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Targeting Behavioral Therapies to Enhance Naltrexone Treatment of Opioid Dependence
Efficacy of Contingency Management and Significant Other Involvement
Kathleen M. Carroll, PhD;
Samuel A. Ball, PhD;
Charla Nich, MS;
Patrick G. O'Connor, MD, MPH;
Dorothy A. Eagan, RN, MPH;
Tami L. Frankforter;
Elisa G. Triffleman, MD;
Julia Shi, MD;
Bruce J. Rounsaville, MD
Arch Gen Psychiatry. 2001;58:755-761.
ABSTRACT
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Background Contingency management (CM) and significant other involvement (SO) were
evaluated as strategies to enhance treatment retention, medication compliance,
and outcome for naltrexone treatment of opioid dependence.
Methods One hundred twenty-seven recently detoxified opioid-dependent individuals
were randomly assigned to 1 of 3 conditions delivered for 12 weeks: (1) standard
naltrexone treatment, given 3 times a week; (2) naltrexone treatment plus
contingency management (CM), with delivery of vouchers contingent on naltrexone
compliance and drug-free urine specimens; or (3) naltrexone treatment, CM,
plus significant other involvement (SO), where a family member was invited
to participate in up to 6 family counseling sessions. Principal outcomes were
retention in treatment, compliance with naltrexone therapy, and number of
drug-free urine specimens.
Results First, CM was associated with significant improvements in treatment
retention (7.4 vs 5.6 weeks; P = .05) and in reduction
in opioid use (19 vs 14 opioid-free urine specimens; P
= .04) compared with standard naltrexone treatment. Second, assignment to
SO did not significantly improve retention, compliance, or substance abuse
outcomes compared with CM. Significant effects for the SO condition over CM
on retention, compliance, and drug use outcomes were seen only for the subgroup
who attended at least 1 family counseling session. The SO condition was associated
with significant (P = .02) improvements in family
functioning.
Conclusion Behavioral therapies, such as CM, can be targeted to address weaknesses
of specific pharmacotherapies, such as noncompliance, and thus can play a
substantial role in broadening the utility of available pharmacotherapies.
INTRODUCTION
IN THE TREATMENT of opioid dependence, naltrexone, an opioid antagonist
that blocks the subjective effects of opioids, has tremendous potential. Relative
to methadone hydrochloride and other maintenance therapies, naltrexone is
nonaddicting, has a benign adverse effect profile, and can be prescribed without
concerns about diversion (eg, naltrexone is rarely traded in the illicit drug
market).1 Moreover, naltrexone is not subject
to the restrictive regulatory requirements associated with methadone and levomethadyl
acetate and hence can be delivered in a range of settings, which may make
it more attractive to those opioid-dependent individuals who would not enter
traditional drug abuse treatment programs. Furthermore, naltrexone may be
less costly, in terms of demands on professional time and patient time, than
the near-daily clinic visits required for methadone maintenance therapy.2 Also important are the behavioral aspects of naltrexone,
as unreinforced opioid use allows extinction of relationships between drug
cues, craving, and drug use.
Naltrexone has not, despite its many advantages, fulfilled its promise.
Naltrexone remains comparatively rare and underused vs methadone maintenance.2 This is in large part due to problems with attrition
and noncompliance, particularly during the induction phase, during which on
average 40% of patients drop out during the first month of treatment and 60%
drop out by 3 months.1 Another factor in reducing
naltrexone's appeal to patients is that it eliminates, without replacing,
the powerful reinforcing effects of opioids. Thus, despite its tremendous
potential, naltrexone has been overshadowed by methadone, and research on
naltrexone has decreased considerably, with the exception of evaluating its
utility among select populations (eg, professionals or individuals mandated
to treatment).1, 3
Combined behavior therapy and pharmacotherapy is considered the optimal
strategy for many psychiatric disorders, including substance dependence.4, 5 However, systematic research identifying
the most effective strategies for combining behavioral and pharmacological
treatments has been infrequent. An important, but rarely evaluated, strategy
is to apply specific behavioral therapies to directly targeted weaknesses
of pharmacotherapies. For example, to compensate for naltrexone's lack of
pharmacological reward, contingency management (CM)6
could be used to reward and thus enhance naltrexone compliance. Similarly,
significant other involvement (SO) in treatment could be used to provide incentives
for retention and encouragement to persist with treatment despite protracted
opioid withdrawal symptoms.
The present study evaluates CM and SO as treatments for recently detoxified
opioid addicts taking naltrexone as maintenance therapy. Three approaches
were evaluated: (1) standard naltrexone, which included naltrexone taken 3
times per week plus weekly cognitive-behavioral group therapy (CBT); (2) standard
naltrexone plus CM, with reinforcement for naltrexone compliance and abstinence;
and (3) standard naltrexone, CM, plus SO. The following research questions
will be addressed: (1) Does adding CM to standard naltrexone treatment enhance
naltrexone compliance and outcome? (2) Does adding SO to CM further enhance
naltrexone compliance and outcome? (3) Are component-specific effects of treatment
detectable? We hypothesized that those assigned to the SO intervention would
report improved family/social functioning relative to subjects who did not
receive SO.
SUBJECTS AND METHODS
SUBJECTS
The subjects were 127 individuals seeking treatment for opioid dependence
who completed outpatient detoxification (95% of subjects) offered through
the Central Medical Unit of The APT Foundation in New Haven, Conn, or inpatient
detoxification at other facilities. All subjects met current DSM-IV criteria for opioid dependence, as confirmed by Structured Clinical
Interview for DSM-IV7
interviews conducted by the master's-level project director (D.A.E.) (reliability
was established in earlier projects and supported through recalibration interviews).
Individuals excluded were those who (1) had significant medical conditions,
such as abnormal liver function or active hepatitis, or any other condition
that would contraindicate naltrexone treatment; (2) did not have a significant
other willing to participate in treatment; (3) met the DSM-IV criteria for lifetime schizophrenia or bipolar disorder; or
(4) had been involved in substance abuse treatment within the past 3 months.
Of 315 individuals screened, 27 did not meet the eligibility criteria
(4 because of medical reasons, 4 because they did not meet the criteria for
opioid dependence, 6 because they could not identify a significant other,
3 because of psychological problems, 6 because of current drug treatment,
3 because of imminent incarceration, and 1 because the individual lived too
far from the clinic to meet the 3 times a week medication schedule). Eleven
individuals dropped out during the pretreatment evaluation process. The 277
individuals who met the eligibility criteria were offered an outpatient detoxification,
using clonidine or clonidine-naltrexone detoxification protocols described
in previous reports,8, 9 or were
referred for an inpatient detoxification at another facility in New Haven.
Of these individuals, 61 dropped out before initiating detoxification, 48
did not complete detoxification, and 41 completed detoxification but did not
return to the clinic for randomization.
The 127 individuals who were randomized were compared with the 150 eligible
individuals not randomized on sex, race, employment status, marital status,
educational level, treatment history, and severity and chronicity of substance
use. The subjects who did not initiate naltrexone treatment were significantly
different from the randomized sample only on sex (there were more women in
the nonrandomized group [ 2 = 4.63, P
= .03]) and number of previous detoxifications (1.50 vs 0.95; F = 4.5, P = .04).
TREATMENTS
Following the completion of detoxification, baseline assessment, and
provision of written informed consent, subjects were randomly assigned, using
an urn randomization program, to 1 of 3 conditions.
Standard Naltrexone Treatment
This treatment, which was delivered to subjects in all 3 conditions,
included naltrexone treatment, 3 times a week (Monday, 100 mg; Wednesday,
100 mg; and Friday, 150 mg), under the supervision of a research nurse (D.A.E.).
Urine specimens were collected 3 times a week, coinciding with medication
visits. In addition, weekly group therapy sessions, consisting of manual-guided
CBT,10 were co-led by a master's-level counselor
and a nurse practitioner who received weekly supervision.
Voucher-Based CM
In addition to standard naltrexone, as previously described, subjects
in this group received vouchers redeemable for goods and services contingent
on targeted behaviors. The voucher system developed by Higgins and colleagues6, 11 was adapted to directly address naltrexone's
weaknesses. We hypothesized that if reinforcement was provided only for naltrexone
ingestion, cocaine and other drug use that would not be subject to behavioral
contingencies might remain problematic or even increase. Therefore, vouchers
were provided for 2 target behaviors on 2 independent reinforcement "tracks":
(1) naltrexone ingestion and (2) submission of drug-negative urine specimens.
Thus, the first time a subject submitted a drug-free urine specimen, the subject
earned the equivalent of $0.80, and the value of vouchers for each consecutive
drug-negative urine specimen thereafter increased by $0.40. Similarly, the
first time the subject took naltrexone, the subject also earned the equivalent
of $0.80, and the value of the vouchers also increased by $0.40 for each consecutive
ingestion of naltrexone thereafter. Failure to submit a urine specimen, specimens
that tested positive for any illicit drug, or missing a naltrexone visit reset
the value of the vouchers for that track back to the starting point ($0.80),
from which point the value could escalate again according to the same schedule.
Subjects who complied perfectly with the naltrexone regimen and whose urine
screen results were all negative could earn a maximum of $561 worth of items
during the 12-week treatment. As in the Higgins system,6, 11
money was not given directly to subjects. Instead, vouchers were redeemed
for items consistent with a drug-free lifestyle (eg, gift certificates for
food and clothing or purchasing robes for singing in a church choir).
Significant Other Involvement
Subjects assigned to this condition, in addition to standard naltrexone
treatment and CM, as previously described, were offered up to 6 additional
family sessions with a non–substance-abusing parent, spouse, child,
sibling, or close friend of the subject's choice. These sessions were manual
guided, adapted from the guidelines described by Budney and Higgins6 for reciprocal relationship counseling, and delivered
by a master's-level social worker. The goals of the sessions included (1)
educating the significant other regarding opioid dependence and ways he or
she could support the subject in complying with treatment and remaining abstinent
and (2) identifying strategies for enhancing relationships with significant
others. This approach was intended to be consistent with and to capitalize
on the availability of vouchers to develop supportive interpersonal relationships
as alternatives to drug use. Subjects were thus encouraged in the family sessions
to redeem vouchers for goods and services that might strengthen relationships
with others (eg, going fishing with a parent or hosting a child's birthday
party).
ASSESSMENT
Subjects were assessed immediately before randomization, weekly during
treatment, and at the end of the 12-week course of treatment, at which time
the CM and SO components were terminated and subjects were transferred to
the naltrexone maintenance program of the Substance Abuse Treatment Unit of
the Connecticut Mental Health Center of Yale University. Primary outcome measures
were (1) compliance with naltrexone treatment (number of times naltrexone
was ingested over 12 weeks), (2) frequency of opioid use (self-reported days
of opioid use and percentage of opioid-free urine specimens during treatment),
and (3) frequency of cocaine use (self-reported days of cocaine use and percentage
of cocaine-free urine specimens during treatment). Primary outcomes were assessed
using the Substance Abuse Calendar, which is similar to the Form 9012 and collects information on treatment involvement,
medication compliance, and substance use on a day-by-day basis and, thus,
allows for a flexible continuous evaluation of outcome with minimization of
missing data. Secondary outcomes included psychosocial functioning, as assessed
by the Addiction Severity Index,13 and human
immunodeficiency virus risk behaviors, using the Risk Assessment Battery.14 The Structured Clinical Interview for DSM-IV7 was used to evaluate current
and lifetime psychiatric disorders in the sample.
The OnTrak TesTcup (Roche Diagnostics Corp, Indianapolis, Ind) was used
to evaluate each urine specimen for the presence of metabolites of opioids,
cocaine, and benzodiazepines. This allowed for rapid feedback to subjects
regarding urine toxicology results, minimizing the delay usually associated
with obtaining urinalysis results from a commercial laboratory. Of 2130 urine
specimens collected from all subjects during the treatment phase of the study,
96.1% were consistent with the subjects' self-reports of opioid use. Of the
83 urine specimens that were inconsistent with self-reports, 16 (0.8% of the
total) indicated no opioid use when the subjects reported they had used opioids
and 67 (3.1% of the total) indicated recent opioid use when the subjects denied
recent use. For cocaine use, 93.1% of the specimens collected were consistent
with the subjects' reports of recent cocaine use (1.0% indicated no recent
use when the subjects reported use, and 5.9% indicated recent cocaine use
when the subjects denied use). In addition, there were no significant (P = .26) differences between groups in the number of missing
urine specimens.
DATA ANALYSES
The principal analytic strategies were analysis of covariance (for aggregate
data, such as number of sessions completed) and random regression models (for
data collected weekly, such as frequency of use by week) for the primary outcome
variables, with 2 orthogonal contrasts: (1) CM contrast, to evaluate the efficacy of CM, the 2 groups that received CM were
compared with the group that received standard naltrexone (CM and SO plus
CM vs standard naltrexone); and (2) SO contrast,
to evaluate the efficacy of adding SO to CM, the SO plus CM group was compared
with the CM group (SO plus CM vs CM).
Analyses were conducted on the intent-to-treat sample, that is, all
subjects randomized. For all analyses, the  level was .05 and tests
were 2-tailed. In cases in which a subject dropped out of treatment, the subject
was followed up and interviewed at the 12-week point. Thus, of the 72 subjects
who dropped out, 62 (86%) were interviewed; of the 5 subjects who were randomized
but did not initiate treatment, 2 were interviewed.
RESULTS
SAMPLE DESCRIPTION
As shown in Table 1, the
127 subjects randomized to treatment were predominantly young (mean age, 32),
male (76%), white (77%), and unemployed (51%). Most (65%) were single or divorced,
and 81% had completed high school. The subjects had substantial legal histories,
with a mean of 6 previous arrests. Most (55%) reported they had been treated
for drug use previously, and 23% reported previous methadone maintenance therapy.
Subjects reported using heroin a mean of 21 of the 28 days before detoxification,
with a mean of 3 "bags" per day. The groups differed significantly on baseline
intensity of opioid use (number of bags per day). Because this variable was
significantly (P<.05) correlated with outcome,
all outcome analyses included baseline intensity of opioid use as a covariate.
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Table 1. Baseline Demographic, Substance Use, and Treatment History
Data by Treatment Group*
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ATTRITION AND COMPLIANCE
Of the 127 subjects randomized, 122 initiated treatment. The mean number
of treatment weeks completed was 7.1 (SD, 4.7). Ten subjects were removed
from the treatment protocol: 3 were removed because of discomfort associated
with naltrexone, 3 because of clinical deterioration (continued high levels
of intravenous drug use), and 1 because of medical complications of the human
immunodeficiency virus; 1 was administratively discharged; and 2 moved from
the area. One subject died of an accidental overdose 1 month after he had
successfully completed the study and had been transferred to a long-term naltrexone
maintenance program. Subjects assigned to the 2 CM groups earned a mean of
$189 (SD, $220) in vouchers. Subjects assigned to the SO plus CM condition
completed a mean of 2.6 (SD, 2.6) significant other sessions (Figure 1).
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Figure 1. Retention by week by treatment
group (N = 127). All subjects were taking naltrexone 3 times a week as maintenance
therapy. CM indicates contingency management; SO + CM, significant other involvement
and CM.
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As shown in Table 2, retention
was significantly higher in the 2 groups assigned to CM compared with the
standard naltrexone group, but significant differences between the SO plus
CM and the CM groups were not seen, suggesting no additional benefit of SO
in addition to CM. Rates of treatment completion were highest in the SO plus
CM group (47%), followed by the CM (42.9%) and standard naltrexone (25.6%)
groups. Similarly, naltrexone compliance was higher in both CM groups (although
this effect fell just short of statistical significance), with no additional
benefit for SO plus CM compared with CM alone.
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Table 2. Treatment Retention and Primary Outcomes by Group for the
127 Subjects in the Intention-to-Treat Sample*
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EFFECTS ON SUBSTANCE USE
In the intention-to-treat sample, for most substance use outcome variables
assessed, subjects assigned to the 2 CM groups had improved outcomes compared
with the group assigned to standard naltrexone, with little additional benefit
associated with the SO condition. For example, subjects assigned to either
CM group had significantly more mean days of abstinence from opioids, significantly
longer periods of consecutive abstinence from opioids, a significantly higher
total number of opioid-negative urine specimens, and a higher percentage of
opioid-negative urine specimens compared with those in the standard naltrexone
group. However, none of the SO contrasts were significant, again suggesting
little additional benefit of adding SO to CM.
As shown in Figure 2, random
regression analyses indicated significant effects for the CM by time contrast
(z = -2.63, P = .008),
suggesting subjects assigned to the 2 CM groups made greater reductions in
their frequency of opioid use over time compared with those assigned to the
standard naltrexone group. Because the model presupposes linearity, and 100%
of subjects reported using opioids weekly at baseline and less than 10% of
those remaining in treatment reported opioid use in the last 4 weeks of treatment,
the estimated slope, or rate of change, is modeled accordingly. An additional
model that included additional post-attrition data from subjects who dropped
out of treatment was consistent with these findings.
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Figure 2. Probability of opioid use by week
by treatment group (N = 127), result of random regression analyses, using
a linear model. All subjects were taking naltrexone 3 times a week as maintenance
therapy. CM indicates contingency management; SO + CM, significant other involvement
and CM.
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Effects of treatment on cocaine use also favored both groups assigned
to the CM condition compared with those assigned to standard naltrexone, with
little additional benefit for SO. That is, there were trends favoring CM for
mean total number of days of abstinence from cocaine and for maximum days
of abstinence from cocaine and number of cocaine-negative urine specimens.
Effects on alcohol use followed a similar trend, but none of the effects were
significant.
Regarding treatment effects on human immunodeficiency virus risk behaviors,
there was a significant reduction in frequency of drug-related risk behaviors
over time across groups (time effect t = 2.7, P = .007); however, neither of the treatment contrasts
were significant, indicating no differential effect of CM or SO compared with
standard naltrexone on drug risk behaviors. Effects for time or treatment
group on frequency of sexual risk behaviors were not significant.
TREATMENT SPECIFICITY
To explore whether the study treatments affected theoretically relevant
outcomes, we evaluated whether SO differentially improved family functioning.
There was a significant contrast by time effect on the family/social composite
score of the Addiction Severity Index13 for
the SO contrast (z = 2.30, P
= .02), suggesting a greater reduction in family problems over time for subjects
assigned to the SO plus CM group compared with those assigned to the CM group.
In addition, exploratory analyses comparing the SO plus CM group with the
other 2 groups also indicated a significant contrast by time effect (z = -2.4, P = .02), suggesting
that the beneficial effect of SO on family functioning was not due to the
influence of CM.
TREATMENT-EXPOSED SUBGROUPS AND OUTCOME
Although confounded with attrition and compliance, analyses evaluating
effects of treatment exposure can be valuable in several respects. Participation
of significant others in treatment requires special efforts on the part of
the subject to identify an appropriate non–substance-abusing family
member and encourage this person to become involved in treatment. Thus, we
repeated our principal analyses using the subgroup (30 [62%]) of subjects
assigned to the SO plus CM condition who attended 1 or more family sessions.
These analyses suggested statistically significant effects for SO plus CM
compared with CM on weeks of treatment (t = 2.61, P = .01), number of naltrexone doses (t = 2.66, P = .009), percentage of opioid-free
urine toxicology screens (t = 2.28, P = .03), and maximum days of abstinence from opioids (t = 2.47, P = .02) and cocaine (t = 2.81, P = .006). However, these analyses
are confounded with treatment retention; only the effect on number of clean
urine specimens was statistically significant after controlling for treatment
retention by adding number of treatment weeks as a covariate.
COMMENT
This evaluation of CM and SO to target retention, compliance, and drug
use in naltrexone treatment of opioid dependence suggested the following.
First, CM significantly improved treatment retention, naltrexone compliance,
and opioid use relative to standard naltrexone treatment. Second, assignment
to family therapy sessions in addition to CM did not significantly improve
retention, compliance, or drug use outcomes compared with CM, but did improve
family functioning. Third, exploratory analyses suggested significant effects
on virtually all outcomes for the subgroup of subjects who attended at least
1 session with SO. Overall, these findings underscore the value of combining
behavioral and pharmacological interventions and point to the promise of systematically
targeting behavioral interventions to address specific weaknesses of particular
pharmacotherapies.
These findings also add to strong empirical support for each of the
therapies evaluated herein. Although a recent meta-analysis15
of family therapy in the treatment of substance dependence indicated a robust
effect size for family therapy, family therapy has infrequently been used
as a strategy to enhance compliance with pharmacotherapy. The present study
involved a comparatively challenging "test" of this approach, because the
study design evaluated whether SO conferred additional benefits over CM. That
the involvement of significant others in treatment greatly improved outcomes
compared with CM for the subgroup of subjects who attended at least 1 session
with a family member underlines the promise of this intervention, as does
the finding that SO differentially improved family functioning.
Adding SO as a component of treatment dramatically increases treatment
complexity, as the patient must be willing to have a family member participate
in treatment and that individual must be willing to attend. In this study,
ability to participate in family therapy was not a significant obstacle to
enrollment, as only 6 individuals screened could not identify a significant
other who was willing to participate. Nevertheless, it was difficult for some
subjects to engage their significant others in the family sessions, given
that subjects had often become estranged from family and friends after years
of drug dependence or the subject's drug use had resulted in serious negative
consequences for the family. Thus, just as outcome for pharmacotherapies has
been shown to be dependent on compliance,16, 17
it should be acknowledged that outcome for behavioral therapies is generally
best among patients who make at least minimal efforts to comply.
The study results also add to strong levels of empirical support for
CM. A recent meta-analysis18 estimated an effect
size of 0.25 for CM in the context of methadone maintenance treatment, the
basis of which was the landmark series of studies by Stitzer and colleagues.19 Those studies demonstrated that behavioral incentives,
such as increases in methadone dose and take-home doses, could be used to
reduce cocaine abuse and other problems frequently seen with methadone maintenance
programs. However, because those studies used reinforcers that occur naturally
in the context of methadone maintenance treatment, their feasibility outside
of methadone maintenance settings had been limited. Thus, a significant advantage
of the highly flexible voucher-based CM approach developed by Higgins and
colleagues6, 11 is that it can
be used in many settings and used to target a wide range of behaviors, including
medication compliance, as demonstrated herein.
The findings supporting CM are consistent with the recent report by
Preston et al,20 which suggested improved retention
and compliance with naltrexone when patients were reinforced for compliance.
However, while results of the present study suggested significant differences
in drug use by treatment condition, the study by Preston et al did not. This
may have occurred because the study by Preston et al targeted naltrexone compliance
only, whereas the present study targeted compliance and abstinence.
It is also notable that naltrexone was found to be safe with this comparatively
large sample, with 3 reports of minor adverse events and 1 death due to overdose
after a subject stopped taking naltrexone during the follow-up phase of the
study. This is in contrast, for example, to a recent report21
of 13 overdoses and 4 deaths due to overdose in a sample of 81 detoxified
opioid addicts treated with comparable doses of naltrexone.
Limitations of the present study include the generalizability of the
sample. Because individuals who were not willing to take naltrexone after
detoxification were excluded, results may not generalize to opioid addicts
seeking detoxification only or those seeking agonist therapies. Second, many
subjects did not complete detoxification or return to the clinic following
detoxification. Although the rates of dropout during detoxification (22%)
and of failure to initiate naltrexone treatment after detoxification (24%)
compare favorably with those of previous studies15, 16
in this setting, attrition during the detoxification phase is an acknowledged
drawback of naltrexone treatment and one that limits its feasibility relative
to agonist approaches. Whether introduction of CM or SO in the detoxification
phase might further improve retention and, hence, the viability of naltrexone
is an area worthy of future investigation. Similarly, despite the effects
of the treatments evaluated herein on retention, attrition remained high overall,
and there was limited power for some analyses. Finally, only 1 therapist delivered
the SO intervention; thus, this introduced a possible therapist or therapy
confound and it is not possible to determine if effects of this condition
were associated with this treatment or with it being delivered by this particular
therapist.
A major implication of these findings is that behavioral therapies can
play a substantial role in broadening the utility of available pharmacotherapies.
Despite the many advantages of naltrexone and the importance of increasing
the availability of treatment for opioid addicts, naltrexone maintenance programs
remain rare. The compliance problems associated with naltrexone have rendered
it a highly specific treatment primarily used with a few special populations
(eg, opioid-abusing physicians and other professionals) for whom special contingencies
(eg, loss of licensure or employment) can be leveraged to monitor and, thus,
enhance naltrexone compliance. Accordingly, it is significant that the present
study involved a population of predominantly unemployed "street addicts" with
substantial prior involvement in drug abuse treatment and the legal system.
That behavioral therapies can be used to make effective pharmacotherapies
available to a wider proportion of substance abusers is a point that has considerable
implications beyond making naltrexone a more viable treatment option. Our
arsenal of effective pharmacotherapies for substance use and other psychiatric
disorders is not unsubstantial, but it has been demonstrated repeatedly that
the effectiveness of these agents is undermined by significant problems with
compliance. Thus, capitalizing on behavioral approaches to enhance pharmacotherapy
outcomes has important implications for improving outcomes among the many
psychiatric patients for whom outcome is particularly compromised by compliance
issues, including the more highly impaired subgroups (eg, patients with dual
diagnoses and those with personality disorders). This also suggests that ongoing
efforts to develop antagonist treatments for cocaine and other substance use
disorders should be informed by the history of naltrexone. Those agents, unless
delivered with a potent behavioral therapy, are likely to be marginalized
in much the same way naltrexone has been.
AUTHOR INFORMATION
Accepted for publication April 3, 2001.
This study was supported by grants P50-DA0924, K05-DA00457 (Dr Carroll),
and KO5-DA00089 (Dr Rounsaville) from the National Institute on Drug Abuse,
Rockville, Md.
We thank Sister Maureen Lewis, MD, Art Woodard, MSW, Monica Canning-Ball,
Carol Eggers, APRN, Susan Henry, RN, Theresa Babuscio, Sister Janet Constantino,
APRN, Roseann Bisighini, Lynn Gordon, RN, MPA, Mark Hayes, MSW, and the staff
of the Central Medical Unit of The APT Foundation, New Haven, for their contributions.
From the Department of Psychiatry, Yale University School of Medicine,
New Haven, Conn. Dr Triffleman is now with the S3 Project, Oakland, Calif.
Corresponding author and reprints: Kathleen M. Carroll, PhD, Department
of Psychiatry, Yale University School of Medicine,, VA CT Healthcare System,
950 Campbell Ave (151D), West Haven, CT 06516 (e-mail: kathleen.carroll{at}yale.edu).
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