The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care.

BACKGROUND: The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. METHODS: The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18-65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. DISCUSSION: This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.

Status migrainosus inpatient treatment with eptinezumab (SMITE): study protocol for a randomised controlled trial.

INTRODUCTION: Status migrainosus is a disabling complication of migraine, which frequently results in hospitalisation. For patients who fail to respond to simple analgesia, triptans and intravenous prochlorperazine or chlorpromazine, there are limited treatment options, and a paucity of high-quality evidence to guide clinical practice. Eptinezumab, an intravenous monoclonal antibody specific for the calcitonin gene-related peptide ligand which achieves maximal plasma concentration immediately following administration and may improve migraines from day one. Intravenous lignocaine is an anaesthetic medication used in treatment of status migrainosus, often requiring prolonged admissions and with potential cardiac adverse events. The aim of this study is to assess the efficacy and safety of eptinezumab in the treatment of status migrainosus in comparison to intravenous lidocaine. METHODS AND ANALYSIS: Status migrainosus inpatient treatment with eptinezumab is a randomised, controlled, single-centre clinical trial conducted in a parallel design with an active comparator conducted in Melbourne, Australia. This study randomises forty patients (1:1) to receive either eptinezumab or an infusion of intravenous lignocaine for up to 5 days. It will assess the effect of eptinezumab compared with intravenous lignocaine in aborting status migrainosus, with the primary outcome of time from infusion until resolution of pain. It will explore several secondary measures including change in health resource utilisation, effect on patient reported outcomes of migraine disability and the safety and tolerability of each medication. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Human Research Ethics Committee of Alfred Health, local reference number 443/21, and all participants will provide informed consent for participation in the trial and dissemination of results. TRIAL REGISTRATION NUMBER: The trial registration number is ACTRN12621001616864. The results of this study will be disseminated through peer-reviewed journals, conference presentations and social media.