Constance H Fung, Cathy Alessi, Jennifer L Martin, Karen Josephson, Lara Kierlin, Joseph M Dzierzewski, Alison A Moore, M Safwan Badr, Michelle Zeidler, Monica Kelly, Jason P Smith, Ian A Cook, Erin Der-Mcleod, Sara Ghadimi, Saadia Naeem, Lisa Partch, Andrew Guzman, Austin Grinberg, Michael Mitchell
{"title":"蒙面减量与行为干预用于停用苯二氮卓受体激动剂：随机临床试验","authors":"Constance H Fung, Cathy Alessi, Jennifer L Martin, Karen Josephson, Lara Kierlin, Joseph M Dzierzewski, Alison A Moore, M Safwan Badr, Michelle Zeidler, Monica Kelly, Jason P Smith, Ian A Cook, Erin Der-Mcleod, Sara Ghadimi, Saadia Naeem, Lisa Partch, Andrew Guzman, Austin Grinberg, Michael Mitchell","doi":"10.1001/jamainternmed.2024.5020","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>Placebo effects are commonly observed in benzodiazepine receptor agonist hypnotic clinical trials. Clinical guidelines recommend discontinuing benzodiazepine receptor agonist hypnotics (particularly in older adults) and administering cognitive behavioral therapy for insomnia (CBTI) as first-line therapy for insomnia. It is unknown whether a novel intervention that masks the daily dose of benzodiazepine receptor agonist during tapering and augments CBTI with novel cognitive and behavioral exercises targeting placebo effect mechanisms improves benzodiazepine receptor agonist discontinuation.</p><p><strong>Objective: </strong>To compare a masked benzodiazepine receptor agonist taper plus augmented CBTI vs an unmasked taper plus standard CBTI.</p><p><strong>Design, setting, and participants: </strong>This randomized clinical trial conducted at an academic medical center and a Department of Veterans Affairs medical center included adults aged 55 years or older who had used lorazepam, alprazolam, clonazepam, temazepam, and/or zolpidem for current or prior insomnia, at doses of less than 8-mg diazepam-equivalent 2 or more nights per week for at least 3 months. Data were collected between December 2018 and November 2023. Data analyses were conducted between November 2023 and July 2024.</p><p><strong>Interventions: </strong>Masked taper plus cognitive behavioral therapy-augmented program (MTcap); standard CBTI plus supervised (unmasked) gradual taper (SGT).</p><p><strong>Main outcomes and measures: </strong>The primary efficacy outcome was percentage achieving benzodiazepine receptor agonist discontinuation 6 months after treatment ended (6-month; intention-to-treat) measured with 7-day self-reported medication logs and for a subset, urine tests. Secondary outcomes were Insomnia Severity Index scores at 1 week posttreatment and 6 months posttreatment, percentage of participants that have discontinued benzodiazepine receptor agonist use at 1 week posttreatment, and benzodiazepine receptor agonist dose and the Dysfunctional Beliefs About Sleep-Medication subscale at 1 week and 6 months posttreatment.</p><p><strong>Results: </strong>Of 338 participants who underwent in-depth screening, 188 participants (mean [SD] age, 69.8 [8.3] years, 123 male [65.4%] and 65 female [35.6%]) were randomly assigned to MTcap (n = 92) or SGT (n = 96). Compared with SGT, MTcap resulted in greater benzodiazepine receptor agonist discontinuation at 6 months (MTcap = 64 [73.4%], SGT = 52 [58.6%]; odds ratio [OR], 1.95; 95% CI 1.03-3.70; P = .04) and 1 week posttreatment (MTcap = 76 [88.4%], SGT = 62 [67.4%]; OR, 3.68; 95% CI, 1.67-8.12; P = .001) and reduced frequency of benzodiazepine receptor agonist use (nights/week) at 1 week posttreatment (-1.31; 95% CI, -2.05 to -0.57; P < .001). Insomnia Severity Index improved with no significant between-group difference at follow-up (baseline to 1 week posttreatment, 1.38; P = .16; baseline to 6 months, 0.16; P = .88).</p><p><strong>Conclusions and relevance: </strong>This randomized clinical trial found that a program combining masked tapering with novel cognitive and behavioral exercises targeting placebo mechanisms improved the percentage of long-term benzodiazepine receptor agonist discontinuation compared with standard CBTI plus an unmasked taper.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03687086.</p>","PeriodicalId":14714,"journal":{"name":"JAMA Internal Medicine","volume":" ","pages":"1448-1456"},"PeriodicalIF":22.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459364/pdf/","citationCount":"0","resultStr":"{\"title\":\"Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial.\",\"authors\":\"Constance H Fung, Cathy Alessi, Jennifer L Martin, Karen Josephson, Lara Kierlin, Joseph M Dzierzewski, Alison A Moore, M Safwan Badr, Michelle Zeidler, Monica Kelly, Jason P Smith, Ian A Cook, Erin Der-Mcleod, Sara Ghadimi, Saadia Naeem, Lisa Partch, Andrew Guzman, Austin Grinberg, Michael Mitchell\",\"doi\":\"10.1001/jamainternmed.2024.5020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>Placebo effects are commonly observed in benzodiazepine receptor agonist hypnotic clinical trials. Clinical guidelines recommend discontinuing benzodiazepine receptor agonist hypnotics (particularly in older adults) and administering cognitive behavioral therapy for insomnia (CBTI) as first-line therapy for insomnia. It is unknown whether a novel intervention that masks the daily dose of benzodiazepine receptor agonist during tapering and augments CBTI with novel cognitive and behavioral exercises targeting placebo effect mechanisms improves benzodiazepine receptor agonist discontinuation.</p><p><strong>Objective: </strong>To compare a masked benzodiazepine receptor agonist taper plus augmented CBTI vs an unmasked taper plus standard CBTI.</p><p><strong>Design, setting, and participants: </strong>This randomized clinical trial conducted at an academic medical center and a Department of Veterans Affairs medical center included adults aged 55 years or older who had used lorazepam, alprazolam, clonazepam, temazepam, and/or zolpidem for current or prior insomnia, at doses of less than 8-mg diazepam-equivalent 2 or more nights per week for at least 3 months. Data were collected between December 2018 and November 2023. Data analyses were conducted between November 2023 and July 2024.</p><p><strong>Interventions: </strong>Masked taper plus cognitive behavioral therapy-augmented program (MTcap); standard CBTI plus supervised (unmasked) gradual taper (SGT).</p><p><strong>Main outcomes and measures: </strong>The primary efficacy outcome was percentage achieving benzodiazepine receptor agonist discontinuation 6 months after treatment ended (6-month; intention-to-treat) measured with 7-day self-reported medication logs and for a subset, urine tests. Secondary outcomes were Insomnia Severity Index scores at 1 week posttreatment and 6 months posttreatment, percentage of participants that have discontinued benzodiazepine receptor agonist use at 1 week posttreatment, and benzodiazepine receptor agonist dose and the Dysfunctional Beliefs About Sleep-Medication subscale at 1 week and 6 months posttreatment.</p><p><strong>Results: </strong>Of 338 participants who underwent in-depth screening, 188 participants (mean [SD] age, 69.8 [8.3] years, 123 male [65.4%] and 65 female [35.6%]) were randomly assigned to MTcap (n = 92) or SGT (n = 96). Compared with SGT, MTcap resulted in greater benzodiazepine receptor agonist discontinuation at 6 months (MTcap = 64 [73.4%], SGT = 52 [58.6%]; odds ratio [OR], 1.95; 95% CI 1.03-3.70; P = .04) and 1 week posttreatment (MTcap = 76 [88.4%], SGT = 62 [67.4%]; OR, 3.68; 95% CI, 1.67-8.12; P = .001) and reduced frequency of benzodiazepine receptor agonist use (nights/week) at 1 week posttreatment (-1.31; 95% CI, -2.05 to -0.57; P < .001). 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Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial.
Importance: Placebo effects are commonly observed in benzodiazepine receptor agonist hypnotic clinical trials. Clinical guidelines recommend discontinuing benzodiazepine receptor agonist hypnotics (particularly in older adults) and administering cognitive behavioral therapy for insomnia (CBTI) as first-line therapy for insomnia. It is unknown whether a novel intervention that masks the daily dose of benzodiazepine receptor agonist during tapering and augments CBTI with novel cognitive and behavioral exercises targeting placebo effect mechanisms improves benzodiazepine receptor agonist discontinuation.
Objective: To compare a masked benzodiazepine receptor agonist taper plus augmented CBTI vs an unmasked taper plus standard CBTI.
Design, setting, and participants: This randomized clinical trial conducted at an academic medical center and a Department of Veterans Affairs medical center included adults aged 55 years or older who had used lorazepam, alprazolam, clonazepam, temazepam, and/or zolpidem for current or prior insomnia, at doses of less than 8-mg diazepam-equivalent 2 or more nights per week for at least 3 months. Data were collected between December 2018 and November 2023. Data analyses were conducted between November 2023 and July 2024.
Interventions: Masked taper plus cognitive behavioral therapy-augmented program (MTcap); standard CBTI plus supervised (unmasked) gradual taper (SGT).
Main outcomes and measures: The primary efficacy outcome was percentage achieving benzodiazepine receptor agonist discontinuation 6 months after treatment ended (6-month; intention-to-treat) measured with 7-day self-reported medication logs and for a subset, urine tests. Secondary outcomes were Insomnia Severity Index scores at 1 week posttreatment and 6 months posttreatment, percentage of participants that have discontinued benzodiazepine receptor agonist use at 1 week posttreatment, and benzodiazepine receptor agonist dose and the Dysfunctional Beliefs About Sleep-Medication subscale at 1 week and 6 months posttreatment.
Results: Of 338 participants who underwent in-depth screening, 188 participants (mean [SD] age, 69.8 [8.3] years, 123 male [65.4%] and 65 female [35.6%]) were randomly assigned to MTcap (n = 92) or SGT (n = 96). Compared with SGT, MTcap resulted in greater benzodiazepine receptor agonist discontinuation at 6 months (MTcap = 64 [73.4%], SGT = 52 [58.6%]; odds ratio [OR], 1.95; 95% CI 1.03-3.70; P = .04) and 1 week posttreatment (MTcap = 76 [88.4%], SGT = 62 [67.4%]; OR, 3.68; 95% CI, 1.67-8.12; P = .001) and reduced frequency of benzodiazepine receptor agonist use (nights/week) at 1 week posttreatment (-1.31; 95% CI, -2.05 to -0.57; P < .001). Insomnia Severity Index improved with no significant between-group difference at follow-up (baseline to 1 week posttreatment, 1.38; P = .16; baseline to 6 months, 0.16; P = .88).
Conclusions and relevance: This randomized clinical trial found that a program combining masked tapering with novel cognitive and behavioral exercises targeting placebo mechanisms improved the percentage of long-term benzodiazepine receptor agonist discontinuation compared with standard CBTI plus an unmasked taper.
期刊介绍：
JAMA Internal Medicine is an international, peer-reviewed journal committed to advancing the field of internal medicine worldwide. With a focus on four core priorities—clinical relevance, clinical practice change, credibility, and effective communication—the journal aims to provide indispensable and trustworthy peer-reviewed evidence.
Catering to academics, clinicians, educators, researchers, and trainees across the entire spectrum of internal medicine, including general internal medicine and subspecialties, JAMA Internal Medicine publishes innovative and clinically relevant research. The journal strives to deliver stimulating articles that educate and inform readers with the latest research findings, driving positive change in healthcare systems and patient care delivery.
As a member of the JAMA Network, a consortium of peer-reviewed medical publications, JAMA Internal Medicine plays a pivotal role in shaping the discourse and advancing patient care in internal medicine.
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