Journal of Substance Abuse Treatment, Vol. 10, pp. 371-382, 1993 074&5472/93 $6.00 + .

OO
Printed in the USA. All rights reserved. Copyright 0 1993 Pergamon Press Ltd.

RESEARCH REPORT

Compliance with Tuberculosis Treatment

in Methadone-Maintained Patients:
Behavioral Interventions

RONITH ELK, PhD,* JOHN GRABOWSKI, PhD,* HOWARD RHOADES, PhD,*

RALPH SPIGA, PhD,* JOY SCHMITZ, pm,* AND WILLIAM JENNINGS, MD?

*Substance Abuse Research Center, Department of Psychiatry and Behavioral Sciences;

TDepartment of Family Practice and Community Medicine,
University of Texas Health Science Center-Houston, Houston, Texas

Abstract - Tuberculosis has increased dramatically in the United States. Noncompliance with treat-
ment is high. The purpose of this investigation was to achieve compliance with prophylactic TB
treatment and simultaneously decrease drug use in a high-risk group of intravenous drug users.
Two studies were conducted. Study I: Subjects were 9 chronic opiate users who testedpositive for
tuberculosis and were placed on isoniazid (INH) and methadone. Methadone was dkpensed con-
tingent upon INH ingestion throughout. A within-subject, A-B design with contingency manage-
ment interventions on drug use was implemented. Results: Compliance with INH was 100% in 8
patients. Cocaine use remained high. Study 2: Two patients, meeting same criteria as Study 1, par-
ticipated in a within-subject A-B multiple baseline design. Methadone was dispensed contingent
upon INH ingestion throughout. Successive decreases in cocaine use were reinforced in the contin-
gent phase. Results: Compliance with INH was high. During contingency, both patients had over
40% cocaine-free urine samples compared with 0% at baseline. This investigation serves as a model
for achieving compliance with TB treatment in opiate users.

Keywords- tuberculosis (TB); compliance; substance abuse; methadone-maintenance; behavioral

interventions.

THE NUMBER OF CASES of tuberculosis (TB) in the

The work was conducted at the Addictive Behaviors Clinic of the United States has increased dramatically in recent years,
Substance Abuse Research Center (Mental Sciences Institute), De-
partment of Psychiatry and Behavioral Sciences, University of Texas
with over 25,000 people infected in 1991 (Barnes,
Health Science Center, Houston, Texas. Block, Davidson, & Snider, 1991; Snider & Roper,
Supported by U.S. Public Health Service/National Institute on 1992). This unprecedented increase is largely related
Drug Abuse Treatment Demonstration Grant DA-06143 to Dr. to the human immunodeficiency virus (HIV) epidemic
Grabowski; Grant FC-32057 from the City of Houston, funded by
(Reider, Cauthen, Kelly, Bloch, & Snider, 1989a; Reider,
the Center for Disease Control; and funds from Dr. Robert Guynn,
Chair, Department of Psychiatry and Behavioral Sciences, UTHSC.
Cauthen, Comstock, & Snider, 1989b; Center for Dis-
The authors acknowledge the valuable collegial support of the fac- ease Control (CDC), 199Oa), with other contributory
ulty of the SARC and the Department of Psychiatry and Behavioral factors such as an increase in homelessness, drug abuse,
Sciences. The systematic and outstanding efforts of both the research immigration from countries with a high incidence of
and clinical staff of the Addictive Behaviors Clinic in sustaining this TB, and crowding in housing among the poor (Snider
work are also gratefully acknowledged.
Requests for reprints should be addressed to Ronith Elk, Pho,
& Roper, 1992).
Department of Psychiatry and Behavioral Sciences, University of Tuberculosis, transmissible during the active phase
Texas Health Science Center, 1300 Moursund, Houston, TX, 77030. via the airborne route, has once again become a major
371
372
public health concern, particularly due to the emergence
of new multi-treatment-resistant strains (Marwick,
1992a; Snider & Roper, 1992; CDC, 1991). Significant
underdetection, and hence undertreatment, of tuber-
culin positivity in HIV positive patients has resulted
from the use of standard definitions of tuberculin pos-
itivity, grossly inadequate in these patients (Huebner,
Villarino, & Snider;1992). Treatment is lengthy, with
daily medications (usually Isoniazid [INH] or Rifam-
pin, pyrazinamide or ethambutol) taken over a six to
nine month period. Side effects include nausea, vom-
iting, neuropathies and hepatotoxicity. The thrust in
the United States has been dual: to identify and treat
those with active tubercular disease as well as those
with subclinical infection (about 5% to 10% of those
infected with the bacillus develop active disease, while
the rates for HIV positive patients are far higher
[Barnes et al., 19911).
Intravenous drug users have the highest risk of tu-
berculosis when compared to other HIV risk groups
(Graham et al., 1992; Theur et al., 1990) and may have
concomitant risk factors such as HIV and homelessness
(Torres, Mani, Altholz, & Brickner, 1990; Reichman,
Felton, & Edsall, 1979; CDC, 1989,199Oa). Treatment
of tuberculosis in this group is hampered by both poor
compliance (Rosenzweig, 1984; Freeman et al., 1987;
Marwick, 1992b) and the risk of hepatotoxicity, which
increases with age, liver disease and frequent alcohol
and other drug use (Van Scoy & Wilkowske, 1983;
Rosenzweig, 1984; Kopanoff, Snider, & Caras, 1978).
A primary consideration and concern in the treatment
of tuberculosis in a drug abusing population is the
combined toxicity of treatment medications with con-
tinued abuse of other agents.
Compliance with the TB treatment regimen is gen-
erally poor. It is estimated that between 20% to 80%
of all patients in the United States do not comply with
the regimen, and the noncompliance rate for patients
receiving prophylactic treatment at the City of Hous-
ton TB Control Clinics is 49% (Penrose, 1992). This
high rate of noncompliance has been identified as one
of the major factors contributing to the emergence of
drug-resistant disease as well as continued disease in-
fectivity (Snider & Roper, 1992). One of the greatest
challenges of tuberculosis control is to achieve com-
pliance with the full regimen. Identifying and imple-
menting techniques that enhance compliance is crucial.
Behavioral pharmacological research has demon-
strated the usefulness of methadone as a positive re-
inforcer than can be used to sustain treatment-oriented
behaviors (Grabowski, Higgins, 8z Kirby, in press).
Contingency-management procedures have been found
to be effective in reducing alcohol consumption (Miller,
Hersen, Eisler, & Watt, 1974; Griffiths, Bigelow, &
Liebson, 1978; Miller, 1975; Bigelow, Griffiths, &
Liebson, 1975) and illicit opiate and benzodiazepine
use by patients in methadone treatment for opiate de-
R. Elk et al.
pendence (Stitzer, Bigelow, & Liebson, 1979, 1980;
Hall, Cooper, Burmaster, & Polk, 1977). They have
also been effective in reducing cocaine abuse (Crowley,
1986; Anker & Crowley, 1982; Crowley & Rhine,
1985).
The purpose of this investigation was to increase
compliance with a prophylactic tubercular treatment
regimen and simultaneously decrease drug use, in a
group of tuberculosis positive intravenous drug users
applying for treatment for substance abuse. Several ap-
proaches were examined and the goal was to identify
behavioral intervention elements that would enhance
compliance. Advantages and disadvantages of each,
and the problems of TB treatment in drug abuse treat-
ment settings are described.
METHOD
Subjects
Subjects were 12 self-referred chronic opiate users who
applied for methadone-maintenance and other substance
abuse treatment. All met the DSM-III-R criteria for opi-
ate dependence, tested positive for tuberculosis (de-
scribed below) and were placed on INH. The procedures
in which subjects participated were approved by the
University of Texas Health Science Center Committee
for the Protection of Human Subjects and subjects pro-
vided consent following extensive explanation prior to
acceptance for participation in the study.
Tuberculin Screening Procedure
All subjects completed an extensive intake screening
procedure which included a wide range of behavioral,
psychological and medical testing. The latter includes
a full physical, blood workup and HIV and TB test-
ing. The Mantoux technique is used with a purified
protein derivative (5 tuberculin units PPD) cut-off of
10 mm induration to detect tuberculosis. In HIV posi-
tive patients the cut-off used is 5 mm (recently changed
to 2 mm), and HIV positive patients with no reaction
have anergy testing with two other antigens (mumps
and trichophyton), as was recently strongly recom-
mended by Graham et al. (1992). Patients with a pos-
itive Mantoux test are referred for a chest X-ray to
determine the presence of active pulmonary tubercu-
losis. In some cases, sputum cultures are also con-
ducted. Patients with current active symptoms of the
disease are treated in isolation during the infectious
state, but are eligible for reentry into the study after
the disease is no longer contagious, usually a 2 week
period. Results of the patient’s liver function tests are
screened (ALT and AST < 2 x normal) to determine
the patient’s ability to tolerate treatment with INH. In
view of the high risk factor of intravenous drug abuse,
INH is indicated in all age groups (CDC, 1990b).
Thirty-three of the 246 patients tested to date (13%)
TB Treatment Compliance 373

had a positive PPD, 20 of whom were patients with tervening days between the twice weekly visits. At
a primary diagnosis of opiate dependence. Eight of intake, and again at the beginning of the contingent
these patients were not treated with INH due to ele- phase, patients were given the list of drugs and other
vated liver functions or a documented history of prior conditions under which they would receive the aver-
treatment. The remaining 12 patients participated in sive consequences (dose decrease and discharge at ~40
the two studies reported here. mg) and the positive reinforcers (dose determination).
Each week, patients were informed of the previous
week’s urine results, as well as their methadone dose
STUDY 1
for the following week. At the end of each week, pa-
tients with drug-free samples specified their preferred
Design
dose for the following week.
In Study 1, self-adjustment of methadone dose was
used in a contingency management procedure, accord- Monitoring of Side Effects. Patients were monitored
ing to a within-subject, A-B design. This intervention very carefully throughout the study. INH toxicity was
was 24 weeks long, consisting of a 2-week baseline and evaluated by the nurse prior to administration of med-
a 22-week contingency phase. This study period is ication at the beginning of each visit. Liver function
consistent with the typical length of INH treatment. tests were conducted routinely on a monthly basis, or
Throughout the study, methadone was dispensed con- whenever any toxic side effects were reported. In cases
tingent upon INH ingestion. No contingencies were of reported side-effects, INH was stopped, and liver
placed on drug use during baseline. During the con- functions reviewed to determine acceptability of con-
tingent phase, two sets of contingencies were placed tinued INH administration.
on urine results:
1. Positive reinforcers: When both samples given in
Measures
a week were drug-free, patients could adjust their
methadone dose for the following week (within a Urine Drug Screens. Video-observed urine samples
range of 50 to 80 mg, in 5 mg increments). were collected twice weekly. Temperature indicators
2. Punishers: One or more drug-positive samples re- (TempTrends, Biosynergy, Inc., Elk Grove Village,
sulted in an automatic dose decrease of 5 mg of IL) were placed on each specimen bottle as an addi-
methadone for the following week. Drug positive tional check for specimen validity. Two procedures
samples at 40 mg resulted in an automatic discharge were conducted to determine the presence of drugs
from the study. Samples were considered drug pos- in the urine sample, thin-layer chromatography and
itive if they included: cocaine, amphetamines, opi- EMIT immunoassay. Quantitative results were deter-
ates, benzodiazepines, barbiturates, antipsychotics, mined for each cocaine-positive sample using the
antidepressants and antihistamines. Missed visits, EMIT procedure.
stalls, invalid urine results and the absence of meth-
adone were also considered drug-positive. Patients Breath Alcohol Levels. The presence of alcohol was
who missed scheduled visits were able to attend the measured using the Alto-Sensor III (Intoxemeters,
clinic on another day to receive INH and metha- Inc., St. Louis, MO). BAL levels of >O.l were con-
done. However, they were not permitted to select sidered positive.
their dose for the following week even if their urine
samples were drug-free. Intervention on alcohol Side-Effects. At each visit, the nurse reviewed and re-
use paralleled that of other drug use, with the ad- corded a list of possible side-effects of INH with the
dition of daily disulfirum administration to patients patient. These included symptoms of nausea, vomit-
with >2 positive Breath Alcohol Levels (BAL) in ing, skin rash, numbness or tingling of fingers, blur-
a month. ring of vision, jaundice and convulsions.

Compliance with INH. Ingestion of INH was recorded

Procedure
Administration of Medication. Patients attended the
clinic twice a week and received INH (900 mg), meth-
adone (baseline of 60 mg) and Vitamin B6 at each visit.
The latter was prescribed as a supplement in this po-
tentially malnourished group since INH increases the
excretion of Vitamin B6 and patients with chronic al-
cohol or drug use may be predisposed to neuropathy.
All medications were ingested in view of the dispens-
ing nurse. Patients received “take-homes” for the in-
at each visit by the nurse. In case of non-ingestion, rea-
sons for this (e.g., patient refusal, non-dispensing due
to reporting of side-effects) were recorded.
Data Analysis
Group and within-subject comparisons were conducted
to evaluate INH compliance and drug use. Differences
between group and individual proportions were evalu-
ated using the Z-test. Two-tailedp values are reported.
374 R. Elk et al.

Results fourth patient reported nausea and vomiting intermit-

tently over the entire 4 month period. He was moni-
Subjects. Since there is an overlap in patients who par-
tored twice weekly, and as his liver functions were <2
ticipated in the two studies, identifying data for all 12
times elevated, he was maintained on INH. In one pa-
patients, from both Study 1 and 2 are presented in Ta-
tient, INH was terminated after 15 weeks due to raised
ble 1. None of the patients had active symptoms of tu-
liver functions (ALT and AST > 3 times normal) al-
berculosis. Two were HIV positive, with one patient
though the patient reported no side-effects.
having being diagnosed with AIDS. Whilst two thirds
were unemployed, only one patient was homeless.
Compliance with ZNH. In 8 of the 9 patients, INH
The remainder of the data presented here are for
compliance was 100%. Compliance for Patient #122
the patients who participated in Study 1. Since one pa-
was 94%. Except for instances related to medically ad-
tient dropped out during baseline, data presented are
vised withholding of doses, or agreed-upon absences
based on 9 subjects.
from the clinic, there was only one instance of failure
to ingest INH (by Patient #122, who reported long-
Patient Retention. Patient retention data are presented
term nausea and vomiting). Unfortunately, there were
in Figure 1. Only 1 patient remained in the study until
3 occasions in which patients were not dosed due to
its completion (end of INH treatment), and one other
a computer programming error.
patient remained until INH was stopped (week 15).
The remaining 7 patients were discharged from the
Alcohol Use. Only three patients registered a BAL
study due to drug-positive urines. The mean duration
of ~0.1, each on one occasion only. None of the pa-
of study participation for these 7 patients was 7 weeks,
tients met the criteria for placement on disulfiram.
ranging from 6 to 20 weeks.

Drug Use.
Side Effects. Four patients experienced side effects,
Grouped data: Mean drug use in baseline and con-
particularly at the beginning of treatment. In three of
tingency for all patients is illustrated in Table 2. The
the patients, these were reported on only one or two
proportion of drug positive urine screens decreased
occasions, and included headaches, dizziness, numb-
during the contingent phase (p < 0.05). This de-
ness/tingling in the fingers and ringing in the ears. The
crease was also seen when examining the propor-
tion of cocaine positive urines. There were no
differences found in the proportions of opiate pos-
TABLE 1 itive and “other” positive urine screens between
Description of Patients (Study 1 and 2) baseline and contingency conditions. Figure 2 illus-
trates drug use patterns over time. During the ini-
Variables N %
tial months of treatment, the percentage of drug
Sex Male 9 75% positive urine samples declined in response to con-
Female 3 25% tingency. The slight increase in cocaine use after
month 3 is due mainly to the increase in cocaine use
Race White 3 25%
Black 5 42% of Subject #177.
Hispanic 4 33% Single subject data: The patterns of drug use for
individual patients are illustrated in Figure 3. There
Age R 41
Range 27-50

Opiate use in Opiate use

last month (non-methadone) 11 92%
TABLE 2
IV Route 10 91 %a
Mean Drug Use: Baseline and Contingent Phase (Study 1)
Cocaine use Cocaine use 9 75%
in last month IV Route 9 1 OO%b Urine i! p value
Samples BASELINE CONTINGENCY Score (e-tailed)
HIV status Positive 2 17%

Living With Family 10 83% # of

arrangements Alone 1 8% samples 33 198
Homeless 1 8% Drug
positive 61% 38% 2.47 0.0068
Current Full-time 2 14% Cocaine-
employment Part-time 2 17% positive 52% 31% 2.311 0.0104
Irregular work/ Opiate-
Unemployed 8 66% positive 33% 21% 1.567 .13
“Other”-
aof opiate users positive 0% 8% 1.635 .lO
bof cocaine users
TB Treatment Compliance 375

I III III I I I I I I I II III III I I I

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
WEEK IN STUDY
FIGURE 1. Patient retention (Study 1).

BASELINE ; MONTH I MONTH2 MONTH3 MONTH 4 MONTH5 MONTH6 MONTH7

#SAMPLES33~ a3 52 30 20 16 8 2
#PATlENTS 9 ! 9 9-6 54 43 $2 1 1

DRUG POSITIVE COCAINE POSITIVE OPIATE POSITIVE YlTHEW POSITIVE

_____ ___ ... ..... ... .... ----

FIGURE 2. Drug use patterns (Grouped data) (Study 1).

376 R. Elk et al.

AH- 194
- 8:c

::w :f

l - : -*

r-: *\ I
’ *\
I I
, d _....! ______ -.

COCAINE
__ + OPIATE
. . . + MEAN METHADONE
- DOBE

B-Baeelh c - Culflngency

FIGURE 3. Drug use patterns (Single-subject data) (Study 1).

TB Treatment Compliance 377

were no statistically significant differences between line were the same as for the first intervention, that
drug use at baseline and contingency for any of is, there were no contingencies for positive urine
the individual patients. Two patients (#178, 134) screens. Two conditions determined entry into the con-
had drug-free samples except for brief time periods. tingency phase: time in baseline was varied in order
These were the two patients who were not discharged to control for temporal effects, and entrance into the
from the study. Four patients (#176, 204, 223, 77) contingent phase was based on evidence of cocaine-
had cocaine-positive samples 100% of time, with positive urine samples. The shaping procedure, of
no difference between baseline and contingency. reinforcement of successive approximations, was im-
Two of these patients also used opiates (neither plemented on cocaine use at the contingent phase. The
#176 nor #223 had a statistically significant decrease reinforcement consisted of: (a) A monetary reinforcer
in opiate use during the contingent phase compared ($10) for a decrease in the quantity of cocaine from
to baseline). Three patients had varying patterns of that of the previous day, with an additional bonus
drug use: patient #179 used opiates 50% of time, ($15) if such a decrease occurred on all 5 days of the
with no decrease during contingency. He was dis- week. (b) Cocaine-free samples were reinforced with
charged from the study and placed in another study $15, with an additional bonus ($20) if all samples for
(not reported here). Upon transfer, without the im- that week were cocaine-free.
plementation of any contingencies, he stopped opi-
ate use altogether and remained drug-free for the
remainder of the INH treatment (13 weeks). The Procedure
remaining two patients had more erratic drug use:
Administration of Medication. Patients attended the
patient #122 initially decreased opiate use, but later
clinic 5 days a week and received methadone (60 mg)
had periods of use and cessation. After an initial
at each visit. The remaining 2 doses were dispensed as
increase in cocaine use in the contingent phase, pa-
“take-homes”. INH (900 mg) and Vitamin B6 were dis-
tient #177 decreased and then ceased cocaine use,
pensed twice weekly.
but reinitiated use at week 12. The patient’s urine
samples in the first 16 weeks were opiate-free, while
Monitoring of Side-Effects. Measurement of side-
in the last 3 weeks in study, opiate use increased for
effects was identical to Study 1.
2 weeks, and then ceased.

Measures
STUDY 2
Urine Screens. Urine samples were collected daily.
Results from Study 1 suggest that, in general, most pa-
Semi-quantitative analyses were conducted using the
tients were compliant with the INH treatment regimen.
EMIT procedure. This is analyzed with a stylized pre-
A somewhat unexpected finding was the high rate of
prepared curve, rather than repeating the curve for
supplemental drug use during methadone treatment,
each sample. The results are computed manually using
resulting in gradual dose reductions and discharge.
interpolation based on the standard curve. The mar-
Thus, a second study was designed to address this
gin of error using this method is approximately 15%.
unacceptably high discharge rate. This study targeted
This margin of error was factored into the calculations
cocaine use only, the drug most frequently abused and
when determining whether decreases in cocaine levels
least responsive to the contingencies in the first in-
had occurred. Urinalysis results were available within
tervention. A shaping procedure was instituted, with
20 to 30 minutes and, during the contingent phase,
reinforcement for successive decreases in the quantity
subjects received immediate feedback about the level
of cocaine, and an additional reinforcer for cocaine-
of cocaine in their urine sample. If conditions of the
free samples. If all 5 samples per week had a level of
contingency were met, payment was immediate, with
cocaine less than that of the previous day, or were
the bonus being paid on the last day of the week.
cocaine-free, patients received an additional bonus.
Using the same methods as in Study 1, Breath
Reinforcement was immediate. No aversive contin-
Alcohol Levels were collected daily, side-effects were
gencies were implemented on drug use.
elicited and compliance with ZNH was recorded at each
visit.

A multiple-baseline across subjects design (with inter- Data Analysis

ventions applied at different times across subjects) was
used. This design is particularly appropriate when a The t-test and Z-test statistics were used to examine
return to baseline conditions would place the subject differences in drug use between baseline and contin-
at risk (Hersen & Barlow, 1976). Conditions in base- gency phases.
378 R. Elk et al.

Results again. All other urine samples had accurate temperature

Subjeccts. Three subjects participated in this study, one
of whom (#223) had also participated in Study 1.
Patient Retention. One patient dropped out at base-
line. This patient had been drug-free throughout his
participation (9 weeks) and therefore no contingencies
had been implemented on drug use. Of the two subjects
who entered the contingency phase, both remained in
treatment until the INH treatment was complete (13
weeks and 27 weeks respectively).
Side Effects. INH was withheld for several days due
to reporting of a skin rash in patient #223, but upon
reinstatement of treatment, the symptoms did not re-
appear. The second patient reported no side-effects.
Compliance with ZNH. Patient #295 had 100% com-
pliance with INH, with no difference between the base-
line and the contingent phase. During baseline, patient
#223 had a compliance rate of 43%. This low rate was
due to the patient’s non-attendance at the clinic. Fol-
lowing the implementation of a contingency specify-
ing the patient would be discharged if she missed more
than three scheduled appointments per month, the pa-
tient’s rate of attendance and concomitant compliance
with INH increased to 97%. Neither patient refused
INH ingestion at any clinic visit.
Drug Use. Both patients had at least one detected
occasion of tampering with urine samples. This was
determined using the TempTrend, and patients were
instructed of discharge consequences if this occurred
readings, and no tampering was observed on camera.
Nevertheless, these patients were subsequently observed
directly by a staff member for the duration of their
participation in addition to video observations. The 3
tampered samples were excluded from the analyses.
Quantitative levels of cocaine (ng/ml) over the dura-
tion of the study are illustrated in Figure 4.
Several trends are apparent: Both patients had ex-
tremely high levels of cocaine at baseline, and both
decreased cocaine use after several weeks in the con-
tingent phase. Both patients were able to maintain suc-
cessive cocaine-free samples. Patient #223 did this on
one occasion (with 11 consecutive cocaine-free sam-
ples), whilst #295, who was in the study for a longer
period, did so on four occasions (14, 13, 11, and 7 con-
secutive cocaine-free samples). The lengths of time
between these periods varied. Overall differences be-
tween baseline and contingent phases are illustrated in
Table 3.
There was a statistically significant decrease in the
mean quantity of cocaine for both patients. Approxi-
mately a quarter of both patients’ urine samples had
levels of cocaine lower than on the previous day, with
no differences between baseline and the contingent
phase. However, during the contingent phase, each
patient had over 40% cocaine-free urine samples, com-
pared to 0% at baseline (p < 0.002). While contingen-
cies were not implemented on other drug use, both
patients had a substantial decrease in their secondary
drug of abuse: #295 decreased benzodiazepine use from
92% at baseline to 30% in contingency (p < O.OOl),
and #223 decreased opiate use from 95% in baseline
to 9% in contingency (p = 0.001).

TABLE 3
Drug Use: Basellm, and Contingent Phase (Study 2)

x295 #233

Ba Cb t test P BB Cb t test P

No. samoles 13 114 22 31

R quantiiy cocaine
(wlml) 219,729 59,218 4.015 <0.0025 283,288 29,521 4.8556 <0.0025
Range (2,063-550,983) (O-649,1 36) (2,498-879,135) (O-169,561)

BB Cb Z test P Ba Cb Z test P

No. cocaine-negative
samples 0 (0%) 56 (49%) 3.4 0.002 0 (0%) 14 (42%) 3.67 0.001
No. consecutive
cocaine negative
samples 0 (0%) 14(12%) 1.35 NS 0 (0%) 11 (33%) 3.1 0.0013
No. opiate-negative
samples 13 (100%) 111 (97%) 0.56 NS 1 (5%) 28 (91%) 6.182 0.0001
No. benzodiazepine-
negative samples 1 (8%) 78 (70%) 4.33 0.001 22 (100%) 26 (85%) 1.97 0.023

aBaseline.
bContingent phase.
TB Treatment Compliance 379

q A 0 A A *
I I I I II I I I I I I l l Ill 11 1 l I I l

-I

5 1,000,m
#223
!i
3 100,000

8
0 10,000

1,000

100

10

0
4 A+** * DO A

1 2 3 4 5 6 ? 8 0 1011121314151617181Q202l2222#25~2725
WEEK IN STUDY
(5 samples/week)

Coc@ve Holiday St@ No Hhow Tamper@ Urine _____

Mean

FIGURE 4. Quantitative levels of cocaine (Single-subject data) (Study 2).

DISCUSSION to minimize the considerable risks of hepatotoxicity in

patients who may already be compromised. The goal
Two critical issues must be addressed in efforts to treat is to identify a combination of behavioral intervention
tuberculosis in drug-abusing patients. First, it is cru- elements that balance the objectives. Studies of treat-
cial to establish compliance with the TB medication ment of a wide variety of illnesses indicate that com-
regimen. Second, this must be done with every effort pliance rates are generally very low (40 to 70%), and
 380 R. Elk et al.

compliance with preventive procedures is even lower tant use of other drugs during INH treatment. Pa-
(Gatchel & Baum, 1983). The extremely high compli- tients’determination of methadone dose has been found
ance rate with the INH regimen found in these two by previous research to be effective in decreasing opi-
studies, clearly demonstrates the efficacy of methadone ate use (Stitzer et al., 1980). However, the simultane-
as a reinforcer. Liebson, Tommasello, and Bigelow ous implementation of this positive reinforcer with the
(1978) had previously demonstrated the effectiveness aversive consequences, proved ineffective in decreas-
of methadone as a reinforcer in enhancing compliance ing drug use, especially cocaine.
with disulfiram in methadone-maintained patients with Although the sample size in the second study is very
concomitant alcoholism. The direct comparison of two small, both patients demonstrated similar patterns.
phases-methadone dispensed non-contingent upon They both responded to the contingency by decreas-
INH ingestion with it dispensed contingently- would ing cocaine use substantially, and maintaining cocaine
have enabled a more direct comparison of the effec- abstinence for several weeks at a time. Other drug use
tiveness of methadone as an independent variable. also decreased substantially in the contingent phase.
However, this was not possible for medical-ethical It is not possible to determine whether it was the im-
reasons. mediacy of the reinforcer, its magnitude, the reinforce-
It is likely that non-specific treatment factors also ment of successive decreases in cocaine use, or the
contributed to the extremely high compliance rate. combination of these factors that contributed to the
These include the dispensing of INH at the same clinic decrease and cessation of cocaine use. Systematic re-
where methadone is received, the clinic atmosphere, search is needed to both replicate and separate these
the extensive education about tuberculosis and INH, aspects. Nevertheless, each factor has merit. While the
as well as the detailed twice-weekly monitoring. This interpolated semi-quantitative urinalysis is not as ac-
is borne out by the subsequent follow-up data on the curate as the standard, lengthier method, the immediate
4 patients discharged to the City clinics. Three of these availability of these results permits direct consequation
patients were required to attend the City TB Control of the target behavior. Immediacy of delivery of rein-
clinic monthly, to receive a supply of medication. The forcement has been widely demonstrated to be more
only patient who complied fully was required to attend effective than delayed delivery. The reinforcement of
the clinic on one occasion only. It is logical to deduce an initial decrease in cocaine use enhances the proba-
therefore, that drug abuse clinics are ideal sites in bility of patients being reinforced, and the additional
which to oversee INH therapy in a drug abusing pop- payment for providing successive decreases or cocaine-
ulation, as was recently suggested by Haverkos (1991). free samples acts as a further incentive. Both patients
It should also be recalled that some patients are con- reported that in addition to receiving payment for com-
sistently compliant with minimal interventions, re- plying with the requirements, the weekly bonus was a
sponding to verbal instructions and education. This major reinforcer.
parallels compliance by other patient groups, includ- The importance of treating drug use in this popu-
ing drug abusing pregnant women who terminate drug lation cannot be underestimated, particularly since the
use for the duration of their pregnancy (Kirby et al., majority of patients in this group administered both
1992). While this factor may have played a part in opiates and cocaine intravenously. While there has
achieving compliance with patients attending the clinic, been an increase in cocaine abuse among methadone-
it no longer held true once they left. Finally, while there maintained patients (Grabowski, Elk, Rhoades, Cowan,
is generally a high clinic attendance rate for metha- Schmitz, & Kirby, submitted), there is little evidence
done-maintained patients, the requirement of only two of consistently effective treatments. In one effective
visits per week in which INH and methadone were dis- study of cocaine abuse treatment, Higgins et al. (1991)
pensed (in the first study) may have also played a part utilized, inter alia, incentives of increasing value for
in achieving the excellent patient attendance and con- continuous abstinence from cocaine. However, review
comitant compliance. of the literature has revealed no other study of the
While drug use in the first study was disappoint- treatment of substance abuse that has utilized the shap-
ing, results in the second are promising. Overall drug ing procedure of successive approximation, despite its
use, specifically cocaine, decreased significantly during obvious effectiveness in laboratory studies. Systematic
the contingent phase in Study 1. However, this was in- replications of this procedure are continuing at our
sufficient to prevent patients meeting the criteria for clinic.
discharge. Despite previous researchers’ findings that A potential criticism of the intervention on drug use
aversive contingencies often lead to a greater drop-out is that the behavioral treatment depends on costly in-
than do positive reinforcers (Stitzer, Bickel, Bigelow, centives. However, the cost of providing the treatment
& Liebson, 1986; Iguchi, Stitzer, Bigelow, & Liebson, is a maximum of $95 per week. Such costs are mini-
1988), we nevertheless implemented the discharge con- mal in comparison to the cost of inpatient hospital-
sequence. This was done primarily due to our concern ization or that of medical care for diseases such as
for the high risk of hepatotoxicity with the concomi- tuberculosis and AIDS, both common risk factors in
TB Treatment Compliance 381

intravenous drug-using patients. Budney, Higgins, Crowley, T.J., & Rhine, M.W. (1985). The substance use disorders.
Delaney, Kent, & Bickel (1991) and Higgins et al. In R.C. Simons & H. Pardes (Eds.), Understanding human be-
(1991) suggest that community businesses and organi- havior in health and illness (pp. 730-746). Baltimore:
Williams/Wilkins.
zations may be willing to donate items or services to Freeman, H.E., Blendon, R.J., Alkin, L.H., Sudman, S., Mulli-
offset the cost to clinics. Finally, while most drug treat- nix, C.F., &Corey, C.R. (1987). Americans report on their ac-
ment centers may not have access to laboratories that cess to health care. Health Affairs, 6, 6-18.
are able to conduct immediate urinalyses, patients Gatchel, R.J., & Baum, A. (1983). An introduction to health psy-
meeting criteria could be reinforced at their next visit. chology. New York: Random House.
Grabowski, J., Elk, R., Rhoades, H., Cowan, K., Schmitz, J., &
While this may not be as effective as immediate rein- Kirby, K.C. Double blind placebo controlled study of fluoxe-
forcers, the use of incentives nevertheless remains an tine in the treatment of cocaine dependence in methadone main-
effective intervention. tained patients. Manuscript submitted for publication.
Implementation of these procedures and interven- Grabowski, J., Higgins, S.T., &Kirby, K.C. (in press). Behavioral
tions in other drug abuse treatment centers in plausible. treatments of cocaine dependence. In F. Tims (Ed.), Treatment
of cocaine abuse. NIDA research monograph series. Washing-
Methadone is an obvious reinforcer in maintaining
ton, DC: DHHS.
compliance. Other reinforcers and combination of Graham, N.M.H., Nelson, K.E., Solomon, L., Bonds, M., Rizzo,
treatment elements must be identified. While the treat- R.T., Savotto, J., Astemborski, J., & Vlahov, D. (1992). Prev-
ment of medication-resistant tuberculosis remains dif- alence of tuberculin positivity and skin test anergy in HIV-l se-
ropositive and intravenous drug uses. Journal of the American
ficult at present, assuring accurate detection of HIV
Medical Association, 267(3), 369-373.
positive patients is now feasible and may be imple- Griffiths, R.R., Bigelow, G., & Liebson, I. (1978). Relationship of
mented with ease. Routine toxicity monitoring and liver social factors to ethanol self-administration in alcoholics. In P.E.
function testing ensure good medical assessments of Nathan, M.A. Marlatt, & T. Loberg (Eds.), Alcoholism: New
patients receiving INH. directions in behavioral research & treatment (pp. 351-379). New
York: Plenum Press.
This investigation serves as a clear model of the ef-
Hall, S.M., Cooper, J.L., Burmaster, S., & Polk, A. (1977). Con-
fectiveness of achieving compliance with a rigorous
tingency contracting as a therapeutic tool with methadone main-
regimen of INH in a high risk population of intrave- tenance clients: Six single subjects studies. Behavior Research
nous drug users. and Therapy, 15, 438-441.
Haverkos, H.W. (1991). Infectious diseases and drug abuse: Pre-
vention and treatment in the drug abuse treatment system. Jour-
REFERENCES nal of Substance Abuse Treatment, 8, 269-275.
Hersen, M.Z., & Barlow, D.H. (1976). Single-case experimentalde-
Anker, A.L., & Crowley, T.J. (1982). Use of contingency contracts signs: Strategies for studying behavior change. Oxford: Perga-
in specialty clinics for cocaine abuse. In L.S. Harris (Ed.), Prob- mon Press.
lems of drug dependence 1981 (Research Monograph No. 41, Higgins, S.T., Delaney, D.D., Budney, A.J., Bickel, W.K., Hughes,
pp. 4X-459). Rockville, MD: National Institute on Drug Abuse. J.R., Foerg, F., & Fenwick, J.W. (1991). A behavioral approach
Barnes, P.F., Block, A.B., Davidson, P.T., & Snider, D.E., Jr. to achieving initial cocaine abstinence. American Journal of Psy-
(1991). Tuberculosis in patient with human immunodeficiency chiatry, 148, 1218-1224.
virus infection. The New England Journal of Medicine, 324(23), Huebner, R.E., Villarino, M.E., & Snider, D.E. (1992). Tubercu-
16441650. lin skin testing and the HIV epidemic. Journal of the American
Bigelow, G., Griffiths, R.R., & Liebson, B.A. (1975). Experimental Medical Association, 267(3), 409-410.
models for the modification of human drug self-administration: Iguchi, M., Stitzer, M.L., Bigelow, G.E., & Liebson, I.A. (1988).
Methodological developments in the study of ethanol self-admin- Contingency management in methadone-maintenance: Effects
istration by alcoholics. Federation Proceedings, 34, 1783-1792. of reinforcing and aversive consequences on illicit polydrug use.
Budney, A.J., Higgins, ST., Delaney, D.D., Kent, L., & Bickel, Drug and Alcohol Dependence, 22, l-l.
W.K. (1991). Contingent reinforcement of abstinence with in- Kirby, K.C., Andre% R.L., Bhatt, P., Davis, M., Spiga, R., Elk,
dividuals abusing cocaine & marijuana. Journal of Applied Be- R., Schmitz, J., & Grabowski, J. (1992). Behavioral treatment
havior Analysis, 24, 657-665. of drug abuse during pregnancy (Tech. Rep. No. SARC-l992-
Centers for Disease Control. (1990a). Guidelines for preventing the 02). Houston: University of Texas Health Science Center, Men-
transmission of tuberculosis in health-care settings, with special tal Sciences Institute, Substance Abuse Research Center.
focus on HIV-related issues. Morbidity and Mortality Weekly Kopanoff, D.E., Snider, D.E., & Caras, G.J. (1978). Isoniazid re-
Report, 39(No. RR-17), 153-156. lated hepatitis. American Review of Respiratory Disease, 117,
Centers for Disease Control. (1990b). Screening for tuberculosis and 991-1001.
tuberculosis infection in high-risk populations and the use of pre- Liebson, I.A., Tommasello, A., & Bigelow, G.E. (1978). A behav-
ventive therapy for tuberculous infection in the United States: ioral treatment of alcoholic methadone patients. Annals of In-
Recommendation of the Advisory Committee for Elimination ternal Medicine, 89, 342-344.
of Tuberculosis (ACET). Morbidity and Mortality Weekly Re- Marwick, C. (1992a). Multi-drug resistant tuberculosis poses chal-
port, 39(No. RR-S), 1-12. lenge. Journal of the American Medical Association, 267, 186.
Centers for Disease Control. (1991). Nosocomial transmission of Marwick, C. (1992b). Do worldwide outbreaks mean tuberculosis
multidrug-resistant tuberculosis among HIV-infected persons, once again becomes ‘captain of all these men of death’? Jour-
Florida & New York, 1988-1991. Morbidity and Mortality Weekly nal of the American Medical Association, 267, 1174-l 115.
Report, 4O(Suppl. RR-5), 585-591. Miller, P.M. (1975). A behavioral intervention program for chronic
Clrowley, T.J. (1986). Doctors’ drug abuse reduced during contin- public drunkenness offenders. Archives of General Psychiatry,
gency contracting treatment. Alcohol and Drug Research, 6, 32, 915-918.
299-307. Miller, P.M., Hersen, M., Eisler, R.M., & Watt, J.G. (1974). Con-
382 R. Elk et al.

tingent reinforcement of lowered blood alcohol levels in an out- among methadone maintenance clients: Contingent reinforce-
patient chronic alcoholic. Behaviour Research & Therapy, 12, ment for morphine-free urines. Addictive Behaviors, 5.333-340.
261-263. Stitzer, M., Bigelow, G., & Liebson, I. (1980). Reducing benzodi-
Penrose, K. (1992). Personal communication. azepine self-administration with contingent reinforcement. Ad-
Reichman, L.B., Felton, C.P., & Edsall, J.R. (1979). Drug depen- dictive Behaviors, 4, 245-252.
dence, a new risk factor for tuberculosis disease. Archives of In- Stitzer, M., Bickel, W.K., Bigelow, G.E., & Liebson, I. (1986). Ef-
ternal Medicine, 139, 337-339. fects of methadone dose contingencies on urinalysis test results
Reider, H.L., Cauthen, G.M., Kelly, G.D., Bloch, A.B., & Snider, of poly-abusing methadone maintenance patients. Drug and Al-
D.E., Jr. (1989a). Tuberculosis in the United States. Journalof cohol Dependence, 18, 341-348.
the American Medical Association, 262, 385-389. Theuer, C.P., Hopewell, P.C., Elias, D., Schecter, G.F., Ruther-
Reider, H.L., Cauthen, G.M., Comstock, G.W., & Snider, D.E., ford, G.W., & Chaisson, R.E. (1990). Human immunodeficiency
Jr. (1989b). Epidemiology of tuberculosis in the United States, virus infection in tuberculosis patients. Journal of Infectious Dis-
Epidemiology Review, 11, 79-98. eases, 162, 8-12.
Rosenzweig, D.Y. (1984). Tuberculosis and other mycobacterial Torres, R.A., Mani, S., Altholz, J., & Brickner, P.W. (1990). Hu-
diseases. In M.W. Rytel & N.J. Mogabgab (Eds.), Clinical man- man immunodeficiency virus infection among homeless men in
ual of infectious diseases (pp. 317-337). Chicago: Chicago Year- a New York City shelter: Association with mycobacterium tuber-
book Medical Publishers. culosis infection. Archives of Internal Medicine, 150,2030-2036.
Snider, D.E., & Roper, W.L. (1992). The new tuberculosis. New En- Van Scoy, R.E., & Wilkowske, C.J. (1983). Antituberculosis agents
gland Journal of Medicine, 326, 703-705. isoniazid, rifampin, streptomycin, ethambutol and pyrazinamide.
Stitzer, M., Bigelow, G., & Liebson, I. (1979). Reducing drug use Mayo Clinic Proceedings, S(4), 233-240.