AI-Supported Therapy for Depression and Anxiety Compared With Standard CBT

This study is a pivotal, randomised, controlled, non-inferiority trial evaluating "Nook," an AI-delivered, neurosymbolic, clinician-supervised digital psychological intervention for depression and anxiety, compared with standard cognitive behavioural therapy (CBT). The trial will recruit 400 participants aged 16-64 years in the UK with moderate depression and/or anxiety symptoms. Participants will be randomised to receive either Nook or therapist-delivered CBT.

The primary objective is to determine whether Nook is non-inferior to CBT in reducing depression and anxiety symptoms, measured using the PHQ-9/PHQ-A and GAD-7 scales. Secondary outcomes include quality of life, functional impairment, sleep quality, treatment engagement, participant satisfaction, safety outcomes, and exploratory health economic measures.

The intervention incorporates clinician oversight and predefined escalation pathways for suicidality and clinical deterioration. Outcomes will be analysed using longitudinal mixed-effects models under an intention-to-treat framework.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Generalized Anxiety Disorder (GAD) Anxiety Disorders Depressive Disorder Depressive Disorder, Major Generalized Anxiety Disorder Major Depressive Disorder (MDD) Mental Disorders Mood Disorders

Age range

16 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Have symptoms of Generalized Anxiety Disorder (GAD) and/or symptoms of --•Major Depressive Disorder (MDD) as the primary reason for seeking treatment (formal diagnosis not required).(as determined by a Psychological Well-being Practitioner).
Meet symptom-severity criteria on either validated screening measure:
Depression: PHQ-9 (or PHQ-A for young persons) total score between 10 and 19, corresponding to moderate to moderately-severe symptoms, and/or
Anxiety: GAD-7 total score between 8 and 21, corresponding to mild to severe symptoms.
Aged 16-64 years
If taking psychotropic medication for depression and/or anxiety, be on a stable regimen for at least 6 weeks prior to screening, with no initiation, discontinuation, or dose change during that period.
Have reliable access to a compatible, internet-connected device and are able to use it for screening/eligibility, and the intervention and assessments (any potential costs to participants will be clearly noted in the PIS).
Possess sufficient English language proficiency and cognitive capacity to engage with the digital therapeutic content and complete questionnaires.
Provide informed consent.
Willing to be randomised and to participate in a clinically-supervised CBT-based AI programme, including completion of scheduled outcome assessments.

Exclusion criteria

Depression: PHQ-9 (or PHQ-A for young persons) total score >≥ 20
Present with a primary or comorbid diagnosis (or history of) that is unsuitable for a digital CBT-based intervention (as judged by the Investigator), including:
Post-traumatic stress disorder (PTSD) or complex trauma
Psychotic disorder, bipolar disorder, and/or mania
Complex or treatment-resistant obsessive-compulsive disorder (OCD)
Personality disorder
Eating disorder
Substance or alcohol use disorder
Exhibit high-risk clinical concerns, including:
Current suicidal ideation with intent or plan (as indicated by PHQ-9 score and/or participant disclosure)
Suicide attempt within the past 12 months
Ongoing self-harming behaviours
Requirement for urgent or crisis mental-health intervention (as indicated by •PHQ-9 score and/or participant disclosure)
In participants aged 25 years and under, current treatment with an antidepressant medication initiated or dose-adjusted within the past 12 weeks (due to the recognised

Treatment and study plan

AI-Digital CBT

Device

An AI-guided course of digital CBT with human clinician oversight

Cognitive Behavioural Therapy

Behavioral

A course of human delivered CBT by qualified therapists

Primary outcomes

Patient Health Questionnaire - 9 items (PHQ-9)

Time frame: Starting at Baseline, taken 3-weekly, to a 9 week end-point post-randomisation

A symptom measure of depression, ranging from 0 to 27. 27 being severe (high).
Patient Health Questionnaire - Adolescent (PHQ-A)

Time frame: Starting at Baseline, taken 3-weekly, with a 9 week end-point post randomisation.

A symptom measure of depression for adolescents, ranging from 0 to 27. 27 being severe (high).
Generalized Anxiety Disorder assessment (GAD-7)

Time frame: Starting at Baseline, taken 9-weekly, to a 9-week end point, post-randomisation

A symptom measure of anxiety, ranging from 0 to 21. 21 being severe (high).

Sponsors and collaborators

Lead sponsor

PsyScale

Industry

Registry information

Official study title

Evaluating the Efficacy of an AI Delivered, Neurosymbolic, Human Supervised Digital Intervention for Depression and Anxiety Versus Standard Cognitive Behavioural Therapy in Young Persons and Adults

Important dates

Study start: 2026
Primary completion: 2026
Study completion: 2027
First posted: Jun 2, 2026
Registry last updated: Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Not Yet Recruiting