This study explores the effects of 7-day losartan (50mg) versus placebo with brief behavioural activation on emotional processing in young volunteers low in positive mood

Behavioural Activation (BA) is a first-line treatment for depression that aims to re-engage patients with rewarding activities, to improve mood. However, patients with low levels of positive mood respond less well to BA than others. Neuroscience has identified deficits in the processing of positive stimuli in this group of people, using cognitive-psychological computer tasks and brain imaging. Losartan, a licensed medication targeting the renin-angiotensin system, has recently been found to improve the processing of positive stimuli in healthy volunteers. Combining losartan with BA may improve treatment response in people with low positive mood, by improving positive information processing. This study will test this hypothesis.

In a double-blind randomised trial, 76 participants with low positive mood will receive 7-day behavioural activation (BA) with daily losartan (50mg) or placebo. Before and after the intervention, they will complete computer tasks measuring processing of positive and negative information.

Inclusion Criteria:

• Willing and able to provide informed consent
• Aged 18-65 years
• Self-reported low levels of positive mood
• Sufficient written and spoken English skills to understand study procedures
• Normal or corrected to normal vision and hearing
• Access to a computer and reliable internet connection

Exclusion Criteria:

• Antidepressant treatment or medication in last three months
• Currently receiving cognitive-behavioural therapy with behavioural activation
• History of psychosis or bipolar disorder
• History of substance dependence
• Use of illegal drugs in last 3 months
• First-degree relative with history of psychosis or bipolar disorder
• Current or past hospitalisation for mental health reasons
• BDI-II score >30
• Judged to be currently at clinical risk of suicide
• Past suicide attempt
• CNS-medication last 6 weeks (including in another study)
• Severely underweight or overweight in a manner that renders them unsuitable for the study in the opinion of the study medic
• Current blood pressure or other heart medication
• Diagnosis of intravascular fluid depletion or dehydration
• History of angioedema
• Impaired kidney function (based on self-report)
• Very low blood pressure following established definitions (at least three consecutive measurements of blood pressure under standardised conditions where either the systolic or the diastolic blood pressure or both are below 90/60 mmHg (in accordance with established standard definitions: https://www.nhs.uk/cond...-pressure-hypotension/)
• Current diagnosis of a developmental disorder (e.g. ADHD, Tourette's syndrome, severe learning disability) according to self-report, where in the opinion of the study team such difficulties would likely interfere with compliance or task performance
• Current diagnosis of a neurological disorder (e.g. epilepsy, MS) according to self-report
• Lifetime history of systemic infection, or clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic, endocrine or pulmonary disease or disorder which, in the opinion of the investigator, may put the participant at risk when participating, or may influence compliance or task performance
• Pregnancy (urine pregnancy test during Baseline Visit), breast feeding or plans to become pregnant during study participation
• Heavy use of cigarettes (smoke > 20 cigarettes per day)
• Severe lactose intolerance (due to losartan containing some lactose monohydrate)

double-blind