Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis

Background Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. Objective To perform a network meta-analysis t...

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Main Authors: Rebeka Bustamante Rocha, Fernanda Ferreira Bomtempo, Gabriela Borges Nager, Giulia Isadora Cenci, João Paulo Mota Telles
Format: Article
Language:English
Published: Thieme Revinter Publicações 2023-05-01
Series:Arquivos de Neuro-Psiquiatria
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Online Access:http://www.thieme-connect.de/DOI/DOI?10.1055/s-0043-1768667
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author Rebeka Bustamante Rocha
Fernanda Ferreira Bomtempo
Gabriela Borges Nager
Giulia Isadora Cenci
João Paulo Mota Telles
author_facet Rebeka Bustamante Rocha
Fernanda Ferreira Bomtempo
Gabriela Borges Nager
Giulia Isadora Cenci
João Paulo Mota Telles
author_sort Rebeka Bustamante Rocha
collection DOAJ
description Background Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. Objective To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. Methods The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). Results We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higher doses relating to a longer TST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = -25.40; 95% confidence interval [95%CI] = -40.02–-10.78), followed by suvorexant 20/15mg (SMD = -25.29; 95%CI = -36.42–-14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = -23.70; 95%CI = -35.89–-11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. Conclusion Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.
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spelling doaj-art-18b02e1b265647f680f25e29a3b0ded32025-08-20T03:17:35ZengThieme Revinter PublicaçõesArquivos de Neuro-Psiquiatria0004-282X1678-42272023-05-01810547548310.1055/s-0043-1768667Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysisRebeka Bustamante Rocha0Fernanda Ferreira Bomtempo1Gabriela Borges Nager2Giulia Isadora Cenci3João Paulo Mota Telles4Universidade Federal do Amazonas, Faculdade de Medicina, Manaus AM, Brazil.Faculdade de Ciências Médicas de Minas Gerais, Faculdade de Medicina, Belo Horizonte MG, Brazil.Universidade Federal do Estado do Rio de Janeiro, Faculdade de Medicina, Rio de Janeiro RJ, Brazil.Faculdade Meridional, Faculdade de Medicina, Passo Fundo RS, Brazil.Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil.Background Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. Objective To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. Methods The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). Results We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higher doses relating to a longer TST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = -25.40; 95% confidence interval [95%CI] = -40.02–-10.78), followed by suvorexant 20/15mg (SMD = -25.29; 95%CI = -36.42–-14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = -23.70; 95%CI = -35.89–-11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. Conclusion Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0043-1768667orexin receptor antagonistssleep initiation and maintenance disorders
spellingShingle Rebeka Bustamante Rocha
Fernanda Ferreira Bomtempo
Gabriela Borges Nager
Giulia Isadora Cenci
João Paulo Mota Telles
Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis
Arquivos de Neuro-Psiquiatria
orexin receptor antagonists
sleep initiation and maintenance disorders
title Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis
title_full Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis
title_fullStr Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis
title_full_unstemmed Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis
title_short Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis
title_sort dual orexin receptor antagonists for the treatment of insomnia systematic review and network meta analysis
topic orexin receptor antagonists
sleep initiation and maintenance disorders
url http://www.thieme-connect.de/DOI/DOI?10.1055/s-0043-1768667
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