Tuesday, 26th September 2017

Research Articles

Benzodiazepines


Benzodiazepines are a class of sedative/transquilliser drugs used in medical practice to treat anxiety, or induce sleep.  The class act on the ‘benzodiazepine receptor’ which regulates the rate of secretion of the inhibitory neurotransmitter GABA (gamma amino butyric acid) in the brain.

 

The class includes many well-known products, notably diazepam (Valium), temazepam, lorazepam (Ativan), and nitrazepam (mogadon).

 

Table 1 – Common Benzodiazepine & Related Drugs

Drug

Trade name

Duration of action

Equivalent Dose[i]

Max Daily Dose

Products

Cost/No of tabs

Alprazolam

Xanax

Short

250µg

3mg

250µg tabs

500µg tabs

£2.97/60

£5.69/60

Bromazepam

Lexotinil

Short-medium

2.5-3mg

30mg

6mg caps

No BNF entry

Chlordiaze-poxide

Librium (generic)

Long

15mg

200mg

5mg caps, 10mg caps

£6.21/100

£13.13/100

Clonazepam

Klonopins

Long

250µg

10mg

0.5mg tabs

1mg tabs

2mg tabs

No BNF entry

Diazepam

Valium (generic)

Long (>6hrs)

5mg

30mg

2mg tabs, 5mg tabs, 10mg tabs

89p/28  90p/28, 92p/28

Flurazepam

Dalmane

Long

15mg

30mg

15mg caps,

30mg caps

£6.73/30, £8.63/30

Flunitrazepam

Rohypnol

Medium-Long

0.5mg

2mg

1mg tabs

2mg tabs

No BNF entry

Loprazolam

Generic

Short

0.5mg

2mg

1mg tabs

£18.00/28

Lorazepam

Ativan (generic)

Short (<4hrs)

0.5mg

10mg

1mg tabs, 2.5mg tabs, 4mg amp

£5.42/20, £7.11p/20, 35p/1ml

Lormetazepam

Generic

Short

0.5mg

1.5mg

0.5mg tabs

1mg tabs

£56.25/30

£54.60/30

Midazolam

Hypnovel

Short

4mg

20mg

Injectable amps

4mg–85p

10mg–72p

Nitrazepam

Mogadon (generic)

Medium

5mg

10mg

5mg

98p/28

Oxazepam

Seranid (generic)

Short

15mg

120mg

10mg tabs, 15mg tabs

£4.85p/28, £5.16/28

Temazepam

generic

Short

10mg

40mg

10mg tabs,

£3.42/28

Triazolam

Halcion

Very short

150µg

0.5mg

125µg tabs

250µg tabs

No BNF entry

Zolpidem

Stilnoct

Short

10mg

10mg

5mg tabs

10mg tabs

£1.41/28

£1.46/28

Zopiclone

Zimovane

Short

7.5mg

7.5mg

3.75mg tabs

7.5mg tabs

£1.34/28

£1.35/28

Effects and abuse potential

All benzodiazepines have the potential to produce physical or psychological dependence when used in high doses or for a prolonged period of time, with doses of 100mg per day of diazepam or 300mg of chlordiazepoxide liable to cause physical dependence[ii].  While  it was common for these drugs to be prescribed on a long-term basis between the 1960s and 1980s, the abuse potential has restricted recommended prescribing regimes to a maximum of 2-4 weeks.  Short-acting benzodiazepines carry the greatest abuse potential.

 

Many long-term dependent users of Benzodiazepines were middle-aged or elderly women who acquired their dependency as a result of medical treatment before such dangers were fully-realised. Among ‘traditional’ groups of drug users, benzodiazepines are rarely the drug of first choice, but may be used in a secondary capacity by opiate users when opiates are unavailable, or by stimulant users seeking to ‘come down’.  There is a limited market for such drugs, as only a small proportion of those who had tried them reported non-prescription prices.

 

Side effects of benzodiazepines include Drowsiness and lightheadedness, confusion and ataxia, amnesia may occur, dependence, paradoxical increase in aggression, occasionally headache, vertigo, hypotension, salivation changes, gastrointestinal disturbances, rashes, visual disturbances changes in libido, amnesia, respiratory depression, urinary retention, blood disorders and jaundice; on intravenous injection: pain, thrombophlebitis and rarely apnoea.  Driving: drowsiness may affect performance of skilled tasks (e.g. driving).  Interactions: effect of alcohol enhanced Alcohol, Neuroleptics, Antidepressants - enhanced sedation.

 

Research on Benzodiazepine Consumption

There is little recent research as to the amounts of benzodiazepines consumed by heavy non-medical drug users.  Robson[iii] reported that a large majority of attenders at drug dependency units use benzodiazpines from time to time, “often in huge doses”, and that “the equivalent of 20-30 times the manufacturers recommended dose is not unusual” due to the development of tolerance.

 

IDMU Drug User Surveys: Data from IDMU survey respondents between 1999 and 2010 (total n=23637) found 11% of respondents reported having used ‘tranx’ or tranquillisers (Table 2), with 1.9% using regularly or daily (17.5% of those who had ever used).  As with other drugs, user ratings were significantly associated with the frequency of use, with regular users giving the highest ratings (higher than daily where dependency may be considered a downside) and never-used the lowest, daily users consumed an average of 95x tabs per week (13.5 tabs/day).

 

Table 2 – IDMU Drug Surveys – Tranx Summary Data

Frequency of Use

Rating

Tabs/week

Spending/mth

Frequency

No. of Reports

% of Total

% of Ever

No.

Mean

No.

Mean

No.

Mean

Experimental

1166

4.9%

44.7%

586

4.06

84

2.5

85

£5.63

Occasional

453

1.9%

17.4%

307

5.52

84

12.4

96

£36.31

Regular

327

1.4%

12.5%

234

6.84

96

17.5

98

£24.60

Daily

130

0.5%

5.0%

89

5.76

45

94.8

41

£73.69

Stopped Using

531

2.2%

20.4%

278

3.62

24

5.9

23

£4.22

Never Used

4968

21.0%

 

1854

1.74

9

12.9

12

£0.25

Blank

16062

68.0%

 

1571

2.04

23

7.8

28

£68.26

Total Ever

2607

11.0%

100.0%

1494

4.81

333

22.0

343

£27.68

Total Regular

457

1.9%

17.5%

323

6.54

141

42.2

139

£39.08

Base/Overall

23637

100.0%

4919

2.77

363

12.76

383

£29.78

 

Less than one percent of the overall sample (6% of ‘ever users) reported buying the drug monthly or more frequently, spending on average a modest £10 (median) to a maximum of £1200 per month on these drugs.  The majority of ‘never used’ and ‘blank’ respondents reported zero values for purchase and spending but both categories included a handful of individuals purchasing relatively large quantities of tablets (presumably dealers).  One quarter of tranx users obtained these drugs on prescription, 20% of whom supplemented their prescriptions with illicit tablets.  Excluding zero values (including spending by those prescribed the drugs), the consumption and spending levels at different percentiles were as follows (table 3).

 

Table 3 – Benzodiazepine Consumption Percentiles

Percentile

Tabs per week

Daily equiv

Monthly Spending

Bottom 5%

0.5

0.071

£1.25

Bottom 10%

1

0.143

£2.00

Bottom 25%

1.25

0.179

£4.00

Median (50%)

4

0.571

£10.00

Top 25%

10

1.43

£25.00

Top 10%

30

4.29

£100.00

Top 5%

100

14.3

£200.00

Top 1%

280

40.0

£1,200

Total

303

150

 

Only a handful of respondents who had tried tranquillisers have reported a regular pattern of use or spending on these drugs, the usage of the vast majority falling within prescribing guidelines, with a small minority of excessive users taking up to 14-40 pills a day.

 

As the paper surveys did not distinguish between different types of tranquilliser due to lack of space, the IDMU Web-surveys (2004-2010) allowed more detailed questions to be asked of respondents. Diazepam has been by far the most common tranquilliser reported by drug users, followed by Temazepam, Alprazolam, Lorazepam & Nitrazepam.  Average weekly use of, spending on and user ratings of the drugs mentioned by at least 2 or more respondents are shown in table 4.  Average consumption of Diazepam was just over 4x tabs per day, Alprazolam 6-7x tabs per day and Temazepam 11x tabs per day.

 

Table 4 – Consumption Indices by ‘Tranx’ type

Drug/Trade Name(s)

Total

Tabs per week

Monthly Spending

Rating

n

n

mean

n

mean

n

mean

Alprazolam/Xanax

48

34

46.88

30

£111.60

45

5.62

Amitryptiline/Triptozal

4

3

11.00

2

£0.00

4

3.75

Bromazepam/Lexotinil

2

0

0.00

0

£0.00

2

3.00

Chlordiazepoxide/Librium

3

2

29.00

0

£0.00

3

3.00

Chlorpromazine/Largactil

3

1

28.00

2

£12.50

3

6.33

Clonazepam/Klonopins/Rivotril

16

12

10.17

6

£11.83

15

6.60

Codeine-type preparations

16

7

29.77

7

£59.43

13

5.08

Diazepam/Valium

369

164

29.86

161

£43.49

331

5.68

Diphenhydramine/Benadryl

2

1

0.00

2

£11.00

1

7.00

Flunitrazepam/Rohypnol

3

1

25.00

1

£80.00

3

4.00

Hydrocodone/Vicodin

9

6

12.33

3

£41.67

8

7.13

Ketamine*

15

2

7.00

5

£11.00

12

5.25

Lorazepam/Ativan

30

16

6.17

8

£19.75

30

6.27

Methaqualone/Mandrax/Quaaludes

3

2

15.00

0

£0.00

3

4.67

Midazolam

1

0

0.00

0

£0.00

1

5.00

Nitrazepam/Mogadon

27

11

9.23

11

£12.14

26

5.69

Oxazepam/Seresta

5

1

18.75

1

£60.00

5

5.20

Oxycodone/Percocet

3

3

3.33

2

£7.50

5

5.60

Quietipine/Seroquel

3

3

10.67

3

£56.40

3

8.33

Temazepam/Jellies

82

30

78.43

32

£75.11

76

5.41

Triazolam/Halcion

3

1

0.00

1

£0.00

3

3.33

Zolpidem/Ambien/Stilnoct

5

3

3.33

1

£25.00

5

3.80

Zopliclone/Zimovane

17

10

12.48

8

£132.10

17

5.77

* Ketamine includes responses in the tranquillisers section only, ketamine liquid/powders were named drugs

Summary

Regular use of benzodiazepines has been discontinued in medical practice due to the risk of dependency.  Regular users of illicitly obtained benzodiazepines can develop tolerance to the effects so as to exceed the recommended maximum dose by a substantial margin.  Our survey data supports the evidence of Robson that daily tranquillizer users may take 20-30 times the recommended therapeutic dose of benzodiazepines.

 

 


 

[i] British National Formulary/MIMS/Wikipedia

[ii] Hoffman FG (1983) A handbook of drug and alcohol abuse.  Oxford University Press p125

[iii] Robson PE (1994) Forbidden Drugs.  Oxford Medical Publications p119-121