Benzodiazepine kinetics contribute to their differential abuse: RESULTS(1)

Benzodiazepine use data

Between 1978 and 1984, total benzodiazepine use was 248 ddd/ 1000 inhabitants/ day. Diazepam represented 38%ofto-taluse, followed by flurazepam (19%). Diazepam had been on the Canadian medications market for 21 years. In contrast, triazolam represented 10% of total use although it had been on the market for only six years (Table 1).

Benzodiazepine abuse data

Clinical characteristics of patients: As previously described, benzodiazepine abusers fall into two groups: those who use only benzodiazepines and multiple drug abusers (mda) . In the latter group, benzodiazepines may be the primary drug of abuse. Patients using benzodiazepines alone were older than mda but the female:male ratio was approximately 1:1 in both groups of patients (Table 2). All patients met dsm-iii-r criteria for sedative hypnotic dependence. The doses of benzodiazepines ingested by these patients were two to four times higher than the highest recommended therapeutic dose (eg, 40 mg for diazepam).

TABLE 1 Benzodiazepine use in Canada 1978-84

Benzodiazepine Defined daily dose (mg) Druguse* Years on the market % of total)’1
Diazepam 10 95 21 22
Triazolam 0.25 26 6 21
Lorazepam 2.5 26 7 18
Flurazepam 30 47 13 18
Oxazepam 50 23 21 5
Chlordiazepoxide 30 (oral),50 (parenteral) 19 24 4
Clorazepate 20 7.2 11 3
Bromazepam 10 1.6 3 3
Nitrazepam 5 2.3 4 3
Alprazolam 1.0 1.0 2 2

*Defined daily dose/1000 inhabitants/day; fBenzodiazepine use/years on the market: expressed as percentage of total (percentages do not sum to 100 due to rounding)

TABLE 2 Clinical characteristics of benzodiazepine abusers admitted to the Clinical Institute, Addiction Research Foundation 1978-84 (n=284)

Multiple drug abusers
Patients abusing only benzodiazepines (n=41) Benzodiazepines – primary drug of abuse (n=131) Benzodiazepines – nonprimary drug of abuse (n=112)
Age in years: mean ± SD (range) 37±11.6* 28±7.6 32±10
Sex – Male: n (%)/Female: n (%) 20 /21 77 /54 52 /60
Daily dose, mg/day1“: mean ± SD (range) 83±92* 167±241 113±205
Duration of use, months: mean ± SD (range) 76.4±60 (0.5-183) 59±56 65±57

*P<0.01 for patients abusing benzodiazepines only versus multiple drug abusers; ‘ Expressed as diazepam equivalents

Observed percentages of total abuse were as follows: diazepam 60%, oxazepam 9%, chlordiazepoxide 8%, lorazepam 7.5%, triazolam 6%, flurazepam 5%, alprazolam 2%,bromaze-pam 1%, clorazepate 1% and nitrazepam 0.5%.

Observed abuse versus expected abuse: To control for overall drug exposure, the use (ddd/ 1000 inhabitants/ day) of each benzodiazepine was divided by the number of years that each benzodiazepine had been on the Canadian market (Table 1). This quotient was used to estimate expected abuse and assumed that the likelihood of exposure to drug increases linearly over time.

This entry was posted in Benzodiazepine and tagged Benzodiazepines, Pharm acoepidem iology, Pharmacokinetics, Substance abuse.