Researchers Urge Small Steps to Better Tailor Insomnia Therapies to Patients

CHARLOTTE, N.C. -- Burgeoning evidence that certain people with chronic insomnia are better suited for certain pharmacotherapies or cognitive behavioral therapy (CBT) could allow the dust to finally settle around the controversy of how to phenotype insomniacs.

Researchers highlighted trazodone's promise as a more reliable treatment for insomnia with short sleep duration, with preliminary data showing improved sleep duration and reduced levels of the stress biomarker cortisol, during a session at the annual SLEEP meeting hosted jointly by the American Academy of Sleep Medicine and the Sleep Research Society.

On the other hand, people self-reporting or objectively showing at least 6 hours of sleep a night have been much more likely to achieve clinical improvement and remission from insomnia after CBT, according to several studies cited by clinical psychologist Jack Edinger, PhD, of National Jewish Health in Denver.

For example, his group reported in 2020 that staged therapy for insomnia involving behavioral therapy or zolpidem produced equivalent responses and remission rates whether one or the other was used first. A secondary analysis showed that remission was nearly twice as likely in people self-reporting at least 6 hours of sleep a night.

This and other studies seem to support the leading approach of phenotyping insomnia, a heterogeneous condition, by hyperarousal.

The key issue is the lack of confidence that a given treatment in today's market will work for someone with insomnia. Despite the existing array of therapies, it has been unclear which patients will respond to which drugs or CBT. The goal would be to optimize treatment outcomes by matching the right insomnia phenotypes to their best treatments, suggested Charles Morin, PhD, a psychologist at Laval University in Québec City.

Categorizing people with insomnia into hyperaroused short sleepers and normal long sleepers on polysomnography (PSG) shows key differences in genetic predisposition and sensitivity of sleep to activation of the arousal and stress systems. Short sleepers tend to have more persistent insomnia, exhibit more impaired neurocognitive functioning, and suffer more cardiometabolic events, according to psychiatrist Alexandros Vgontzas, MD, of Penn State Health in Hershey, Pennsylvania.

Morin said that it's been known for decades that hyperarousal is a core feature of chronic insomnia that can manifest as autonomic dysfunction and systemic inflammation -- potentially resulting in hypertension, atherogenesis, and high lipid levels.

Yet the hyperarousal system to phenotyping has its limitations. There are concerns that PSG findings are not stable, for example, and that it is too expensive.

On the flip side, sleep diaries are subject to sleep misperception -- short sleepers tend to overestimate their sleep duration, whereas long sleepers underestimate it. Additionally, there is no standard battery of patient-reported insomnia outcomes agreed upon in the insomnia field, said psychologist Julio Fernandez-Mendoza, PhD, also of Penn State Health.

What, then, are clinicians to do with the limited evidence and lack of specific guideline recommendations regarding treatment by insomnia phenotype?

"Make the least bad decision" after evaluating the patient's history, risk factors, and comorbidities, offered Daniel Buysse, MD, a psychiatrist at the University of Pittsburgh. "You factor into it insurance authorizations, which you can't ignore."

He noted that the community can't be sure whether certain medications work better for people with various insomnia phenotypes with just the few comparative efficacy trials published.

"What we really need is a database approach. We don't have it yet. Until then, everything is opinion," Buysse emphasized.

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