Pharmacological interventions for insomnia disorder in adults – Authors' reply

We thank Matthew J Reid and colleagues for commenting on our systematic review and network meta-analysis.1De Crescenzo F D'Alò GL Ostinelli EG et al.Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.Lancet. 2022; 400: 170-184Summary Full Text Full Text PDF PubMed Scopus (72) Google Scholar Although the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders does not use the term secondary insomnia, the criteria for insomnia disorder are more nuanced than Reid and colleagues suggest. For example, the diagnosis is excluded if a coexisting mental disorder can “adequately explain the predominant complaint of insomnia”, which is not always an easy judgement. We agree, however, that the presence of genuine comorbidity is important because, as Reid and colleagues point out, it could have implications for the utility of cognitive behavioural therapy for insomnia versus pharmacotherapy, and thereby aid individual treatment decision making. We also agree that sleep disorders include a spectrum of heterogeneous clinical presentations.2Meyer N Harvey AG Lockley SW Dijk DJ Circadian rhythms and disorders of the timing of sleep.Lancet. 2022; 400: 1061-1078Summary Full Text Full Text PDF PubMed Scopus (44) Google Scholar Currently available interventions, whether pharmacological or non-pharmacological, do not work for everyone. Ideally, treatments should be tailored to the individual patient, considering specific phenotypes. In clinical practice, however, identifying the best approach for each patient is often a matter of trial and error. In general, treatment effects are optimised by limiting risks and costs and incorporating individual patient preferences.3Tomlinson A Furukawa TA Efthimiou O et al.Personalise antidepressant treatment for unipolar depression combining individual choices, risks and big data (PETRUSHKA): rationale and protocol.Evid Based Ment Health. 2020; 23: 52-56Crossref PubMed Scopus (32) Google Scholar In our systematic review and meta-analysis, we only analysed average treatment effects. However, ranking treatments according to their mean performance across multiple outcomes runs the risk of assuming each outcome to be equally important. The relative importance of these non-competing outcomes for individual patients needs to be carefully addressed when planning treatment. It should also be noted that our analysis only included patients recruited for randomised trials, and the patients included in these trials tend to be highly selected. Although this might limit the applicability of the results to real-world practice, it was intended as a methodological strength to assure transitivity in the network.4Cipriani A Higgins JP Geddes JR Salanti G Conceptual and technical challenges in network meta-analysis.Ann Intern Med. 2013; 159: 130-137Crossref PubMed Scopus (718) Google Scholar Unfortunately, we did not have access to individual patient data, which would allow for the analysis of results for specific subgroups of participants across studies and the assessment of differential treatment effects between individuals. A network meta-analysis of individual patient data would be an important step towards the generation and validation of prognostic stratified models,5Hingorani AD Windt DA Riley RD et al.Prognosis research strategy (PROGRESS) 4: stratified medicine research.BMJ. 2013; 346e5793Crossref PubMed Scopus (329) Google Scholar and could shed light on the heterogeneous clinical scenarios and different treatments of insomnia disorder. AC is supported by the NIHR Oxford Cognitive Health Clinical Research Facility, by an NIHR Research professorship (RP-2017-08-ST2–006), by the NIHR Oxford and Thames Valley Applied Research Collaboration, and by the NIHR Oxford Health Biomedical Research Centre (BRC-1215–20005). AC has also received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials about seltorexant in depression, sponsored by Janssen. EGO is supported by NIHR Applied Research Collaboration Oxford and Thames Valley at Oxford Health National Health Service Foundation Trust, by the NIHR Oxford Cognitive Health Clinical Research Facility, and by the NIHR Oxford Health Biomedical Research Centre (BRC-1215-20005). EGO has also received research and consultancy fees from Angelini Pharma. PJC declares no competing interests. Pharmacological interventions for insomnia disorder in adultsA meta-analysis published in 2022 by Franco de Crescenzo and colleagues1 suggested poor efficacy of pharmacotherapeutics in the treatment of insomnia disorder, which sits contrary to the outcomes of earlier meta-analyses. Despite such striking findings from transparent and rigorous methodology, there are multiple clinical scenarios and nuances in the pharmacotherapeutic treatment of sleep disorders that should also be considered. Full-Text PDF