Abstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects.
Methods: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication.
Discussion: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration: ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.
| Original language | English |
|---|---|
| Article number | 37 |
| Number of pages | 20 |
| Journal | Trials |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 11 Jan 2024 |
Funding
We thank all participants and all investigators and research support staff, past and present, at participating centres and sites. This study has been designed and delivered in collaboration with the Bristol Trials Centre (BTC), a UKCRC-registered clinical trials unit. Recognition goes to all trials unit staff at the BTC who contributed to the central management of the study. This study was also supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. We thank the members of the trial oversight committees and our autistic advisory group. We thank Autistica for helping set up our autistic advisory group through the Autistica Network. We thank Martin House, Database Manager at Bristol Trials Centre, for the development and management of the STRATA database. We thank Liz McCullagh, Lead Clinical trials Pharmacist, University Hospitals Bristol and Weston NHS Trust for helping develop and review the trial pharmacy procedures. We thank all organisations and individuals who supported the study. Study data were collected and managed using REDCap (Research Electronic Data Capture), Harris PA, et al. J Biomed Inform. 2009 Apr;42(2):377-81) hosted at the University of Bristol. This project was funded by the NIHR Research Health Technology Assessment Programme (NIHR127337) and is also supported by the NIHR Bristol Biomedical Research Centre. The views and opinions expressed are those of the authors and do not necessarily reflect those of the HTA, NIHR, NHS or the Department of Health and Social Care. The Australian component of this study is funded by the NHMRC (GNT1171206). The contents of the published material are solely the responsibility of the individual authors and do not reflect the views of NHMRC. The funders have no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. DSB has received research funding from several pharmaceutical and biotechnology companies (including Pfizer Ltd., the developers of sertraline). He has attended advisory boards hosted by Idorsia (daridorexant), Liva Nova (transcranial direct current stimulation), and Mundipharma (methoxyflurane), any honoraria being paid to University of Southampton. He has received editorial honoraria from Wiley publishers, for editorship of Human Psychopharmacology.
| Funders | Funder number |
|---|---|
| Pfizer | |
| University Hospitals Bristol NHS Foundation Trust | |
| Manchester Academic Health Science Centre | |
| NIHR Bristol Biomedical Research Centre | |
| Health Technology Assessment | NIHR127337 |
| University of Bristol | |
| National Health and Medical Research Council | GNT1171206 |
Keywords
- Adults
- Antidepressant
- Anxiety
- Asperger
- Autism
- Mental health
- Placebo
- Randomised controlled trial
- Selective Serotonin reuptake inhibitors
- Sertraline
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Pharmacology (medical)
