A Comprehensive Pharmacologic-Psychosocial Treatment Program for HIV-Seropositive Cocaine- and Opioid-Dependent Patients

Journal of Substance Abuse Treatment, Vol. 15, No. 3, pp. 261–265, 1998 Copyright © 1998 Elsevier Science Inc. Printed in the USA. All rights reserved 0740-5472/98 $19.00 1 .00

PII S0740-5472(97)00226-2

BRIEF REPORT

A Comprehensive Pharmacologic-Psychosocial Treatment Program for HIV-Seropositive Cocaine- and Opioid-Dependent Patients Preliminary Findings

S. Kelly Avants, phd, Arthur Margolin, phd, Dominick DePhilippis, phd, and Thomas R. Kosten, md Yale University School of Medicine, Substance Abuse Center, New Haven, CT

Abstract – HIV-seropositive opioid-dependent patients maintained on an opiate-agonist who continue to use cocaine and to engage in other high-risk behaviors may benefit from enhanced treatment services; however, there is currently little data to guide the formulation of such services. We report on a preliminary study in which six HIV-seropositive opioid- and cocaine-dependent patients were provided a 12week comprehensive pharmacologic/psychosocial treatment program developed specifically to meet the treatment needs of HIV-seropositive drug users. This program was comprised of buprenorphine (12 mg/ day), bupropion (150 mg/day), and twice weekly manual-guided group therapy. Results showed significant decreases in intravenous cocaine use, cocaine craving, and symptoms of depression. A post-hoc comparison to outcomes of eight HIV-seropositive patients receiving standard methadone-maintenance found no improvements for patients receiving standard care. Controlled investigation of enhanced drug treatment programs for HIV-seropositive patients may be warranted. © 1998 Elsevier Science Inc. Keywords – HIV; cocaine; methadone; buprenorphine; bupropion.

INTRODUCTION

Cocaine use is associated with a variety of HIV risk behaviors (Larrat & Zierler, 1993), including use of injection paraphernalia and unprotected sexual activity. Moreover, both HIV disease and cocaine abuse are potentially neurotoxic (e.g., Majewska, 1996; McKegney et al., 1990; Woods et al., 1991) and, in conjunction, may lead to or exacerbate cognitive deficits that potentially interfere with the ability of HIV-seropositive patients to benefit from standard psychoeducational drug treatment. Treatments for cocaine abuse that consist of pharmacotherapies in conjunction with minimal counseling may lack efficacy because they do not address the numerous psychosocial problems faced by inner-city methadonemaintained patients (cf. Arndt, Dorozynsky, Woody, &

THE POTENTIAL BENEFITS of maintaining HIV-seropositive opioid-dependent patients on an orally administered opiate, such as methadone, buprenorphine, or l-alphaAcetylmethadol (LAAM), in reducing the spread of HIV, can be undermined by patients’ continued use of cocaine.

Supported by grants DA00277 (SKA), DA08754 (SKA), DA00112 (TRK) and DA04060 (Clinical Research Center) from the National Institute of Drug Abuse, National Institutes of Health. Requests for reprints should be addressed to S. Kelly Avants, PhD, Yale School of Medicine, Substance Abuse Center, 34 Park Street, Room S-105, New Haven, CT 06519.

Received April 21, 1997; Accepted July 22, 1997.

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McLellan, 1992; Kosten, Morgan, Falcioni, & Schottenfeld, 1992; Margolin et al., 1995; McLellan, Arndt, Metzger, Woody, & O’Brien, 1993; Meyer, 1992). This may be especially true for HIV-seropositive drug users, who face significant problems associated with HIV disease for which additional services are required (Dennis, Karuntzos, & Rachal, 1992; Fernandez & Ruiz, 1992; Mor, Piette, & Fleishman, 1989). The study described here was an investigation of a combined pharmacologic/ psychosocial intervention for the treatment of opioidand cocaine-dependence in HIV-seropositive patients in order to gather preliminary data prior to embarking on a randomized clinical trial. The 12-week comprehensive treatment program comprised three components: opiateagonist maintenance therapy with buprenorphine (12 mg/ day); cocaine “anti-craving” therapy with the antidepressant bupropion (150 mg/day); and twice-weekly group therapy. We selected buprenorphine, a mixed opioid agonist-antagonist because it has been shown to be an effective opioid maintenance agent (Lewis, 1985) and, in combination with antidepressant pharmacotherapy, has shown promise for the treatment of cocaine abuse (Kosten, Oliveto, Falcioni, & Schottenfeld, 1996). We included bupropion, a “second-generation” monocyclic antidepressant, for several reasons: (a) the relatively high rates of depression among HIV-seropositive patients (Perry, 1994); (b) findings of reduced cocaine use by the subset of depressed drug users in a recently completed randomized clinical trial of bupropion (Margolin et al., 1995); (c) bupropion’s nonsedating side-effect profile, which may be especially important to consider in the treatment of neuropsychiatrically impaired patients (Fernandez & Ruiz, 1992); and (d) previous positive findings for the use of other antidepressants with HIVpositive cocaine abusers (cf. Batki, Manfredi, Jacob, & Jones, 1993). The psychosocial component of this program was developed specifically for HIV-seropositive cocaine users with the potential for cognitive impairment (Avants, 1996), and was based on previous findings of impairment in our patient population (Avants, Margolin, McMahon, & Kosten, 1997; Margolin, Avants, DePhilippis, & Kosten, in press). It includes case management and twice-weekly, manual-guided group therapy, using cognitive remediation strategies. These strategies include multimodal presentation of material, simplification of content, frequent review of material with quizzes and feedback, and extensive use of memory books and behavioral games. Content is tailored to address the special treatment needs of HIV-seropositive drug users, with particular emphasis on health promotion and risk reduction. In order to gain a preliminary estimate of the efficacy of this comprehensive treatment program, we compared outcomes of 6 patients who received the comprehensive program to outcomes of historical controls (Pocock, 1976)—HIV-seropositive cocaine-dependent patients who had received standard methadone maintenance treatment (i.e., daily methadone, case management, and weekly

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group therapy) from the same clinical treatment team at the same site.

METHOD Participants Participants in the comprehensive program were 6 (3 male, 3 female) HIV-seropositive patients who met criteria for cocaine and opioid-dependence using the Structured Clinical Interview for DSM-III-R (SCID; Spitzer, Williams, & Gibbon, 1987). Patients included in the comparison group were 8 (5 male, 3 female) HIV-seropositive patients who also met SCID criteria for dependence and who had received standard methadone maintenance treatment in the same facility during the same time period. Patients receiving the comprehensive treatment program did not differ from patients receiving standard care on any measured sociodemographic or drug-use history variable, with the exception of race. All patients receiving the comprehensive treatment program were White; patients receiving standard treatment were equally balanced between White and African American participants. The mean age of the entire sample was 38 (range 26–46); 50% had completed high school; 100% were unemployed. They had been using heroin for 17 (67) years and cocaine for 12 (67) years. All had numerous unsuccessful drug treatments prior to entering treatment. The majority (86%) used cocaine by intravenous route of administration; 14% used by smoking (freebasing).

Procedure and Assessments Buprenorphine and bupropion were provided to patients daily by clinic nursing staff. The manual-guided psychotherapy groups were provided twice weekly by master’s level clinicians, and attendance was recorded (patients attended an average of 20 groups out of a possible 24 [range 18–23]). Cocaine use was assessed by three times weekly urine toxicology screens analyzed using the Tdx method (Poklis, 1987); benzoylecognine levels greater than 300 ng/ml were regarded as positive. All patients provided a cocaine-positive urine within 1 week of entry into treatment, verifying current cocaine use status. Cocaine craving was assessed pre- and posttreatment on a 0 (none) to 10 (extreme) scale. Change in depressive symptomatology was assessed using the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961) pre- and posttreatment.

Strategy for Data Analysis Data analysis proceeded as follows: (a) retention in treatment was analyzed using chi-square analysis; (b) differences between the two treatment groups on rates of co-

A Comprehensive Treatment Program for HIV-Seropositive Injection Drug Users

caine-positive urines were analyzed using a t-test for independent samples (urine screens missed by treatment noncompleters after discontinuation from treatment were coded using end-point values for the remainder of the study period; any missed urine screens that occurred during treatment were coded as positive for cocaine); (c) changes in craving and depressive symptoms were assessed using a 2 (treatment group) 3 2 (time: pre/post) mixed analyses of variance (ANOVA). RESULTS Retention Eleven of the 14 patients (79%) completed 12 weeks of treatment; 87% (7/8) of patients receiving standard treatment completed 12 weeks; 67% (4/6) of patients receiving the comprehensive treatment program completed 12 weeks. This difference was not statistically significant. All noncompleters completed at least 8 weeks of treatment. Outcomes by type of treatment received are shown in Table 1.

Cocaine Use and Cocaine Craving Patients receiving the comprehensive treatment program provided significantly fewer cocaine-positive urines during the study than patients receiving standard care, t(12) 5 2.23, p , .05, and reported significantly greater reductions in cocaine craving (Treatment 3 Time Interaction: F[1, 12] 5 15.96; p , .002). Four of the 6 patients (67%) assigned to the comprehensive program were cocaine abstinent at treatment completion (i.e., provided three consecutive cocaine-free urines). Two of the 8 patients receiving standard treatment (25%) were abstinent from cocaine by study completion. Depression There was a significant Treatment Program 3 Time interaction for Beck depression scores, F(1, 12) 5 9.57;

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p , .009. Improved Beck scores were found for patients assigned to the comprehensive treatment program, whereas Beck scores of patients receiving standard treatment tended to worsen. At entry into treatment, 4 of the 6 patients assigned to the comprehensive program and 4 of the 8 patients assigned to standard treatment had scores in the range of moderate clinical depression (BDI $ 17). At posttreatment, one comprehensive treatment completer and four of the standard treatment completers had Beck scores above 17. The two depressed patients who entered and completed the comprehensive program were cocaine abstinent at study completion, and both had improved Beck scores posttreatment relative to baseline. Only 1 of the 4 depressed patients who completed standard treatment was abstinent by study completion; this patient’s Beck score was elevated at posttreatment relative to baseline. DISCUSSION This preliminary study employed a quasi-experimental design, utilizing historical controls, to compare the outcomes of HIV-seropositive opioid- and cocaine-dependent patients receiving a comprehensive treatment program to the outcomes of patients receiving standard methadone maintenance. There was a significant difference between treatments on the objective measure of cocaine use, as well as significant Treatment 3 Time interactions on self-reported ratings of cocaine craving and depression; patients receiving the comprehensive program submitted significantly fewer cocaine-positive urines than patients receiving standard care and also reported decreases in cocaine craving and depression. Rates of abstinence initiation in the comprehensive treatment program were particularly encouraging. Four of the 6 patients receiving the comprehensive program were abstinent from cocaine at treatment completion, three had been abstinent for 6 or more weeks. Given that these patients reported administering cocaine intravenously at intake, reduced risk of HIV transmission may be an additional favorable outcome. In contrast to the outcomes of patients receiving the comprehensive program, only 2 of the 8 standard care

TABLE 1 Outcomes by Treatment Type

Outcome

Cocaine use: Positive urines (%) Cocaine craving: Pretreatment Posttreatment Beck Depression: Pretreatment Posttreatment

Comprehensive Treatment (n 5 6)

Standard Treatment (n 5 8)

Significance

38.2 (633.3)

74.5 (627.6)

t(12) 5 2.23, p , .05

6.17 (63.4) 0.75 (60.7)

3.43 (62.6) 4.07 (62.1)

Time 3 Tx Interaction F(1, 12) 5 15.96, p , .002

19.8 (613.2) 8.0 (65.7)

13.9 (69.5) 20.1 (612.0)

Time 3 Tx Interaction F(1, 12) 5 9.57, p , .009

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patients were abstinent at treatment completion; 50% of patients receiving standard care achieved no degree of abstinence (i.e., provided cocaine-positive urines every week of the study). We also found that patients receiving standard care tended to report increased depression and cocaine craving over the 12-week study period. The finding of unabated cocaine use by a majority of the patients receiving standard methadone maintenance is of significant concern given the association between cocaine use and HIV transmission (e.g., unsafe needle use, unsafe sexual practices, impaired judgment), as well as between cocaine use and HIV disease progression (Camacho, Brown, & Simpson, 1996; Larrat & Zierler, 1993). Given that our “standard care” treatment program, which included daily methadone, case management, and weekly group therapy, may constitute a more intensive “standard” treatment for cocaine-abusing methadone patients than is typically offered in methadone programs across the country (Ball & Ross, 1991), the need for more effective interventions for this patient population is clear. This preliminary study had several obvious limitations, including a small sample size, lack of random assignment, and an inability to dismantle the effects of the different components of the comprehensive program. The evaluation of comprehensive treatment programs is methodologically complex even with large sample sizes. However, given the recent call by the National Institutes of Health (NIH, 1997) for the development of treatments tailored specifically toward reducing high-risk behaviors by HIV-seropositive individuals, and in light of suggestions that pharmacotherapies are enhanced by the addition of a psychosocial intervention (Onken, Blaine, & Boren, 1995), a multimodal, comprehensive treatment approach may warrant further investigation. Because HIVseropositive patients can be particularly difficult to treat in traditional drug treatment settings, and represent a primary vector of HIV infection to others, the costs of including specialized comprehensive treatment approaches in methadone maintenance programs may be offset by the gains to society in decreased cocaine use and decrease in the spread of HIV. REFERENCES Arndt, I.O., Dorozynsky, L., Woody, G.E., & McLellan, A.T. (1992). Desipramine treatment of cocaine dependent methadone-maintained patients. Archives of General Psychiatry, 49, 888–893. Avants, S.K. (1996). Risk reduction therapy (RRT) for HIV-positive injection drug users. Unpublished treatment manual. Avants, S.K., Margolin, A., McMahon, T., & Kosten, T.R. (1997). Association between self-report of cognitive impairment, HIV status, and cocaine use in a sample of cocaine-dependent methadonemaintained patients. Addictive Behaviors, 22, 599–611. Ball, J.C., & Ross, A. (1991). The effectiveness of methadone maintenance treatment. New York: Springer-Verlag. Batki, S.L., Manfredi, L.B., Jacob, P., & Jones, R.T. (1993). Fluoxetine for cocaine dependence in methadone maintenance: Quantitative plasma and urine cocaine/benzoylecgonine concentrations. Journal of Clinical Psychopharmacology, 13(4), 243–250.

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