Lisdexamfetamine. pour le traitement de la dépendance à la méthamphétamine

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1 Lisdexamfetamine pour le traitement de la dépendance à la méthamphétamine Adrian Dunlop Director & Addiction Medicine Senior Staff Specialist, Hunter New England Local Health District Conjoint Professor, Faculty of Health, University of Newcastle, Australia Chief Addiction Medicine Specialist, NSW Ministry of Health Merci: Associate Professor Nadine Ezard, St Vincent s Hospital Sydney, UNSW

2 Traitement de la dépendance à la méthamphétamine Thérapies psychologiques Soins standard actuels (counselling, CBT/ACT) Efficace pour réduire l'utilisation d'amphétamines Modeste taux d'induction et de rétention avec de nombreux effets perdus lors du suivi Incertitude dans la réduction des comportements sexuels à risque L'utilisation de base prédit la réponse: de meilleurs résultats pour une utilisation moins fréquente Thérapies pharmacologiques Dexamphetamine, modafinil, methylphenidate Diminuer withdrawal et cravings, augmenter la rétention Cochrane reviews a souligné la nécessité de poursuivre la recherche Studies often underpowered or underdosed Pilote de dexamphetamine at Newcastle & St. Vincents since 26 Shearer J Subst Abuse Treat. 27;32(1):1 52.Lee et al Drug Alcohol Rev. 28;27(3):39-17 Baker et al; Addiction. 21;96(9): ; Hillhouse et al Addiction. 27;96(9):8-95; Perez-Mana Cochrane 213; Galloway GP et al.. Clin Pharmacol Ther. 211;89(2): ; Shearer J. Addiction. 21;96(9): Page 2

3 Lisdexamfetamine Prodrug de dexamphetamine Licenced for use in Australia for ADHD to 7mg Autorisé pour une utilisation en Australie pour le ADHD à 7 mg Theoretical advantages ne contient pas de dexamphétamine libre reduction abuse-related liking IV par rapport à dexamphetamine Administré une fois par jour once daily Slower onset, lower peak concentration, and longer duration of action than dexamphetamine Jasinski, D.R. and S. Krishnan, J Psychopharmacol, (): p ; Heal, D.J., et al., Journal of Psychopharmacology, (6): p Page 3

4 Lisdexamfetamine - metabolism lisdexamfetamine L-lysine

5 The Lisdex Study Dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence Étude de phase 2 de la dose de la lisdexamfétamine administrée par voie orale à des adultes atteints de dépendance à la méthamphétamine A/Prof Nadine Ezard, St Vincent s Hospital/UNSW Prof Adrian Dunlop, Hunter New England Local Health District/ University of Newcastle Prof Andrew Carr, St Vincent s Hospital/UNSW A/Prof, Raimondo Bruno, University of Tasmania Brendan Clifford, St Vincent s Hospital / University of Sydney Prof Nicholas Lintzeris, South East Sydney Local Health District/ University of Sydney BMC Psychiatry 216 Page 5

6 Visit Dose of Lisdexamfetamine The Lisdex Study: design/conception Two centres, open-label, single group, outpatient trial 25mg dose approximately equivalent to 8mg dexamphetamine used in current substitution programs Participants >2yr history of MA use disorder, have used MA for for 1 days out of the previous 28 Five capsules dispenses at daily visits, with ratio of active:placebo according to regimen Participants and dispensers (clinic nurses) blinded to dose change Screening Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up ( weeks) Page 6

7 The Lisdex Study: résultats Primary measures were safety (adverse event rates), tolerability (TSQM tolerability scale) and retention (proportion remaining in treatment at each week) Blood pressure and pulse were checked daily, with additional measures of craving, withdrawal, physical/mental health, neurocognition, psychosocial functioning, other substance use, risk behaviours and potential for misuse also taken at intervals Preliminary efficacy measures were number of days methamphetamine use out of the previous 28 (self-report; and weekly urine drug screen) Weekly counselling offered, but not compulsory Participants were discontinued if they missed 3 or more doses in one 7-day period of the same dose or missed more than one planned data collection episode Page 7

8 Sample Characteristics (N = 16) Demographics % (n) Medical History % (n) MA use Mean (sd) Mean age (SD) 1 (6.7) HIV 19% (3) Age at first use 22 (9) Male 75% (12) Hep C 31% (5) Years of problem use 12 (8.) Female 25% () ADHD 13% (2) Days use of prev (5.) Aboriginal/Torres Strait 13% (2) Wender Utah* >6 % (7) Injecting Use % (n) 69 (12) Sexual Identity OST 13% (2) Other Substance Use % (n) - Heterosexual 56% (9) Tobacco 63% (1) - Gay or lesbian 19% (3) GHB 25% () - Bisexual 19% (3) Cannabis 31% (5) - Something else 6% (1) *Wender Utah score of >6 suggestive of childhood ADHD Ward AJ Psychiatry. 1993;15(6): Page 8

9 No. of participants Regimen Achèvement Pt remaining Dose Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 1mg 15mg 2mg 25mg 25mg 2mg 15mg 1mg Page 9

10 Safety - les événements indésirables Adverse Event Rates 12 1 Mild Moderate Severe mg 15mg 2mg 25mg 25mg 2mg 15mg 1mg Follow-up Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 There were 2 adverse events (AEs) reported: 38 mild (9%), 3 moderate (7%) anger, viral illness, hypomania (post study) 1 severe (2%) suicidality (EoS) Adverse Events occurring in two or more participants (n) Agitation () Headache (3) Loose stool (3) Decreased appetite (2) Jaw clenching (2) Page 1

11 mmhg mmhg La sécurité cardiovasculaire - BP Mean Systolic Blood Pressure Screen Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up Mean Diastolic Blood Pressure Screen Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up Dose 1mg 15mg 2mg 25mg 25mg 2mg 15mg 1mg Page 11

12 Beats/minut e La sécurité cardiovasculaire - pulse Heart Rate Screen Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up 1mg 15mg 2mg 25mg 25mg 2mg 15mg 1mg No clinical changes to ECGs recorded at weeks 2 (15mg) and week (25mg) when compared to baseline. Page 12

13 Sécurité psychiatrique Hostility Suspiciousness Baseline Week 1 Week 2 Week 3 Week Follow-up Baseline Week 1 Week 2 Week 3 Week Follow-up Hallucinatory Behaviour Unusual Thought Content Baseline Week 1 Week 2 Week 3 Week Follow-up Baseline Week 1 Week 2 Week 3 Week Follow-up Brief Psychiatric Rating Scale (BPRS) items (1 no symptoms present, 7 very severe) Overall JE, Gorham DR. Psychol rep. 1962;1(3): Page 13

14 Weight (kg) Autres mesures de sécurité Insomnia Severity Index Weight Physical Health (PHQ15) Baseline Week 2 Week Week 6 Week 8 Follow-up Screening Week Follow-up Baseline Week Week 8 Follow-up Depression (PHQ9) Anxiety (GAD-7) Baseline Week 2 Week Week 6 Week 8 Follow-up Baseline Week 2 Week Week 6 Week 8 Follow-up Bastien Sleep Med. 21;2():297 37; Kroenke Psychosom Med. 22;6(2):258 6; Kroenke J Gen Intern Med. 21;16(9):66 13; Spitzer Arch Intern Med. 26;166(1):192 7 Page 1

15 Tolérance 11 Treatment Satisfaction Questionnaire for Medications Side-effects item No side effects Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up Atkinson Health Qual Life Outcomes. 2;2(1):12 Page 15

16 Efficacité - Utilisation de la méthamphétamine Days Use /28 UDS negative for MA (number) Screening Week Week 8 Follow-up Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up Sobell & Sobell Toronto: Addiction Research Foundation; 1996 Page 16

17 Craving & Withdrawal Methamphetamine Craving Scale (VAS, max 1mm) Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up Amphetamine Withdrawal Questionnaire (max ) Baseline Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up Lee Addictive dis their treat. 22;1():1 2; Srisurapanont. : I. ANZJPsychiatry. 1999;33(1): Page 17

18 Participant déclaré efficacité 1 Treatment Satisfaction Questionnaire for Medications Effectiveness Scores Week 1 Week 2 Week 3 Week Week 5 Week 6 Week 7 Week 8 Follow-up Atkinson Health Qual Life Outcomes. 2;2(1):12 Page 18

19 Other Substance Use Participant 1 Participant Screening Baseline Week Week 8 Follow-up Screening Baseline Week Week 8 Follow-up GHB Alcohol Ma GHB Ma Participant 3 Participant Screening Baseline Week Week 8 Follow-up Screening Baseline Week Week 8 Follow-up GHB Alcohol Tobacco Ma Cannabis Alcohol Ma Four participants (25%) increased other substance use as measured by TimeLine Follow Back (TLFB). Page 19

20 Risk Behaviour OTI - HIV Risk Scores OTI - Crime Baseline Week Follow-up -2 Baseline Week Follow-up OTI HIV risk (max score of 85), OTI crime (max score is 16). Darke British Journal of Addiction (1992) 87, Page 2

21 Drug Liking How similar is this drug to methamphetamine? Comer. Pain. 212;153(12): NDARC Symposium Page 21

22 Drug Liking (DEQ-5, VAS mm) Morean Psychopharmacology (Berl). 213;227(1):

23 Discussion L'innocuité et la tolérabilité de doses plus élevées de LDX que celles utilisées pour le ADHD ou les troubles de l'alimentation excessive chez une population dépendante de la méthamphétamine. Neurocognitive data to be presented separately: Poster Raimondo Bruno Feasibility to conduct study (retention, adherence to study protocol) Further efficacy research warranted Multisite RCT commencing October 217 (Adelaide, Newcastle, Inner Sydney, Western Sydney n=16) Page 23

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