Optimizing Response to Li Treatment Through Personalized Evaluation of Individuals With Bipolar I Disorder: The R-LiNK Initiative

N/AUnknownNCT04209140

Assistance Publique - Hôpitaux de Paris320 enrolled

Overview

Bipolar disorder (BD), especially BD type I, is a highly prevalent mental disorder and a is a highly prevalent mental disorder and an important factor for suicide. Lithium is the key treatment for prevention of BD relapse and has a proven suicide prevention effect. Whilst many cases become asymptomatic with lithium treatment, the majority show sub-optimal response. The objectives of this project are to: * improve outcomes of bipolar I disorder (BDI) cases prescribed lithium through the application of stratified approaches * optimize the early prediction of lithium response using a set of multi-modal biomarkers ("blood omics", Magnetic Resonance Imaging and Li7-Magnetic Resonance Spectroscopy derived-markers) * develop a multidisciplinary multinational network of experts to undertake this and future projects on personalized diagnostics and therapeutics and * implement new, powerful technologies to characterize brain lithium distribution and the blood molecular signature of lithium in responders and non-responders. This cutting edge approach will identify the eligibility criteria for treatment with lithium in BD in terms of response, safety and tolerability.

Study Type

OBSERVATIONAL

Enrollment

320

Conditions

Bipolar I Disorder

Interventions

lithium treatment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Decision to prescribe Li as a prophylactic treatment based on clinicians' assessment * Confirmed diagnosis of BD1 according to DSM-5 criteria * Aged 18-70 years. * Able and willing to give written informed consent * consents to blood sample for the purpose of the RLiNK study * Covered by a Social Security Insurance where applicable * Patients on Curatorship (consent form signed by the patient and specific consent form for the curator) Exclusion Criteria: * Trial of Lithium undertaken within the last 6 months * Lifetime history of mood disorder better explained by a DSM-5 definition for schizoaffective disorder * Pre-lithium screening suggest that Lithium initiation is contraindicated: * Incompatible concurrent treatments: long-term use of non- steroidal anti-inflammatory drug or diuretics for a known and established comorbid disorder with no possible alternative treatment (i.e. absolute contra-indication to Li treatment) * Health issues (risk of worsening of a pre-existing condition) Psoriasis, Brugada syndrome * Renal dysfunction: Glomerular Filtration rate below 60mL/min/1.73m 2 * On-going Pregnancy or planned pregnancy on the next 2 years * Lactating and breast feeding women (see SmPc) * Pregnant women

Outcomes

Primary Outcomes

Responder

Good Responder The individual meets criteria for sustained remission, namely they experience euthymia (defined as a score on the Quick Inventory of Depressive Symptoms (qIDS)\<6 and the Bech Rafaelson Mania Scale (BRMS)\<7) for at least 8 weeks during the two-year follow-up period without evidence of relapse into a syndromal episode of BD at any time after achieving sustained euthymia. AND No addition of a new mood stabilizer with the purpose of promoting mood stabilisation after lithium initiation Non Responder The individual: Fails to meet criteria for sustained remission (euthymia defined as a score on the qIDS\<6 and the BRMS\<7 for a minimum period \>=8 consecutive weeks) during the two-year follow-up. OR Experiences \>=1 relapse into a syndromal episode of BD of any polarity during the two-year follow-up period without any period of sustained remission Definition of a Partial Responder All cases not fulfilling the criteria of Good Responders or Non Responders

Time frame: month 24

Secondary Outcomes

Adherence

Adequate adherence will be defined as the individual taking at least 70% of the Li prescribed (i.e. either \>70% prescribed dose \&/or \>70% of the time) based on the monthly assessment of adherence

Time frame: Month 24

Alda Scale

Alda scale defined in the following article : Grof P, Duffy A, Cavazzoni P, Grof E et al. Is response to prophylactic lithium a familial trait? J Clin Psychiatry. 2002 Oct;63(10):942-7.

Time frame: Month 24

Responder - sensitivity

Good Responders= Recorded improvement of illness activity is \>=70% AND no addition of mood stab after Li initiation Non Responders= Recorded improvement of illness activity is \<=30% whatever the treatment has been Partial Responders = Recorded improvement of illness activity is between 70 and 30% whatever the treatment has been OR Recorded improvement of illness activity is \>=70% but the addition of mood stab after Li initiation has occurred

Time frame: Month 24

Time to new BD

Time to a new Bipolar Disorder (BD) episode, defined as the delay between inclusion and the date of the diagnosis of new Bipolar disorder

Time frame: Month 24

Time to BD hospitalization

Time to a new hospitalization for BD, defined as the delay between inclusion and the date of new hospitalization for Bipolar disorder

Time frame: Month 24

Time to new mood stabilizer

Time to prescription of a new mood stabilizer, defined as the delay between inclusion and the date of prescription of a new mood stabilizer

Time frame: Month 24

Monthly qIDS

Quick Inventory of Depressive Symptoms (qIDS)