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. 2024 Jan 11;25(1):37.
doi: 10.1186/s13063-023-07847-3.

Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial

Dheeraj Rai  1   2   3 , Doug Webb  4   5 , Amanda Lewis  4   5 , Leonora Cotton  4   5 , Jade Eloise Norris  4   5 , Regi Alexander  6 , David S Baldwin  7 , Traolach Brugha  8 , Madeleine Cochrane  4   5 , Maria Chiara Del Piccolo  9 , Emma J Glasson  10   11 , Katherine K Hatch  11 , David Kessler  4   12 , Peter E Langdon  13   14 , Helen Leonard  10   11 , Stephanie J MacNeill  4   12   5 , Nicola Mills  4   12 , Maximiliano Vazquez Morales  4   5 , Zoe Morgan  8 , Raja Mukherjee  9 , Alba X Realpe  4   12   5 , Ailsa Russell  15 , Sergio Starkstein  11 , Jodi Taylor  4   5 , Nicholas Turner  4   5 , Joanna Thorn  4   5 , Jack Welch  16 ; STRATA autistic advisory group; Nicola Wiles  4   12
Collaborators, Affiliations

Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial

Dheeraj Rai et al. Trials. .

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.

Keywords: Adults; Antidepressant; Anxiety; Asperger; Autism; Mental health; Placebo; Randomised controlled trial; Selective Serotonin reuptake inhibitors; Sertraline.

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Conflict of interest statement

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.

TSB has provided a one off consultancy for Roche, the honorarium being paid to the University of Leicester. HL was previously paid for one hour of consultancy by BioMedical Insights (San Francisco) in relation to CDKL5 deficiency disorder. She has also consulted for Marinus, Acadia, Avenix, Orion, Avanex and Newron on topics unrelated to this project, and all remuneration has been paid to her department.

RM has received honoraria for talks on management of ADHD from Takeda and MEdice Pharmaceuticals, the funds directed to his team.

All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
STRATA trial flowchart
Fig. 2
Fig. 2
Schedule of data collection
See this image and copyright information in PMC

References

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