Patterns of drug use among methadone maintenance patients in Los Angeles county

Sections

Abstract
Introduction
Method - POPULATION SAMPLE
COLLECTION OF URINE SPECIMENS
SCREENING METHODS
CONFIRMATION
QUALITY CONTROL
Discussion of findings
TABLE 1 - Results summary
TABLE 2 - Drugs found per specimen a
Conclusions

Details

Author: Naresh C. JAIN, Robert BUDD, Thomas SNEATTH
Pages: 45 to 53
Creation Date: 1977/01/01

Patterns of drug use among methadone maintenance patients in Los Angeles county

Director of Toxicology Naresh C. JAIN
Rancho Los Amigos Hospital, and Associate Professor, Departments of Pharmacology and of Community Medicine and Public Health, University of Southern California Medical School, Los AngelesToxicologist Robert BUDD
Supervising Toxicologist Thomas SNEATTH
Rancho Los Amigos

Abstract

Any evaluation of the effectiveness of methadone maintenance programmes in rehabilitating heroin addicts is inherently complex and subject to varied interpretations, both scientific and philosophical. From a scientific perspective, it is necessary to accumulate sufficient factual data to validate any hypothetical, conclusions. A retrospective survey of drug-use patterns among the, methadone maintenance population of Los Angeles County was undertaken in an effort to provide some such information. Over 5,000 urine samples from 730 patients were analysed for eleven drugs over a two-month period in 1975. Over 23 per cent of these samples were found positive for a drug other than methadone and 80 per cent of these positives were attributed to illicitly used drugs. The opiates (codeine and morphine) comprised almost 74 per cent of the drugs found while barbiturates and amphetamine and/or methamphetamine contributed 16 per cent and 10 per cent to the total, respectively.

Introduction

Methadone maintenance programmes represent an important, if controversial tool in the treatment of heroin-dependent individuals. Methadone, a synthetic narcotic analgesic similar in chemical structure to propoxyphene (DARVONR), is administered to the addicted patients as a substitute for heroin but in progressively smaller amounts until a dosage is established to maintain an individual. This gradual physical withdrawal from opiate dependence is accompanied by psychological counselling and medical monitoring.

Los Angeles County methadone maintenance programmes are highly regulated by California state and federal authorities and the distribution of methadone is strictly controlled. Each enrollee in a methadone programme is required to submit regular urine samples for drug testing. This urine testing serves a multiple purpose: (1) ensuring that the patient is actually consuming all of the methadone given him (i.e. not diverting it); (2) determining that the patient has not returned to heroin use; (3) monitoring levels of drugs administered for therapeutic purposes, including methadone; and (4) checking for the abuse of certain other drugs.

Over 5,200 urine samples from persons enrolled in methadone clinics were analysed by our laboratory in the autumn of 1975 for the following drugs: amphetamine, methamphetamine, allylbarbital, amobarbital, butabarbital, pentobarbital, phenobarbital, secobarbital, codeine, morphine, and methadone. Those specimens found negative for methadone were further analysed for its primary metabolite (2-ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine). Results show the relative frequency of occurrence of these drugs in the urine of persons in the methadone maintenance programme during that period.

Data of this type can be of considerable value to agencies responsible for analysing the effectiveness of methadone maintenance programmes. With as much controversy as has surrounded these programmes, it is indeed vital to accumulate objective data along potential parameters of evaluation. Those seeking insight into more pervasive questions, e.g., the rehabilitative potential of addicts through methadone therapy, may require comprehensive information in many subcategories such as patterns of miscellaneous drug abuse, incidence of methadone diversion, etc. in order to make proper judgements.

Method - POPULATION SAMPLE

The population group consisted of persons enrolled in Los Angeles County administered methadone maintenance programmes. These programmes are operated primarily on a voluntary basis although some individuals may be enrolled in compliance with legal or probationary conditions. Enrollees may be terminated from the programme for violation of methadone regulations, i.e. continued use of heroin, misuse of methadone, etc.

The methadone maintenance population for this survey was made up of approximately 730 persons, 73 per cent males and 27 per cent females. Ethnicity breakdown showed 44 per cent Mexican-American, 43 per cent white, 11.5 per cent black, and 1.5 per cent from other ethnic backgrounds (including Asians, Puerto Ricans, Filipinos). Age ranged from 19 to over 65, with the majority being between 26 and 45 years old. The length of time in the programme ranged from 1 day to well over 25 months; about 18 per cent had been in the programme less than 3 months and included de-tox patients, 20 per cent had been in for 12 months, 15 per cent for 13 to 24 months, and 37 per cent for longer than 24 months. Slightly over one-third of those tested were on probation and/or parole. Most (62 per cent) were employed or in a job-training programme, 20 per cent were unemployed; 10 per cent were homemaker/houseparents, and 8 per cent were disabled. Nearly 97 per cent of the patients were receiving some methadone each day with most (89 per cent) on a dosage of 20 to 80 mg per day. No one received more than 119 mg/day. Almost two-thirds of those tested had some form of methadone take-home privileges.

COLLECTION OF URINE SPECIMENS

Urine specimen collection was handled at the individual methadone clinics under the supervision of methadone clinic personnel. By state law, all persons enrolled are required to be tested at least weekly on a random time, short notice basis for methadone and morphine, and monthly for certain other drugs, however, more frequent testing is at the discretion of the methadone clinic supervisors. Specimens were kept under refrigeration from time of collection through analysis except while being transported to the laboratory. Results of analyses were reported back to the clinics within 96 hours from time of specimen collection, in compliance with state regulations.

SCREENING METHODS

Enzyme multiplied immunoassay technique (1) and radioimmunoassay (2, 3) were used to screen the urine samples for amphetamine, methamphetamine, barbiturates, methadone and opiates. Both of these methods are sensitive and reasonably specific for a particular class of drugs. During analysis, appropriate controls, blanks, and samples of known concentrations of the various drugs were included to ensure the accuracy and specificity of the screening systems.

CONFIRMATION

All urine specimens that indicated the presence of an opiate, barbiturate, or amphetamine and methamphetamine by the screening procedures were confirmed by an appropriate gas and/or thin layer chromatographic procedure (4-7). Those specimens screened negative for, or showing a low level of methadone were both confirmed and analysed for methadone metabolite by gas and thin layer chromatography (8).

QUALITY CONTROL

Double-blind state quality control specimens submitted with the methadone maintenance samples and blind federal quality control specimens have been analysed regularly with 100 per cent accuracy by the methods described. In addition, one double-blind intralaboratory quality control specimen was included for every 25 specimens tested and had to be analysed correctly before any results were reported.

Internal standards were included in all gas chromatographic analyses to ensure proper extraction of individual urine specimens and routine external controls were employed for all screening and confirmation procedures.

Discussion of findings

The over-all results of the survey are shown in table 1 which indicates that 97.7 per cent of the specimens were positive for methadone and/or methadone metabolite and that 23 per cent (or nearly one out of every four) were positive for one or more of the other drugs tested. The minimum detection level for all drugs was 0.5 ug/ml.

TABLE 1 - Results summary

   

Number

Percentage

A.
Methadone and primary methadone metabolite
   
 
Urine samples analysed
5 261 100.0
 
Samples positive for methadone
5 066 96.3
 
Samples positive for metabolite only (negative for methadone)
74 1.4
 
Samples negative for methadone and metabolite
119 2.3
B.
Drugs other than methadone and primary metabolite of methadone
   
 
Urine samples analysed
5 261 100.0
 
Samples positive for one or more drugs
1 211 23.0
 
Samples negative for drugs other than methadone and its metabolite
4 050 77.0
 
Samples positive for codeine and/or morphine
950 18.1
 
Samples positive for barbiturates
267 5.1
 
Samples positive for amphetamine and/or methamphe tamine
135 2.6

The percentage of persons positive for methadone and/or methadone metabolite (97.7) agrees quite well with the percentage of persons actually receiving methadone (96.9). The slight difference may be due to persons who have been taken off methadone after a programme of gradual reduction in dosage, but who are still eliminating some of the drug or its metabolite in their urine.

The 2.3 per cent of specimens negative for methadone are of special interest to the methadone clinic supervisors since although most may be due to persons just beginning the programme who have not yet received methadone at the time of specimen collection, some may come from persons who have illicitly diverted part or all of their methadone dose. Diversion is a problem of particular import as it has been implicated in both primary methadone addiction and methadone overdose deaths [ (9)] . It can be seen that 18.1 per cent of the samples analysed were positive for opiates (codeine or morphine), 5.1 per cent for barbiturates and 2.6 per cent for either amphetamine or methamphetamine. No attempt was made by our laboratory to distinguish amphetamine positives resulting from methamphetamine metabolism [ (10)] or morphine produced by codeine metabolism [ (10)] from the parent drugs. Similarly, no effort was made to identify codeine present from contaminated heroin [ (11)] or methamphetamine from contaminated phentermine as such.

Tables 2 through 5 tabulate data for the 23 per cent of the samples in which drugs other than methadone and its metabolite were found. These positive findings must be dealt with by the methadone clinic personnel to ascertain whether the results represent legitimate or illicit drug use. While about 20 per cent of the positive samples in this survey were found to represent prescription drugs, the other 80 per cent were "dirty" urines containing drugs not prescribed by a doctor. Thus, about 18 per cent of the total urine samples tested actually evidenced continued drug abuse.

TABLE 2 - Drugs found per specimen a

Number of different drugs found/specimens

Number of different combinations

Number of specimens

Percentage of specimens analysed

Percentage of positives

0
-
4 050 77.0
-
1 10 742 14.1 61.2
2 23 396 7.5 32.7
3 17 62 1.2 5.1
4 5 8 0.2 0.7
5 2 2
<0.1
0.2
6 1 1
<0.1
0.1
TOTAL
58 5 261 100.0 100.0
a

Other than methadone and methadone metabolite.

Table 2 shows the frequency of multiple drug findings in the specimens. Nearly 40 per cent of the positive specimens contained more than one drug and in one case, six different drugs were detected in a single urine specimen.

The relative frequency of occurrence for each of the drugs of interest other than methadone or its metabolite is indicated in table 3. Morphine made up 51 per cent of the drugs identified - found more times than all the other drugs combined - and opiates, as a group, made up 74 per cent of the drugs detected. This is to be expected to some extent since it is assumed that all persons in the methadone maintenance programme have an admitted opiate-use problem. The high percentage may to some extent reflect opiates still in the body due to use before entering the programme, but of special interest to the methadone maintenance personnel are those persons found to return to or continue opiate use while on methadone therapy. Such opiate positives may be grounds for terminating an individual from the methadone programme.

TABLE 3 - Frequency of occurrence for each drug a

Drug

Number of times found

Percentage of positives

Percentage of all samples analysed

Morphine
902 51.0 17.1
Codeine
406 23.0 7.7
Phenobarbital
186 10.5 3.5
Amphetamine
120 6.8 2.3
Methamphetamine
51 2.9 1.0
Secobarbital
39 2.2 0.7
Amobarbital
23 1.3 0.4
Pentobarbital
18 1.0 0.3
Butabarbital
13 0.7 0.2
Allylbarbital
10 0.6 0.2
TOTAL
1 768 100.0  
a

Other than methadone and methadone metabolite.

Table 3 shows that phenobarbital made up over 10 per cent of the drugs found. This is due not only to its frequent prescription and use, but to its slow excretion from the body. The five other barbiturates, amphetamine, and methamphetamine together made up only slightly more than 15 per cent of the drugs found. The relatively low findings for some of the barbiturates do not necessarily reflect their infrequent use but may be due to a characteristically more rapid rate of excretion from the body. As with any similar drug survey, our results must be interpreted with the caveat that rates of metabolism vary greatly, not only among the different drugs, but between individuals as well.

Table 4 illustrates the most common drugs and drug combinations reported out. It can be seen that morphine or codeine-morphine was by far the most frequent result reported.

As can be seen in table 5, some drugs such as codeine and to a lesser extent amobarbital, butabarbital, methamphetamine, and secobarbital, were generally found in combination with other drugs. Phenobarbital was the only drug to occur significantly more frequently alone than in combination with other drugs. A high combination percentage for a drug may be an indication of metabolism, common use of a pharmaceutical preparation containing more than one drug, treatment for abuse of one drug by prescription of a second drug, common therapeutic treatment with drug combinations, and/or abuse of two or more drugs for combination effects or counteraction of side effects.

Large concentrations of codeine were nearly always found with smaller concentrations of morphine, giving evidence for the partial metabolism of codeine into morphine (10), and large morphine concentrations were generally found with trace amounts of codeine, confirming the presence of codeine contamination in heroin reported by Yeh (11). Methamphetamine was always found with smaller concentrations of amphetamine, although sometimes the amphetamine concentration was too low to be reported as positive. This could support the theory of partial metabolism of methamphetamine to amphetamine (10). Methamphetamine was also frequently found in combination with its isomer, phentermine, which was not analysed for intentionally but showed up during the gas chromatographic analysis for amphetamine and methamphetamine. The methamphetamine was always at a much smaller concentration than the phentermine, suggesting that it is a contaminant in the phentermine. The high incidence of the amobarbital-secobarbital combination represents the use of a preparation containing both drugs (TUINALR). The frequency of other drug combinations can be attributed to the use of more than one drug, either therapeutically or illicitly.

TABLE 4 - Most common positive specimen results reported a

Drug

Number of times reported

Percentage of positive specimens

Morphine
488 40.3
Codeine and morphine
300 24.8
Phenobarbital
122 10.1
Amphetamine
63 5.2
Codeine
34 2.8
Morphine and phenobarbital
23 1.9
Amphetamine and methamphetamine
23 1.9
Codeine, morphine and phenobarbital
21 1.7
Others
137 11.3
TOTAL
1 211 100.0
a

Other than methadone and methadone metabolite.

TABLE 5 - Frequency of finding a drug alone versus finding it in combination with other drug(s) a

 

Only drug presents

In combination with other drugs

Drug

Number

Percentage

Number

Percentage

Allylbarbital
4 40.0 6 60.0
Amobarbital
4 17.4 19 32.6
Amphetamine
63 52.5 57 47.5
Butabarbital
3 23.1 10 76.9
Codeine
34 8.4 372 91.6
Methamphetamine
11 21.6 40 78.4
Morphine
488 54.1 414 45.9
Pentobarbital
6 33.3 12 66.7
Phenobarbital
122 65.6 64 34.4
Secobarbital
7 18.0 32 82.0
TOTAL
742 42.0 1 026 58.0
a

Not including methadone and methadone metabolite.

Conclusions

The problem of continued use of drugs other than methadone by patients on methadone maintenance programmes has been documented by a number of researchers. Perkins and Bloch (12) reported a positive rate of 20 per cent for a group of methadone patients in New York. Goldstein (13) reported that 30 per cent of methadone patients had positive urines for heroin use after six months in a maintenance programme and that after one year of treatment, positives continued to run between 5 and 10 per cent. Bourne (9) suggested that the incidence of positive urines for non-opiate drugs, principally amphetamines and barbiturates, generally runs between 5 and 10 per cent for most programmes and remains stable over time. Our survey corroborated this, showing a total of 7.4 per cent positive urines for barbiturates, amphetamine and/or methamlphetamine.

Our over-all positive rate of 23 per cent and "dirty" positive rate of 18 per cent for drugs other than methadone do not seem out of line with the previously reported figures, taking into consideration the fact that these figures represent a general methadone maintenance population undelineated by length of enrolment or other commonly used variables. For comparison purposes, it is interesting to note that a similar urine drug survey of a less selective population (separatees from the various U.S. military branches) showed a positive rate of only 0.6 - 3.0 per cent (14) over-all. The statistical selectivity of our sample population is obvious, of course, in terms of predilection toward drug abuse, and it is made even more selective by the fact that persons who continue to use drugs while in the programme may be tested more frequently. It is significant to point out that frequently abused drugs such as propoxyphene, cocaine, phencyclidine and methaqualone were not tested for. Had they been, our positive rate would have been even higher.

It was suggested by Bourne (9) that the degree of illicit drug use by methadone maintenance patients may he closely correlated with the calibre of management and quality of service offered by individual clinics and that, accordingly, positive rates for urines will vary consistently from clinic to clinic within a single programme. This interesting hypothesis will be approached in future analyses of our data.

References

001

EMIT Amphetamine Assay, Enzyme Immunoassay for Rapid Analysis of Amphetamine in Urine, Syva Corp., Palo Alto, Ca., 1973.

002

AbuscreenR , Radioimmunoassay for Barbiturates, Roche Diagnostics, Div. of Hoffman-LaRoche, Inc., Nutley, N.J.

003

AbuscreenR , Radioimmunoassay for Morphine, Roche Diagnostics, Div. of Hoffman-LaRoche, Inc., Nutley, N.J.

004

Jain, N.C., T.C. Sneath, R.D. Budd and W.L. Leung, Gas Chromatographic/Thin-Layer Chromatographic Analysis of Acetylated Codeine and Morphine in Urine, Clin. Chem. 21 : 1486-1489, 1975.

005

Jain, N. C., R. D. Budd, T. C. Sneath, D.M. Chinn and W. L. Leung, Mass Screening and Confirmation of Barbiturates in Urine by RIA/Gas Chromatography, Clin. Tox. 9:2 : 221-233, 1976.

006

Jain, N.C., T. Sneath, R. Budd, D. Chinn, W. Leung and B. Olson, Gas Chromatographic Separation of Allylbarbital and Butabarbital, J. Chromatog. 116 : 194-196, 1976.

007

Jain, N. C., T. C. Sneath and R. D. Budd, Rapid Gas-Chromatographic Determination of Amphetamine and Methamphetamine in Urine, Clin. Chem. 20 : 1460-1462, 1974.

008

Jain, N.C., W.J. Leung, R.D. Budd and T.C. Sneath, Thin-Layer Chromatographic Screening and Confirmation of Basic Drugs of Abuse in Urine, J. Chromatog. 115 : 519-526, 1975.

009

Bourne, Peter G., Methadone, Benefits and Shortcomings, Drug Abuse Council, Inc., 1828 L St. N.W., Washington, D.C., 1975.

010

Clarke, E.G.C., The Isolation and Identification of Drugs, Pharmaceutical Press, London, 1969.

011

Yeh, S.Y., Question About the Formation of Norcodeine from Morphine in Man, J. Pharm. Pharmac. 27 : 214-215, 1975.

012

Perkins, M.E. and H.I. Bloch, Survey of a Methadone Maintenance Treatment Program, Am. J. Psychiatry 126:10: 1389-1396, 1970.

013

Wilmarth, S.S. and A. Goldstein, Therapeutic Effectiveness of Methadone Maintenance Programs in the U.S.A., Geneva, World Health Organization, 1974.

014

Winter, P.E., C.J. Stahl, L.R. Goldbaum and A.M. Dominguez, Drug Excretion in the Urine of Military Separatees: A Pilot Study, J. Forensic Sci. 19: 317-324, 1974.