Durability of treatment response to zolpidem using a partial reinforcement regimen: does this strategy require priming?
Insomnia
Partial reinforcement
Placebo
Treatment
Zolpidem
Journal
Sleep medicine
ISSN: 1878-5506
Titre abrégé: Sleep Med
Pays: Netherlands
ID NLM: 100898759
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
06
04
2021
accepted:
07
04
2021
pubmed:
13
9
2021
medline:
7
1
2022
entrez:
12
9
2021
Statut:
ppublish
Résumé
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. 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. 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). These results suggest that intermittent dosing with placebos can maintain effects but do not allow for the additional clinical gains afforded by continuous treatment.
Sections du résumé
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.
Identifiants
pubmed: 34509775
pii: S1389-9457(21)00440-8
doi: 10.1016/j.sleep.2021.04.041
pmc: PMC9014427
mid: NIHMS1796682
pii:
doi:
Substances chimiques
Hypnotics and Sedatives
0
Pyridines
0
Zolpidem
7K383OQI23
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
56-61Subventions
Organisme : NHLBI NIH HHS
ID : K23 HL141581
Pays : United States
Organisme : NIA NIH HHS
ID : K24 AG055602
Pays : United States
Organisme : NIA NIH HHS
ID : L30 AG060532
Pays : United States
Organisme : NHLBI NIH HHS
ID : R25 HL105444
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier B.V.
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