Michael L Perlis1, Knashawn H Morales2, Ivan Vargas3, Alexandria Muench4, Mark Seewald4, Nalaka Gooneratne4, Michael A Grandner5, Michael E Thase6, Ted J Kaptchuk7, Robert Ader8. 1. Behavioral Sleep Medicine Program, Department of Psychiatry, University of Pennsylvania, USA; Center for Sleep and Circadian Neurobiology, Department of Medicine, University of Pennsylvania, USA; School or Nursing, University of Pennsylvania, USA. Electronic address: mperlis@upenn.edu. 2. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, USA. 3. Department of Psychological Science, University of Arkansas, USA. 4. Behavioral Sleep Medicine Program, Department of Psychiatry, University of Pennsylvania, USA; Center for Sleep and Circadian Neurobiology, Department of Medicine, University of Pennsylvania, USA. 5. Department of Psychiatry, University of Arizona, USA. 6. Behavioral Sleep Medicine Program, Department of Psychiatry, University of Pennsylvania, USA. 7. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, USA. 8. In memoriam.
Abstract
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.
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.
Authors: Michael T Smith; Michael L Perlis; Amy Park; Michelle S Smith; JaeMi Pennington; Donna E Giles; Daniel J Buysse Journal: Am J Psychiatry Date: 2002-01 Impact factor: 18.112
Authors: Michael Perlis; Michael Grandner; Jarcy Zee; Erin Bremer; Julia Whinnery; Holly Barilla; Priscilla Andalia; Phil Gehrman; Knashawn Morales; Michael Thase; Richard Bootzin; Robert Ader Journal: Sleep Med Date: 2015-07-07 Impact factor: 3.492
Authors: Robert Ader; Mary Gail Mercurio; James Walton; Deborra James; Michael Davis; Valerie Ojha; Alexa Boer Kimball; David Fiorentino Journal: Psychosom Med Date: 2009-12-22 Impact factor: 4.312