What sleep medications do not cause prolonged QT(c) (QT interval) interval?

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Last updated: May 21, 2025View editorial policy

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From the Guidelines

Sleep medications that do not cause prolonged QTc include melatonin, ramelteon, and suvorexant, as well as traditional benzodiazepines like temazepam, lorazepam, and clonazepam, and certain non-benzodiazepine "Z-drugs" like zolpidem and eszopiclone, according to the most recent evidence 1.

Key Considerations

  • When prescribing sleep medications, it's essential to consider individual patient factors, including existing cardiac conditions, other medications that might prolong QTc, and electrolyte abnormalities.
  • For patients with known QTc prolongation or risk factors, starting with the lowest effective dose and monitoring is advisable.
  • Certain medications, such as antipsychotics (quetiapine, olanzapine) and tricyclic antidepressants, should be avoided in QTc-sensitive patients due to their potential to prolong QTc interval.

Medication Options

  • Melatonin: a natural hormone that regulates sleep-wake cycles, available over-the-counter.
  • Ramelteon: a melatonin receptor agonist, FDA-approved for sleep-onset insomnia.
  • Suvorexant: an orexin receptor antagonist, FDA-approved for sleep-onset and maintenance insomnia.
  • Traditional benzodiazepines: temazepam, lorazepam, and clonazepam, which have minimal effects on QTc interval when used at recommended doses.
  • Non-benzodiazepine "Z-drugs": zolpidem and eszopiclone, which have minimal effects on QTc when used at recommended doses.

Important Notes

  • The American Heart Association recommends considering the potential risks and benefits of sleep medications in patients with cardiovascular disease, and choosing medications with minimal effects on QTc interval 1.
  • Cognitive behavioral therapy for insomnia is recommended as first-line treatment before initiating sedating antidepressants or melatonin receptor agonists 1.
  • Hypnotics like zolpidem and eszopiclone should be prescribed with caution due to the risk of cognitive impairment and increased fall risk 1.

From the Research

Sleep Medications and QTc Interval

  • The provided studies do not directly address the issue of sleep medications that do not cause prolonged QTc interval.
  • However, the studies focus on ramelteon, a selective melatonin receptor agonist, and its effects on sleep disorders.
  • Ramelteon has been shown to be effective in reducing sleep latency and improving sleep quality without significant adverse events, including no potential for abuse or dependence 2, 3, 4, 5, 6.
  • The studies do not mention the specific effect of ramelteon on the QTc interval, but they highlight its unique mechanism of action as a melatonergic agonist, which may suggest a lower risk of QTc interval prolongation compared to other sleep medications.
  • Further research is needed to determine the specific effects of ramelteon and other sleep medications on the QTc interval.

Ramelteon's Safety Profile

  • Ramelteon has been shown to be well-tolerated, with mild adverse events, including somnolence, fatigue, and dizziness 3, 4, 5.
  • The medication has no potential for abuse or dependence, and it is not associated with next-morning hangover effects or reductions in alertness 2, 3, 4.
  • Long-term investigations have supported the conclusion that ramelteon is a well-tolerated and effective drug for the treatment of insomnia 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

A review of ramelteon in the treatment of sleep disorders.

Neuropsychiatric disease and treatment, 2008

Research

Ramelteon.

CNS drugs, 2005

Research

Pharmacokinetic and pharmacodynamic evaluation of ramelteon : an insomnia therapy.

Expert opinion on drug metabolism & toxicology, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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