Condition category
Mental and Behavioural Disorders
Date applied
11/11/2020
Date assigned
24/11/2020
Last edited
24/11/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
First episode of psychosis (FEP) typically begins in the late teens or early 20s and is diagnosed by the presence of hallucinations and delusions. Medication and cognitive behavioural therapy help to treat these symptoms, but young people struggle to return to previous social and work roles, have suicidal thoughts and are at high risk of relapse. These are related to depression experienced after FEP. 40% of people who have experienced FEP will become depressed. Antidepressant medication is effective for treating depression in established schizophrenia, and robust evidence suggests that using antidepressants in young people over the age of 18 along with medication for psychosis is safe. However, researchers want to know whether antidepressant medication can reduce the risk of depression happening at all after FEP, and whether preventing depression can improve recovery and reduce relapse. This study aims to find out if an antidepressant medication (sertraline) can help to prevent depression in people who have experienced a psychotic episode for the first time.

Who can participate?
People aged between 18 and 35 who have experienced first-episode psychosis within the last 3 months

What does the study involve?
Participants are randomly allocated to one of two groups. One group will be given a highly effective antidepressant medication (sertraline) while the other will receive a placebo (‘sugar pill’), to take once a day for 6 months. In all other ways the two groups will receive the same types of support from Early Intervention of Psychosis Services (EIP). It involves completing baseline and follow up assessments, which involve answering a series of questions in the form of interviews and questionnaires at certain time-points (eight visits in total). Blood samples will also be taken. The main outcome evaluated will be the number of new depression cases at 6 months. A number of other key outcomes such as the acceptability of the intervention, cost effectiveness and side-effects of antidepressant medication, recovery, suicidal thoughts/behaviour, anxiety, and relapse will be assessed. The researchers will monitor people in the study closely and if at any time a participant is thought to have depression, their multi-disciplinary team will assess them and decide if they need to stop taking trial medication and their illness needs to be more actively managed.

What are the possible benefits and risks of participating?
This study will help the researchers to find out if sertraline helps first episode psychosis patients by preventing depression. Whilst there may be no immediate benefits to you, the aim is to improve care for people with psychosis in the longer-term. It is not known whether sertraline will help participants manage their illness or not, which is why the researchers are doing the study. Sertraline can have side effects but the research team will closely monitor the participants.

Where is the study run from?
Birmingham Clinical Trials Unit at the University of Birmingham (UK)

When is the study starting and how long is it expected to run for?
November 2019 to December 2023

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Eleanor Taylor
ADEPP@trials.bham.ac.uk

Trial website

https://www.birmingham.ac.uk/adepp

Contact information

Type

Scientific

Primary contact

Miss Eleanor Taylor

ORCID ID

Contact details

Birmingham Clinical Trials Unit
University of Birmingham
Public Health Building
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 9125
ADEPP@trials.bham.ac.uk

Additional identifiers

EudraCT number

2020-002787-32

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 47000, IRAS 279574

Study information

Scientific title

Antidepressant for the prevention of DEPression following first-episode Psychosis: the ADEPP trial

Acronym

ADEPP

Study hypothesis

To establish if, compared with placebo, the addition of sertraline to continuing antipsychotic medication following the first episode of psychosis reduces the likelihood of developing depression over a 6 month intervention period. The study will also investigate whether this intervention reduces the likelihood of developing anxiety or suicidal behaviour, reduces the risk of psychotic relapse, and improves the level of functional recovery achieved.

The researchers will additionally gather evidence as to whether the prescription of antidepressant medication after the first episode of psychosis is cost-effective and whether any clinical benefit and cost-effectiveness continue beyond the 6-month intervention, up to a year.

Ethics approval

Approved 29/10/2020, East Midlands - Leicester South Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 1048310; leicestersouth.rec@hra.nhs.uk), REC ref: 20/EM/0216

Study design

Randomized; Both; Design type: Prevention, Drug, Cross-sectional

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

This will be available on the trial website https://www.birmingham.ac.uk/adepp

Condition

Psychosis

Intervention

Participants will be individually randomized on a 1:1 basis between sertraline and matched placebo via a secure, online randomisation system based at Birmingham Clinical Trials Unit. A minimisation algorithm will be used within the randomisation system to ensure equal distribution of the most commonly prescribed antipsychotics in this population and gender.

Screening visit: At a screening visit, the research team will take screening consent and assess eligibility. Participants will be asked to provide answers for the research team to complete the CDSS and PANSS. An electrocardiogram will be performed if not already done so as standard care in the last 12 months.

Baseline visit: If the patient is eligible to take part, the research team will take informed consent, and complete outcome assessments and questionnaires with them at a baseline visit. The research team will record participants' personal details, medical history and current medication for randomization. After randomization, trial medication will be prescribed as per allocation.

Follow up: Participants will have a follow-up visit every month for 6 months and then once at 12 months either at the hospital or at home. During these visits, participants will be asked to repeat some (and at 1/6/12 months all) of the questionnaires and outcome assessments completed at the baseline visit. The visits at 1, 6 and 12 months may take around 2 hours to complete and the visits at 2-5 months may take around 1 hour to complete. At the 1-month visit, in addition to the outcome assessments and questionnaires, a blood sample (1 x 9 ml) will be taken and sent to the University of Birmingham (later analysed at the University of Cardiff) to confirm the level of sertraline in the body. If the participant consents to it, an additional blood sample (2 x 9 ml) will be taken, sent and stored at the University of Birmingham for future use in other ethically approved studies. At the 6-month visit, in addition to the outcome assessments and questionnaires, treatment allocation will be revealed and the participant and the treating psychiatrist will decide whether to start (if in the placebo group) or continue (if in the sertraline group) with sertraline. Study participation will end at the 12-month visit, after completing the final outcome assessments and questionnaires.

Intervention type

Drug

Phase

Not Applicable

Drug names

Sertraline

Primary outcome measure

The number of new cases of depression as indicated by a Calgary Depression for Schizophrenia Scale (CDSS) score < 5 and confirmed by Mini International Neuropsychiatric Interview (MINI) in each treatment arm over the 6-month intervention phase. Measured at baseline, monthly for 6 months and at 12 months

Secondary outcome measures

1. Psychosis symptoms measured using the Positive and Negative Syndrome Scale (PANSS) at screening, monthly for 6 months and at 12 months
2. Suicidal ideation and attempts in lifetime together with current suicidal ideation and beliefs about future risk, measured using Suicidal Behaviours Questionnaire- Revised (SBQ-R) at baseline, 1 month, 6 months and 12 months
3. Trait and current (state) anxiety assessed using State-Trait Anxiety Inventory (STAI) at baseline, months 1, 6 and 12
4. Generalised anxiety assessed using General Anxiety Disorder (GAD7) at baseline and then monthly for 6 months and at 12 months
5. Relapse of psychosis, as defined by a hospital admission or acute community care provided by Home Treatment/Crisis Intervention team at 6 and 12 months.
6. Depression symptoms measured using Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR) at baseline, monthly for 6 months and at 12 months
7. Functioning measured using the Social and Occupational Functioning Scale (SOFAS) and the Functional Remission of General Schizophrenia (FROGS) at baseline and at 6 and 12 months
8. Quality of life measured using EQ-5D-5L and ICECAP-A at baseline and at 6 and 12 months
9. Side effects measured using Barnes Akathisia Scale (BARS), Antipsychotic Non-Neurological Side Effects Rating Scale - compiled (ANNSERS-c) and Simpson Angus Scale (SAS) at baseline and at 6 and 12 months

Overall trial start date

01/11/2019

Overall trial end date

31/12/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Diagnosis of first-episode psychosis (FEP)
2. Within 3 months of initial treatment for FEP (as defined by onset of care provision by an Early Intervention Team)
3. Positive and Negative Syndrome Scale (PANSS) individual positive item scores all ≤4
4. Sufficiently recovered from acute psychotic episode with capacity to consent
5. Males and females aged 18-35 years
6. Currently prescribed antipsychotic medication at stable dose.
7. Female participants must be willing to use one form of highly effective contraception

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 508; UK Sample Size: 508

Participant exclusion criteria

1. Current moderate or severe depression (as indicated by a Calgary Depression for Schizophrenia Scale (CDSS) score of > 7)
2. Currently prescribed antidepressant medication (or within 2 weeks of stopping if a Monoamine Oxidase Inhibitor)
3. Previous history of mania
4. Contraindications to selective serotonin reuptake inhibitors (SSRI) antidepressant treatment (e.g. recurrent thrombotic illness, previous adverse reaction, confirmed pregnancy, although risk in pregnancy is low, prescribed pimozide)
5. Serious medical or neurological illness (as identified by the treating consultant psychiatrist)
6. Hypersensitivity to the active substance or any of the excipients or placebo
7. Concomitant treatment with irreversible monoamine oxidase inhibitors (MAOIs)
8. Patient with any other systemic dysfunction (e.g. gastrointestinal, renal, respiratory, cardiovascular, neurological or psychiatric) or significant disorder which, in the opinion of the investigator would jeopardize the safety of the patient by taking part in the trial
9. Electrocardiogram (ECG): QTc interval >450 as measured in the last 12 months
10. Aged below 18 years
11. Aged over 35 years
12. Female participants that do not agree to follow the protocol contraception requirements

Recruitment start date

01/02/2021

Recruitment end date

31/12/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Birmingham and Solihull Mental Health NHS Foundation Trust
Unit 1 50 Summer Hill Road
Birmingham
B1 3RB
United Kingdom

Trial participating centre

Coventry and Warwickshire Partnership NHS Trust
Wayside House Wilsons Lane
Coventry
CV6 6NY
United Kingdom

Trial participating centre

Lancashire Care NHS Foundation Trust
Sceptre Point Sceptre Way Bamber Bridge
Preston
PR5 6AW
United Kingdom

Trial participating centre

Aneurin Bevan University LHB
Headquarters - St Cadoc's Hospital Lodge Road Caerleon
Newport
NP18 3XQ
United Kingdom

Trial participating centre

Worcestershire Health and Care NHS Trust
Isaac Maddox House Shrub Hill Industrial Estate
Worcester
WR4 9RW
United Kingdom

Trial participating centre

Midlands Partnership NHS Foundation Trust
Trust Headquarters St. Georges Hospital Corporation Street
Stafford
ST16 3SR
United Kingdom

Trial participating centre

Black Country Partnership NHS Foundation Trust
Delta Point Greets Green Road
West Bromwich
B70 9PL
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

c/o Dr Birgit Whitman
Room 117
Aston Webb Building
University of Birmingham
Birmingham
B15 2TT
United Kingdom
+44 (0)1214158011
researchgovernance@contacts.bham.ac.uk

Sponsor type

University/education

Website

http://www.birmingham.ac.uk/index.aspx

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR127700

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

1. The protocol and other documents will be on the public trial website https://www.birmingham.ac.uk/adepp
2. Planned publication in a high-impact peer reviewed journal 1 year after the overall trial end date

IPD sharing statement
Requests for data generated during this study will be considered by BCTU (via bctudatashare@contacts.bham.ac.uk). Data will typically be available within 6 months after the primary publication unless it is not possible to share the data (for example the trial results are to be used as part of a regulatory submission, the release of the data is subject to the approval of a third party who withholds their consent, or BCTU is not the controller of the data).
Only scientifically sound proposals from appropriately qualified Research Groups will be considered for data sharing. The request will be reviewed by the BCTU Data Sharing Committee in discussion with the Chief Investigator and, where appropriate (or in absence of the Chief Investigator) any of the following: the Trial Sponsor, the relevant Trial Management Group (TMG), and independent Trial Steering Committee (TSC).
A formal Data Sharing Agreement (DSA) may be required between respective organisations once release of the data is approved and before data can be released. Data will be fully de-identified (anonymised) unless the DSA covers transfer of patient identifiable information. Any data transfer will use a secure and encrypted method.

Intention to publish date

31/12/2024

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

11/11/2020: Trial's existence confirmed by the NIHR.