RELMED-I(CPMS 64366, IRAS 345935)

UPDATED - 10/07/2025

We want to understand how antidepressant medications work. Over the past 20 years, research has revealed that antidepressants can alter the brain's learning processes. However, it remains unclear if this is how antidepressants treat depression. Computer-based tasks that resemble games are used in research to study learning processes. The different ways people complete these tasks provide insights into how learning occurs in the brain. Our aim is to find out if two different antidepressants, escitalopram and bupropion, affect learning processes in distinct ways.

People with low mood or depression who have no known contraindications to escitalopram and bupropion and who are eligible to take part will be recruited from GP practices at five sites in and around London, Oxford, Bristol, Nottingham and Newcastle. People who participate in the study will be randomly allocated to take either escitalopram or bupropion for 6 months (or in some cases a placebo for the first two weeks, thereafter one of the two antidepressants) and asked to complete a few of these learning tasks on the computer at home. Everyone will complete the same tasks, but people in different groups will take different medications.

We will also ask participants to complete some questionnaires and we will invite participants to take part in two optional electroencephalography (EEG) sessions. We will ask participants to complete the learning tasks and/or the questionnaires again on six occasions in the first six months and one last time after one year. At the end of the study we will compare the learning processes in the different groups. We hope this will help improve the way doctors decide which antidepressant to give each person.

INCLUSION CRITERIA:

- Meeting diagnostic criteria for a DSM-5 Major Depressive Episode on the affective disorder sections of the Mini International Neuropsychiatric Interview (MINI).

 - Patient Health Questionnaire (PHQ-9) total score > = 10 - Under care of GP in the UK.

 - Age 18 or above. 

- Able to provide informed consent to participate in the trial.

 - Women of childbearing potential (WOCBP) must be willing to use an effective method of contraception (hormonal or barrier method of birth control; true abstinence) from the time consent is signed until six weeks after treatment discontinuation and inform the trial if pregnancy occurs. For the purpose of clarity, true abstinence is when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence, withdrawal, spermicides only or lactational amenorrhoea method for the duration of a trial, are not acceptable methods of contraception.

 - Women of Child Bearing Potential (WOCBP) must have a negative urine pregnancy test prior to randomisation

EXCLUSION CRITERIA:

 - Unwilling or unable to perform the online behavioural assessments.

 - Contraindications to treatment with bupropion: acute alcohol withdrawal; acute benzodiazepine withdrawal; history of mania; CNS tumour; current or past eating disorders; history of seizures; severe hepatic cirrhosis; concomitant use of monoamine oxidase inhibitors (MAOIs).

 - Contraindications to treatment with escitalopram: history of seizures; history of mania; QT-interval prolongation; known difficulty to control hypertension; active cardiac disease. 

- Known hypersensitivity or allergies to escitalopram, bupropion or their excipients.

 - Pharmacological treatment for depression in past 6 weeks.

 - Current medication for depression (e.g. with a mood stabiliser, antipsychotic or antidepressant), or any other dopaminergic, noradrenergic or serotonergic medication.

 - Significant neurological impairment.

 - Significant active suicidality - Current clinically significant substance use disorder - Clinically significant medical conditions under investigation or acute treatment

 - Pregnant, breast-feeding or planning pregnancy.

Study Resources

Access for the SystmOne and EMIS study resources can be requested below.

For further guidance on using the resources, please refer to the guidance documents and further useful information on the PRIDES page.

The searches have been created with the study specific inclusion and exclusion criteria. 

If you require any further information or help, please contact the IT Specialists:

EMIS: Jodie Button – jodie.button@nihr.ac.uk 

SystmOne: James Baslington – james.baslington@nhs.net

Disclaimer:

Please note the resources provided are designed to assist with the identification of potentially suitable patients and to appropriately code these patients if required.

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