Amphetamine-Type Stimulants (ATS)€¦ · Alertness Increased stamina and energy Reduced need for sleep Increased libido Reduced appetite Enhanced task performance Increased physical

1

+

Amphetamine-Type Stimulants (ATS)

Dr Jonathan BrettClinical toxicology and addiction medicineSt. Vincent’s Hospital Sydney

+Amphetamine-type stimulants

What are they?

Why are they addictive?

Specific substances

Drug testing

Harms

Treatment Withdrawal management

Relapse prevention

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2

+ Amphetamine-type stimulants

1. Synthesised Compounds

Pharmaceuticals• Pseudoephedrine • Dexamphetamine• Methylphenidate (Ritalin®)• Diethylpropion (Tenuate®)• Phentermine (Duromine)

Illicitly produced• Amphetamine sulphate i.e.

speed• Methamphetamine

e.g. ice, base, speed• Amphetamine analoguese.g. MDMA (Ecstasy), PMA

Tobacco (nicotine) CaffeineAdrenaline CocaineKhat GuaranaCocoa (chocolate) Others...

2. Naturally Occurring Compounds

+ Why are Psychostimulants so Popular?

They feel good!

Elevated mood – euphoria

Enactogen/emphathogen: experiences of emotional communion, oneness,

relatedness, emotional openness

Confidence

Alertness

Increased stamina and energy

Reduced need for sleep

Increased libido

Reduced appetite

Enhanced task performance

Increased physical strength

Increase talkativeness

SCII.001.001.0002

3

+Structure-Activity Relationships

Methyl group substitution increases bioavailability and potency

Methamphetamine

aaa

Amphetamine

aaa

Amphetamine MethamphetaminePhenethylamine

+Structure-Activity Relationships

Amphetamine3, 4 MethyleneDioxy-MethAmphetamine (MDMA)

aaa CH 3

I NH

SCII.001.001.0003

4

aaa

+aaa

Weakly inhibits Mll.O

0

direct agonist

activity

-Some dired receptl,,--~-------'

Inhibits VMJI.T increases cytosolic

Blocks reuptake by Dll.T Syrnportexchange

Dopamine Release

0 1 2 3 4

Time (h)

- Food - Sex EtOH - Nicotine - Morphine - Cocaine - Methamphetamine

5

Chris Hurt. Reprinted with permission. Adapted from Rawson, R. FRONTLINE: The Meth Epidemic. 2006.

SCII.001.001.0004

5

+Terminology

Misuse/extra-medical use

Dependence

Substance Use Disorder

Brain reword pathways

Preftontal oortex y

PFC

OFC

NucNMJS accumbens

El Non-addk:ted brain

Control& sett-regulation

(PFC, CG)

t

II Addicted brnln

NOT Go

CD-

Control& 5ett-regulatloo

(PFC, CG) ";

l

TENTH REV ISION

0 ICD-10 is a new code set for reporting

medical diagnoses & inpatient procedures.

SCII.001.001.0005

6

+Terminology

Dependence = ≥3 of:

Strong desire to take

Difficulties controlling (onset, termination, levels)

Withdrawal

Tolerance

Neglect of other interests (salience)

Persisting use despite harms

Substance use disorder

Taking in larger amounts

Not being able to cut down/stop

Time consumed

Cravings/urges

Work/school affected

Relationships affected

Neglect of other activities

Persisting use despite harm

Tolerance

Withdrawal

Mild = 3, Mod =4-5, Sev = ≥6

+

Amphetamine and methamphetamine

'Ice 'epidemic': Prime Minister Tony Abbott announces task force to tackle crystal meth 'menace' ., ___ """"" __ _ The Primo Mlo~ .. , hnla~nclled•natlonal INklorcetohalptacklothagrowlngand

:;:i~n~::"1c~.crys,.l..........,p,_,,I,,.,

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7

+ Methamphetamine (“crank”)

Powdered (meth)amphetamine (“speed”) Typically snorted or injected

Base methamphetamine (“base”) Waxy, oily resin Typically injected

Crystalline methamphetamine (“Ice”) Typically smoked

Methamphetamine pills (“Fake ecstasy”) Typically ingested

Purity -FIGURE 15: Annual median purity of methylamphetamine samples, 2004--05 to 2013-14

- NSW - VIC OLD - SA - WA - TAS 100

90

80

70

l 60

~ 50 ·c: cf 40

30

20

10

0

i ! ... ~ I i

N .., ....

i ... J 1 ~ ;i, ~ ~ ~ ~ ~ ~

SCII.001.001.0007

8

+Kinetics

Route Dose Bioavailability Cmax (µg/l)Tmax(minutes)

T1/2(hours) 

Time to peak effect

Intravenous 30mg* 100%  108 6 9.1 <15 

Smoking 30mg 67% / 90±10%  47 150 12 18

Oral 30mg 67%  94 216 9.1 180

Intra‐ nasal 50mg 79%  113 169 11 ≤15

Cruickshank CC, Dyer KR. A review of the clinical pharmacology of methamphetamine. Addiction. 2009 Jul;104(7):1085-99.

*typical dose

+Metabolism

50%

Methamphetamine

I °'NH2

Amphetamine

vY Phenylacetone

HO ~ 4-Hydroxyphenylacetone

~ ' HOV I

4-Hydroxymethamphetamine

~ NH2

HO~ I ~ 4-Hydroxyamphetamine ~ I NH2

OH

OH / HO "'--~ NHz / 4-Hydroxynorephedrine

u 1 Norephedrine

0

(Y'oH Benzoic acid

~ Nl(OH

V H 0 Hippuric acid

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9

+Methamphetamine clearance

Amino group on side chain - basic

Acidification of urine promotes net excretion (ion trapping)

Uncontrolled urine pH - 30% excreted unchanged in first 24h

Acidified urine – 75% excreted unchanged in first 24h

+Laboratory testing

Matrix DoseLLOQ/cut‐off (µg/l)

Typical detection time (single dose) 

Maximum detection time (repeated dosing)

Plasma10mg intravenous 1 36–48 Not reported

Plasma35mg intravenous 1 36–48 Not reported

Plasma10mg oral, slow‐release 2.5 24Not reported

Oral fluid10mg oral, slow‐release 2.5 243 days

Urine10mg oral, slow‐release 2.5 877 days

Urine 22mg smoking 300 60Not reported

Cruickshank CC, Dyer KR. A review of the clinical pharmacology of methamphetamine. Addiction. 2009 Jul;104(7):1085-99.

*Reactivity of assays variesbetween commercial assays

H I N- CH3

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10

+How are drugs tested for?

Matrix Blood, urine, oral fluid, hair, primary substance

Immunoassay First line screening High throughput Binding of drug to antibodies Cross reactivity issues

Chromatographic techniques Confirmatory Gas/liquid Separate out compounds Detect – colour (Liquid or gas chromatography), molecular mass

(mass spectrometry) Reference standards vs reference libraries Lower limits of quantification

+Hair

Hair growth 1cm / month

Estimates only made in months (per cm)

May appear in hair 24-48h after use

Cut off for amphetamines 0.5ng/mg

Pitfalls Racial bias

Cosmetic hair treatments

Passive contamination – metabolite ratios, decontamination

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11

+Oral fluid

Roadside testing

Depends on ability of drugs to filter across mucous membrane – amphetamines ok

Pitfalls Particulates/blood in mouth

Heat instability

Oral contamination

Oral fluid versus serum (for amphetamines) Accuracy 93.1%, positive predictive value 81.4%, negative

predictive value 98.9%

+Drug checking (aka ‘pill testing’)

Primary substance testing

On-site at festivals vs fixed site testing

Range of assays: Fourier-Transform Infra-red spectroscopy (FTIR)

Mass reduction techniques

Thin layer chromatography

Combined with harm reduction messages

Initial results from Australia and UK promising 1 in 5 disposed drug, 1 in 6 moderated intake

1 in 5 not as sold or acquired (2x more common if inside venue) – of these 2 in 3 disposed drug

Measham FC. International Journal of Drug Policy. 2018 Dec 9.

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+Natural history MA useVMAX

Lanyon C, Journal of addiction medicine. 2019 Mar 1;13(2):159-65.

+Natural history MA use VMAX

Associations with past-month MA Male Poor physical health

Associations with methamphetamine dependence Poor physical health Low self-perceived social support Current mental health medication prescription Current engagement with drug treatment services for

methamphetamine use.

Engagement with treatment and health/support services low (12%–22%) over the study period.

Lanyon C, Journal of addiction medicine. 2019 Mar 1;13(2):159-65.

TABLE 2 Methamphetamine Use and Dependence Trajec­tories Over 5 Years

Past -month se ot Me0,amphetami ne eslt o)'

Consistent past-month use Past-month ~e to abstinenoc Past-month ~e, abstincnoc, return to use

1eth:uuphetamine Dependence (SO, Score ~ 4)

ever dependent ondependcnt, dependent, noo-dependent

Consistently dependent Dependent, non-dependent, dependent

Ol dependent 10 dependent Dependent to non-dependent

SOS, Severity of Dependeooe.

11 = 102, II ( o)

45/102 (44) 43/102 (42) 14/102 (14)

28/102 (27) 2/102 (2)

23/102 (23) 5/102 (5)

13/102 (13) 31/102 (30)

• All paniciparus reported pasi-month methamphelamine use a t baseline, per study inclusM>n criteria.

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13

+Natural history MA useVMAX

General practitioners most common source of professional support (24%)

Service utilisation associated with: riskier methamphetamine use patterns (e.g., injecting),

professional support access for other issues (e.g., mental health),

greater experience of methamphetamine-related harms (e.g., adverse social consequences).

Quinn. Journal of substance abuse treatment. 2013 Aug 1;45(2):235-41.

+

‘Dance party’ stimulants

MDMA & novel psychoactive stimulants

SCII.001.001.0013

14

+MDMA

Synthesized by Merk 1912 – diet pill,

Psychological warfare 1950 (US army),

Psychotherapy 1970s

Clubbing scene since 1980s

Risk of dependence low

Risks of other harms: Hyperthermia Seizures Electrolyte disturbance (low sodium) Liver injury

+LuckyDip

Tanner-Smith, Drug and alcohol dependence83.3 (2006): 247-254.

Pharmacological conteni of ecstasy tablets: 1999- 2005 Dance-Safe postings

Tablets with this Tablets with this ingredient only ingredient in pan ("/,) ("/,)

MDMA 38.96 54.04 S-MeO-DiPT .66 .66 Acetaminophen .58 1.73 AIIUtriptyline 08 08 Amphetamine .25 .33 Aspirin .16 .82 Benzylpiperazine .16 1.48 Caffei ne 2.14 16.56 Carisoprodol .16 .25 Cocaine .OS .33 Codeine .08 .25 Dextromelhorphan (DXM) 4.94 7.99 Diazepa.m .33 .41 Dietbylpropion 08 .08 Diphenhydra.mine .41 .66 Dimethoxyamphetamine (DOB) .OS .OS Guaifenesin .33 .91 Heroin 0 .OS Ketamine .41 2.n Lidocaine .OS .16 Methylenedioxyamphf'lamine SJ9 1260

(MDA) Methylenedioxyethylamphetamine .91 Si l

(MOE) Mf'tandienone .OS .JJ Methamphetamine 1.48 8.65 Methyl s.alicylate 16 1.48 Phencyclidine (PCP) .OS us Paramethoxyampbetamine (P11A.) .16 .16 Pseudo-ephedrine LIS 7.58 Trifluoromethylpbenylpiperazine .OS 1.32

monobydrochloride Unknown 10.87 11.78 Zolpidem 16 .16

SCII.001.001.0014

15

+MDMA kinetics

+Novel psychoactive substances

<o~1

""' NHCH3 __ c_w_2_0_6_ •ti Hox;n::~ NHCH:i

0 ,✓,; CH 3 ,,,;; CHJ HO

MOMA HHMA

1CfP286 1CYP286

(/)

80

70

60

~ 50 0 ai 40

.0

E ~ 30

20

10

CYP206 HOx;r(Nfii ----► I

,,-:;:, CH3 HO HHI\

2005 2006 2007 2008 2009 2010 2011 2012 2013

Figure 1 Number of novel psychoactive compounds notified for the first t ime to the European Early Warning System since May 2005. Data by EMCDDA (2013, 2014a).

SCII.001.001.0015

16

+

Phenethylamine

+

Others e.g. PMA PMMA 4-MTA TMA TMA-2 2MA 3MA

Amino-indans e.g.

2Al 2AT MMAJ

+

Methylenedioxy-phenethylamines

Ring substiluted methylene-dioxyphenethylamioes

2C Series Others ~ ketonated MOMA e.g. cathinones e.g. e .g. substituted MDEA DOB e.g. e.g. 2CB Mesc.aline methylene MDA DOC bromo- mephedrone 2CI Tyramine dioxyphene DOI dragon- methedrone 2CD Dopamine thylamines Amino DOM Fly methcathinone 2CT-2 e.g. indans DON (ABDF) DOEF DOE'f 2C-B-

bupropion 2CT-7 N-beozyl

ethylone e.g. flephedrooe 2CP methylene MDAI ethcathinone 2CE

derivatives 51Al

DOPR Fly DOTFM Aleph- I

2CN e .g.

MOPY MBDB Pyrrolidioe 2CT-8

2CBCB-MDPPP

derivatives 2CT-9 BOMe

6APB Aleph-6 e.g. 2CT-21 6APDB Aleph-7 oPPP 2CF Ariadne MPPP 2cc Beatrice MOPPP 2C-TFM G3 Naphyrooe G5

PMA: 'not just at Warning over fake ecstasy tablets after story' seven people die in Scotland

DNEWS CJ Just In Politics World Business Sport Science Health Arts Analysis F

Ill, Print 181 Email ll Facebook CJ Twitter Iii More

Potentially lethal 'Superman' drug could be on sale in Australia, police warn Updated 25 Feb 2015, 5:13pm

sin logos

'death'

iwing the death of a 25

-'fl9" .

' I . . iJ. 4 Some of the fake ecstasy tablets, which contain the dangerous stimulant PMA, are green and bear an imprint of the RoleK logo. Pholograph, PoLice Scotland/PA

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+Challenges

Legislation

Ease of derivative manufacture

Laboratory analysis

Lack of clinical experience and unknown toxicities

Marketing and regulation

+

ADHD medicationsMethylphenidate and dexamphetamine

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+

2004 2006 2008 2010 2012 2014

0

50

100

150

200

Nu

mb

er

of e

ve

nts

Methylphenidate Dexamphetamine

MethamphetamineAtomoxetineModafinil

2 0 0 4 2 0 0 6 2 0 0 8 2 0 1 0 2 0 1 2 2 0 1 4

0 .0 0 0

0 .0 0 1

0 .0 0 2

0 .0 0 3

Y e a r

Illi

cit

Ca

lls

/All

In

ten

tio

na

l C

all

s

O b se rve d

2 0 0 4 -2 0 1 4 A P C = 1 3 .7 6^

‘Illicit use’ calls to PICCalls to PIC

+Who?

Surveys (U.S.) National: 3.4% of those aged 12 years and older had experienced

nonmedical use of ADHD medications.

University/college students:

life-time prevalence 7–17% prescribed stimulant misuse Vsgeneral population (0.3–2.1%).

Improve concentration, ‘get high’

EDRS - NDARC: regular ecstasy users (Australia): 90% diverted (non-prescribed) – friend, relative, dealer

50% illicit lifetime

30% illicit in the last six months

ADHD medication overdose and misuse: the NSW Poisons Information Centre experience, 2004-2014

Cairns R, D8Iliels B, Brett}. MJA M8ICh 2016

.. ... + ... +

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+ADHD medications: Why?

Cairns et al. 2016

+Polydrug use

Polydrug use is the norm (88%) for amphetamine users

Use of nicotine, benzodiazepines, analgesics, alcohol is common

Cocaine and concurrent alcohol use is popular because their combination creates cocaethylene which has an extended half-life (from 30 minutes to 2 hours)

Most psychostimulant users tend to use other drugs to medicate the ‘come down’ (CNS depressants)

2004 National Drug Strategy Household Survey

3.0

2.0

-a- Methylphenidate

1.0 ....... oexamphetaimine

--- Modafini t

....... AcomoxetlnE!

0 ■ ■ ■ ■ ■ ■ ■ ■--- ■ ■

.004 2006 2008 2010 2012 2014

Year

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+

Amphetamine-Type Stimulant harms

Harm caused by drugs 100-maximum

Alcohol

Heroin

Crack cocaine

Methamphetamine

Cocaine

Tobacco

Amphetamine

c.annabis

GHB

Benzodia,epenes

Ketamine

Methadone

Mephedrone

Butane

Qot

Anabolic steroids

Ecstasy

LSD

Buprenorphine

Mushrooms

10 20 30

Source: "'Drug harms in the UK", by David Nutt et.at. Thel.anat

40

~ng ---md

• Harm to others • Harm to users

50 60 70 80

-

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21

+Number of deaths in which illicit amphetamines were detected post-mortem NSW by quarter 2003-2013

McKell & Burns NSW Drug Trends 2013 NDARC, Sydney 2014 p73, data source Forensic Toxicology Laboratory database, NSW Health

Amphetamine hospital episodes

R. McKetin & J. McLarenThe Methamphetamine Situation in Australia:A review of routine data sourcesNDARC Technical Report No. 172

4% 3%

•. 52%

□ Psychos is

l!I Dependence

la Harmful use

D Intoxicat ion

□ Withdrawa l

■ Other/unspecified

-

SCII.001.001.0021

22

+ STIMULANT PSYCHOSIS

Tactile hallucinations (formication or “cocaine bugs”)

Suspiciousness, paranoid delusions

Auditory hallucinations (“voices”)

Visual (‘snow lights”), gustatory, olfactory

Repetitive, compulsive behaviour common

Mood - fearful, agitated, often labile

Orientated but no insight

Violent behaviours

• Prevalence (Sydney)• 13% overt

• 25% ‘prepsychotic’

• Behavioral sensitization

• Reverse tolerance

• Kindling

• Cross sensitization

Ujike, H. Current Psychiatry Reports 2002, 4:177–184

McKetin, Rebecca, et al" Addiction 101.10 (2006): 1473-1478.

Stimulant psychosis

--METH psychOses (human)

iPhenotype

!Brain pathology

Re lapse

Psychoses/craving

Susceptibility to relapse of psychoses I

tttttttttt t t

Chronic schizophrenia

iPhenotype

!Brain pathology

Abuse of METH

Psychotic symptoms

Re-use Stressors of METH

Re lapse

Prodro~ ~nl'1n<N>nnl•s sensitization

period I

I I I Stressors

Stimulant use Discontinuance of medication

SCII.001.001.0022

23

+Toxicological

Generally: Sympathomimetic Syndrome

Seizures

Hyperthermia

HTN, atherosclerosis and ACS

Cerebrovascular event

Cardiomyopathy (reverse takotsubo)

Rhabdomyolysis

Acute liver and kidney injury

Specifically Amphetamines smoked, cocaine:

‘Crack lung’

MDMA: Hyponatraemia

+Executive and memory function impairments

Impairments in executive function (working memory, cognitive flexibility, inhibitory control) and visual memory functions

Amphetamine use disorder > opioid use disorder

No difference in current UD and abstinent ≥ 1 year Long term impairment

Ersche. Neuropsychopharmacology. 2006 May;31(5):1036.

2.5

;,, 2.0

~ ~ ~ 1.5 - 0 !? a. Q. ..

I 1 1.0 .. 0

~"' J 0.5

--o-- Amphetamine

• •>.• • Opiate

~ .. -- Control

O+---~-~--~--~--~-~ 1-move 2-moves 3-moves 4-moves 5-moves 6-moves

SCII.001.001.0023

24

+Risky behaviors

Injecting and sexChemsex

Blood Borne Viruses: HIV, HCV, HBV

Association with HIV independent of behavior and faster HIV progression

Injuries: MVA, burns

Child safety issues

+Impact on society

Significant rates of increase in: Poverty Domestic Violence Crime Assaults Absenteeism Maternal effects on foetus

SCII.001.001.0024

25

+Driving

Acute/chronic use increased dangerous driving RR 8.67 (95% CI 3.23 - 23.32) for crashes resulting in property damage,

RR 6.19 (95% CI 3.46 - 11.06) for injury accidents,

RR 5.17 (95% CI 2.56 - 10.42) for fatal accidents

Cognitive functions such as working memory and movement perception can be impaired

Prospective studies of driving impairment <10x less than used in real-life

Blood cut-off values proposed: 20 to 600 ng/mL for amphetamine,

20 to 200 ng/mL for methamphetamine,

20 to 300 ng/mL for MDMA

Busardo Current neuropharmacology. 2018 Jan 1;16(1):84-96

+Driving

878 cases with amphetamine only drug present in the blood samples of impaired drivers

73% of cases were judged as impaired

Ceiling effect above 0.27-0.53 mg/l

Busardo Current neuropharmacology. 2018 Jan 1;16(1):84-96

SCII.001.001.0025

26

+

Treatment

+Treatment seeking

5 year gap between problem use and treatment seeking

More likely to see treatment if: Riskier use (eg IV)

Seeking support for other problems (eg mental health)

Less likely to seek treatment if Women,

Born outside Australia,

Full-time employed

Non-injectors

Perception of use as non-problematic even if dependent and experiencing MA-related harm

B. Quinn et al 2013 Journal of Substance Abuse Treatment 45; 235–241; Quinn et al 2013 Int J Drug Policy 24(6) 619–623 ; Lee et al 2012 Advances in Dual Diagnosis 5(1)23-31.

SCII.001.001.0026

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+ Barriers to treatment access

Cumming. Drug and alcohol dependence. 2016 Nov 1;168:263-73.

+Treatment

Harm reduction

Withdrawal management

Relapse prevention

Humber of Ploponloo , ...... .,..,...,. &mltf ,tudlft pooled 11i-a1

11 _.., ts7 It (S< • &S) 322,1, ---20n,g ...... ~, 122 '° (2J. 51) J6 5 incontral d dlug u1•

1 .... • l ct.t•• lO~ en o-, 2 Ill &S) - •-551(5 S2 J

4 llNwJrt olhowlOKCIHltHUI'~ J02 21(U •2) ,,, ... 0..e 10 ktep US"'O MA ,,, ,, (11 27) 17""" ,e __ .,,,_

50(S<-'7) 221% --1 Lie ots - S24 J1121 • 3') 30911, ...

3 ,,, 12(7 11) 596 -"'"""'' 26, 21 (9 34) 402,1, -

10 W•t,,gl1tSI00'°"9 245 It (3 34) 502,1,•

11 T 122 1' 11-251 70 ,,.. --"'" m 31 (21 -SS) 42 0%

1l l.ogii•lc• (work._ chide..,. b•npod) 2 221 19(U-24) 31 5 ---""'-Y '_,.aolty,onc..,.. 2 l2T 511" s,1 2'5 ---15 F .. d llllltr«C )OJ JI (26 • 36)

,. .. ,. '"o«OOi ·- .,POOltd, ........ ••,,co001

SCII.001.001.0027

28

+Harm reduction

Needle syringe programs

Safe injecting rooms

Peer support workers/contact centre

‘Play packs’

BBV screening, vaccination and treatment

PREP/condoms

Pipe distribution (Canada)

+MA withdrawal

DSM-5 stimulant withdrawal: Dysphoria; fatigue; sleep disturbance; increased appetite;

psychomotor agitation or retardation; and vivid dreams

Crash Withdrawal

• 12-24h post cessation• Lasts 2-3 days• Hypersomnia/insomnia• Restlessness• Flat mood• Cravings• Aches and pains

• Lasts 2-4 weeks• Peaks day 7-10• Strong cravings, mood fluctuations,

irritability, restlessness, anxiety, agitation, fatigue, muscle tension,increased appetite, poor concentration.

SCII.001.001.0028

29

+

• 2009: 4 RCTs• Amineptine• Mirtazepine

• No evidence based treatments

• In-patient vsoutpatient

+Treatment

Psychosocial treatmentStandard careGroup work1:1 counseling Contingency managementEffect size 0.28

Pharmacological intervention

Treatment for amphetamine withdrawal (Review)

Shoptaw SJ, Kao U, Hoinz.orling K, Ling W

THE COCHRANE COLLABORATION ®

SCII.001.001.0029

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+

+Pharmacological intervention

D-amphetamine/Lis-d-amphetamine*

Modafinil

Methylphenidate

N-acetylcysteine

Buproprion

Varenicline

Risperidone

Naltrexone

Efficacy of psychostimula nt drugs for amphetamine a buse or d epe nde nce (Review)

Pin-z..Mana C, Gutell, X. Torren, M, Capella D, Fa.rre M

THE COCHRANE

' -i.) C_ochrane ~. Library

Psychosoc1al interventions for psychostimulant misuse (Review)

Minozzi S,Saulle R,0..CffKfflzo f,Amato L

BJCP British Journal of Clinical Pharmacology

Pharmacological approaches to methamphetamine dependence: a focused review Laurent Karila, 1 Aviv Weinstein, 2 Henri .Jean Aubin, 3

Amin e Be nyamina, 3 Mi chel Reynaudi- & Steven L Batkih

~ ) C_ochrane \:!, Library

Cognltive--behavioural treatment for amphetamlne--type stimulants (ATS)-use disorders (Review)

Harada T, TsutomiH, Mon R,Wilson DB

SCII.001.001.0030

31

+Treatment outcomes:MATES (NDARC) - Sydney

3 year study n=300 treatment entrants – 267 followed up

10% deceased/incarcerated at 3 years

Initial treatment: residential rehabilitation (n =126), counselling (n = 19) or detoxification (n = 51)

+Treatment outcomes:MATES (NDARC) MATES (NDARC)

a. 100

90

i 80

70 ~

i 60

• 50

f .. 30

20

10

8'WIIM J montM 1~,, 3 yHO

b. u u c

t l .4 ~ t:1.2 :!. i I

• 0~ t 0.6

0.4

0.2

Slset.-.e 3 months l yHt 3-;ears

100 ~ ,0

f 80 e 70 i 60

1~ : -s 30 l 20 0 10

j

100 5 90

j : ~ 60 ..__ 50

~ ~ 40 -s 30 l 20 0 10

] 0 8uellne

NotrHltnenl

O.todficat,on

)months ! year

Re$ident~I reNbihation

I

,,..,.

■ ]tdays/wffl

01· 2~ys/wet-k

0 les.s I han Wffkly

■ Noust"

SCII.001.001.0031

32

+Treatment outcomes:MATES (NDARC)

Outcomes: 53% re-entered drug treatment 34% had remitted from dependence without any further drug

treatment 13% were dependent on methamphetamine but had not returned

to drug treatment

Long-term treatment success: Longer treatment duration -counselling and residential rehabilitation

Poor outcomes More frequent use prior to treatment Injecting Psychosis/distress

McKetin Addiction. 2012 Nov;107(11):1998-2008.

+Treatment outcomes:Stimulant treatment program

McKetin. Drug and Alcohol Review 2013, 32, 80–87

I Baseline 3 months 6 months

(11- 105) (11 -86) P-value (11 -83) P-value

Methamphetamine use in the past month Any use (%) 79 53 <0.00 1 55 <0.00 1 Days of use (median) 6 I <0.00 1 I <0.001 Severity of dependence (median SOS score) 7 3 <0.00 1 2 <0.00 1 Dependent (%) 76 47 <0.00 1 39 <0.00 1

Other drug use in the past month (%) Tobacco 78 76 0.999 75 0.999 Alcohol 61 63 0.629 69 0.108 Cannabis 43 38 0.118 42 0.824 Heroin 6 7 0.999 6 0.999 Cocaine 12 2 0.0 16 7 0.508 Ecstasy 17 10 0.791 17 0.832

Health and social functioning in the past month (%) Physical health disability 27 17 0.076 23 0.263 Mental health disability 68 50 0.006 43 <0.00 1 Psychotic symptoms 26 12 0.024 16 0.108 Hostility 4 1 25 0.020 23 0.020 Injected 55 42 <0.001 46 0.001 Injected with used needle 7 6 0.999 2 0.688 Sexually active 70 65 0.383 71 0.999 Unprotected casual sex 22 16 0.581 27 0.648 Crime 30 24 0.701 29 0.999

SCII.001.001.0032

33

+Treatment outcomes:LGBTI

Lea. PloS one. 2017 Feb 16;12(2)

+

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Basel ine (n • 101) Follow-up 1 (n • 60) Follow-up 2(n • 32) OR(95% CI)

Methamphetarrine use in past 4 weeks

use (%) 82.2 < .001

Days used (median) 2 .001

SOS"""" (median) 5 < .001

SOS dependence (%) 92.1 78.3 71 .9

Other substance ~ t 4weeks %

Arr,alcohol 70.3 80.0 78.1 1.02 (0 .97- 1.06) .48

MadiLm- or higt-risk alcdlol• 15.8 20.0 18.8 0.94 (0 .90--0.99) .01

_[}ail),1-a:o 23.8 13.3 25.0 0.98 ~ 1.03 .50

cannabis 18.8 0.96 .90-1 .02 .15

Benzodiazepines 28.1 1.03(0.97- 1.09) .39

Cocaine 7.9 12.5 1.01 ~ 1.06 .70

Other iici augs 24.8 25.0 31 .3 1.00(0.93--~ .89 ectii dru USl8 in

Injected any drug 62.5

18.8

27.7 16.7 21 .9

26 16.5 0.04(0.01~ <.001

31 .3 0.83 .n-o.89 <.001

24 9.06 .87- 21.23 < .001

SCII.001.001.0033