi/content/abstract/86/8/3787)