Add-on MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Antipsychotics affects the brain's dopamine system, and the drugs reduce delusions, hallucinations, and disorganized thinking, which are cardinal symptoms of psychotic disorders. However, negative symptoms e.g. anhedonia, avolition, and social withdrawal, as well as cognitive deficits, are not sufficiently treated.

Memantine is used to treat Alzheimer's disease and affects the brain's glutamate system. AMEND is a 12-week, double-blind, placebo-controlled, randomized clinical trial (RCT) testing effects of add-on memantine to initial antipsychotic treatment in never-treated patients with first-episode psychosis.

The main aim is to reduce negative symptoms. Secondary outcomes are cognition, psychotic symptoms, side effects. Glutamate levels in the brain will be measured before and after 12 weeks using an ultra-high field strength (7 Tesla) magnetic resonance scanner.

AMEND will apply rational drug repurposing to optimize treatment of patients experiencing their first psychotic episode.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bjorn H. Ebdrup
• Collaborators: Danish Research Centre for Magnetic Resonance; Lundbeck Foundation; Novo Nordisk A/S; University of Copenhagen
• Treatments: Amisulpride; Memantine

Criteria

Inclusion Criteria:

• Patients:

• Antipsychotic-naïve, first episode psychosis

• Fulfilling the diagnostic criteria of schizophrenia, persistent delusional disorder, acute and transient psychotic disorders, schizoaffective disorder, other non-organic psychotic disorders and unspecified non-organic disorders (ICD-10: F20.x; F22.x; F23.x; F24.x; F25.x; F28; F29); verified by PSE interview.

• Age: 18-45 years

• Legally competent (In Danish: 'myndige og habile i retslig forstand')

Healthy controls:

• No first-degree relative with known major psychiatric disorder (ICD-10: F1x; F2x; F3x)

• Age 18-45 years

• Legally competent (In Danish: 'myndige og habile i retslig forstand')

Exclusion Criteria:

• Patients

• Prior use of antipsychotic medication

• Treatment with antidepressant medication the last 7 days

• Current substance dependence ICD-10 (F1x.2) or substance abuse in any period up to 3 months prior to referral (exception: tobacco/nicotine, F17.2)

• Head injury with more than 5 minutes of unconsciousness, lifetime

• Any coercive measure

• Metal implanted by operation

• Head or neck tattoos

• Pacemaker

• Pregnancy (assessed by urine HCG)

• Female patients: Unwillingness to use safe contraception (Intra Uterine Device/System or hormonal contraceptives) during the study period.

• Severe physical illness

• Allergies to any of the ingredients in the amisulpride tablets or memantine tablets

Healthy controls:

• Lifetime substance abuse/dependence ICD-10 (F1x.1/F1x.2) (exception: tobacco/nicotine, F17.1/F17.2)

• Lifetime treatment with antidepressants

• Head injury with more than 5 minutes of unconsciousness

• Metal implanted by operation

• Head or neck tattoos

• Pacemaker

• Pregnancy (assessed by urine HCG)

• Severe physical illness