By Michael Haederle

Commonly Used Insomnia Treatments Fail to Help Dialysis Patients, UNM Health Sciences Research Finds

Nearly half of people undergoing long-term hemodialysis due to end-stage kidney disease are also suffering from chronic insomnia, which severely affects their quality of life.

A new study published in the Annals of Internal Medicine tested two commonly used approaches for treating sleeplessness – cognitive behavioral therapy and an antidepressant drug called trazodone – in dialysis patients and found that neither made a meaningful difference in their symptoms.

The results were unexpected, especially the failure of cognitive behavioral therapy for insomnia (CBT-I), said Mark Unruh, MD, professor and chair of The University of New Mexico’s School of Medicine Department of Internal Medicine, who was joined in the study by Maria-Eleni Roumelioti, MD, an associate professor of Medicine at UNM, Raj Mehrotra, MD, MBBS, at the University of Washington and Daniel Cukor, PhD, at the Rogosin Institute in New York.

“Without a doubt, that’s surprising,” Unruh said. “CBT-I is the standard for insomnia among adults. With this particular population we need to dig deeper to sort out what other sleep issues there are and whether there are medications that are having side effects.”

Dialysis machines filter waste products from the blood when failing kidneys can no longer do the job. The treatment prolongs life, but it is not a cure, and patients must visit a clinic for four-hour dialysis sessions up to three times a week.

“We went into this reflecting what the concerns of patients being treated with end-stage renal disease are,” Unruh said. “When we ask patients what their research priorities are, you would expect them to say, ‘improve transplants or prevent death,’ but in reality they just want us to be able to help them sleep better and have energy and be able to participate in their lives.”

This is a population that has multiple reasons to have disturbed sleep. Is it that we’re treating insomnia, but they also have sleep apnea and restless legs and circadian rhythm disorder?
Mark Unruh, MD, UNM School of Medicine

The study was conducted at 26 dialysis centers in Albuquerque and Seattle, starting in 2018, he said. “We screened 933 patients, and a little under 50% of them had moderately severe insomnia. Of those, a little more than a quarter agreed to participate in the trial. There was a lot of interest in it.”

In the end, 126 participants were divided into three groups. One group was treated with CBT-I, a standardized intervention that was delivered via Zoom by master’s degree-trained therapists. CBT-I helps people restructure their inaccurate or unhelpful beliefs about sleep and provides behavioral training to promote relaxation and healthy sleep habits. 

A second group received trazodone, an older antidepressant drug that is widely prescribed off-label for insomnia due to its sedative effects. The third group was randomly selected to receive an inert pill as a placebo in place of trazodone. Each group underwent six weeks of treatment, and then their insomnia symptoms were assessed at seven weeks and again at 25 weeks.

Sleep quality was assessed using wrist-mounted devices that recorded how much patients tossed and turned during the night, as well as via questionnaires in which patients reported their symptoms, such as sleepiness and anxiety.

“It was interesting that when all of the interventions, including placebo, were overlaid -there was no demonstrable effect – either with the CBT-I or the trazodone intervention,” Unruh said.

“The study’s findings were a little bit disappointing, but that’s how it works,” he said. “Most studies aren’t positive. Most studies are negative, and you want to design them so they’re still informative. I think this one is.”

Although it wasn’t intended for this purpose, the study did detect a higher risk of serious cardiac complications in patients who were prescribed trazodone, Unruh said. “This is actually something that’s plausible given observations in other studies.”

Meanwhile, there are a number of possible explanations for the failure of either intervention to improve sleep among dialysis patients, he said. One is that dialysis itself might somehow be causing the symptom. Another is that dialysis patients tend to have more than one serious medical condition.

“This is a population that has multiple reasons to have disturbed sleep,” Unruh said. “Is it that we’re treating insomnia, but they also have sleep apnea and restless legs and circadian rhythm disorder? Maybe as a practice you should have a lower threshold for referring them to a sleep medicine doctor.”

A related possibility is that the insomnia is driven by the side effects or interactions of multiple medications that many dialysis patients are taking for their ailments, he said.

“The average dialysis patient takes 13 medications – at least 19 pills a day,” Unruh said. “They bring their comorbidities, and then there are medications that go along with having end-stage renal disease.”

While a kidney transplant is the only cure for people with end-stage renal disease, Unruh and his colleagues share an interest in improving patients’ quality of life. They previously partnered for a study of depression treatments for dialysis patients that has been adopted by a major network of dialysis centers.

“That was why we went into this area,” he said. “When you do these large studies and you do surveys, you see that a huge proportion of people who are on dialysis have sleep disorders and sleep problems, and those were largely not being addressed.”

Categories: Research, School of Medicine