Special Topic Section
Pharmacological Treatment of Addiction
Eur Addict Res 2003;9:53–58DOI: 10.1159/000068808 Experiences with an Outpatient Relapse
Program (Community Reinforcement Approach)
Combined with Naltrexone in the
Treatment of Opioid-Dependence:
Effect on Addictive Behaviors and the
Predictive Value of Psychiatric Comorbidity

H.G. Roozen A.J.F.M. Kerkhof W. van den Brink Department of Clinical Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands Key Words
nence. At baseline, the treatment group and the refer- Addiction W Treatment W Naltrexone W Opiates W Relapse ence group were similar on nearly all variables except for the number of times clients were arrested. Within thetreatment group, a comparison was made between thecontinuous abstinent and those who relapsed into fre- Abstract
quent opioid use. Differences were significant in the clus- Background: There is increasing interest in naltrexone,
ter-B personality disorders and in polydrug users. Con-
an opiate antagonist, in the treatment of opiate addicts.
clusion: The combination of naltrexone plus intensive
The effects of naltrexone are often compromised by a CRA in an outpatient setting appears to be promising. A lack of compliance and drop-out. The effects of this com- high score on cluster-B and polydrug use is associated pound are probably more favorable when combined with a psychosocial intervention such as the Community Reinforcement Approach (CRA). Aim: To explore the
effects of a combination therapy (naltrexone plus CRA
treatment) and the predictive value of sociodemographic
and psychopathologic characteristics. Method: Using a
The editor in chief of the Dutch Journal of Psychiatry (Tijdschrift before-and-after design, heroine addicts (n = 24) receiv- voor Psychiatrie) has given permission to submit for publication arevised English version of ‘Ervaringen met een terugvalpreventie- ing a combined naltrexone plus CRA treatment are com- programma (CRA) gecombineerd met naltrexon bij opiaatafhanke- pared with a group (n = 20) on methadone maintenance lijken: effect op verslavingsgedrag en predictieve waarden van psy- therapy (reference group). Results: Over a period of 6
chiatrische comorbiditeit’ in European Addiction Research. The
months, 58% (14/24) did not relapse, after 1 year at least original manuscript was published in the May 2000 issue of the 55% (12/22) still met the initial goal of continuous absti- Tijdschrift voor Psychiatrie (42:307–317). Department of Clinical Psychology, Vrije Universiteit Amsterdam Tel. +31 62041 1930, Fax +31 20444 8758, E-Mail [email protected] Introduction
Table 1. Retention characteristics of the treatment population
In the field of opiate addiction treatment, there has been an increase in the use of pharmacological com-pounds such as naltrexone. After induction, this agent can be effective in the prevention of recurrent heroin use.
During naltrexone maintenance treatment, the effects of heroine will be blocked, leading to lesser anticipation of the desired effects and a decrease in the relapse rate. Simi- lar to other forms of therapy aimed at abstinence, patient compliance is often a problem and many patients relapseafter having discontinued taking medication [1].
Displayed are numbers, percentages, means, standard deviations, One study [2] showed good results with naltrexone (61% abstinence after 6 months) with highly motivatedparticipants, such as business people and doctors. In addi-tion, in southern Europe, good results with naltrexone(40% abstinence after 6 months treatment) have beenreported [3]. The result is attributed to the traditional study, a comparison on relevant variables was made with family structure and other forms of social interactions a group of heroine addicts participating in a methadone These findings suggest that a combination of naltrex- The following questions were addressed: (1) is the one maintenance and psychosocial therapy may lead to an study population comparable to the group of addicts par- increase in therapy compliance and a decrease in the ticipating in a methadone maintenance program; (2) what is the outcome in heroin addicts treated with naltrexone A promising approach is the Community Reinforce- plus CRA, and (3) what is the predictive value of the ment Approach (CRA) [4]. CRA encompasses elements sociodemographic characteristics and psychiatric comor- such as social network and enhancing motivation and is bidity in patients treated with naltrexone plus CRA? often supported by a variety of pharmacological interven-tions (i.e. naltrexone) and procedures to enhance com-pliance with the recommended medication regimen.
First, there are interventions aimed at enhancing thesocial network (for example interventions including part- Study PopulationTreatment Group. The treatment group consist of 24 heroin ners and parents, aimed at compliance). CRA pays atten- addicts treated with naltrexone in a CRA program from February tion to the expectations, motivation, coping skills, social, 1996 until evaluation in May 1998. The treatment took place at the outpatient treatment center for addiction Kentron in Roosendaal However, combined forms of therapy also suffer often (! 100,000), the Netherlands. Subjects were recruited from metha- from early dropout and lack of therapy compliance. An done programs through newspaper articles and via addiction clinicsthroughout The Netherlands. During the research period 60 persons important factor which effects compliance and dropout is showed interest in participating by at least one contact. 24 persons psychiatric comorbidity [5]. In general the severity of psy- chiatric symptoms worsens the prognoses [6]. Research All 24 subjects were opiate-dependent and 21 of these were par- suggests that the prevalence of psychiatric disorders ticipants in a methadone program. Subjects were included during a among heroine addicts is high. There is a relationship 24-month period. Table 1 shows that follow-up varied between 6 and24 months (mean length of treatment 16.6; s.d. 5.3 months).
between drug addiction and depression, anxiety and per- Detoxification of 19 subjects consisted of a rapid detoxification sonality disorders [7]. Personality disorders are seen as procedure [9]. In this procedure naltrexone was administered in negative predictors of treatment outcome [8].
increasing dosage: 12.5 mg/day on day 1, 25 mg/day on day 2, and up The aim of this open-label study is to optimize the to 50 mg/day on days 3 and 4. To ameliorate withdrawal symptoms, effects of using a combination of CRA and naltrexone.
clonidine, diazepam, midazolam and ondansetron were used as indi-cated. The other 5 patients were detoxified by a methadone-tapering The present study consists of a naturalistic follow-up procedure either in a regular clinic or at home. Patients from the study with before-and-after comparison without a control latter group had to pay a fee of Eur 227.00 (n = 5), and patients from group. In order to assess a possible generalization of the the rapid detoxification program had to pay an extra fee of Eur 1,818.00 (n = 19). Detoxification was followed by naltrexone mainte- (c) For the presence and severity of personality pathology the nance. Subjects were stimulated and expected to bring a non-using VKP was used. This self-reporting questionnaire is based on the partner, spouse or good friend to assist as a coach during detoxifica- International Personality Disorder Examination (IPDE) of the WHO [19]. The VKP provides severity ratings on all 13 DSM-III-R [20] Reference Group. To check selection bias, a reference group of 20 personality disorders. An important advantage of the VKP (next to participants randomly drawn from a regular methadone program was cost-effectiveness) is the fact that during testing there is no systematic bias or interview tendencies [21]. Compared to an interview, theVKP has a high sensitivity and a low specificity.
(d) VGIT: in this study intelligence was tested by using the short After naltrexone induction, all subjects received a maintenance version of the GIT [14] consisting of the 3 subtests: numerical, a card dosage of naltrexone of 25 mg/day. The treatment consisted of medi- lay puzzler and a word puzzler. The short version correlates 0.91 with cal support, psychosocial interventions followed by a consistent and the complete version (10 subtests) of the GIT. The results can be strict policy towards compliance (naltrexone) and control of sub- stance abuse by urine analysis. The importance of the social networkwas emphasized. CRA implemented: diagnostic interview (function- al analysis), psycho-education, pharmacotherapy, compliance thera- To assess the predictive value of psychiatric comorbidity compar- py, urine analyses/monitoring, marriage/relation therapy, and sup- isons were made between the abstinent and relapsed group concern- port of the social network, career orientation, job counseling, educa- ing sociodemographic background, intelligence, juridical conflict, tion and hobbies, problem solving, social skills and cognitive restruc- psychopathology and personality disorders.
Differences in the means of continuous variables were tested by The therapist (first author) has several years experience in the using the Student’s t test. ¯2 statistics and Fisher’s exact test (two- addiction setting. On regular basis, he received supervision from the sided) were used to test differences in categorical data. Because of the second author and from multidisciplinary coworkers. The CRA pro- small sample size and the explorative nature of the study, the signifi- gram was tailored to the work of Meyers and Smith [10]. Treatment integrity was guarded on the basis of monitoring forms and stored infiles. Data collection, extraction and interviewing was done by anindependent researcher.
During the first month of treatment, counseling sessions averaged 2–3 sessions of 45 min/week, which was reduced to 1 weekly sessionof 45 min after 3–6 months, and, during the last phase, to monthly Comparison of Treatment Group with Regular sessions. After 9 months the dosage of naltrexone was reduced to 12.5 mg/day. Abstinence was verified by means of controlled urine Table 2 shows that the 2 groups are similar on all vari- ables except for the number of times clients were arrested (96% naltrexone vs. 57% methadone, p ! 0.05).
Subjects in the treatment group were interviewed prior to detoxif- ication regarding baseline characteristics. The reference group was Treatment Outcomes of the Naltrexone Group After a 6-month treatment period, 14 of 24 clients were still abstinent (58%). After 1 year, 12 of 22 were still absti- InstrumentsThe following questionnaires and tests were included in this nent (55%). One client used heroin incidentally after study: (a) SCL-90 (Symptom Check List) [11]; (b) ABV (Amster- detoxification without relapse into frequent opiate abuse.
damse Biografische Vragenlijst) [12]; (c) VKP Questionnaire on Per- All 10 clients who relapsed into frequent opiate abuse, did sonality Traits (Vragenlijst kenmerken van de persoonlijkheid) [13], so within 7 months after the start of treatment (table 1).
and (d) the VGIT, the shortened version of the GIT (Groningse Intel- Of 11 frequent cocaine users, 9 used cocaine a couple (a) The SCL-90 is a multidimensional self-report on mood and of times during treatment. One of them had a period of somatic complaints. This list has been translated into Dutch [15].
some weeks of extensive cocaine use. In that scenario the There is a relationship between the scales of depression and anxiety treatment was intensified and adapted to cocaine use, in the SCL-90 and relevant categories in the DSM-III(R) [16]. The which ceased. Three clients who regularly used amphet- SCL-90 has proven to be a reasonable indicator of the severity of amines ceased using this drug. One of them started taking psychopathology among psychiatric patients [17].
(b) The ABV is a personality questionnaire measuring the dimen- drugs again after 5 months in treatment, but ceased using sions: N = neurotic instability; NS = neurotic somatic complaints; the substance again after 9 months. Of 8 benzodiazepine E = social extravertism, and T = test attitude. The T dimension users, 6 stopped their benzodiazepine use. One of them ranges from a self-criticizing attitude (low score) to a self-defending persisted in irregular use of benzodiazepines, another attitude (high score) in answering the questionnaire. The N and NS slowly decreased his use to a stable maintenance level.
scales are highly inter-correlated. The test-retest index is satisfactory[18].
The use of cannabis remained the same for almost allclients.
Table 2. Characteristics and
psychopathology among naltrexone-
Displayed are numbers, percentages, meanscores, standard deviations and significant levels (p ! 0.05) for subscales and total scores of the SCL-90 and ABV.
Predictive Value of Sociodemographic Characteristics Discussion
and Psychiatric ComorbidityThe abstinent (n = 14) and relapsed clients (n = 10) The results of this pilot study, 55% drug free for a peri- were compared with regard to sociodemographic back- od of at least 12 months, are promising considering that ground, intelligence, social integration, juridical conflict, this group of heroine addicts had a long addiction history psychopathology and personality disorders. Of the 43 dif- and a long-term history of failed attempts to become ferent comparisons made, only three showed statistical abstinent. These results were achieved by rapid detoxifi- significance: (1) 90% of the relapse population were poly- cation and by means of psychosocial outpatient treatment drug users compared to 50% in the abstinence group; (2) with naltrexone support. For the interpretation of these the T score of the ABV showed a small but significant dif- results it is important to investigate the selectivity of the ference, a highly critical self-evaluation indicates a risk of treatment group. A comparison with a reference group of relapse, and (3) those who relapsed had a higher total methadone patients showed that both groups were simi- score on the B-cluster personality disorder measured at a lar. There was no difference as to drug abuse history and the amount and severity of (comorbid) psychopathology Table 3. Personality pathology according to
DSM-III(R) axis II as measured by VKP,
Displayed are means, standard deviations and significance levels (p ! 0.05) of the dimen- sional scores and cluster total scores.
were not less in the naltrexone group. The only difference tion supporting their claim), there was a possibility of rais- was the fact that the subjects participating in naltrexone ing the complete amount of money from a charity founda- treatment had been arrested more frequently than the tion, from the municipality or from social benefits as a subjects of the regular methadone program.
gift. Prior to acceptance, potential candidates and their It is, however, likely that those subjects who applied for coaches took part in a couple of informative meetings participation in the naltrexone group were more moti- where they were motivated and prepared for treatment. It vated than those participants following regular programs.
is the experience of the authors that this preparation prior Patients, in the treatment group could afford to pay a fee, to detoxification should not be underestimated.
or had a person in their network willing to pay for the As to any connection between the type of addict and treatment. Probably only a limited and selective propor- success rate, we found that the risk of dropout was greatest tion of heroin addicts maintain good contacts with non- among polydrug users, although even here 7 of the 16 addicts in order to find a non-drug using partner, spouse polydrug users (44%) benefited from the treatment. In or friend willing to assist as a coach during treatment. In addition, cluster-B personality disorder was found to be sum, participants in the naltrexone treatment group were an indicator for dropout, but was insufficient to be a con- probably better motivated and integrated in the commu- traindication for participation [22].
Considering a 55% abstinence rate covering an average However, this can hardly be used as an objection period of 12 months and comparing these results with against the study results, because motivating subjects is other studies we find the results promising. Although it is one of the key elements of treatment as a whole. When the tempting to credit the results to the applied intervention fee was a problem, or when the patient or the network was (naltrexone plus CRA), this is not possible until a ran- incapable of financing the treatment (objective informa- domized experimental design is followed.
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