Trazadone and CBT no more effective than placebo for improving insomnia among long-term dialysis patients

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.  
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1. Trazadone and CBT no more effective than placebo for improving insomnia among long-term dialysis patients

Abstract: https://www.acpjournals.org/doi/10.7326/M23-1794

Editorial: https://www.acpjournals.org/doi/10.7326/M23-3448

URL goes live when the embargo lifts  

A clinical trial of more than 120 persons undergoing hemodialysis found that cognitive behavioral therapy for insomnia (CBT-I) or trazodone were no more effective than placebo for improving mild to moderate chronic insomnia. These findings are important given the prevalence of insomnia among long-term dialysis patients. The study is published in Annals of Internal Medicine.

Insomnia affects up to 50 percent of persons undergoing long-term dialysis. Because insomnia is associated with exacerbated fatigue, depression, pain perception, and poor quality of life, patients

place a high priority on finding effective treatments for this condition. CBT-I and trazodone are commonly used interventions to treat insomnia in the general population, but evidence for efficacy and safety of insomnia treatments cannot be extrapolated to persons undergoing long-term dialysis.

A team led by researchers from the University of Washington randomly assigned 126 persons undergoing hemodialysis and experiencing chronic insomnia to 6 weeks of CBT-I, trazadone, or placebo to compare the effectiveness of the interventions. Participants were assessed for severity of insomnia at 7 and 25 weeks using the Insomnia Severity Index (ISI) questionnaire. The authors found that the change in ISI scores were the same for patients regardless of the intervention used, but serious adverse events occurred more frequently in participants using trazodone. According to the authors, given the high burden of insomnia in dialysis patients and high priority placed by patients for symptom relief, more trials are needed to investigate additional therapies for this condition.

An accompanying editorial by Ronald B. Postuma, MD, MSc highlights how the different causes of insomnia impact its treatment. The author notes that lack of efficacy observed with CBT-I in this study is remarkable, given the extremely strong evidence base for its utility in primary insomnia, suggesting that the typical psychophysiological drivers of insomnia in the general population may be simply less pertinent in hemodialysis patients. The authors also highlights that future studies should explore medications specifically designed for insomnia and treatments that target restless legs and neuropathic pain.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Rajnish Mehrotra, MD, MS, please email rmehrotr@uw.edu.

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2. Gabapentinoids associated with severe exacerbation of COPD

Abstract: https://www.acpjournals.org/doi/10.7326/M23-0849        

URL goes live when the embargo lifts   

A population-based cohort study of more than 10,000 persons using gabapentinoids found that their use was associated with an increased risk of chronic obstructive pulmonary disease (COPD) exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. The study is published in Annals of Internal Medicine.

Gabapentinoid drugs are anticonvulsant drugs indicated for the treatment of epilepsy and neuropathic pain. Despite limited indications, its prescription has surged across North America and Europe, which may partly stem from excessive off-label prescribing. However, these drugs have been reported to cause central nervous system depression leading to sedation and respiratory depression in animal and human studies. This safety issue may be of particular concern in patients with respiratory disease like COPD.

Researchers from McGill University and Lady Davis Institute for Medical Research studied insurance data for 356 gabapentinoid users with epilepsy, 9,411 with neuropathic pain, and 3,737 with other chronic pain. The gabapentinoid users were matched 1:1 to nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. The authors found that compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation among users taking these drugs for epilepsy, neuropathic pain, and chronic pain and peak increase in risk for severe COPD exacerbation occurred after approximately 6 months of continuous use. Among patients with neuropathic pain and other chronic pain, the risk was observed regardless of age, sex, number of prior COPD exacerbations, prior use of inhaled corticosteroids (ICS), number of respiratory medications used, or opioid or benzodiazepine use. According to the authors, physicians should consider these potential risks before prescribing gabapentin and pregabalin to patients with COPD.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Christel Renoux, MD, PhD, please email Pascal Fischer at Pascal.Fischer@ladydavis.ca.

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