Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)

Alzheimer Disease Clinical Trial

Official title:

Comparison of Therapeutic Strategies With Cholinesterase Inhibitors: Stop or Still (SOS) Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03454646
• Other study ID #: CHUBX 2016/27
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 1, 2024
• Est. completion date: September 15, 2027

Study information

• Verified date: October 2023
• Source: University Hospital, Bordeaux
• Contact: Jean-François DARTIGUES, M.D., Ph.D
• Phone: 05 57 82 01 16
• Email: jean-francois.dartigues[@]u-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cholinesterase inhibitors (CI) remain the only drugs with a recognized efficacy in mild to moderate Alzheimer's disease (AD) in spite of enormous research efforts. However, these drugs presented as "symptomatic treatment" of AD are considered as having only a weak effect on the course of AD. The reimbursement of these drugs is regularly challenged due to the lack of evidence for the impact of these drugs on milestones stages of AD evolution (survival without severe dementia, restriction in Basic Activities of Daily Living - BADL) and on major consequences in public health (hospitalization and institutionalization). The great majority of previous randomized controlled trials conducted with CI have had a too short duration and the end points were limited to cognition (ADAS Cog scale), IADL (Instrumental Activities of Daily Living) function and Global Impression of Change. New evidences from the DOMINO trial (1) conducted in UK, independently of the pharmaceutical industry, showed that the true effect of CI might be more to avoid or to delay the cognitive or functional decline in AD than to improve patients; the institutionalisation (2) was also delayed. However, this trial was conducted in patients with moderate to severe AD, and the interest of the drugs at the mild to moderate stage remains questionable.

The investigators have shown that a good surrogate marker of survival without severe dementia would be an increase of ADAS Cog scale of more than six points (3). A post hoc reanalysis of the pivotal RCT with two CI showed that in mild to moderate patients, CI was associated with a 15% decrease of patients with a deterioration of ADAS-Cog of more than six points in six months. Thus at the beginning of dementia the real effect of CI might be more of delaying the cognitive and functional decline, than to improve the patients. The main objective of the SOS trial is to demonstrate that the benefit of CI at the early phase of dementia is the same as at the later phase.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1205
• Est. completion date: September 15, 2027
• Est. primary completion date: April 27, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• New case of AD referring to a CMRR or MC.

• Diagnosis of probable or possible AD, defined according to the NINCDS-ARDRA criteria

• Mild to moderate stage, defined by a MMSE score above 15 at the time of pre-inclusion

• Patients with indication to CI treatment

• Patients Naïve to CI treatment

• Patients aged 50 years or more

• Menopause or effective contraception (for women)

• Affiliated person or beneficiary of a social security scheme

• Patients with AD LTI (Long Term Illeness)

• Patients agree to participate, with free, informed and written consent signed by the patient and his caregiver

Non Inclusion Criteria:

• Patients diagnosed with Lewy bodies disease, fronto-temporal dementia, or dementia from a cause other than Alzheimer Disease

• More severe stage of the disease, defined by a MMSE equal or below 15 at the time of inclusion

• Patients with contraindication to CI treatment

• Patients residing in an institution at the time of pré-inclusion or randomization

• Patients with a complete dependency for bathing and dressing at the time of pré-inclusion or randomization ( ADL de Katz, score 2/2 for the item "bathing" and/or "dressing")

• Patients under tutorship or curatorship, patients unable to express consent

• Patients with unstable severe general disease compromising the follow-up

• Patients without caregiver

• Patients included in another pharmacological trial

• Pregnant or breastfeeding women

Exclusion Criteria:

• CI responder patients for whom the MMSE score remained stable or became higher after 6 months of treatment

• Patients with complete dependency for bathing and dressing at the randomization visit

• Patients residing in an institution at the randomization visit

Related Conditions & MeSH terms

• Alzheimer Disease
• Cholinesterase Inhibitors

Intervention

Drug:
• cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine)
The choice of the treatment will be done by the specialist according to his habits; the specialist will monitor the treatment as usual. All the recruited patients will be treated by CI according to the recommendations of the French HAS and the clinician's habits to choose the type of CI and adjust the dosage. After a 6-month period under CI treatment, patients will be classified according to the evolution of the Mini Mental State Examination (MMSE) as "non-responders" or responders. Responders patients will continue their treatment according to the habits of the clinician. Non-responder patients will be included in the RCT, with individual randomization in two groups: one group who stops the CI, one group who continues the CI. All randomized patients will then be followed-up for two years with regular assessment of judgment criteria every 6 months.

Locations

Country	Name	City	State
France	CHU d'Amiens Centre Mémoire Ressources Recherche	Amiens
France	CHU d'Angers Centre Mémoire Ressources Recherche	Angers
France	CHU de Bastia Centre Mémoire Ressources Recherche	Bastia
France	CHU de Besançon Centre Mémoire Ressources Recherche	Besançon
France	CHU de Bordeaux - Service de Neurologie - Centre Mémoire Ressources Recherche -	Bordeaux
France	CHRU Cavale Blanche Service de Gériatrie	Brest
France	Service de Neuropsychologie Hôpital Neurologique Pierre Wertheimer	Bron
France	CHU Côte de Nacre Service de neurologie et CMRR	Caen
France	CHU de Clermont Ferrand Centre Mémoire Ressources Recherche	Clermont-Ferrand
France	Hôpital Pasteur Service de Neurologie	Colmar
France	CHU de Dijon- CMRR	Dijon
France	Chu de Grenoble CMRR, Neurologie	Grenoble
France	Hôpital Roger Salengro CMRR	Lille
France	CHU Limoges Service de neurologie et CMRR	Limoges
France	AP-HM	Marseille
France	CHU Montpellier Hôpital Gui de Chauliac CMRR	Montpellier
France	CHU de Nantes Clinique Neurologique Hôpital GR Laennec	Nantes
France	Institut Claude Pompidou Centre Mémoire de Ressources et de Recherche	Nice
France	APHP Groupe Hospitalier Saint Louis Lariboisière Fernand Widal CMRR	Paris
France	APHP Hôpital Broca	Paris
France	Hôpital Universitaire de la Pitié Salpêtrière Pavillon François Lhermitte	Paris
France	CHU La Milétrie Pôle de Gériatrie	Poitiers
France	CHU Reims Hôpital Maison Blanche Court Séjour Gériatrique	Reims
France	CHU de Rennes - Hôpital Pontchaillou / Service de Neurologie	Rennes
France	CHU de Rouen Hôpital Charles Nicolle Service Neurologie	Rouen
France	Chu de Saint-Etienne, CMRR	Saint-Étienne
France	Chu de Strasbourg Hôpital Ka Robertsau Pôle de Gériatrie - CMRR	Strasbourg
France	Centre de Recherche Clinique du Gérontopôle Cité de la Santé	Toulouse
France	CHRU de Bretonneau Unité de gérontopsychiatrie	Tours
France	CHU Nancy Service de Gériatrie-CMRR	Vandoeuvre les nancy
France	Hospice Civil de Lyon Hôpital des Charpennes	Villeurbanne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome is a combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 2 years after randomization.	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.; Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.; For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.	at 30 months after patient's inclusion
Secondary	BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].	Each of the components of the combined primary outcome, as defined above, analyzed separately.; As previously demonstrated, bathing and dressing are the first ADL losses, also defined by Katz et al. as the thresholds of disability [17] [18]. A total limitation in bathing and dressing will be considered (each item is coded from 0 - no limitation, to 2 - total limitation).	at inclusion
Secondary	BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].	Each of the components of the combined primary outcome, as defined above, analyzed separately.; As previously demonstrated, bathing and dressing are the first ADL losses, also defined by Katz et al. as the thresholds of disability [17] [18]. A total limitation in bathing and dressing will be considered (each item is coded from 0 - no limitation, to 2 - total limitation).	at 6 months
Secondary	BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].	Each of the components of the combined primary outcome, as defined above, analyzed separately As previously demonstrated, bathing and dressing are the first ADL losses, also defined by Katz et al. as the thresholds of disability [17] [18]. A total limitation in bathing and dressing will be considered (each item is coded from 0 - no limitation, to 2 - total limitation).	at 12 months
Secondary	BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].	Each of the components of the combined primary outcome, as defined above, analyzed separately As previously demonstrated, bathing and dressing are the first ADL losses, also defined by Katz et al. as the thresholds of disability [17] [18]. A total limitation in bathing and dressing will be considered (each item is coded from 0 - no limitation, to 2 - total limitation).	at 18 months
Secondary	BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].	Each of the components of the combined primary outcome, as defined above, analyzed separately As previously demonstrated, bathing and dressing are the first ADL losses, also defined by Katz et al. as the thresholds of disability [17] [18]. A total limitation in bathing and dressing will be considered (each item is coded from 0 - no limitation, to 2 - total limitation).	at 24 months
Secondary	BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].	Each of the components of the combined primary outcome, as defined above, analyzed separately As previously demonstrated, bathing and dressing are the first ADL losses, also defined by Katz et al. as the thresholds of disability [17] [18]. A total limitation in bathing and dressing will be considered (each item is coded from 0 - no limitation, to 2 - total limitation).	at 30 months
Secondary	Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.; Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.; For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.	at inclusion
Secondary	Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.; Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.; For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.	at 6 months
Secondary	Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.; Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.; For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.	at 12 months
Secondary	Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.; Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.; For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.	at 18 months
Secondary	Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.; Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.; For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.	at 24 months
Secondary	Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.; Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.; For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.	at 30 months
Secondary	Institutionalization with date of entry	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.	at inclusion
Secondary	Institutionalization with date of entry	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.	at 6 months
Secondary	Institutionalization with date of entry	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.	at 12 months
Secondary	Institutionalization with date of entry	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.	at 18 months
Secondary	Institutionalization with date of entry	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.	at 24 months
Secondary	Institutionalization with date of entry	Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information.	at 30 months
Secondary	Death and date of death	Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.	at inclusion
Secondary	Death and date of death	Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.	at 6 months
Secondary	Death and date of death	Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.	at 12 months
Secondary	Death and date of death	Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.	at 18 months
Secondary	Death and date of death	Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.	at 24 months
Secondary	Death and date of death	Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status.	at 30 months
Secondary	the ADL scale	ADL DE KATZ BATHING :+-+/2 0 bathes self completely; needs help in bathing only one part of the body; needs help with bathing more than one part of the body or not bathed DRESSING :+-+ /2; 0 gets clothes and gets completely dressed without assistance; 1 gets clothes and gets dressed without assistance, except for assistance in tying shoes 2 receives assistance in getting clothes or in getting dressed, or stays partly or completely undressed TOILETING :+-+/2 0 toileting without assistance (may use cane, walker, or wheelchair); 1 receives assistance 2 doesn't go to room termed " toilet ". TRANSFER:+-+/2 0 transfer without assistance (may be using cane or walker); transfer with assistance; doesn't get out of bed. FEEDING :+-+/2; 0 feeding without help; need help cutting meat or buttering bread; needs total help or requires parenteral feeding. TOTAL : +---+/10 If the patient has a result of 2 at bathing and or dressing he can't be included at T0.	at inclusion
Secondary	the ADL scale	ADL DE KATZ BATHING :+-+/2 0 bathes self completely; needs help in bathing only one part of the body; needs help with bathing more than one part of the body or not bathed DRESSING :+-+ /2; 0 gets clothes and gets completely dressed without assistance; 1 gets clothes and gets dressed without assistance, except for assistance in tying shoes 2 receives assistance in getting clothes or in getting dressed, or stays partly or completely undressed TOILETING :+-+/2 0 toileting without assistance (may use cane, walker, or wheelchair); 1 receives assistance 2 doesn't go to room termed " toilet ". TRANSFER:+-+/2 0 transfer without assistance (may be using cane or walker); transfer with assistance; doesn't get out of bed. FEEDING :+-+/2; 0 feeding without help; need help cutting meat or buttering bread; needs total help or requires parenteral feeding. TOTAL : +---+/10 If the patient has a result of 2 at bathing and or dressing he can't be randomized at T6M	at 6 months
Secondary	the ADL scale	ADL DE KATZ BATHING :+-+/2 0 bathes self completely; needs help in bathing only one part of the body; needs help with bathing more than one part of the body or not bathed DRESSING :+-+ /2; 0 gets clothes and gets completely dressed without assistance; 1 gets clothes and gets dressed without assistance, except for assistance in tying shoes 2 receives assistance in getting clothes or in getting dressed, or stays partly or completely undressed TOILETING :+-+/2 0 toileting without assistance (may use cane, walker, or wheelchair); 1 receives assistance 2 doesn't go to room termed " toilet ". TRANSFER:+-+/2 0 transfer without assistance (may be using cane or walker); transfer with assistance; doesn't get out of bed. FEEDING :+-+/2; 0 feeding without help; need help cutting meat or buttering bread; needs total help or requires parenteral feeding. TOTAL : +---+/10	at 12 months
Secondary	the ADL scale	ADL DE KATZ BATHING :+-+/2 0 bathes self completely; needs help in bathing only one part of the body; needs help with bathing more than one part of the body or not bathed DRESSING :+-+ /2; 0 gets clothes and gets completely dressed without assistance; 1 gets clothes and gets dressed without assistance, except for assistance in tying shoes 2 receives assistance in getting clothes or in getting dressed, or stays partly or completely undressed TOILETING :+-+/2 0 toileting without assistance (may use cane, walker, or wheelchair); 1 receives assistance 2 doesn't go to room termed " toilet ". TRANSFER:+-+/2 0 transfer without assistance (may be using cane or walker); transfer with assistance; doesn't get out of bed. FEEDING :+-+/2; 0 feeding without help; need help cutting meat or buttering bread; needs total help or requires parenteral feeding. TOTAL : +---+/10	at 18 months
Secondary	the ADL scale	ADL DE KATZ BATHING :+-+/2 0 bathes self completely; needs help in bathing only one part of the body; needs help with bathing more than one part of the body or not bathed DRESSING :+-+ /2; 0 gets clothes and gets completely dressed without assistance; 1 gets clothes and gets dressed without assistance, except for assistance in tying shoes 2 receives assistance in getting clothes or in getting dressed, or stays partly or completely undressed TOILETING :+-+/2 0 toileting without assistance (may use cane, walker, or wheelchair); 1 receives assistance 2 doesn't go to room termed " toilet ". TRANSFER:+-+/2 0 transfer without assistance (may be using cane or walker); transfer with assistance; doesn't get out of bed. FEEDING :+-+/2; 0 feeding without help; need help cutting meat or buttering bread; needs total help or requires parenteral feeding. TOTAL : +---+/10	at 24 months
Secondary	the ADL scale	ADL DE KATZ BATHING :+-+/2 0 bathes self completely; needs help in bathing only one part of the body; needs help with bathing more than one part of the body or not bathed DRESSING :+-+ /2; 0 gets clothes and gets completely dressed without assistance; 1 gets clothes and gets dressed without assistance, except for assistance in tying shoes 2 receives assistance in getting clothes or in getting dressed, or stays partly or completely undressed TOILETING :+-+/2 0 toileting without assistance (may use cane, walker, or wheelchair); 1 receives assistance 2 doesn't go to room termed " toilet ". TRANSFER:+-+/2 0 transfer without assistance (may be using cane or walker); transfer with assistance; doesn't get out of bed. FEEDING :+-+/2; 0 feeding without help; need help cutting meat or buttering bread; needs total help or requires parenteral feeding. TOTAL : +---+/10	at 30 months
Secondary	the MMSE score	The MMSE score will be assessed by the clinician, the psychologist or the speech therapist according to the habits of the center, using the French version of the MMSE (GRECO version)	at inclusion
Secondary	the MMSE score	The MMSE score will be assessed by the clinician, the psychologist or the speech therapist according to the habits of the center, using the French version of the MMSE (GRECO version)	at 6 months
Secondary	the MMSE score	The MMSE score will be assessed by the clinician, the psychologist or the speech therapist according to the habits of the center, using the French version of the MMSE (GRECO version)	at 12 months
Secondary	the MMSE score	The MMSE score will be assessed by the clinician, the psychologist or the speech therapist according to the habits of the center, using the French version of the MMSE (GRECO version)	at 18 months
Secondary	the MMSE score	The MMSE score will be assessed by the clinician, the psychologist or the speech therapist according to the habits of the center, using the French version of the MMSE (GRECO version)	at 24 months
Secondary	the MMSE score	The MMSE score will be assessed by the clinician, the psychologist or the speech therapist according to the habits of the center, using the French version of the MMSE (GRECO version)	at 30 months
Secondary	the number of hospitalizations	The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;	at inclusion
Secondary	the number of hospitalizations	The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;	at 6 months
Secondary	the number of hospitalizations	The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;	at 12 months
Secondary	the number of hospitalizations	The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;	at 18 months
Secondary	the number of hospitalizations	The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;	at 24 months
Secondary	the number of hospitalizations	The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;	at 30 months
Secondary	Pharmacologie treatments consumed by the patient	All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.	at inclusion
Secondary	Pharmacologie treatments consumed by the patient	All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.	at 6 months
Secondary	Pharmacologie treatments consumed by the patient	All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.	at 12 months
Secondary	Pharmacologie treatments consumed by the patient	All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.	at 18 months
Secondary	Pharmacologie treatments consumed by the patient	All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.	at 24 months
Secondary	Pharmacologie treatments consumed by the patient	All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.	at 30 months