LAI: Linee guida ed esperienze internazionali

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1 LAI: Linee guida ed esperienze internazionali LAI: Guidelines and interna5onal experience PM Llorca CHU Clermont-Ferrand EA 7280 Université Clermont Auvergne

2 Disclosures Advisory board: Allergan, Jansen, Lilly, Lundbeck, Otsuka, Roche, Teva Involvement in clinical trials for: Janssen, Lundbeck, Otsuka Educa5onal grants for research, honoraria and travel support for ac5vi5es as a consultant/advisor and lecturer/faculty member for pharmaceu5cal companies: Astra Zeneca, Janssen, Lundbeck, Otsuka, Sanofi

3 Objec5ves Interna5onal Guidelines for the use of LAI in schizophrenia Type of Guidelines Evolu5on of Guidelines AWtudes of Pa5ents toward treatment and more specifically toward LAI Interest of Guidelines in clinical prac5ce Implementa5on of Guidelines

4 What are Clinical Guidelines? Means to improve health care 1990 modern guideline era began: systema'cally developed statements to assist prac''oner and pa'ent decisions about appropriate health care for specific clinical circumstances 1 Based on best available evidence Systema5c methods used to iden5fy and evaluate the evidence 1. Field et al (1990)

5 The Evidence Based Medicine (EBM) Triad Clinical decision relies on three main components 1 : Best external evidence Individual clinical experience Pa5ent Values and expecta5ons Individual clinical experience EBM Pa0ents values and expecta0ons The EBM triad Best external evidence Good doctors use both individual clinical exper5se and the best available external evidence, and neither alone is enough. Without clinical exper5se, prac5ce risks becoming tyrannised by evidence, for even excellent external evidence may be inapplicable to or inappropriate for an individual pa5ent. Without current best evidence, prac5ce risks becoming rapidly out of date,to the detriment of pa5ents Sacke@ et al (1996)

6 Individual clinical experience EBM Best external evidence Pa0ents values and expecta0ons The EBM triad Best external evidence Interest of Evidence Based Guidelines for the use of LAI

7 Evidence-based guidelines Evidence-based guidelines (EBG) 1 : recommenda5ons drawn up by a task force acer cri5cal analysis of available data (selected and ranked according to their level of evidence). First-line treatment: defined according to a higher level of evidence, (randomized controlled trials - RCT - ) Second- or Third-line treatments: based on evidence from noncontrolled or non-randomized studies or on expert advice EBG can be considered as way of organizing the best clinical evidence in recommenda5ons of clinical prac5ce 1. Samalin et al (2012)

8 Evolu5on of Evidence Based guidelines related to LAI use in schizophrenia

9 American Psychiatric Associa5on In the update of the APA Guidelines in 2010, LAI was only proposed in case of repeated non adherence for chronic pa0ents 1. Lehman et al (2010)

10 Evidence Based guidelines in 2012 Interest of LAI for maintenance treatment Regarding non-adherence, most of the guidelines and algorithms (except PORT 2009) stated that depot an0psycho0cs are effec0ve approach 1 Some guidelines (CPA, 2005; MOH, 2011; NICE, 2009; PORT 2009) actually recommended that switching formula0on of an0psycho0cs from oral to depot should be considered in the maintenance treatment. All of the guidelines and algorithms failed to comment on whether oral or depot has a specific interest, except in terms of adherence, in the maintenance phase of treatment. 1. Takeushi et al (2012)

11 Evolu5on of guidelines for the WFSBP (Mainly RLAI & PP1M) 2 Atypical or typical depot prepara5ons should be a treatment op5on when a pa5ent expresses a preference for such treatment because of its convenience, or an essen5al part of a treatment plan in which the avoidance of covert nonadherence with an5psycho5c drugs is a clinical priority (Level D) For op5mum effec5veness in preven5ng relapse, depot prepara5ons should be prescribed within the standard recommended dosage and interval range (Level A) There is good evidence to support the use of long-ac5ng injectable Risperidone for the treatment of schizophrenia (Category of evidence A, Recommenda5on grade 1) There is some evidence for the use of long-ac5ng injectable Risperidone in first-episode schizophrenia pa5ents and elderly pa5ents suffering from schizophrenia (Category of evidence B, Recommenda5on grade 3) 1. Falkai et al (2006) 2. Hasan et al (2013)

12 Evolu5on of guidelines for the Royal Australian and New Zealand College of Psychiatrists Depot medica5on should be reserved for two groups. Firstly those who clearly opt voluntarily for this route of administra5on. Atypical injectable agents are preferred because of beser tolerability and reduced risk of tardive dyskinesia. Secondly, those who despite a series of comprehensive psychosocial interven5ons aimed at promo5ng adapta5on and adherence, repeatedly fail to adhere to necessary medica5on and relapse frequently Long-ac5ng injectable an5psycho5c agents should be offered to pa5ents early in the clinical course of schizophrenia Long-ac5ng injectable an5psycho5c agents are recommended in the treatment of schizophrenia and first-episode psychosis: Ø when it is the individual s preference Ø as part of treatment plan where adherence has been poor or uncertain Ø as part of the treatment algorithm where there has been a poor response to oral medica5on 1. RANZP (2005) 2. Galletly et al (2016)

13 Individual clinical experience EBM Best external evidence Pa0ents values and expecta0ons The EBM triad Individual clinical experience Interest of Consensus Based Guidelines

14 Consensus-based guidelines Consensus-based guidelines (CBG) 1 : recommenda5ons based on the advice issued from the knowledge of the literature and the prac0cal experience of a panel of experts, who are asked to consider specific clinical ques5ons or situa5ons: This methodology enables the assessment of clinical situa5ons for which evidence (from randomized controlled trials) are scarce or debated. CBG can be considered as way of integra5ng the individual clinical experience of experts in recommenda5ons of clinical prac5ce 1. Samalin et al (2012)

15 Guidelines for depot an5psycho5c treatment in schizophrenia (ECNP) Who should be considered for depot drugs? Any pa0ent for whom long-term treatment is indicated receiving should be considered. Those pa5ents who are irregular in taking medica0ons are par5cularly good candidates. Even in pa5ents who ini5ally refuse this op5on, clinicians should work with them (through the therapeu0c alliance) to help the pa0ents understand the poten0al advantages. When should the treatment start? As soon as possible and feasible, acer the improvement of acute symptoms Which drug? In choosing which drug the clinician should consider previous experience, personal pa0ent preference, pa0ents history of response (both therapeu5c and adverse effects) and pharmacokine5c proper5es. There is no definite evidence that any one depot drug is superior to another in terms of efficacy, though they may differ in side effect profile. 1. Kane et al (1998)

16 Long-Ac5ng Injectable An5psycho5cs: Recommenda5ons for Clinicians 1 Canadian Psychiatric Associa5on Specific proposi0ons For All Phases The existence and poten'al use of LAIs for AP therapy should be discussed with pa'ents and families at all phases of illness, including the cri'cal period of the first 2 to 5 years. Informed Pa0ent Decision Informa'on regarding LAIs should be carefully and systema5cally discussed with pa5ents in a collabora5ve environment, taking into considera'on pa'ents and their families views regarding such use In all cases, pa5ents opinion about the choice of an LAI should be considered regarding knowledge of its effec'veness, ease of administra'on, frequency of injec'ons, and cost. Clinical Stability and Pa0ents Change in Opinions and AXtudes Psychiatrists and other clinicians should be prepared to see pa'ents aatudes toward medica'on, issues related to adherence to treatment, and need for LAIs as protean and not sta'c phenomena. Aber a period of stability, pa'ents may develop a different and more posi've aatude toward their treatment, experience an improved therapeu'c rela'onship, and be in a be@er posi'on to evaluate their op'ons of oral, compared with LAI, medica'ons. Hence con5nued discussion regarding various formula5ons of medica5ons is recommended. 1. Malla et al (2013)

17 Guidelines for the use and management of LAI AP in serious mental illness 1 French Society for Biological Psychiatry Keypoints LAI an'psycho'cs are indicated in pa5ents with schizophrenia, schizoaffec5ve disorder, delusional disorder and bipolar disorder. LAI SGA are recommended as maintenance treatment azer the first episode of schizophrenia. LAI an'psycho'cs have long been viewed as a treatment that could only be used for a small subgroup of pa'ents with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI an'psycho'cs should be considered and systema5cally proposed to any pa5ents for whom maintenance an5psycho5c treatment is indicated. In order to improve the acceptance and understanding of the benefits of an LAI an'psycho'c, it is recommended to deliver to each pa5ent specific informa5on concerning the advantages and inconveniences of the LAI formula5on, in the framework of shared decision-making. 1. Llorca et al (2013)

18 Individual clinical experience EBM Best external evidence Pa0ents values and expecta0ons The EBM triad Best external evidence and individual clinical judgment Interest of Evidence Based Guidelines and Consensus Based Guidelines

19 Strengths and limita5ons of both strategies EBG: Strengths Developed from scien5fic evidence (not from opinion or judgment) Recommenda5ons are ranked (based on the level of evidence) Limita5ons No possible recommenda5ons if there is no evidence available CBG: Strengths Applicable for the pa5ent treated in everyday clinical prac5ce and not only to pa5ents according the restric5ve inclusion criteria of RCT Applicable in specific situa5ons for which there is no evidence (e.g. specific popula5ons ) Limita5ons Based on opinion and judgment Difficulty to define exper5se Both are useful and synergic in terms of help for clinicians 1. Samalin et al (2012)

20 Evolu5on of Guidelines During the last 15 years Evidence Based Guidelines (EBG) and Consensus Based Guidelines CBG) both highlighted : The interest of LAI not only in case of non adherence and mul0ple relapses The interest of an earlier use of LAI as a new paradigm in the treatment of schizophrenia This evolu0on is based on: New evidences and more specifically 2 RCTs 1, 2 New experts consensus in various countries 3, 4 1. Subotnik et al (2015) 2. Schreiner et al (2015) 3. Malla et al (2013) 4. Llorca et al (2013)

21 Individual clinical experience EBM Best external evidence Pa0ents values and expecta0ons The EBM triad Pa'ent Values and expecta'ons Pa5ents awtudes towards LAI

22 Pa5ents awtudes toward treatment Interest in clinical prac'ce Beliefs about Medicines Ques0onnaire (BMQ) 1 can be used: 2 To evaluate axtudes toward treatment using 2 specific subscales (Necessity and Concern) To define 4 groups of awtudes toward treatment: Accep0ng Ambivalent Indifferent Skep0cal To iden0fy the rela0on between axtude and adherence to treatment 1. Horne et al (1999) 2. Samalin et al (2017)

23 Rela5on between adherence and awtudes Cross sec5onal study (n=120) 1 Evalua0on of axtudes toward treatment, adherence, insight and symptomatology, and side effects Adherence: Low/medium: 30.4% High: 69.6% High necessity Adherence: Low/medium: 50.0% High: 50.0% Choice of a treatment with a low level of side effects Low concerns Accep0ng n=46 (38.3%) Beliefs Ambivalent n=44 (36.7%) High concerns Indifferent n=8 (6.7%) Skep0cal n=22 (18.3%) Adherence: Low/medium: 37.5% High: 62.5% Adherence: Low/medium: 86.4% High: 13.6% Interest of a psychoeduca5on program Low necessity Interest of careful monitoring of adherence 1. Samalin et al (2016)

24 AWtudes of pa5ents towards LAI during Ethnographic informa5on collected from a nonrandom sample of 69 prescriber-pa0ent conversa0ons during treatment visits 1 : 60 with community mental health center psychiatrists 9 with nurse-prac55oners (14 psychiatrists and 60 pa5ents) the consulta5on Pa5ents naive to treatment are more neutral or favorable than unfavorable to LAI LAIs were not discussed by psychiatrists in 50% of pa0ents taking oral an0psycho0cs. 1. Potkin et al (2013)

25 AWtudes of pa5ents in an early interven5on service towards LAI Qualita5ve study conducted in a sample of 11 pa5ents asending an early interven5on service 1 : Par5cipants valued their psychiatrist s recommenda0on as to the most appropriate an0psycho0c AWtudes to LAIs were most posi0ve among those currently receiving a LAI Lack of awareness of LAIs as a treatment op0on among those not prescribed a LAI. Perceived advantages : Convenience Avoiding forgexng to take tablets Disadvantages : Injec0on pain Fear of needles Coercion 1. Das et al (2014)

26 In clinical prac5ce Are Guidelines useful and are they used?

27 Are guidelines useful? Prescrip5on of An5psycho5cs In a cohort of 2132 pa5ents, con5nuous prescrip5on of AP according to the guidelines, induces a decrease of mortality when compared to pa5ents treated in a discon5nuous way 1 Monitoring of Physical Health Meta analysis of 48 studies (n= ) 2 Following recommenda5ons improves: Weight in 75.9% of the pa5ents BP in 75.2% of the pa5ents Glycemia in 56.1% of the pa5ents Lipid profile in 28.9% of the pa5ents 1. Cullen et al (2013) 2. Mitchell et al (2012)

28 Are guidelines useful? Study designed to compare the impact of the use of GL vs «treatment as usual» (522 pa5ents treated during 12 months) 1 - Dusseldorf: Systema5c use of GL + algorithme with numeric support - Freiburg: Systema5c use of GL numeric support - Munich 1: «treatment as usual (control group) - Munich 2: «treatment as usual» + quality monitoring PANSS posi5ve sub-score PANSS nega5ve sub-score 1. Janssen et al. (2010)

29 But Are they used? Guidelines concerning the use of treatment Sample of 819 schizophrenia pa5ents 1 : 52.3% are prescribed 1 AP 47.7% are prescribed between 2 to 4 AP Guidelines concerning the physical health monitoring Meta analysis of 48 studies(n= ) 2 Monitoring of: BP in 69.8 % of the pa0ents Triglycerides in 59.9% of the pa0ents Cholesterol in 41.5% of the pa0ents Weight in 47.9% of the pa0ents Despite the interest for pa5ents, most of the clinicians do not follow Guidelines. 1. Stein et al (2012) 2. Mitchell et al (2012)

30 How to implement Guidelines

31 Consequences of the implementa0on of treatment guidelines for specialist mental health care 1 Objec0ves : Examine the efficacy of guideline implementa0on strategies in improving process outcomes(performance of healthcare providers) and pa5ent outcomes. Only 6 selected studies 1. Bighelli et al (2016)

32 Key points EBG and CBG considered LAI as a valuable op0on in the maintenance treatment at all phases of the illness Pa5ents considered the LAI as an op0on, but they frequently lack of informa0on Their axtudes and knowledge have to be explored Guidelines improve the quality of Care, but they are insufficiently used Need to be ac0vely implemented

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34 Ques5on with mul5ple choice. 1 Evidence based Guidelines recommend the use of LAI in schizophrenia : 1. For non compliant pa5ent 2. For pa5ents having a preference for this formula5on 3. For For resistant pa5ents 4. For pa5ents during all the phases of the illness 5. For pa5ents with addic5ve comorbidity

35 Ques5on with mul5ple choice. 1 Evidence based Guidelines recommend the use of LAI in schizophrenia : 1. For non compliant pa5ent 2. For pa5ents having a preference for this formula5on 3. For resistant pa5ents 4. For pa5ents during all the phases of the illness 5. For pa5ents with addic5ve comorbidity

36 Ques5on with mul5ple choice. 2 Consensus based Guidelines recommend for the use of LAI in schizophrenia : 1. To use a strategy of shared decision making 2. To use have a con5nuous discussion with pa5ents about the use of this formula5on 3. To associate this strategy with cogni5ve remedia5on 4. To include family and caregivers in the decision process 5. Not to use it acer a First Episode of Psychosis

37 Ques5on with mul5ple choice. 2 Consensus based Guidelines recommend for the use of LAI in schizophrenia : 1. To use a strategy of shared decision making 2. To use have a con5nuous discussion with pa5ents about the use of this formula5on 3. To associate this strategy with cogni5ve remedia5on 4. To include family and caregivers in the decision process 5. Not to use it acer a First Episode of Psychosis

38 Ques5on with mul5ple choice. 3 When evalua5ng awtudes toward treatment in schizophrenia pa5ents, they can can stra5fied in: 1. Accep5ng 2. Reluctant 3. Ambivalent 4. Indifferent 5. Scep5cal

39 Ques5on with mul5ple choice. 3 When evalua5ng awtudes toward treatment in schizophrenia pa5ents, they can can stra5fied in: 1. Accep5ng 2. Reluctant 3. Ambivalent 4. Indifferent 5. Skep5cal