{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:11:54Z","timestamp":1788948714727,"version":"build-2803163510"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"DOI":"10.1186\/s13063-026-09949-0","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:33:26Z","timestamp":1788399206000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PrEgabalin for Treatment Resistant generalised Anxiety disorder (PETRA): study protocol for a double-blind randomised controlled trial set in the UK"],"prefix":"10.1186","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0093-3877","authenticated-orcid":false,"given":"Larisa","family":"Duffy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Chew-Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C. F.","family":"Ching","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley","family":"Chipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liz","family":"Deane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakim-Moulay","family":"Dehbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Freemantle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Gafoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Harding-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berry","family":"Jude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Marston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver J","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P","family":"Roiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Wiles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glyn","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"9949_CR1","unstructured":"McManus S, Bebbington P, Jenkins R, Brugha T. Mental health and wellbeing in England: adult psychiatric morbidity survey 2014. Leeds: NHS Digital. 2016. Available from: https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/556596\/apms-2014-full-rpt.pdf."},{"issue":"3","key":"9949_CR2","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1192\/bjp.2020.159","volume":"218","author":"A Slee","year":"2021","unstructured":"Slee A, Nazareth I, Freemantle N, Horsfall L. Trends in generalised anxiety disorders and symptoms in primary care: UK population-based cohort study. Br J Psychiatry. 2021;218(3):158\u201364. https:\/\/doi.org\/10.1192\/bjp.2020.159. PubMed PMID: 32895062.","journal-title":"Br J Psychiatry"},{"issue":"11","key":"9949_CR3","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1037\/bul0000111","volume":"143","author":"NC Jacobson","year":"2017","unstructured":"Jacobson NC, Newman MG. Anxiety and depression as bidirectional risk factors for one another: A meta-analysis of longitudinal studies. Psychol Bull. 2017;143(11):1155\u2013200. https:\/\/doi.org\/10.1037\/bul0000111. PubMed PMID: 28805400.","journal-title":"Psychol Bull"},{"key":"9949_CR4","first-page":"1","volume-title":"Generalised anxiety disorder in adults: the NICE guideline on management in primary, secondary and community care","author":"NCCMH","year":"2011","unstructured":"NCCMH. Generalised anxiety disorder in adults: the NICE guideline on management in primary, secondary and community care. London: RCPsych BPS; 2011. p. 1\u2013465."},{"issue":"1","key":"9949_CR5","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1002\/wps.20089","volume":"13","author":"P Cuijpers","year":"2014","unstructured":"Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds CF. Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis. World Psychiatry. 2014;13(1):56\u201367. https:\/\/doi.org\/10.1002\/wps.20089. PubMed PMID: 24497254.","journal-title":"World Psychiatry"},{"key":"9949_CR6","doi-asserted-by":"publisher","unstructured":"Chen S, Huang W, Zhang M, Song Y, Zhao C, Sun H, et al. Dynamic changes and future trend predictions of the global burden of anxiety disorders: analysis of 204 countries and regions from 1990 to 2021 and the impact of the COVID-19 pandemic. EClinicalMedicine. 2025;79. https:\/\/doi.org\/10.1016\/j.eclinm.2024.103014.","DOI":"10.1016\/j.eclinm.2024.103014"},{"key":"9949_CR7","doi-asserted-by":"publisher","unstructured":"Punton G, Dodd AL, McNeill A. \u2018You\u2019re on the waiting list\u2019: an interpretive phenomenological analysis of young adults\u2019 experiences of waiting lists within mental health services in the UK. PLoS One. 2022;17(3 March). https:\/\/doi.org\/10.1371\/journal.pone.0265542.","DOI":"10.1371\/journal.pone.0265542"},{"issue":"10173","key":"9949_CR8","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S0140-6736(18)31793-8","volume":"393","author":"A Slee","year":"2019","unstructured":"Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet. 2019;393(10173):768\u201377. https:\/\/doi.org\/10.1016\/S0140-6736(18)31793-8. PubMed PMID: 30712879.","journal-title":"Lancet"},{"issue":"5","key":"9949_CR9","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1017\/S1461145710001434","volume":"14","author":"DS Baldwin","year":"2011","unstructured":"Baldwin DS, Waldman S, Allgulander C. Evidence-based pharmacological treatment of generalized anxiety disorder. Int J Neuropsychopharmacol. 2011;14(5):697\u2013710. https:\/\/doi.org\/10.1017\/S1461145710001434. PubMed PMID: 21211105.","journal-title":"Int J Neuropsychopharmacol"},{"key":"9949_CR10","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1192\/bjp.bp.105.012799","volume":"189","author":"DS Baldwin","year":"2006","unstructured":"Baldwin DS, Huusom AK, Maehlum E. Escitalopram and paroxetine in the treatment of generalised anxiety disorder: randomised, placebo-controlled, double-blind study. Br J Psychiatry. 2006;189:264\u201372. https:\/\/doi.org\/10.1192\/bjp.bp.105.012799. PubMed PMID: 16946363.","journal-title":"Br J Psychiatry"},{"issue":"3","key":"9949_CR11","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1097\/YIC.0b013e328350b133","volume":"27","author":"K Rickels","year":"2012","unstructured":"Rickels K, Shiovitz TM, Ramey TS, Weaver JJ, Knapp LE, Miceli JJ. Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. Int Clin Psychopharmacol. 2012;27(3):142\u201350. https:\/\/doi.org\/10.1097\/YIC.0b013e328350b133. PubMed PMID: 22302014.","journal-title":"Int Clin Psychopharmacol"},{"key":"9949_CR12","doi-asserted-by":"publisher","unstructured":"Yuen ASC, Chen B, Chan AYL, Hayes JF, Osborn DPJ, Besag FMC, et al. Use of gabapentinoid treatment and the risk of self-harm: population based self-controlled case series study. BMJ. 2025. https:\/\/doi.org\/10.1136\/bmj-2024-081627.","DOI":"10.1136\/bmj-2024-081627"},{"issue":"10","key":"9949_CR13","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1001\/archinte.166.10.1092","volume":"166","author":"RL Spitzer","year":"2006","unstructured":"Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092\u20137. PubMed PMID: 16717171.","journal-title":"Arch Intern Med"},{"issue":"11","key":"9949_CR14","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1007\/s11606-007-0333-y","volume":"22","author":"S Gilbody","year":"2007","unstructured":"Gilbody S, Richards D, Brealey S, Hewitt C. Screening for depression in medical settings with the Patient Health Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern Med. 2007;22(11):1596\u2013602. PubMed PMID: 17874169.","journal-title":"J Gen Intern Med"},{"issue":"18","key":"9949_CR15","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1001\/jama.282.18.1737","volume":"282","author":"RL Spitzer","year":"1999","unstructured":"Spitzer RL. Validation and utility of a self-report version of PRIME-MD.\u00a0The PHQ Primary Care Study. JAMA. 1999;282(18):1737. https:\/\/doi.org\/10.1001\/jama.282.18.1737.","journal-title":"JAMA"},{"issue":"11","key":"9949_CR16","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/S2215-0366(19)30366-9","volume":"6","author":"G Lewis","year":"2019","unstructured":"Lewis G, Duffy L, Ades A, Amos R, Araya R, Brabyn S, et al. The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): a pragmatic, double-blind, placebo-controlled randomised trial. Lancet Psychiatry. 2019;6(11):903\u201314. https:\/\/doi.org\/10.1016\/S2215-0366(19)30366-9. PubMed PMID: 31543474.","journal-title":"Lancet Psychiatry"},{"key":"9949_CR17","doi-asserted-by":"publisher","unstructured":"Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727\u201336. https:\/\/doi.org\/10.1007\/s11136-011-9903-x. PubMed PMID: 21479777. 2011\/04\/12.","DOI":"10.1007\/s11136-011-9903-x"},{"issue":"9","key":"9949_CR18","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1097\/01.mlr.0000135827.18610.0d","volume":"42","author":"JE Brazier","year":"2004","unstructured":"Brazier JE, Roberts J. The estimation of a preference-based measure of health from the SF-12. Med Care. 2004;42(9):851\u20139. https:\/\/doi.org\/10.1097\/01.mlr.0000135827.18610.0d. PubMed PMID: 15319610.","journal-title":"Med Care"},{"issue":"9864","key":"9949_CR19","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/S0140-6736(12)61552-9","volume":"381","author":"N Wiles","year":"2013","unstructured":"Wiles N, Thomas L, Abel A, Ridgway N, Turner N, Campbell J, et al. Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial. Lancet. 2013;381(9864):375\u201384. https:\/\/doi.org\/10.1016\/S0140-6736(12)61552-9. PubMed PMID: 23219570.","journal-title":"Lancet"},{"key":"9949_CR20","doi-asserted-by":"publisher","unstructured":"Kessler DS, Macneill SJ, Tallon D, Lewis G, Peters TJ, Hollingworth W, et al. Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). https:\/\/doi.org\/10.1136\/bmj.k4218.","DOI":"10.1136\/bmj.k4218"},{"key":"9949_CR21","doi-asserted-by":"publisher","unstructured":"Crawford AA, Lewis S, Nutt D, Peters TJ, Cowen P, O\u2019Donovan MC, et al. Adverse effects from antidepressant treatment: randomised controlled trial of 601 depressed individuals. Psychopharmacology (Berl). 2014;231(15):2921\u201331. https:\/\/doi.org\/10.1007\/s00213-014-3467-8. PubMed PMID: 24525810. 2014\/02\/15.","DOI":"10.1007\/s00213-014-3467-8"},{"issue":"2","key":"9949_CR22","doi-asserted-by":"publisher","first-page":"305","DOI":"10.15288\/jsa.2005.66.305","volume":"66","author":"A G\u00f3mez","year":"2005","unstructured":"G\u00f3mez A, Conde A, Santana JM, Jorr\u00edn A. Diagnostic usefulness of brief versions of Alcohol Use Disorders Identification Test (AUDIT) for detecting hazardous drinkers in primary care settings. J Stud Alcohol. 2005;66(2):305\u20138. https:\/\/doi.org\/10.15288\/jsa.2005.66.305. PubMed PMID: 15957683.","journal-title":"J Stud Alcohol"},{"issue":"4","key":"9949_CR23","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1007\/s11135-017-0574-8","volume":"52","author":"B Saunders","year":"2018","unstructured":"Saunders B, Sim J, Kingstone T, Baker S, Waterfield J, Bartlam B, et al. Saturation in qualitative research: exploring its conceptualization and operationalization. Qual Quant. 2018;52(4):1893\u2013907. https:\/\/doi.org\/10.1007\/s11135-017-0574-8. PubMed PMID: 29937585.","journal-title":"Qual Quant"},{"key":"9949_CR24","unstructured":"Clarke V, Braun V, Hayfield N, editor. Qualitative psychology: a practical guide to research methods. 3rd ed. Sage. 2015."},{"issue":"3","key":"9949_CR25","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1111\/bjhp.12295","volume":"23","author":"M Sekhon","year":"2018","unstructured":"Sekhon M, Cartwright M, Francis JJ. Acceptability of health care interventions: A theoretical framework and proposed research agenda. Br J Health Psychol. 2018;23(3):519\u201331. https:\/\/doi.org\/10.1111\/bjhp.12295. PubMed PMID: 29453791.","journal-title":"Br J Health Psychol"},{"issue":"1","key":"9949_CR26","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s13012-018-0758-1","volume":"13","author":"CR May","year":"2018","unstructured":"May CR, Cummings A, Girling M, Bracher M, Mair FS, May CM, et al. Using normalization process theory in feasibility studies and process evaluations of complex healthcare interventions: a systematic review. Implement Sci. 2018;13(1):80. https:\/\/doi.org\/10.1186\/s13012-018-0758-1. PubMed PMID: 29879986.","journal-title":"Implement Sci"},{"key":"9949_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S0033291720003700","volume":"3","author":"D Kounali","year":"2020","unstructured":"Kounali D, Button KS, Lewis G, Gilbody S, Kessler D, Araya R, et al. How much change is enough? Evidence from a longitudinal study on depression in UK primary care. Psychol Med. 2020;3:1\u20138. https:\/\/doi.org\/10.1017\/S0033291720003700. PubMed PMID: 33138872.","journal-title":"Psychol Med"},{"issue":"2","key":"9949_CR28","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.cct.2011.10.016","volume":"33","author":"LJ Thomas","year":"2012","unstructured":"Thomas LJ, Abel A, Ridgway N, Peters T, Kessler D, Hollinghurst S, et al. Cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment resistant depression in primary care: the CoBalT randomised controlled trial protocol. Contemp Clin Trials. 2012;33(2):312\u20139. https:\/\/doi.org\/10.1016\/j.cct.2011.10.016. PubMed PMID: 22101205.","journal-title":"Contemp Clin Trials"},{"key":"9949_CR29","unstructured":"StataCorp. Stata Statistical Software: College Station, TX: StataCorp LLC.; 2023."},{"key":"9949_CR30","unstructured":"R Core Team. R: A language and Environment for statistical computing [Computer software]. Vienna, Austria. 2024."},{"issue":"15","key":"9949_CR31","doi-asserted-by":"publisher","first-page":"3269","DOI":"10.1017\/S0033291715001270","volume":"45","author":"KS Button","year":"2015","unstructured":"Button KS, Kounali D, Thomas L, Wiles NJ, Peters TJ, Welton NJ, et al. Minimal clinically important difference on the Beck Depression Inventory\u2013II according to the patient\u2019s perspective. Psychol Med. 2015;45(15):3269\u201379. https:\/\/doi.org\/10.1017\/S0033291715001270. PubMed PMID: 26165748.","journal-title":"Psychol Med"},{"key":"9949_CR32","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.conctc.2018.03.008","volume":"10","author":"J Twisk","year":"2018","unstructured":"Twisk J, Bosman L, Hoekstra T, Rijnhart J, Welten M, Heymans M. Different ways to estimate treatment effects in randomised controlled trials. Contemp Clin Trials Commun. 2018;10:80\u20135. https:\/\/doi.org\/10.1016\/j.conctc.2018.03.008.","journal-title":"Contemp Clin Trials Commun"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-026-09949-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-026-09949-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-026-09949-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:05:54Z","timestamp":1788948354000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13063-026-09949-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9949"],"URL":"https:\/\/doi.org\/10.1186\/s13063-026-09949-0","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"assertion":[{"value":"22 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study has been approved by the National Research Ethics Service committee, East Midlands\u2014Leicester Central Research Ethics Committee (ref: 23\/EM\/0192). Clinical trial authorisation was given by the Medicines and Healthcare Products Regulatory Agency (MHRA).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate {30}","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"GlynL acknowledges grant support from NIHR and Wellcome Trust. GlynL was given travel and subsistence to attend ECNP 2023. GeL is a Wellcome Sir Henry Dale Fellow. JPR receives funding from the Leverhulme Trust and the Wellcome Trust. OR acknowledges funding from European Research Council. CCG is part-funded by NIHR Applied Research Collaboration West Midlands (NIHR200165) and other NIHR funding. NW acknowledges grants (to University of Bristol) from NIHR, Wellcome Trust and MRC. KW receives funding from the NIHR and Alzheimer's Society; and sits on the NIHR Three Schools Prevention Programme and the NIHR Mental Health Research Group funding panels. OR acknowledges European Research Council funding. NF received funding from NIHR, MRC, Cure Parkinson\u2019s trust, EU and consulting fees from ALK, Sanofi Aventis, Gilead.","order":3,"name":"Ethics","label":"Competing interests {7b}","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"566"}}