ASCEnD: Aripiprazole/Sertraline combination: clinical and cost-effectiveness in comparison with Quetiapine for the treatment of bipolar depression. An open label randomised controlled trial.

Principal Investigator: Neil Nixon

The study is being done to test the effectiveness and usefulness of the drugs sertraline with aripiprazole or quetiapine as treatments for people living with bipolar who are currently experiencing depression.

Study participation is for 24 weeks. Following a Baseline assessment and Randomisation there will be weekly follow ups with an RA. There will be pregnancy testing for women of childbearing potential.

Inclusion criteria

Patients must fulfil all of the following criteria to progress to randomisation:

1. Aged 18 or over at the point of consent.

2. Able to provide written informed consent.

3. A current (i.e., within 7 days) Diagnostic and Statistical Manual-5-Text Revision (DSM-5-TR) (153) confirmed diagnosis of a major depressive episode within bipolar disorder. This will be confirmed using the SCID-5-RV (153).

4. A current (i.e., within 7 days) QIDS-SR greater than 10.

5. Clinical uncertainty regarding the next course of treatment and judgement that the sertraline/aripiprazole combination and quetiapine treatment arms are both clinically appropriate and represent equipoise. This judgment includes consideration of reproductive risks.

6. In the opinion of the clinician, the participant is able to follow trial prescription instructions, complete weekly questionnaires and engage in weekly telephone calls with the cRAs throughout the 24 week follow up period of the trial.

Current recruitment end date: tbc

For more information please contact:

Study Lead, Rhianne Bostock, Senior Research Delivery Officer – This email address is being protected from spambots. You need JavaScript enabled to view it.

COMBINER: The effectiveness of lithium plus quetiapine COMBination versus lithIum versus quetiapiNe monothErapy in the maintenance treatment of bipolar disordeR: the COMBINER trial.

Principal Investigator: Mike Skelton

COMBINER is a pragmatic, observer-blind, multi-centre, 3-arm, parallel group randomised controlled trial (RCT) with an internal pilot and full economic evaluation. The aim of the study is to evaluate the clinical and cost-effectiveness of combination lithium and quetiapine therapy compared with lithium or quetiapine alone for maintenance treatment in adults with bipolar disorder (BD)

Inclusion criteria:

1. Diagnosis of BD type I or II according to the DSM-5 confirmed by the Mini-International Neuropsychiatric Interview (MINI).
2. Aged ≥18 years.
3. Not currently experiencing major depression or mania according to the DSM-5, defined as a score on the Longitudinal Interval Follow-up Evaluation (LIFE) of 4 or below.
4. If already on lithium or quetiapine, the patient and clinician are willing to consider the trial and potentially switch treatment.
5. QT interval as measured by electrocardiogram confirmed within safe limits in the clinical opinion of the investigator.
6. Able to provide informed consent.

Exclusion criteria:

1. Primary diagnosis of substance dependence or organic mood disorder.
2. Acute risk to self (clinician opinion).
3. Unstable medical illness that requires acute care (e.g. hospitalisation).
4. Contraindication to lithium or quetiapine:
   • Evidence of renal impairment (participant must have an eGFR ≥60 mls/min/1.73m² within two months prior to consent).
   • Neutrophil count <1.0 x 109/L (within two months prior to consent).
   • Sodium level <133 mmol/L (or the lowest level of the accepted normal range for sodium according to the testing lab) (within two months prior to consent).
   • Medical conditions in which lithium use presents a risk (untreated hypothyroidism, Addison’s disease, untreated epilepsy, cardiac insufficiency, rhythm disorders including Brugada syndrome or family history thereof, psoriasis).
   • Incompatible concurrent treatment (such as long term NSAID, diuretic, ACE-I or ARB) for a known medical condition for which no alternative treatment is available.
   • Concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone.

5. Females who are breast-feeding.
6. Females of child-bearing potential only:
   • Pregnant. Note: Spot urine test will be performed before randomisation to rule out pregnancy in females of child-bearing potential.
   • Not willing to take highly effective contraceptive measures during the study intervention period AND for 30 days following the last trial medication dose.

End Date – 30 July 2027

For more information please contact:

Study Lead: Rhianne Bostock, Senior Research Delivery Officer - This email address is being protected from spambots. You need JavaScript enabled to view it.

DRAIG: A Phase 2 Double-blind, Randomised, Placebo-controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of DT-101 in Adults with Major Depressive Disorder

Principal Investigator: Dr Paul Briley

We want to find out whether a new investigational medication, DT-101, can reduce symptoms of major depressive disorder (MDD). Participants will be randomly assigned to receive either DT-101 or a placebo (a treatment with no active medicine), and neither they nor the study team will know which treatment they are receiving. During the study, participants will attend regular study visits over approximately three to four months, where they will complete questionnaires and interviews, have physical health checks, and provide blood and urine samples. By comparing the two groups, we hope to understand whether DT-101 is a safe and effective treatment for people with MDD.

Inclusion Criteria:

1. The participant is able to read, understand and communicate in the local language used at the study site, and is willing to provide written informed consent.
2. Male or female (assigned at birth, inclusive of all gender identities) participant must be 18 to 75 years of age, inclusive at the time of signing the informed consent.
3. Has recurrent depression (defined as at least one prior episode excluding the current one), as diagnosed by DSM 5-TR (Diagnostic and Statistical Manual of Mental Disorders, 2022).

Exclusion Criteria:

1. Pregnant or breastfeeding or plans to become pregnant during the study.
2. Unstable medical condition or unstable chronic disease.
3. Significant neurological abnormality.
4. History of moderate or severe alcohol or drug use disorder as per DSM-5-TR in the 6 months prior to Screening.
5. History of seizure.
6. In the investigator's opinion, the participant is not capable of adhering to the protocol requirements.

For more information please contact: Study Coordinator, Chia-Ping Chou, Research Assistant - This email address is being protected from spambots. You need JavaScript enabled to view it.

RELMED-I study: Reinforcement learning mechanisms of pharmacological treatments for depression: a double-blind, four-arm, placebo-controlled multi-site trial in UK primary care.

Principal Investigator: Neil Nixon

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.

Inclusion criteria:

1. Meeting diagnostic criteria for a DSM-5 Major Depressive Episode on the affective disorder sections of the Mini International Neuropsychiatric Interview (MINI)
2. Patient Health Questionnaire (PHQ-9) total score ≥10
3. Under care of GP in the UK
4. Age 18 or above
5. Able to provide informed consent to participate in the trial
6. Women of childbearing potential 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
7. Women of Childbearing Potential will have a negative urine pregnancy test prior to randomisation.

Exclusion criteria:

1. 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).
2. Contraindications to treatment with escitalopram: history of seizures; history of mania; QT-interval prolongation; known difficulty to control hypertension; active cardiac disease.
3. Known hypersensitivity or allergies to escitalopram and bupropion or their excipients.
4. Pharmacological treatment for depression in past 6 weeks
5. Current medication for depression (e.g. with a mood stabilizer, antipsychotic or antidepressant), or any other dopaminergic, noradrenergic or serotonergic medication
6. Significant neurological impairment
7. Significant active suicidality
8. Current or past non-affective psychotic symptoms
9. Current clinically significant substance use disorder
10. Clinically significant medical conditions under investigation or acute treatment
11. Pregnant, breast-feeding or planning pregnancy
12. Incomplete first online behavioural assessment and call

For more information please contact:

Study Lead: Holly Griffiths - This email address is being protected from spambots. You need JavaScript enabled to view it.

RENEW: A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Arm Study to Investigate the Efficacy and Safety of Adjunctive Treatment with Brenipatide in Delaying Time to Relapse Compared with Placebo in Adult Participants with Major Depressive Disorder (RENEWMDD-1)

Principal Investigator: Dr Neil Nixon

We want to find out if a new investigational medication can help people with major depressive disorder (MDD) stay well for longer. This study is for adults whose current antidepressant treatment is helping to manage their symptoms. Everyone taking part will continue with their usual depression treatment and will also receive either the investigational medication or a placebo (a treatment with no active medicine). Neither participants nor the study team will know which treatment each person receives. By comparing these groups, we hope to understand whether the investigational medication is safe and can reduce the likelihood of depressive symptoms returning.

Inclusion Criteria:

1. Meet the diagnostic criteria for major depressive disorder
2. Be on stable standard of care for major depressive disorder
3. Be reliable and willing to make themselves available for the duration of the study and attend required study visits, and are willing and able to follow study procedures as required, such as
   1. self-inject study intervention
   2. store and use the provided blinded study intervention, as directed
   3. maintain electronic and paper study diaries, as applicable, and complete the required questionnaires

Exclusion Criteria:

1. Have ever a diagnosis of the following:
   • schizophrenia or other psychotic disorder
   • bipolar disorder
   • borderline personality disorder, or any eating disorder
2. Have type 1 diabetes mellitus, or a history of
   • ketoacidosis, or
   • hyperosmolar state or coma
3. Have evidence of moderate or severe substance or alcohol use disorder within 180 days of screening
4. Be actively suicidal or deemed a significant risk for suicide
5. Have participated in a clinical study and received active treatment, or unknown if they received active treatment, within 90 days or 5 half-lives (whichever is longer) before screening

For more information, please contact:

Jack Cheshire, Senior Research Delivery Officer – This email address is being protected from spambots. You need JavaScript enabled to view it.;

Chia-Ping Chou, Research Assistant – This email address is being protected from spambots. You need JavaScript enabled to view it.

SNAPPER: The clinical and cost-effectiveness of Stimulant compared with Non-stimulant medication for adults with Attention-deficit/hyperactivity disorder and a history of Psychosis or biPolar disordER

Principal Investigator: Dr Z. Katshu

The aim of the snapper trial is to investigate how effective a stimulant medication (Lisdexamfetamine) is compared to a non-stimulant medication (Atomoxetine) in reducing the symptoms of ADHD in patients who also have bipolar or psychosis. Both medications are routinely used to treat ADHD and participants are randomly allocated to either the stimulant or non-stimulant group by a computer. Participants will meet with the research team at the beginning of the trail and at 3, 6, 9 and 12 months. During these visits, questionnaires and interviews will be completed. Blood pressure and pulse will also be monitored regularly during the first 4 months by the clinical care team (this is done routinely for all patients taking either of these medications, whether or not they are taking part in the trial). After the trial visits finish, your doctor will discuss with you whether the treatment allocated to you in the trial will stop and if any changes are required to your medication.

The research team will give you £25 as a thank you for your time and support after completing the first visit, and then again after the visits at 6 and 12 months. We can also pay for your travel expenses if you had to travel to these visits. Please speak to a member of the research team for more details.

Planned recruitment end date: May 2026

For more information please contact:

Matea Svigac, Research Delivery Officer - This email address is being protected from spambots. You need JavaScript enabled to view it.

Catherine Jeynes, Senior Research Delivery Officer - This email address is being protected from spambots. You need JavaScript enabled to view it.

Dr Katshu, Principal Investigator - This email address is being protected from spambots. You need JavaScript enabled to view it.