Heroin and OST*-related deaths from a forensic toxicology

perspective in France (Data from DRAMES 2015 and previous)

M. MALLARET, N. FOUILHÉ SAM-LAÏ, H. EYSSERIC,and French analytical toxicologists and forensic specialists

CEIP-Addictovigilance Grenoble (France)

EMCDDA Lisboa september 19th 2017

*Opioid substitution treatment

Results

2011 2012 2013 2014 2015

Evaluated fatalities 388 446 398 394 482

Included cases 316 346 328 283 395

Experts 36 41 32 38 45

Drug directly induced

fatalities 280 310 285 243 343

Drug indirectly induced

fatalities 36 36 43 40 52

Excluded cases 72 (19%) 100 (22%) 70 (18%) 111 (28%) 87 (18%)

Clinical data 2011

n = 316

2012

n = 346

2013

n = 328

2014

n = 283

2015

n = 395

Drug

dependence 79 % 89 % 81 % 73 % 74 %

Alcohol

dependence 34 % 36 % 41 % 27 % 31 %

Nicotine

dependence 7 % 7 % 9 % 10 % 11 %

Associated

diseases 36 % 30 % 34 % 40 % 41 %

Stage of

abuse

Known abuse 44 % 48 % 57 % 55 % 54 %

During

withdrawal ttt 7 7 6 6 3

During

substitution ttt 41 % 34 % 34 % 35 % 38 %

Naive patient 18 22 10 8 9

Drug directly induced fatalities

Nb of experts

482 cases

395 included cases

343 directly

induced

fatalities

52 Indirectly

induced

fatalities

OST directly induced fatalities

2011

n = 280

2012

n = 310

2013

n = 285

2014

n = 243

2015

n = 343

methadone

(57%)

120 (43%)

(11 naives)

(60%)

140 (45%)

(19 naives)

(54%)

108 (38%)

(8 naives)

(55%)

106 (44%)

(6 naives)

(41%)

104 (30%)

(8 naives)

buprenorphine

39 (14%)

47 (15%)

(3 naïves)

41 (14%)

(1 naive)

26

(11%)

2 naives

35

(10%)

methadone +

buprenorphine 1 0 4 2 1

level 1 of imputability (1.0 à 1.3)

OST directly induced fatalities

0

20

40

60

80

100

120

140

160

co-dominante 1,2 ou 1,3

prédominante 1,1

seule 1,0

Methadone induced fatalities

0

20

40

60

80

100

120

140

160

co-dominante 1,2 ou 1,3

prédominante 1,1

seule 1,0

121 F / 45 445 treated patients

2,7 F. / 1000 patients

[Met] median : 382 µg/L

[12 – 4000]

112 F. / 46 970 patients traités

2,4 F. / 1000 patients

[Met] médian : 445 µg/L

[58 – 3100]

140 F / 46 387 ttt patients

3,0 F. / 1000 patients

[Met] median : 377 µg/L

[61 – 3113]

108 F /48 635 treated patients

2,2 F. / 1000 patients

[Met] mdian : 358 µg/L

[26,6 – 6455]

105 F. / 51 630 trated patients

2 F. / 1000 patients

[Met] median : 519 µg/L

[34 – 3478]

40 F / 111 000 treated patients

0,36 F. / 1000 patients

[Bup] median : 3,2 µg/L

[0,34 – 709,8]

Buprenorphine induced fatalities

0

20

40

60

80

100

120

140

160

co-dominante 1,2 ou 1,3

prédominante 1,1

seule 1,0

47 F / 112 965 treated patients

0,42 F. / 1000 patients

[Bup] median : 4,0 µg/L

[0,2 – 112]

45 F. / 109 816 ttt patients

0,41 F / 1000 patients

[Bup] median : 3,5 µg/L

[0,1 – 185]

28 F / 113 616 treated patients

0,25 F / 1000 patients

[Bup] median : 3,2 µg/L

[0,5 – 152]

36 F. / 113 390 treated patients

0,32 F. / 1000 patients

[Bup] median : 4 µg/L

[0,7 – 60]

Illegal narcotics directly induced fatalities

2011

n = 280

2012

n = 310

2013

n = 285

2014

n = 243

2015

n = 343

heroin

89 (32%)

43 (15%)

106 (34%)

39 (13%)

124 (44%)

53 (19%)

114 (47%)

50

(21%)

212 (62%)

90

(26%)

cocaine 19 (7%)

28

(9%) 21

(7%)

21

(9%)

31

(9%)

heroin + cocaine 11 (4%)

8 (2,5%)

4 (1,5%)

12

(5%)

13

(4%)

cannabis 6 15 (5%)

31 (11%)

19

(8%)

36

(10,5%)

amphetamines 8 15 (5%)

14 (5%)

8

(4%)

30

(8,5%)

cannabis +

amphetamines 1 0 0 0 0

GBL/GHB 1 1 1 1 1

cathinones 2 2 11

(dt 2x+MXE)

ethylphenidate 1

ibogaïne 1

(+MDMA)

level 1 of imputability (1.0 à 1.3)

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

2011 2012 2013 2014 2015

Cathinones

Amphet

Cannabis

Héro+ Coc

Cocaïne

Héroine

Illicit narcotics direct fatalities 2011 à 2015

Pou

rcen

tage

du

nom

bre

de d

écès

dire

cts

Substances 2011

n = 280

2012

n = 310

2013

n = 285

2014

n = 243

2015

n = 343

morphine 23 19 19 10* 16*

tramadol 9 1 5 4 5

fentanyl 2 3 3 1 4**

pholcodine 3 5 1 3 3

codeine 8 6 5 5 3

oxycodone 2 2 2 1

dihydrocodeine 1

Total*** 39 36 35 23 32

Legal* Opioid induced Fatalities (OST excluded)

*known origin of morphine : 4 Skénan, 1 laudanum ** Unknown origin (black market) **several substances may be associated

Level 1 of imputability(1.0 à 1.3)

Discussion :

Bias :

1/3 of fatalities (Justice ; voluntary toxicological analysts)

Insufficiencies :

Anonymous data : no information ; drug prescription or black market ?

• Relative risk fatality /1,000 treated patients : X 6 with

methadone / buprenorphine

• Comparison methadone 60,000 users /heroin (107,000 users) (Janssen 2016) ?

• Which number of french morphine sulfate abusers ?

Conclusion :

Even if there are identified bias

• Opioids are still the main cause of fatalities in drug users

• Methadone is the main substance responsible of fatalities…

• Even if heroin fatalities increase again

• Buprenorphine (partial agonist) is less frequently responsible

• Morphine fatalities need to be more detailed

• Comparison with other french data

• Fentanyloids appear in France

Thanks to

Toxicologists experts C Abbara, JC Alvarez, A Barret, F Bévalot, J Bourgine, A Cesbron, M Chèze, F Deschamps, E Dailly, G Deffontaine, M Delage, M Deveaux, V Dumestre-Toulet, H Eysseric, A Fouley, Y Gaillard, C Ganière, P Guérard , G Hoizey, L Humbert, L Imbert, F Klintzig, C Le Meur, B Lelièvre, V Lelong Boulouard, AS Lemaire-Hurtel, M Loilier, H Marty, O Mathieu, N Milan, P Mura, AL Pélissier-Alicot, G Pépin, A Pineau, P Pok, E Roman, C Roussel, F Saint-Marcoux, T Salmon, E Saussereau, P Sibille, K Titier, A Turcant

Department NEURHO of ANSM

Members of Addictovigilance centers N Authier, A Boucher, A Daveluy, S

Deheul, S Djezzar, C Eiden, M Gérardin, R Le Boisselier, H Lomenech, A Roussin, M Spadari

Forensics ; Anatomopathologists F Abriat, C Bidat, Boyer, V Lopez

2011

n = 316

2012

n = 346

2013

n = 328

2014

n = 283

2015

n = 395

Sex

male 81 % 81 % 80 % 82 % 84 %

female 18,5 % 18,5 % 20 % 18 % 15,5 %

unknown 2 2 2

Age

mean 34,3 ans 35,1 ans 35 ans 36,1 ans 36,2 years

male 34,2 ans 36,7 ans 36,1 years

female 34,7 ans 33,5 ans 36,5 years

extremes 13-78 13-63 12-64 11-65 15-63