Rebecca Strawbridge1, Ben Carter2, Lindsey Marwood3, Borwin Bandelow4, Dimosthenis Tsapekos5, Viktoriya L Nikolova6, Rachael Taylor5, Tim Mantingh7, Valeria de Angel8, Fiona Patrick5, Anthony J Cleare9, Allan H Young10. 1. Post-Doctoral Research Associate,Department of Psychological Medicine,Institute of Psychiatry, Psychology and Neuroscience,King's College London,UK. 2. Senior Lecturer in Biostatistics,Department of Biostatistics,Institute of Psychiatry,Psychology and Neuroscience,King's College London,UK. 3. Post-Doctoral Trial Manager,Department of Psychological Medicine,Institute of Psychiatry,Psychology and Neuroscience,King's College London,UK. 4. Professor of Psychiatry and Neurology,Department of Psychiatry and Psychotherapy,University Medical Centre,Göttingen,Germany. 5. Department of Psychological Medicine,Institute of Psychiatry,Psychology and Neuroscience,King's College London,UK. 6. Research Assistant,Department of Psychological Medicine,Institute of Psychiatry,Psychology and Neuroscience,King's College London,UK. 7. Research Assistant,Department of Psychological Medicine,Institute of Psychiatry,Psychology and Neuroscience,King's College LondonandSouth London and Maudsley National Health Service Foundation Trust,UK. 8. Research Assistant,Department of Psychological Medicine,Institute of Psychiatry,Psychology and Neuroscience,King's College LondonandSouth LondonandMaudsley National Health Service Foundation Trust,UK. 9. Professor of Psychopharmacology,Department of Psychological Medicine,Institute of Psychiatry,Psychology and Neuroscience,King's College LondonandSouth London and Maudsley National Health Service Foundation Trust,UK. 10. Professor of Mood Disorders,Department of Psychological Medicine,Institute of Psychiatry,Psychology and Neuroscience,King's College LondonandSouth London and Maudsley National Health Service Foundation Trust,UK.
Abstract
BACKGROUND: Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD. METHOD: Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions. RESULTS: Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25-1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23-1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81-1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.80-1.30) and psychological (ES = 1.43, 95% CI 0.50-2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66-0.91) and psychological control (ES = 0.94, 95% CI 0.36-1.52). CONCLUSIONS: Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.Declaration of interestIn the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.
BACKGROUND:Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD. METHOD:Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions. RESULTS: Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25-1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23-1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81-1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.80-1.30) and psychological (ES = 1.43, 95% CI 0.50-2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66-0.91) and psychological control (ES = 0.94, 95% CI 0.36-1.52). CONCLUSIONS: Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.Declaration of interestIn the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.
Authors: Rachael W Taylor; Lindsey Marwood; Emanuella Oprea; Valeria DeAngel; Sarah Mather; Beatrice Valentini; Roland Zahn; Allan H Young; Anthony J Cleare Journal: Int J Neuropsychopharmacol Date: 2020-12-03 Impact factor: 5.176
Authors: Lucas McKeown; Rachael W Taylor; Elana Day; Rupal Shah; Lindsey Marwood; Helena Tee; Jess Kerr-Gaffney; Emanuella Oprea; John R Geddes; R Hamish McAllister-Williams; Allan H Young; Anthony J Cleare Journal: J Psychopharmacol Date: 2022-04-27 Impact factor: 4.562
Authors: Elana Day; Rupal Shah; Rachael W Taylor; Lindsey Marwood; Kimberley Nortey; Jade Harvey; R Hamish McAllister-Williams; John R Geddes; Alvaro Barrera; Allan H Young; Anthony J Cleare; Rebecca Strawbridge Journal: BJPsych Open Date: 2021-05-14