Durability of treatment response to zolpidem using a partial reinforcement regimen: does this strategy require priming?

Michael L. Perlis, Knashawn H. Morales, Ivan Vargas, Alexandria Muench, Mark Seewald, Nalaka Gooneratne, Michael A. Grandner, Michael E. Thase, Ted J. Kaptchuk, Robert Ader

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Previous research has shown that after one month of full dose nightly treatment with zolpidem (priming), subjects with chronic insomnia (CI) switched to intermittent dosing with medication and placebos were able to maintain their treatment responses. This approach to maintenance therapy is referred to as partial reinforcement. The present study sought to assess whether priming is required for partial reinforcement or whether intermittent dosing with placebos (50% placebos and 50% active medication) can, by itself, be used for both acute and extended treatment. Method: 55 CI subjects underwent a baseline evaluation (Phase-1) and then were randomized to one of two conditions in Phase-2 of the study: one month of (1) nightly medication use with standard-dose zolpidem (QHS [n = 39]) or (2) intermittent dosing with standard-dose zolpidem and placebos (IDwP [n = 16]). In Phase-3 (three months), the QHS group was re-randomized to either continued QHS full dose treatment (FD/FD) or to IDwP dose treatment (FD/VD). Treatment response rates and Total Wake Time (TWT = [SL + WASO + EMA]) were assessed during each phase of the study. Results: In Phase-2, 77% (QHS) and 50% (IDwP) subjects exhibited treatment responses (p = 0.09) where the average change in TWT was similar. In Phase-3, 73% (FD/FD), 57% (FD/VD), and 88% (VD/VD) of subjects exhibited continued treatment responses (p = 0.22) where the average improvement in TWT continued with FD/FD and remained stable for FD/VD and VD/VD (p < 0.01). Conclusion: These results suggest that intermittent dosing with placebos can maintain effects but do not allow for the additional clinical gains afforded by continuous treatment.

Original languageEnglish (US)
Pages (from-to)56-61
Number of pages6
JournalSleep Medicine
StatePublished - Nov 2021


  • Insomnia
  • Partial reinforcement
  • Placebo
  • Treatment
  • Zolpidem

ASJC Scopus subject areas

  • Medicine(all)


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