Double-blind, randomized, monocentric study to evaluate the efficacy and safety of memantine in adolescents with Bipolar Disorder

Prior treatment

• exposure to any medicine that can interfere with assessments of safety, tolerability, or efficacy of memantine or placebo, or with the conduct/interpretation of the study; specifically: antipsychotic-antimanic agents including haloperidol, risperidone, quetiapine, aripiprazole, olanzapine, ziprasidone, carbamazepine, lamotrigine, valproate, and antidepressants; ketamine or other NMDA antagonists in last the month prior to enrolment

Other illness

• patient with serious forms of cardiovascular disease (severe and moderate congenital heart disease: severe and moderate ventricular septal defect, severe and moderate atrial septal defect, Tetralogy of Fallot, complete Transposition of the Great Arteries; severe and moderate valvular stenosis and prolapses; cardiac hypertrophy,), arrhythmias (atrial fibrillation, Paroxysmal supraventricular tachycardia (PSVT), atrial flutter, WolfParkinson-White (WPW), ventricular fibrillation, ventricular tachycardia, Brugada syndrome, severe Sinus bradycardia FC<40 bp/m)
• intellectual disability (IQ <70), organic mental disorder, or mental disorder due to a general medical condition or substance abuse (DSM-5 criteria);
• comorbid DSM-5 diagnosis of Substance Abuse Disorder
• a serious or unstable general medical illness or clinically significant abnormal vital signs or ECG abnormality
• known hypersensitivity to the active substance or to any of the excipients

Lab values

• patient with severe renal impairment (glomerular filtration rate, GFR < 29 mL/min/1.73 m2)
• patient with severe hepatic impairment: at least one of the following parameters >= 2 ULM (referred to the range of normality of this age group and judged clinically significant by the investigators/ specialist medical consultant and/or needing medical treatment: alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT), bilirubin)

Other

• YMRS item 8 (delusions; hallucinations) score = 8
• significant current risk of suicide (in the opinion of the Investigator or a "yes" response to suicidal ideation questions 4 or 5 on the Columbia-Suicide Severity Rating Scale [C-SSRS]) within the last 6 months;

• either sex, aged 13-17 years at baseline
• DSM-5 diagnosis of BD (Type I, Type II, Cyclothymic Disorder, Unspecified) with mild to moderate symptom-severity, with current manic, mixed, or hypomanic symptoms (not psychotic) based on expert clinical assessment confirmed with structured diagnostic assessment (with Kiddie-Schedule for Affective Disorders and Schizophrenia for Schoolaged Children, Present and Lifetime version [K-SADS-PL])
• YMRS total score of 20-40 at baseline
• CGI-BP severity score of 4-6 at baseline
• providing assent to participate and signed consent by a parent or legal representative
• girls deemed to be of reproductive potential, must have a confirmed negative urine pregnancy test at intake, and use adequate contraception throughout the study