EMCDDA Sep. 25th 2014Dr Saket Priyadarshi

Associate Medical DirectorNHS Greater Glasgow and Clyde

Vice-Chair, National Forum on Drug Related Deaths

Scottish Blues- Benzodiazepines and Drug Related Deaths in Scotland

Scottish Blues:

Benzodiazepines and Drug Related Deaths:

• Introduction to Benzodiazepine pharmacology, use and misuse

• Benzodiazepines and drug related deaths• Benzodiazepines and High Risk Drug Users• Supply and availability • Reducing benzodiazepine use in HRDUs

A class of psychoactive drugs which have a common structure (benzene and diazepine rings) and common effects.

Chlordiazepoxide discovered 1955Diazepam marketed since 1963.

Effects Prescribing Indications

• Anxiolytic Grief/Bereavement/InsomniaPanic/Fear of Flying/etc etcAnxiety disorders/Trauma

• Sedative Psychosis/Behavioural Problems

• Anticonvulsant Seizures• Muscle relaxant Back Pain

• Hypnotic / Amnesic Anaesthesia

DetoxificationShort or Long-acting?2-4 weeks maximumMax Dose 30mg Diazepam

Harms:

• Recreational Use/Abuse• Risk Taking Behaviour/Accidents• Paradoxical Stimulation

• Dependency• Emotional Blunting• Cognitive Impairment• Anxiety and Agoraphobia• Pregnancy

Overdose?

CN

S E

FF

EC

TS

INCREASING DOSES

Coma BARBITURATES

DepressionBENZODIAZEPINES

Anesthesia

Hypnosis

Sedation, Anti-Anxiety Possible selective

anticonvulsant & muscle-

relaxing activity

Felice Nava

BZDPs and DRD:

Implicated• Synergistic/potentiating effects• In combination with other depressants

Present• Found at toxicology but not directly involved in poisoning

but…• Contributed to risk behaviour?

Not an exact science!» Tox levels don’t help» Forensic pathology decision- subjectivity and

practice is variable

2012

Drugs Implicated/

Drugs Present % Implicated

Alcohol 75/176 42.6

Amphetamines 9/14 64.3

Anti-Depressants 48/176 27.3

Cannabis 0/67 0.0

Cocaine 12/24 50.0

Codeine 14/53 26.4

Diazepam 136/361 37.7

Dihydrocodeine 49/71 69.0

Ecstasy 3/5 60.0

Heroin/Morphine 168/200 84.0

Methadone 186/200 93.0

NPS 16/26 61.5

Tramadol 18/27 66.7

Likelihood of a drug that is present in post mortem toxicology being implicated in a drug death:(National Drug Related Deaths Database, ISD)

No. of BZDP drugs implicated in DRDs in Scotland

1996-2013 (NRS)

0

100

200

300

400

500

600

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Year

No

. o

f D

RD

s

All DRDs

Any Benzo

Diazepam

Temazepam

Drug Related Deaths in Scotland:(National Records Scotland)

% of DRDs with BZDPs implicated / present- 2011 and 2012

28.437.7

78.8 75.4

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

% Implicated

%Present

National Drug Related Deaths Database:Information Services Division

BZ

DP

S d

rug

s p

rese

nt

in b

od

y a

t P

ost

Mo

rte

m

05

01

00

15

02

00

25

03

00

35

04

00

Diaze

pam Tem

azep

amO

xaze

pam Phenaz

epam

Zopicl

one Nitraze

pam

Chlord

iaze

po...Alp

azola

mEt

izola

m

Benzo -

unspec

...

20

10

20

11

20

12

ND

RD

Dat

abas

e 20

10-2

012:

Combination Drugs found in Toxicology

with Diazepam present, 2010-2012

0%

10%

20%

30%

40%

50%

60%

Heroin &

Diazepam

Methadone &

Diazepam

Diazepam &

Alcohol

Heroin,

Diazepam &

Alcohol

Methadone,

Diazepam &

Alcohol

2010

2011

2012

Gender for DRDs with BZDPs present

78.2 78.4 75.3

21.8 21.6 24.7

0.0

20.0

40.0

60.0

80.0

100.0

2010 2011 2012

Years

% o

f B

ZD

P D

RD

Male

Female

Age Bands for DRD with BZDPs present

0.0

10.0

20.0

30.0

40.0

50.0

under 25 25-34 35-44 45-54 55 and

over

Age Bands

% o

f D

RD

s w

ith

BZ

DP

s

pre

sen

t

2010

2011

2012

Deprivation and DRDs with BZDPs present

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

SIMD1 SIMD2 SIMD3 SIMD4 SIMD5

Scottish Index of Multiple Deprivation (1=most deprived; 5= least

deprived)

% o

f D

RD

s w

ith

BZ

DP

s

pre

sen

t

2010

2011

2012

DRDs with BZDPs present known to

have used drugs prior to death

88.9 93.8 91.0

11.1 6.3 9.0

0.0

20.0

40.0

60.0

80.0

100.0

2010 2011 2012

Year

% o

f D

RD

s w

ith

BZ

DP

s p

rese

nt

yes

no

BZDPs are Class C Controlled Drugs, UK Misuse of

Drugs Act 1971

DRDs with BZDPs present who were prescribed ORT at time of

death

27.0 27.7

40.6

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

2010 2011 2012

Year

% o

f D

RD

s w

ith

BZ

DP

s p

rese

nt

Breakdown of

Benzodiazepine presence in

DRDs within NHS GG&C in

2012/13

28 15

123

87

36

36

0

20

40

60

80

100

120

140

160

180

200

2012 2013Implied Present but not implied Not present

BZDPs present and implied in DRDs in GG&C 2012 and 2013

65.70% 63.00%

15.30%10.90%

19.30% 26.10%

0%

20%

40%

60%

80%

100%

2012 2013

Not present

Implied

Present but not implied

Breakdown of Benzodiazepines

present in DRDs within NHS

GG&C in 2012/13

145

87

15

24

0

20

40

60

80

100

120

140

160

180

2012 2013

Temazepam

Phenazepam

Nitrazepam

Midazolam

Lorazepam

Etizolam

Diazepam

Chlordiazepoxide

Alprazolam

Breakdown of

Benzodiazepines Implied in

DRDs within NHS GG&C in

2012/13

19

6

3

8

8

0

5

10

15

20

25

30

35

2012 2013

Temazepam

Phenazepam

Nitrazepam

Midazolam

Lorazepam

Etizolam

Diazepam

Chlordiazepoxide

Alprazolam

In previous year

BZDPS and High Risk Drug Users:

• General population:– “one in seven British adults take benzodiazepines at some time

during the year and 1 in 40 take them throughout the year”– The proportion of women using prescribed psychotropics is double

the proportion of men. Drugscope

• HDRUs’:– Almost 60,000 PDUs in Scotland (opiate and/or benzodiazepines)

=Prevalence 1.71% of 15-64 years.ISD 2011

Scottish Drug Misuse Database, ISD

Benzodiazepines as an illicit drug by clients reporting to the SDMD, by

gender and main and secondary drug; 1995/96 - 2012/13

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

1995/

96199

6/97

1997/

98199

8/99

1999/

00200

0/01

2001/

02200

2/03

2003/

04200

4/05

2005/

06200

6/07

2007/

08200

8/09

2009/

10201

0/11

2011/

12201

2/13

Financial Year

% o

f th

ose

usi

ng

Dru

gs

at

an

In

itia

l

Ass

ess

me

nt

Male Main Drug

Female Main Drug

Male Secondary Drug

Female Secondary Drug

Benzodiazepine use and ORT NHS GG&C:

Site of Audit % Random Urines positive for benzodiazepines

Comments

Glasgow- Methadone and Suboxone

55% Women> MenNot age relatedInverse relationship to dose

Renfrewshire-Methadone and Suboxone

65% (non-prescribed bzdp)

Women>MenAssociated with anti-depressant prescribing

25% of ORT patients prescribed bzdps at any time either through specialist addiction service or GPs. (PIS)

But very variable practice: co-prescribing rates of 0-60% (GAS)

Sources and supply:

Prescribing Resources Team, Pharmacy and Prescribing Support Unit, NHS Greater Glasgow and Clyde

Prescribing Resources Team, Pharmacy and Prescribing Support Unit, NHS Greater Glasgow and Clyde

Macdougall-Heasman et al

Abertay University

Robert Gordon University

Police Scotland

Street Blues:

Guidance but no consensus!

Acknowledgements

• Dr Tony Martin- GG&C Addiction Services• Garry Hecht-NHS National Services Scotland, Information Services

Division• Andrew McAuley- NHS Health Scotland, Public Health Science

Directorate • Kenny Simpson- STOP Unit, Police Scotland• Denise McKeown – Forensic Medicine, Glasgow University• National Fatalities Unit• Dr Lee Middleton- Glasgow Addiction Services• Dr Claire Duncan- Renfrewshire Drug Services• Sean MacBride-Stewart- Medicines Management Resource Lead,

GG&C• Ben Tait and Lee Barnsdale- Information Services Devision• Felice Nava, Vice-Preident Italian Society of Addiction Medicine