Lemborexant bests placebo, zolpidem for insomnia in older adults

  • Rosenberg R & al.
  • JAMA Netw Open
  • 2 Dec 2019

  • International Clinical Digest
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Takeaway

  • Lemborexant, an investigational oral orexin receptor antagonist, outperformed placebo and zolpidem for improving objective measures of insomnia in older adults.

Why this matters

  • Current pharmacotherapeutic options have adverse effects and limited effectiveness in this population.

Key results

  • Change in log-transformed sleep latency (SL) vs placebo (least-squares geometric mean treatment ratio):
    • Lemborexant 5 mg: 0.77 (P<.001>
    • Lemborexant 10 mg: 0.72 (P<.001>
  • Change in sleep efficiency vs placebo (least-squares mean [LSM] treatment difference):
    • Lemborexant 5 mg: 7.1% (P<.001>
    • Lemborexant 10 mg: 8.0% (P<.001>
  • Change in wake-after-sleep onset (WASO) vs placebo (LSM treatment difference):
    • Lemborexant 5 mg: –24.0 minutes (P<.001>
    • Lemborexant 10 mg: –25.4 minutes (P<.001>
  • Change in WASO in second half of night vs zolpidem (LSM treatment difference):
    • Lemborexant 5 mg: –6.7 minutes (P=.004).
    • Lemborexant 10 mg: –8.0 minutes (P<.001>
  • Serious adverse events:
    • 4 patients in zolpidem group.
    • 2 patients in lemborexant 5 mg group.

Expert comment

  • Authors of invited commentary note that no specific values were reported for sleep diary SL and WASO despite claims of statistically significant improvement.
  • The lack of this information, they say, precludes understanding "how the variables that represent the patients’ presenting concerns were affected.”

Study design

  • North American, European phase 3 randomized controlled trial: 1006 adults ages ≥55 years with confirmed insomnia disorder.
  • Randomization: placebo vs zolpidem extended release (6.25 mg) vs lemborexant (5 or 10 mg) for 1 month at bedtime.
  • Main outcome: polysomnographic SL for lemborexant vs placebo.
  • Funding: Eisai.

Limitations

  • Unknown long-term outcomes.
  • Use of fixed-dose zolpidem.
  • Differences between objective, subjective WASO.