PrEgabalin for Treatment Resistant generalised Anxiety disorder (PETRA): study protocol for a double-blind randomised...

Generalised anxiety disorder (GAD) is common and increasingly recognised in primary care. Although antidepressants and psychological therapies are first-line treatments, many patients have residual anxiety and limited access to therapy. Evidence for effective next-step pharmacological options for treatment resistant anxiety remains limited. This paper describes the protocol for the PETRA trial, which will evaluate the clinical and cost-effectiveness of adding pregabalin to antidepressant treatment, compared with placebo, for people with GAD who have not responded or partially responded to antidepressant treatment.

PETRA is a multicentre, individually randomised, double-blind, placebo-controlled superiority trial conducted in UK primary care. Participants are recruited by the study team from approximately 150 General Practices and randomised in a 1:1 ratio, using minimisation, to either pregabalin or a matching placebo for 26 weeks (followed by a tapering period where their dosage is reduced over approximately 4 weeks). Sample size is 498. Eligible participants are adults aged 18-74 years, who have been taking antidepressant medication for at least 8 weeks, received treatment with at least one other antidepressant before their current antidepressant and meet ICD-11 criteria for GAD and score ≥ 12 on the revised clinical interview schedule (CIS-R) total score. Follow-up assessments are at 3, 6, 12, 26 and ~ 30 weeks. Our primary outcome measure will be anxiety symptoms measured with GAD-7 at 12 weeks (continuous score). Secondary outcomes are anxiety (GAD-7) at other time points, depressive and panic symptoms, suicidal thoughts, self-rated global improvement, adherence to study medication, serious adverse events, adverse effects, alcohol consumption and benzodiazepine use, quality of life and resources and costs used. The ~ 30-week assessment will investigate symptoms during the withdrawal from pregabalin. Exploratory analyses will include cognitive tasks. A cost-effectiveness analysis and a nested qualitative study will evaluate the implementation and intervention acceptability.

The trial findings will inform primary care prescribing practice by providing an accurate and generalisable estimate of the clinical and cost-effectiveness of prescribing pregabalin to individuals with generalised anxiety who have not responded or only partially responded to antidepressant treatment.

Controlled Trials ISRCTN Registry, ISRCTN 16993990, registered on 19/09/2023. First participant enrolled in January 2024.