SerTRaline for AnxieTy in adults with a diagnosis of Autism (STRATA)

INTERVENTION: The research project is a two parallel group multi‐centre pragmatic randomised controlled trial (RCT) of sertraline versus placebo for reducing anxiety in adults with a diagnosis of autism. The active investigational medicinal products are over‐encapsulated 25mg or 50mg Sertraline tablets with a back fill of microcrystalline cellulose powder. All participants will receive a daily oral dose of 25mg sertraline or placebo for 2 weeks followed by 2x25mg for 4 weeks. Following this initiation period, the medication will be dispensed in 50mg capsules and depending upon tolerability, the dose will be flexibly increased by 50mg every 4‐weeks to reach the optimal dose. The dose will only be increased if the participant is tolerating it and agrees to try an increased dose, and the prescribing clinician is satisfied that it is appropriate to do so based on the participant’s responses to the safety check questionnaire and discussion with the study research staff. The dose may go up to a maximum of 200mg by week 14, although it is anticipated that for many patients the optimal dose may be lower than this amount (e.g. 50mg, 100mg or 150mg) and reached before this time. Participants will take this optimal dose for up to 52‐weeks post‐randomisation, which will be the maximum planned time unless there are indications to stop earlier. Participants can choose to withdraw for any reason at any time during their involvement in the trial. Participants can withdraw from: (a) taking study medication, although participants who have taken at least one study medication capsule will be informed that they should take the treatment regimen for at least 16‐weeks (i.e. until the primary outcome timepoint) before deciding if the treatment works or not; and (b) providing data to t CONDITION: Anxiety;Autism; ; Anxiety ; Autism Mental Health ‐ Anxiety Mental Health ‐ Autistic spectrum disorders PRIMARY OUTCOME: To determine the difference in Generalised Anxiety Disorder Assessment (GAD‐7) anxiety scores at 16‐weeks between adults with a diagnosis of autism treated with sertraline and those treated with placebo.; Instrument used: GAD‐7 anxiety score [16 weeks post randomisation.] SECONDARY OUTCOME: To describe the adverse effects reported by adults with a diagnosis of autism treated with sertraline versus those treated with placebo over 52‐weeks ; Instrument used: Modified Toronto side effects scale and open‐ended questions (including suicidality item)[At baseline, 1 or 2, 4, 8, 12, 16, 24, 36 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on carer burden and quality of life ; Instrument used: (composite secondary outcomes) Caregiver Burden Scale, Carer Experience Scale (CES) and EQ‐5D‐5L questionnaire [At baseline, 16 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on depressive symptoms ; Instrument used: Patient Health Questionnaire‐9 (PHQ‐9)[At baseline, 1 or 2, 4, 8, 12, 16, 24, 36 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on functioning and disability ; Instrument used: any changes in GAD‐7 scores ; [At screening, baseline, 1 or 2, 4, 8, 12, 24, 36 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on social anxiety ; Instrument used: Social Phobia Inventory (SPIN)[At baseline, 16, 24 and 52 weeks post randomisation] To measure adherence to the study medication ; Instrument used: study specific questionnaire (adapted from previous trials trials)[At 1 or 2, 4, 8, 12, 16, 24, 36 and 52 weeks post randomisation] INCLUSION CRITERIA: 1. Adults aged greater than or equal to 18 years. ; Instrument used: World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)[At baseline, 16, 24 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on obsessive compulsive symptoms ; Instrument used: Obsessive Compulsory Inventory Revised (OCI‐R)[At baseline, 16, 24 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on panic attacks ; Instrument used: Brief Patient Health Questionnaire (PHQ) from Primary Care Evaluation of Mental Disorders (PRIME‐MD)[At baseline, 16, 24 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on patient reported effect of medication on symptoms ; Instrument used: Study‐specific questionnaire[At 1 or 2, 4, 8, 12, 16, 24, 36 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on quality of life ; Instrument used: EuroQol‐ 5 Dimension 5 Level (EQ‐5D‐5L) questionnaire[At baseline, 12, 16, 24 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on repetitive behaviours ; Instrument used: Adult Repetitive Behaviours Questionnaire‐2 (RBQ‐2A)[At baseline, 16, 24 and 52 weeks post randomisation] To determine the effect of up to 52‐weeks of treatment with sertraline versus placebo on response to anxiety symptoms 2. A diagnosis of autism made by a specialist including those with a co‐occurring mild intellectual disability [autism diagnostic terms may include autism/autistic spectrum disorder or other variations, Asperger syndrome/disorder or pervasive developmental disorder]. 3. Anxiety as measured by GAD‐7 score greater than or equal to 10 at screening Carer Burden Nested Sub Study For the purpose of this carer burden sub‐study, it is up to the STRATA (main trial) participant to define who their carer is; where feasible, it would be one carer who knows them well and is likely to continue caring for them over the 52‐week trial period. All named carers will be approached and invited to participate in the carer sub study.