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Treatment of Substance Use Disorders 

Treatment of Substance Use Disorders
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Treatment of Substance Use Disorders
DOI:
10.1093/9780195173642.003.0019
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date: 16 October 2018

The high rate of adolescent substance abuse in the United States (Johnsten, O'Malley, & Bachman, 1998) makes the identification of effective treatment approaches a significant priority. Effective early intervention is crucial. Adolescents who initiate alcohol use by age 14 are significantly more likely to develop alcohol dependence as adults than those who initiate use by age 20, with significant reductions in the odds of developing dependence for each year of delayed initiation (Grant & Dawson, 1997). Effective early intervention is also crucial with substance-abusing adolescents because it can play a preventive role in later years (Borduin et al., 1995; Kazdin, 1991, 1993; Santisteban et al., 2003).

While alcohol remains the most commonly used substance (illegal among adolescents; Kandel, & Faust, 1975; Kandel & Yamaguchi, 1993), a marked trend in recent years is the increased use of cannabis among adolescents, which has led to an increased demand for cannabis treatment. From 1992 to 1998, the number of adolescents with primary, secondary, or tertiary problems related to cannabis who presented to the U.S. public treatment system grew from 51,081 to 109,875 (a 115% increase) (Dennis et al., 2002). In 1998, over 80% of these adolescents received treatment in an outpatient setting. The bulk of treatment evaluation studies and clinical trials report the most prevalent types of substance use in clinical populations are alcohol and marijuana, with some cocaine, heroin, methamphetamine, hallucinogen, and polysubstance use as well, based on setting and sample.

Treatment of substance-abusing adolescents is complicated by a number of factors that appear to be particularly prevalent or problematic among adolescents (although they complicate treatment for adults as well). First, as noted previously, adolescents in treatment samples usually use multiple substances, typically alcohol and marijuana with occasional cocaine use (Henggeler, Pickrel, Brondino, & Crouch, 1996; Kaminer, Burleson, & Goldberger, 2002; Winters, Stinchfield, Opland, Weller, & Latimer, 2000) and, increasingly, heroin as well.

Second, as highlighted at several points throughout this volume, substance-using adolescents have very high rates of comorbid psychiatric disorders, which can greatly complicate treatment delivery and outcome. For example, Henggeler et al. (1996) reported that 35% of participants in a clinical trial of family approaches (described in more detail below) met criteria for conduct disorder, 19% for social phobia, 12% for oppositional defiant disorder, and 9% for major depression. In Waldron, Slesnick, Brody, Turner, and Peterson's (2001) sample, 89.8% had a history of significant delinquent behavior, 29.7% met criteria for anxiety and depressive disorders, and 27.3% had attention problems. Kaminer and colleagues (2002) reported that 55% met criteria for an externalizing disorder, 39% for conduct disorder, 18% for attention-deficit hyperactivity disorder (ADHD), 22% for depression, and 26% for an anxiety disorder. As discussed in more detail below, the presence of a comorbid disorder often indicates the need for evaluation for pharmacotherapy as well and for close monitoring of treatment adherence and response. The presence of conduct disorder is particularly significant among substance-abusing adolescents as it is often associated with poor long-term treatment outcome and persistence of antisocial behavior in this population (Myers, Stewart, & Brown, 1998). Moreover, in some circumstances (e.g., deviant adolescents assigned to interactional groups), inclusion of a high proportion of adolescents with conduct disorders in some types of unstructured groups may lead to generally poor outcomes (Arnold & Hughes, 1999; Dishion, McCord, & Poulin, 1999).

Treatment of substance-abusing adolescents is also complicated by high rates of substance abuse in their immediate families. Henggeler et al. (1996) reported that a substance abuse problem was present in 18% of birth mothers and 56% of the fathers of youth in their treatment sample. Winters et al. (2000) reported that 66% of participants had at least one parent with substance use disorder. This complication is significant because parental substance use is associated with poor parenting practices and low levels of parent monitoring, which can further exacerbate adolescent substance use (Chilcoat, Dishion, & Anthony, 1995). Furthermore, exposure to drug use and drug-related cues within the household is likely to provoke craving in established, adolescent substance abusers.

Another obstacle to treatment for adolescents is that adolescents rarely seek treatment voluntarily but are usually coerced at some level after experiencing school, legal, or medical problems (Brown, 1993). Treatment is also complicated by their involvement in the multiple systems in which their legal, school, and medical problems are being addressed, as these problems may be identified prior to recognition of the presence of a substance use disorder (Henggeler, Borduin, & Melton, 1991).

Finally, high attrition from treatment is a particular problem among adolescents, with treatment completion rates for adolescents in therapeutic communities estimated at less than 20%. Completion rates for outpatient programs are generally estimated at 50% (Henggeler et al., 1996).

PSYCHOSOCIAL TREATMENTS

Treatment Evaluation Studies

There are few rigorous evaluations of the effectiveness of standard treatment approaches for adolescents. As of 2001, two major reviews identified between 32 and 53 published studies (Dennis & White, 2003; Williams et al., 2000), 21 of which were published in the last 5 years. Overall, most of these were program evaluation studies of inpatient services, and only about 15 were randomized clinical trials in outpatient settings. The older studies tend to suffer from a range of methodological problems. A number of newer studies have been recently published or are under way. These studies are more likely to have high inclusion rates (over 80%), experimental designs, manualized protocols, standardized measures, validation substudies, repeated measures, long-term follow-up (e.g., 12 or more months), and high follow-up rates (80% to 90% or more). They also include economic analysis of the cost and benefits to society (Dennis & White, 2003).

The existing program evaluation research has focused primarily on four types of programs. First, the bulk of studies have focused on the “Minnesota model,” generally a 4-to 6-week inpatient program that offers a range of services (i.e., individual, group, and family counseling, and school and recreational activities). Many of these programs are guided by an Alcoholics Anonymous or Narcotics Anonymous Twelve-Step orientation. A second major class of treatment delivery is outpatient drug-free programs. These usually consist of individual and group counseling, often with some family involvement. A third, less commonly studied treatment approach for adolescents is the “therapeutic community.” Based on adult therapeutic community approaches, these programs are typically highly disciplined, 6-to 12-month residential programs that tend to offer a Twelve-Step orientation. The final form of treatment that has been investigated is the Outward Bound or life skills training programs. These wilderness programs typically last 3 to 4 weeks and use the challenges of survival and group interdependency as the key therapeutic ingredients.

Until recently, the three more intensive programs (inpatient, residential, and Outward Bound) had received the most attention from investigators. Roughly 30 to 40 studies exist, which involved primarily uncontrolled evaluations of a single treatment program (Williams et al., 2000). In these studies, it is difficult to determine the relative effectiveness of the approach because few included any type of comparison or control group; however, in some studies, patients who dropped out of treatment served as a quasi-experimental control group (although this is clearly not an ideal comparison because of the possibility of selection bias). The primary outcome measures used in these studies are typically abstinence, drug use reduction, and treatment retention, although different studies tend to define these differently. Outcomes are almost always measured by self-report and often taken from clinical records, rather than assessed by an independent evaluator. The use of validated outcome measures or biologic indicators of substance use is rare. Thus, the highly positive outcomes typically reported by these studies should be tempered by an understanding of the substantial limitations of their designs. On average about 50% of patients reported significant decreases in substance use, typically measured as days of any drug use (Williams et al., 2000). Given that most of these programs emphasized complete abstinence, on average only 38% of those followed reported complete abstinence at 6 months.

Evaluation of Outpatient Approaches

Although residential and inpatient treatment warrants more research, focus on improving the effectiveness of outpatient services seems the most promising, given that nearly 80% of adolescents with substance abuse at least initially receive outpatient treatment. In addition, outpatient services have many benefits (e.g., ability to characterize or dictate specific treatments, potential use of randomized designs, larger sample size, etc.).

Although few well-designed treatment evaluations of outpatient services exist, there are some important large-scale studies that involve primarily cannabis use, and these are summarized here. These multisite studies of existing practice generally defined minimal or no treatment as less than 90 days (13 weeks) of outpatient service, even though nearly 80% met that criteria. Changes in days of marijuana use were assessed in most of these studies, allowing some cross-study comparison. Among the 111 to 158 youths (under age 21) followed through the Drug Abuse Reporting Program (DARP; Simpson, Savage, & Sells, 1978; Sells & Simpson, 1979) in the early 1970s, cannabis use rose from 3% to 10% in the 3 years following their discharge. Among the 87 adolescents receiving outpatient treatment in the Treatment Outcome Prospective Study (TOPS; Hubbard, Cavanaugh, Craddock, & Rachel, 1985) in the early 1980s, the change in daily cannabis use from the year before to the year after treatment varied from a decrease of 42% (for those with less than 3 months of treatment) to an increase of 13% (for those with 3 or more months of treatment). Among the 156 adolescents receiving treatment (predominantly outpatient) in the Services Research Outcome Study (SROS) during the late 1980s to early 1990s (Office of Applied Studies, 2000), cannabis use rose 2% to 9% between the year before and 5 years after treatment. Among the 236 adolescents in the National Treatment Improvement Evaluation Study (NTIES; Center for Substance Abuse Treatment [CSAT], 1999; Gerstein & Johnson, 1999) during the early 1990s, there was a 10% to 18% reduction in use between the year before and year after treatment. Among the 445 adolescents followed up after outpatient treatment in the Drug Abuse Treatment Outcome Study of Adolescents (DATOS-A; Grella, Hser, Joshi, Rounds-Bryant, 2001; Hser et al., 2001) in the mid-to late 1990s, there was a 21% to 25% reduction in cannabis use between the years before and after treatment.

The Effectiveness of Specific Approaches: Randomized Clinical Trials

Randomized clinical trials are the gold standard for establishing the efficacy of a given approach, as they are the most rigorous approach that clinical investigators have for evaluating the effectiveness of a given treatment in comparison with a well-defined control treatment and while controlling for multiple threats to internal validity. Although the number of well-designed controlled clinical trials of well-defined treatment approaches for substance-abusing adolescents is steadily increasing, the knowledge base regarding effective treatments continues to lag well behind that for adult substance use disorders. Drawing firm conclusions about treatment outcome and the relative benefits of different approaches is difficult, as there remain only a few controlled clinical trials that meet the rigorous standards required for determining that a treatment be called “empirically supported” (Chambless & Hollon, 1998). Many of the studies reviewed here are characterized by several threats to internal validity, including differential attrition, lack of validated independent outcome measures with objective evaluation of drug use, small sample sizes, lack of specification and evaluation of treatment fidelity and quality, dilution of interventions, and limited follow-up (Cottrell & Boston, 2002; Deas & Thomas, 2001; Kaminer et al., 2002; Waldron, 1997). Thus, with only a few exceptions, caution must be used in making conclusions about the effectiveness of these approaches.

Family and Multisystem Therapies

A key defining feature of family and multisystem approaches is that they treat adolescents in the context of the family and social systems in which substance use develops and may be maintained. Thus, inclusion of family members in treatment (often with the provision of home visits) is seen as a critical strategy for reducing attrition and addressing multiple issues simultaneously (Henggeler et al., 1996; Liddle et al., 2001). Because they are grounded solidly in the knowledge base on adolescents and development and thus are well suited to the specific problems of this population, family-based approaches have been among the most widely studied approaches for adolescents in controlled trials and have the highest levels of empirical support (Deas & Thomas, 2001; Liddle & Dakof, 1995; Waldron, 1997). Waldron et al. (2001) summarizes their success as follows:

Reviews of formal clinical trials of family-based treatments have consistently found that more drug-abusing adolescents enter, engage in, and remain in family therapy than in other treatments and that family therapy produces significant reductions in substance use from pre-to post-treatment.In seven of eight studies comparing family therapy with a non-family-based intervention, adolescents receiving family therapy showed greater reductions in substance use than did those receiving adolescent group therapy, family education, and individual therapy, individual tracking through schools, or juvenile justice system interventions.

Moreover, the high level of support for family and multisystemic approaches parallels findings from large meta-analyses pointing to the effectiveness of family therapies for adult substance users (Stanton & Shadish, 1997). It should be noted that family-based approaches are diverse, and many combine a variety of techniques, including family and individual therapies and skills and communication training, which may broaden the benefits of treatment by allowing greater individualization and enabling clinicians to address multiple factors in treatment (Waldron et al., 2001). Those family-based approaches with the highest level of support with this population include multisystemic therapy (MST) (Henggeler & Borduin, 1990), brief strategic family therapy (Szapocznik & Hervis, 2003), and multidimensional family therapy (Liddle et al., 2001).

Multisystemic therapy (MST) is a manualized approach that addresses the multiple determinants of drug use and antisocial behavior. It is intended to promote fuller family involvement through engaging family members as collaborators in treatment, stressing the strength of the youth and their families, and addressing a broad and comprehensive array of barriers to attaining treatment goals. Therapists must be familiar with several empirically based therapies (including structural family therapy and cognitive-behavioral therapy) and make frequent visits to the home and be available on a full-time basis to families. Henggeler and colleagues (1996) conducted a controlled trial with 118 substance-abusing or substance-dependent juvenile offenders (mean age 16) in which participants were randomly assigned to home-based MST and compared with usual community treatment services. The comparison condition involved referral by the youth's probation officer to outpatient adolescent group meetings. Ninety-eight percent of families completed a full course of treatment (an average of 130 days and 40 hr of service provision), compared with very little service access among the youth assigned to the control group (78% of youths received no substance abuse or mental health services, and only 5% received both substance use and mental health services). In other studies, MST has been shown to reduce re-arrest rates up to 64% and to be associated with significantly lower rates of substance-related arrests (Henggeler et al., 1991; Henggeler, Melton, Brondino, Scherer, & Hanley, 1997).

Brief strategic family therapy (BSFT; Szapocznik & Hervis, 2003) is a somewhat less intensive approach (as it targets fewer systems and can be delivered through a once-per-week office- based format) that has also achieved an impressive level of empirical support. In BSFT, patterns of interaction in the family system are targeted that have been shown to influence adolescent drug abuse. The therapy consists of three classes of interventions: engaging all family members in treatment, identifying family strengths as well as roles and relationships linked to adolescent problems, and developing new family interactions (e.g., improved parenting skills and conflict resolution) to protect the adolescent. Home visits and use of specific engagement strategies are encouraged. In a study of 126 drug-abusing adolescents and their families that compared BSFT to a group control condition, 75% of those assigned to BSFT showed reliable improvement and 56% could be classified as recovered. In the control condition, only 14% showed reliable improvement, whereas 43% showed reliable deterioration in marijuana use (Santisteban et al., 2003). Brief strategic family therapy has also been shown to be associated with improved retention (Santisteban et al., 1996; Szapocznik et al., 1988) as well as significant reductions in the frequency of externalizing behaviors (aggression, delinquency) (Szapocznik, Kurtines, Foote, Perez-Vidal, & Hervis, 1986).

Multidimensional family therapy (MDFT) is a multicomponent, staged, family therapy that targets the substance-abusing adolescents, their families, and their interactions. Liddle and colleagues (2001) assigned 182 substance-abusing adolescents who were referred by the criminal justice system or the schools to either MDFT, group therapy, or multifamily education. Treatment was delivered in weekly sessions over 6 months, with roughly 70% of participants completing treatment across conditions. Superior outcomes for the adolescents assigned to MDFT relative to other approaches were seen at termination and 1-year follow-up. At termination, 42% of those assigned to MDFT, 25% of those in group therapy, and 32% of those in family education had clinically significant reductions in their drug use. Positive outcomes have also been reported for other models of family therapy, including family system therapy (Joanning, Thomas, & Quinn, 1992) and functional family therapy (Friedman, 1989).

Behavioral Therapies

A wide range of individual behavioral interventions, including those which seek to provide alternate reinforcers to drugs or reduce reinforcing aspects of abused substances, are based on operant conditioning theory and recognition of the reinforcing properties of abused substances (Aigner, 1978; Bigelow, Stitzer, & Liebson, 1984; Thompson & Pickens, 1971). Among adult substance users, these approaches have among the highest of empirical support (Griffith, Rowan-Szal, Roark, & Simpson, 2000; National Institute on Drug Abuse [NIDA], 2000). Examples include the work of Stitzer and colleagues, which has demonstrated that methadone-maintained opi-oid addicts will reduce illicit drug use when incentives such as take-home methadone are offered for abstinence (Stitzer & Bigelow, 1978; Stitzer, Iguchi, & Felch, 1992; Stitzer, Iguchi, Kidorf, & Bigelow, 1993). Contingency management incentive systems (Budney & Higgins, 1998; Budney, Higgins, Radonovich, & Novy, 2000; Higgins, Delany, Budney, Bickel, Hughes, et al., 1991, 1999; Kirby, Marlowe, Festinger, Lamb, & Platt, 1998; Petry, Martin, Cooney, & Kranzler, 2000; Silverman et al., 1996) offer incentives for targeted treatment goals (e.g., retention, drug-free urines) on an escalating schedule of reinforcement.

Behavioral approaches have only recently begun to be evaluated among substance-abusing adolescents. Azrin, Donahue, and Besalel (1994) assigned 26 substance-using adolescents to supportive counseling or behavior therapy, which consisted of therapist modeling and rehearsal, self-monitoring, and written assignments. After 6 months, urine toxicology screens and self-reports suggested significantly less substance abuse among the group assigned to behavioral therapy relative to supportive counseling, as well as better school and family functioning.

Contingency management approaches have not yet been widely used or evaluated with adolescents. In a feasibility study that involved adolescent smokers as a model for drug use, Corby, Roll, Ledgerwood, and Schuster (2000) found that providing cash incentives for not smoking to adolescents enrolled in a smoking cessation project (as assessed by twice daily CO levels) re duced adolescent smoking and appeared to improve their mood. In a pilot study involving young adult marijuana users referred by the criminal justice system, Sinha, Easton, and Kemp (2003) studied the use of vouchers that could be used to purchase items in neighborhood stores. By providing these vouchers as rewards contingent on session attendance, treatment retention improved significantly.

Cognitive-Behavioral Therapies

Cognitive-behavioral approaches, based on social learning theory, are among the approaches with highest levels of empirical support for the treatment of adult substance use disorders. Key defining features of most cognitive-behavioral approaches for substance use disorders are (1) an emphasis on functional analysis of drug use, that is, understanding instances of substance use with respect to its antecedents and consequences, and (2) emphasis on skills training and self-regulation. Cognitive-behavioral therapy (CBT) has been shown to be effective across a wide range of substance use disorders (Carroll, 1996; Bowers, Dunn, & Wong, Irvin, 1999), including alcohol dependence (Miller & Wilbourne, 2002; Morgenstern & Longabaugh, 2000), marijuana dependence (MTP Research Group, 2001; Stephens, Roffman, & Curtin, 2000), cocaine dependence (Carroll, Rounsa-ville & Nich, 1994; Carroll, Nich, Ball, McCance-Katz, & Rounsaville, 1998; McKay, 1997; Rohsenow, Montl, Martin, Michalec, & Abrams, 2000), and nicotine dependence (Fiore, Smith, Jorenberg, & Baker, 1994; Hall, 1998; Patten et al., 1998). These findings are consistent with evidence supporting the effectiveness of CBT across a number of other psychiatric disorders as well, including depression, anxiety disorders, and eating disorders (DeRubeis & Crits-Christoph, 1998).

Cognitive-behavioral therapy has also been evaluated as a treatment for adolescent substance use disorders. In an extremely well-done study, Waldron and colleagues (2001) randomly assigned 120 adolescents who were abusers of illicit drugs (primarily marijuana) to one of four treatment conditions: family therapy alone (functional family therapy), individual CBT alone, a combination of individual and family therapy, and a psychoeducational group. Completion rates were high (70% to 80% across groups). In general, while there were meaningful reductions in drug use in all conditions, there were larger and more durable reductions in substance use for the combined and family conditions relative to the individual CBT and group conditions. Treatment effects were strongest immediately after treatment but persisted through a 7-month follow-up.

Kaminer and colleagues (2002) compared group CBT to psychoeducational substance abuse treatment for 88 adolescents referred for treatment of a substance abuse problem. Eighty-six percent of the sample completed treatment and 9-month follow-up data were available for 65% of the sample. The presence of a conduct disorder was associated with treatment dropout. Cognitive-behavioral therapy was significantly more effective than psychoeducation only for male subjects; females appeared to improve regardless of treatment condition. Nevertheless, there were no significant differences between the two conditions at the 9-month follow-up. The relatively high rates of relapse in this sample (52% had a urinalysis that was positive for marijuana at the 9-month follow-up evaluation) suggest that an eight-session stand-alone approach may not be adequately intensive or structured for this population.

Motivational Approaches

Motivational approaches are brief treatment approaches designed to produce rapid, internally motivated change in addictive behavior and other problem behaviors. Grounded in principles of motivational psychology and patient-centered counseling, motivational interviewing (MI; Miller & Rollnick, 1991, 2002) arose out of several recent theoretical and empirical advances (Miller, 2000). Motivational interviewing has a high level of empirical support in the adult substance abuse treatment literature (Burke, Arkowitz, & Menchola, 2003; Dunn, Deroo, & Rivara, 2001; Miller, 2002; Wilk, Jensen, & Havighurst, 1997). The core principles of MI are as follows: (1) express empathy; (2) develop discrepancy; (3) avoid argumentation; (4) roll with resistance; (5) support self-efficacy. Motivational interviewing makes the important assumption that ambivalence and fluctuating motivations define substance abuse recovery and need to be thoroughly explored rather than confronted harshly. Ambivalence is considered a normal event, not something that indicates the patient is unsuitable for treatment or needs vigorous confrontation in hopes of forcing a sudden change. The patient's point of view is respected, which in some cases may mean accepting that major change, or even any change, is not what the patient wants, at least at the present time (Carroll, Ball, & Martino, 2004). Thus, while the bulk of research on efficacy of MI is in the adult literature, this nonconfrontational approach appears quite well suited for application to adolescents and young adults, given its flexibility around goals and recognition of abstinence as part of the change process.

Another distinct advantage of using MI with adolescent populations is that it can be implemented in a range of settings, given that adolescents with substance abuse problems rarely seek treatment of their own volition in traditional substance abuse settings. Monti and colleagues (1999) studied 94 adolescents treated at an emergency room for a problem related to alcohol use (e.g., injuries related to drinking, drunk driving). They were randomly assigned to MI or standard care, with all interventions and assessments conducted in the emergency room. At a 6-month follow-up, there were significantly fewer incidents of drunk driving, traffic violations, and alcohol-related problems in the group assigned to receive MI. Not only does this study suggest the promise of brief motivational approaches for this population, but it also underlines the importance of intervening with adolescents in nontraditional settings.

Disease Model Approaches

While disease model treatments and other approaches associated with the Twelve Steps of Alcoholics Anonymous dominate the treatment system for both adults and adolescents, there are no randomized controlled trials evaluating the effectiveness of these approaches in adolescents. Recent reports from randomized controlled trials evaluating the efficacy of manualized Twelve-Step approaches have found evidence to suggest their effectiveness with adult substance users (Carroll et al., 1998; Crits-Christoph et al., 1999; Project MATCH Research Group, 1997). It is important to note, however, that these manual-guided approaches are highly structured, delivered as individual (rather than group) therapy, and might be quite different from the nonmanualized group approaches typically delivered in community settings with adolescents. In addition, since individual drug counseling emphasizes and encourages frequent Twelve-Step group attendance, its effectiveness might reflect increased patient involvement in rehabilitative groups. It is important to note that the absence of sufficient research on Twelve-Step treatment should not lead one to conclude that this widespread and popular approach is ineffective.

Data on the effectiveness of more traditional programs are beginning to emerge, but no data from randomized trials comparing these approaches to alternatives are available. Winters and colleagues (2000) reported on a large nonrandomized evaluation comparing a group of substance-abusing youth who completed the Twelve-Step Minnesota Model treatment to similar individuals who did not complete treatment and to a group on a waiting list for treatment. The treatment was multimodal, based on the principles of the Twelve Steps of Alcoholics Anonymous, and included group therapy and individual counseling, family therapy, lectures about the Twelve Steps, and reading assignments. Better substance use and psychosocial outcomes at 6 and 12 months were reported for those who completed treatment compared with those who did not complete or who did not receive treatment. Although a high rate of abstinence was reported among treatment completers, it is difficult to interpret these findings, given the self-selection due to lack of randomization and lack of measurement of treatment delivery or process.

Multisite Studies Comparing Several Approaches

Recently, the Center for Substance Abuse Treatment (CSAT) funded the largest multisite clinical trial comparing an array of diverse outpatient treatments targeting adolescent marijuana abuse and dependence. The study, conducted at four sites, involved 600 randomized patients and evaluated five manualized treatments. Notably, the study had a follow-up rate of 95% for up to 30 months. Treatment modalities covered the full range of treatments (individual, group, family, and comprehensive multicomponent) that took place between 5 and 12 weeks and included 6 to 21 sessions (Diamond et al., 2002). All five treatments performed equally well and were associated with marked (50%) reductions in frequency of marijuana use; these improvements were maintained through a 30-month follow-up evaluation. It is noteworthy that these very promising outcomes were seen even for the less costly 6-week, five-session treatment.

Process Research and Mechanisms of Action

As new effective therapies for adolescents are identified, it is imperative that the field move toward evaluating how these treatments exert their effects, by looking at mediators and moderators of outcome. Several recent investigations have examined these variables. In terms of retention and engagement, Szapocznik and colleagues' impressive work on engaging teens and families in treatment has been replicated and further developed (e.g., Coatsworth, Santisteban, McBride, & Szapocznik, 2001; Santisteban et al., 1996). Henggeler and colleagues (1996) demonstrated a 98% treatment completion rate for home-based MST (Szapocznik et al., 1983). They have also demonstrated that adherence to the treatment was significantly associated with better treatment outcome. Liddle and colleagues have conducted several process studies looking at mechanisms of change, including in-session patterns of change associated with the resolution of parent–adolescent conflict (Diamond & Liddle, 1996) and the link between improvement in parenting and better substance use outcome (Schmidt, Liddle, & Dakof, 1996). These kinds of studies will help identify key treatment ingredients that might lead to increased treatment potency.

Assessment

Another area relevant to treatment research that may be influenced by developmental perspective concerns assessment. While self-report of substance use by adolescents has been confirmed as fairly reliable (Buchan, Dennis, Tims, & Diamond, 2002), recent analysis from the Cannabis Youth Treatment Study suggests the addition of parent reports adds additional information not provided by the adolescent. Although adolescents and parents reported about the same number of substance use symptoms, there was a very low concordance between the types of symptom endorsed. Parents tended to report more symptoms related to role failure, tolerance, and substance-induced psychological problems (Dennis, Babor, Roebuck, & Donaldson, 2002). Similar findings were discovered regarding mental health symptoms. Specifically, parents tended to endorse more symptoms of depression and attention problems (Diamond, Panichelli-Mindel, Shera, Tims, & Ungemack, in press). This was particularly true for African-American adolescents. Thus parent report may have a unique contribution when working with a minority population, a community that has been characterized as suspicious of the research community.

The Challenge of Comorbidity

One area that has received strikingly little research with adolescents is the integration of substance use and other mental health services that can treat adolescents with both kinds of disorders. Historically there has been a divide between treatment systems for substance abuse and mental health disorders. Substance abuse counselors often have little or no training in mental health issues, and programs either ignore co-occurring problems or refer patients to other systems during (parallel) or after (sequential) substance abuse treatment. There is emerging consensus that lack of integration leads to poor coordination of services, interagency miscommunication, and funding conflicts, all of which contribute to attrition and poor outcomes for patients (Osher & Drake, 1996; Report to Congress, 2002). This is particularly troubling since co-occurring mental health distress is associated with substance use severity, greater psychosocial impairment, treatment resistance, and poorer long-term prognosis (Diamond, Panichelli-Mindel, Shera, Tims, & Ungemack, in press; Drake, Mueser, Clark, & Wallach, 1996; Shane et al., under review). Consequently, the most severe and chronic patients often receive the poorest care, leading to repeated visits to hospital emergency rooms and inpatient and residential facilities (Richardson, Craig, & Haughland, 1995). The end result is that comorbid patients in need of care are consuming a major portion of treatment funding (Ridgely, Goldman, & Willenbring, 1990).

The gap between substance abuse and mental health dates back to the 1930s (Rosenthal & Westreich, 1999). At that time, psychodynamic therapists, who dominated the treatment world, believed that addicts' personality structure was not amenable to the analytic method, and therefore addicts were not treatable. This attitude may persist today among practitioners in the mental health community, who tend to view addiction as inhibiting treatment of other “underlying” problems. Simultaneously, the self-help movement developed independent of the mental health community, and as the self-help philosophies and programs matured, educational and professional licensure pathways emerged that legitimized and strengthened these approaches (Rosenthal & Westreich, 1999). As often happens, these ideological differences became institutionalized and perpetuated a division that does not reflect the clinical realities of the patients.

Recognition of this schism has inspired many attempts to integrate substance abuse and mental health treatment programs for adult dual-diagnosis populations (Drake, Mchugo, & Noordsy, 1993; Miller & DelBoca, 1994; Minkoff & Drake, 1991). At least 36 studies have evaluated different versions of integrated programs at all levels of care (e.g., outpatient, day treatment, inpatient, residential, etc). Some studies added a substance abuse group to outpatient mental health services, resulting in reduced dropout, decreased hospitalization, and increased abstinence (e.g., Hellerstein, Rosenthal, & Miner, 2001; Osher & Kofoed, 1989). Studies that combined substance abuse services with inpatient, day treatment, and residential care have also shown some benefits as long as patients remained in the program. Unfortunately, attrition was often high and once patients were discharged, relapse rates were high as well (e.g., Rahav et al., 1995).

A major contribution to this area was the 1987 funding of 13 dual-diagnosis demonstration projects. These studies demonstrated that integrated programs could be implemented in a number of settings, resulting in increased engagement and services utilization and reduced drug use. Five recent studies were conducted on comprehensive integrated systems using more sophisticated treatment programs and quasiexperimental or true experimental designs (e.g., Drake, Mercer-McFadden, Muesser, McHugo, & Blond, 1998; Ridgely & Lambert, 1999; Godley, 1994; Jerrell & Ridgely, 1995). These studies showed significant reductions in substance use, program readmission, and hospitalization and improvement in other functional outcomes (Drake et al., 1998). However, there has been little or no comparable research on the effectiveness of integrated programs for adolescent substance users.

Summary of Psychosocial Treatment

Clinical research during the past 10 years has identified a number of effective treatments for adolescent substance users. Although the field is still young, this growing body of work has yielded several important findings that support the effectiveness of carefully implemented, structured behavioral approaches for adolescent substance use (Liddle & Rowe, in press; Stanton & Shaddish, 1997; Williams et al., 2000). These can be summarized as follows:

  • The field has been inadequately studied.

  • Most studies indicate that treatment can be effective for most adolescents. In most stud ies, well-defined structured approaches tend to be more effective and durable at reducing adolescent substance use and improving related problems than no treatment, treatment as usual, or other comparison approaches. Treatments that focus on broad aspects of functioning seem to be most promising (Williams et al., 2000). That is, in addition to addressing substance use, interventions should also target other domains such as family functioning, school success, delinquency, peer group associations, and other risky behaviors.

  • Adolescents who complete treatment tend to have the best outcomes, although this may be related to factors such as higher motivation for treatment, better or more intact family and social supports, less severe substance use, better school competency, and less psychopathology, all of which are associated with more treatment success.

  • In general, inclusion of family members improves retention and outcome among substance-using adolescents. To date, there is no evidence from controlled studies that involvement of family members in treatment has a negative effect on outcome. In the studies of family-based therapy reviewed here, retention rates were generally high (in the 70% to 80% range), and retention was often sustained over comparatively long periods. At least two studies have demonstrated that outpatient family therapy was more effective and less costly than residential placement (Liddle & Dakof, 2002; Schoenwald et al., 1996). Finally, long-term effectiveness of family-based models has also gained some empirical support (Henggler, Schoenwald, Borduin, Rowland, & Cunningham, 1998; Stanton & Shadish, 1997).

  • Behavioral therapies, especially those that target multiple systems, also appear to have some promise. However, contingency management approaches, which have been shown to be highly flexible and effective with a range of adult populations, have only rarely been applied to adolescents. The success of these approaches among adult populations suggests great promise in the treatment of adolescents. Contingency management approaches might be used, for example, to target retention, encourage patients to meet specific treatment goals (e.g., reducing truancy and improving school performance), or enhance compliance with pharmacotherapies (Carroll, Ball, & Martino, 2004). The literature indicates that adults with antisocial personality disorders respond relatively well to contingency management approaches (Messina, Farabee, & Rawson, 2003). In view of the high rates of conduct and externalizing disorders among substance-abusing adolescents, further evaluation of contingency management approaches with this population is warranted.

  • Cognitive-behavioral approaches appear to have some promise, but the existing evidence suggests they may be most effective when delivered in conjunction with family therapy. The delayed emergence of effects after CBT that have been noted after termination of treatment with adults (Carroll, Rounsaville, Nitch, et al., 1994; Rawson et al., 2002) has not been reported among adolescent populations. However, CBT has generally been delivered to adolescents in a group format and for a comparatively brief period. Longer or more intensive CBT approaches, or delivery of CBT as an individual treatment, may be necessary with this population.

  • The data suggesting that some deviant, high-risk adolescents may escalate problem behavior in the contexts of interventions delivered in peer groups (Dishion et al., 1999) have important implications for behavioral treatments of substance-using youth. While poor outcomes for group approaches for adolescents have not uniformly been reported in the studies reviewed here, it is clearly important to be aware of this possibility when group approaches are used, to monitor behavior closely, and to involve adults and parents as well.

PHARMACOLOGICAL TREATMENTS

Pharmacotherapy for substance dependence is a relatively young field of medicine, and the proven treatments for adults have not been adequately researched in adolescents. Therefore, few conclusions regarding this modality can be stated conclusively at this time. However, the actual usage of pharmacotherapy for psychiatric syndromes has been steadily increasing among adolescents and children for the last 15 years, despite lack of data. Prescriptions for these young patients between 1987 and 1996 rose 300% overall (Magno Zito et al., 2003). By 1996 stimulants and antidepressants were ranked first and second in terms of total prescriptions. These two medications also had the greatest increase in prescribing (400% each): stimulant prescribing rose from 10/1,000 youth to 40/1,000 youth, and antidepressants rose from 3/1,000 to 13/1,000.

What does this phenomenal increase in psychopharmacology reflect in the medical and psychiatric evaluation of adolescents? Does it have any relationship to substance abuse, which has also been rising among these adolescents and children? There is probably a strong association, since adolescents who abuse drugs and have substance use disorders typically have behavioral problems, skills deficits, academic difficulties, family problems, and mental health problems (Tarter, 2002; Tims et al., 2002). While these problems usually reflect more than neurochemical defects that may be reversed with medications, adolescents with substance dependence and comorbid psychiatric disorders can benefit from pharmacotherapy. But pharmacotherapy should be justified by careful evaluations of the diagnoses in these young patients. These medical and psychiatric evaluations can be informed by structured interviews for common comorbid disorders such as depression and bipolar disorders, ADHD, and substance dependence. Medical disorders including infections, endocrine problems, and various developmental disorders also need consideration, but are beyond this review.

Adolescents who enter substance abuse treatment programs are more likely than non–drug-abusing peers to have experienced abuse or neglect, to have significant family problems, and to have developed a psychiatric disorder during childhood such as ADHD and mood disorder. These behavioral, psychosocial, and mental health problems are coupled with the neurohormonal changes of puberty and lead to poor adjustment in the school environment, thereby increasing the risk for school failure (Riggs & Whitmore, 1999; Tarter, 2002). These school experiences may also lead to the early onset of substance abuse (Crowley & Riggs, 1995; Rutter, Giller, & Hagell, 1998). Substance abuse exacerbates preexisting psychiatric disorders such as ADHD as well as mood and anxiety disorders (Kruesi et al., 1990; Markou, Kosten, & Koob, 1998; Rutter et al., 1998).

The multidimensionality of the problems that substance-abusing youth typically bring to treatment underscores their need for multimodal treatment that addresses a broad range of mental health and psychosocial problems integrated with treatment for drug abuse. The role of pharmacotherapy targeted specifically to substance abuse may therefore be relatively limited, and there is no research base to provide guidance on dosing or duration of treatment for adolescents with dependence on alcohol, nicotine, opiates, or other addictions for which we have pharmacotherapies. Furthermore, the other most commonly abused drug, cannabis, has no specific pharmacotherapy. Pharmacotherapies are also entirely lacking for club drugs such as MDMA, GHB, and various hallucinogens.

Specific Pharmacotherapy for Substance Use Disorders in Adolescents

Given the clinical importance of drug euphoria and drug craving, most pharmacological strategies for addiction target these primary reinforcers. Drug-induced reward is attenuated in animal models by a number of agents, depending on the drug in question. These medications act on dopamine, opioid, glutamate, or GABA systems. These reward-blocking medications have been tested in human substance abusers to determine whether they reduce drug euphoria under controlled settings or promote abstinence in clinical trials. Other means of reducing reward have also been tested, including vaccines that block the entry of an addictive substance into the brain, and agents like disulfiram that produce aversive symptoms when alcohol is consumed. In addition to strategies that reduce drug euphoria, strategies that reduce craving have also been tested and prescribed. Agonist treatment (prescribing a substance that replaces the addictive drug) has been used in opioid (e.g., methadone, buprenorphine) and nicotine (e.g., nicotine gum) dependence with considerable success, providing a means of bypassing dangerous routes of administration or hazards associated with drug procurement. The reversing of clinically relevant neuroadaptations associated with chronic exposure to addictive substances has the theoretical ability to reduce craving and other aversive aspects of addiction.

Unfortunately, there has been little research directed toward the pharmacological treatment of substance dependence in adolescents. For a number of reasons, there are no controlled trials evaluating the effectiveness of substitution or replacement therapies (e.g., methadone, buprenorphine), antagonists (e.g., naltrexone), aversive therapies (e.g., disulfiram), or anticraving medications (e.g., bupropion, naltrexone) in this subpopulation. Therefore, if such medications are used in adolescents, they must be used with caution, careful monitoring, and consideration of the developmental characteristics that distinguish adult patients from adolescents (e.g., greater impulsivity and polydrug use; Solhkhah & Grenyer, 1998). More research is clearly needed in this area.

Since the most commonly abused substances by adolescents are nicotine, alcohol, and cannabis, these are the most likely drugs for which pharmacotherapy questions might arise. We will review these medications briefly, starting with those used in detoxification. Advances in our understanding of the mechanisms of drug craving and drug-induced euphoria should guide future research and shed light on more effective pharmacological treatments for addiction in adolescents.

Detoxification

Medical detoxification is required for alcohol, sedatives, and opiates, but not for other abused drugs. Detoxification from alcohol dependence can be effectively attained by using benzodiazepines or barbiturates, and anticonvulsants such as valproate and carbamazepine to block or reverse withdrawal symptoms (Kosten & O'Connor, 2003). These detoxification medications should be used in adolescents if withdrawal symptoms are significant, particularly because alcohol withdrawal is potentially life threatening. Detoxification from sedative hypnotic dependence can also be accomplished by prescribing descending doses of benzodiazepines and barbiturates.

For opioid dependence, the most common means of detoxification involves prescribing descending doses of methadone for a period of 2 to 4 days while carefully monitoring the patient's response. Methadone is a long-acting opioid agonist that reverses heroin withdrawal by replacing heroin at the opioid receptor. Since methadone has the potential to cause lethal opioid overdose, and opioid withdrawal is not medically dangerous, it is imperative to avoid prescribing an excessive dose of methadone to adolescents. The appropriate dose is best selected by closely monitoring the signs of opioid withdrawal, which should be given more weight than reported symptoms that might be exaggerated or feigned by drug-seeking patients.

A new treatment for detoxification and maintenance, the partial agonist buprenorphine, was made available in the United States in 2003. It may be ideally suited to adolescents and is currently in clinical trials in this population. Detoxification with this medication is very simple because overdose is almost impossible. The patient can be transferred from the opiate of abuse to buprenorphine and then the dose is gradually reduced with minimal or absent withdrawal symptoms. Yet another option is the nonopioid clonidine, an antihypertensive medication that blocks many of the opiate withdrawal symptoms (Gold, Dackis, & Washton, 1984). Most patients prefer methadone or buprenorphine because of greater comfort.

The treatment of heroin and other opioid dependence often begins with inpatient detoxification of heroin withdrawal that should also involve specialized drug rehabilitation and aftercare referral (Dackis & O'Brien, 2003b). Unfortunately, considerable availability and access problems preclude many adolescents from receiving appropriate inpatient treatment. Still, hospitalization is the safest and most conservative treatment approach to this potentially lethal condition (Dackis & Gold, 1992). Inpatient treatment provides a controlled environment in which abstinence can be assured while a comprehensive medical and psychiatric evaluation is conducted. The high mortality rate in intravenous adolescent heroin users results not only from overdose but also from trauma, medical conditions related to the use of needles, and the concomitant use of other drugs and alcohol. Therefore, as reviewed elsewhere (Dackis & Gold, 1992), a comprehensive physical examination, medical history, and laboratory evaluation are indicated in all addicted adolescents.

Familiarity with the medical and psychiatric complications of heroin dependence enhances the clinician's ability to identify and treat these commonly occurring conditions. Infections related to intravenous heroin use include acquired immunodeficiency syndrome (AIDS), viral hepatitis, endocarditis, meningitis, tuberculosis, abscesses, infected injection sites, and pneumonia. Additionally, unprotected sex is common among addicted adolescents (Crome, Christian, & Green, 1998), leading to a preponderance of sexually transmitted diseases. Heroin often produces irregular menses in women and sexual performance problems in men, apparently by dysregulating the hypothalamic–pituitary–gonadal axis (Malik, Khan, Jabbar, & Iqbal, 1992). The most common psychiatric problem associated with heroin dependence is depression (Handelsman, Aronson, Ness, Cochrane, & Kanof, 1992), which should be expeditiously identified and appropriately treated to avoid the risk of suicide and to facilitate the recovery process.

Inpatient detoxification treatment should not be restricted merely to the medical management of heroin withdrawal. This intensive intervention provides the physician with an ideal opportunity to establish a therapeutic alliance with adolescent patients by concomitantly addressing the critical treatment issues of honesty, openness, trust, denial, and engagement. Inpatient detoxification also provides an opportunity to fully evaluate the patient, assess their readiness for change, and provide critical family therapy. Since families require education, support, and guidance throughout the process, clinicians should be familiar with psychosocial as well as medical aspects of heroin addiction. It is essential to emphasize that detoxification, in and of itself, is not sufficient treatment for heroin dependence and must therefore be followed by ongoing outpatient drug rehabilitation. The recent fad of very rapid detoxification with general anesthesia has not been shown to produce better outcomes than standard detoxification.

Abstinence and Relapse Prevention

The nature of addiction requires that, after detoxification, complete abstinence be the treatment goal for addicted adolescents, rather than the mere reduction of drug and alcohol use. Once the cycle of addiction has become entrenched, casual use is seldom possible. Indeed, even the use of other addictive agents, such as alcohol by a cocaine-dependent adolescent, often leads to relapse to the drug of choice. Thus, total abstinence from all addicting drugs should be the goal when treating adolescents. After attaining abstinence, preventing relapse to drug dependence is the primary clinical target in adolescents, and to that end, medications for relapse prevention are likely to be useful. A few specific relapse prevention pharmacotherapies are U.S. Food and Drug Administration (FDA) approved for nicotine and alcohol, but none has been tested in adolescents. For nicotine the medications are nicotine replacement and bupropion, and for alcohol the medications are disulfiram and naltrexone. However, before medicating adolescents, it is imperative to determine that they will be cooperative, that parental consent has been obtained, and that the adolescents and parents have the same understanding of treatment goals and approaches.

Adolescent Smoking Cessation Research

Despite the prevalence of adolescent tobacco use and nicotine dependence, there have been relatively fewer studies that evaluate adolescent smoking treatment programs. The settings for and approaches to the treatment of adolescent tobacco use are similar to those described for adolescent smoking prevention, with the addition of pharmacological approaches. However, the challenges inherent in adolescent smoking treatment appear to be greater than those for prevention. Recruitment to adolescent smoking treatment programs is difficult, in part because of adolescents' desires to keep their smoking practices confidential. Moreover, among those adolescents who enroll in treatment programs, attrition rates are very high (Mermelstein, 2003).

For the most part, available data on the effectiveness of adolescent smoking treatment have been disappointing. Quit rates for adolescents receiving behavioral smoking cessation treatment are roughly 10% to 15%, compared with 5% to 10% in control conditions (Pomerleau, Pomerleau, & Namenek, 1998). The results of pharmacological trials using nicotine replacement therapy (e.g., nicotine patch) have also been disappointing, yielding 6-month quit rates of only 5% (Hurt et al., 2000; Smith et al., 1996). While not yet thoroughly investigated, interventions delivered by pediatricians and family physicians may have great promise for assisting youth to quit smoking (Pbert et al., 2003). Adolescents with comorbid psychiatric conditions are an important target group for treatment, given the greater predisposition to tobacco use (Moolchan, Ernst, & Henningfield, 2000).

Medications for Smoking Cessation

Because nicotine replacement therapy (NRT) is readily available in over-the-counter preparations, many adolescents have already used these agents before seeing practitioners. Low-dose NRT is clearly preferable to smoking cigarettes, given the risks of lung damage that are associated with inhaling carbon monoxide and carcinogens. The forms of NRT include patches, gum, inhalers (oral absorptions), nasal spray, and lozenges (McCance & Kosten, 1998). If NRT is used, it should probably be discontinued after 8 to 12 weeks to avoid continued nicotine dependence. Although some patients continue to use nicotine gum for up to a year, such an extended duration of treatment should probably be discouraged in NRT-treated adolescents. In summary, NRT may be a reasonable treatment for adolescents who want to quit smoking and are experiencing acute withdrawal symptoms that interfere with abstinence.

Bupropion has a long record of relatively safe use in depression, and several large studies have shown its efficacy for smoking cessation in adults, with higher success rates than NRT alone (McCance & Kosten, 1998). Thus, this medication is another option for treating adolescents who want to quit smoking. Recent discussion has considered vaccines for nicotine dependence (Kosten & Biegel, 2002). These immunotherapies can attenuate the rewarding effects of nicotine and have been considered as a potential prophylactic for preventing nicotine dependence. Immunotherapies might also be used as a secondary prevention for adolescents who have begun to smoke (Kosten & Biegel, 2002). However, this type of invasive and long-lasting intervention has potential ethical problems, particularly in adolescents who do not want to stop smoking.

Medications for Alcohol Abuse and Alcoholism in Adolescents

One of the actions of alcohol in the body is to release endogenous opioids. Thus a drug such as naltrexone that blocks opiate receptors will reduce the reward of alcohol and help to prevent relapse. The majority of controlled studies have shown that naltrexone increases abstinence. Although there are case reports in adolescents (Lifrak et al., 1997), no controlled studies of naltrexone have been conducted in this population. Side effects of naltrexone in adults have generally been minimal at usual doses. Naltrexone also has substantial hormonal effects that include raising cortisol and various sex hormone levels (e.g., luteinizing hormone), and these actions could interfere with growth and development in adolescents (Morgan & Kosten, 1990).

Disulfiram promotes abstinence by blocking the metabolism of alcohol, resulting in the production of acetaldehyde, a noxious compound. It can produce severe reactions, including death, when mixed with alcohol, and there is significant risk associated with prescribing this medication to impulsive adolescent alcohol abusers. Thus, disulfiram is rarely used for younger patients. Other medications such as acamprosate and topiramate have been found effective in re lapse prevention in clinical trials in adult populations but have not yet received FDA approval. There have been no studies of these medications in adolescents.

Medications for Long-Term Treatment of Opioid Dependence

Opioid dependence is relatively uncommon in adolescents, particularly those seeking treatment. However, many regions of the United States have experienced a rise in opioid addiction, particularly with the availability of potent, smokable heroin. Naltrexone, by blocking opiate receptors, can absolutely prevent relapse to opioid dependence as long as it is ingested. Adolescents, however, are not likely to take this medication regularly. Several naltrexone depot preparations are currently in clinical trials. When these become available, a monthly injection will effectively prevent relapse.

Agonist maintenance with methadone or buprenorphine is the most generally effective treatment for adolescent opioid addiction currently available (Gonzalez, Oliveto, & Kosten, 2002). Buprenorphine, which became available in 2003, may be particularly promising in adolescent opioid patients because of the ease of detoxification and legal status that permits prescribing from an individual practitioner's office. A large multiclinic trial of buprenorphine in adolescents is currently in progress.

These pharmacological treatments should be integrated with psychosocial interventions including individual, family, and group therapy approaches to promote continued abstinence from the drug of abuse. Agonist treatment with methadone or buprenorphine replaces intravenous heroin with a prescribed, long-acting oral agent that is administered in a clinic. The need to procure heroin on a daily basis is eliminated and the risk of medical complications associated with intravenous use is averted. When combined with psychosocial treatment, methadone has been shown to stabilize adult patients and reduce medical complications associated with needle use (Sees et al., 2000).

Heroin-addicted patients continue to crave heroin even after they have completed detoxification, however, and are particularly vulnerable to craving that is evoked by environmental cues previously associated with heroin use. Cue-induced craving, often precipitated by viewing syringes, visiting places where heroin was previously used, or interacting with people using heroin, can actually be associated with physiological symptoms of heroin withdrawal even after months or years of abstinence (O'Brien, Childress, McLellan, & Ehrman, 1992). Consequently, an essential strategy of drug rehabilitation involves avoiding situations that might expose recovering adolescents to cue-induced craving. Treatment recommendations often involve terminating friendships with addicted friends, eliminating risky social events, and otherwise changing one's lifestyle in ways that might not be palatable to adolescents who are focused on peer interactions and achieving autonomy. Denial also contributes to the adolescent's reluctance to follow treatment recommendations that involve motivation, sacrifice, and protracted effort. Practitioners trained in addiction treatment should use age-appropriate clinical approaches to engage adolescent heroin users in this challenging process. Considerable therapeutic flexibility and skill are often required to negotiate a therapeutic alliance that can help adolescents overcome their pleasure-reinforced compulsion to use heroin.

Treatments for Stimulant Abuse and Dependence

There has been little research on the treatment of adolescent stimulant dependence and most regions of the United States do not provide adequate treatment options for the large population of afflicted adolescents. Unfortunately, no pharmacological treatments with proven efficacy have been identified for cocaine dependence in general, and few clinical trials have even included adolescents. Similarly, psychosocial treatments have been minimally researched in stimulant addicted adolescents. Group-based treatments, following the principles of Alcoholics Anonymous (AA) and Narcotics Anonymous (NA), are commonly employed in specialized adolescent treatment programs in the United States. Adolescents will naturally resist treatment approaches that ignore normal developmental issues, including their need for peer acceptance, autonomy, and individualization. In addition, they cannot be treated in a vacuum and it is important to address maladaptive family patterns with family therapy. Parents should also receive education about cocaine addiction that includes the warning signs of relapse and specific behavioral guidance.

Treatment approaches have limited effectiveness when adolescent patients do not view their use as problematic or are not sufficiently motivated to quit using cocaine. It is even more difficult to establish a therapeutic alliance when adolescents have been pressured into treatment by their parents, the legal system, or school authorities. Even internally motivated adolescents are often difficult to engage, and treatment facilities should be staffed with practitioners who are familiar with the dynamics of addiction, normal adolescent development, and the nuances of treating adolescent patients.

A large number of medications have been examined and some hold promise, such as disulfiram and several agents that enhance GABA activity, such as baclofen, topiramate, and tiagabine (Kosten, in press). Experimental agents include immunotherapies, such as a cocaine vaccine (Kosten & Biegel, 2002). Glutamatergic agents such as modafinil may promote abstinence by reducing cocaine euphoria and cocaine craving (Dackis et al., 2003). At present, however, no medication has been consistently beneficial in preventing relapse to stimulant abuse and dependence.

Treatment of Co-occurring Psychiatric Disorders in Adolescents

Current research provides fairly solid support for integrated pharmacotherapy of co-occurring psychiatric disorders and substance dependence in adolescents. The first consideration in this research is that adolescents with substance dependence and comorbid psychiatric disorders have poorer treatment outcomes than those with single disorders. If the comorbid disorders are left untreated, the likelihood of successful engagement, retention, and completion of substance treatment is reduced (Grella, Hser, Joshi, & Rounds-Bryant, 2001; Lohman, Riggs, Hall, Mikulich, & Klein, 2002; Whitmore et al., 1997; Wise, Cuffe, & Fischer, 2001). Second, pharmacotherapy of comorbid disorders alone is not likely to reduce or “treat” substance abuse in the absence of specific substance treatment interventions in adolescents with substance dependence. This has been demonstrated in controlled trials for comorbid ADHD, bipolar disorder, and depression (Deas & Thomas, 2001; Geller et al., 1998; Lohman et al., 2002; Riggs, Mikulich, & Hall, 2001). Third, treatment of substance dependence (or achievement of abstinence) alone does not “treat” comorbid psychiatric disorders, such as ADHD, bipolar disorder, or major depression, in the absence of specific pharmacotherapy for the comorbid disorder. Even depression is much less likely to remit with abstinence in adolescents compared to findings in depressed adults with chronic alcohol or drug dependence (Bukstein, Glancy, & Kaminer, 1992; Riggs et al., 1996). Fourth, controlled trials indicate that some medications commonly used to treat psychiatric disorders in children and adolescents may be safe and effective in treating comorbid disorders in adolescents with substance dependence, even if the adolescent is nonabstinent. Specific studies have examined fluoxetine for depression (Lohman et al., 2002), lithium for bipolar disorder (Geller et al., 1998), and pemoline for ADHD (Riggs et al., 2001).

Taken together, current research supports integrated, concurrent treatment of comorbid psychiatric disorders and substance abuse in adolescents. Sequential treatment models requiring adolescents to first complete substance treatment and achieve abstinence as a prerequisite for medicating comorbidity are much less effective and probably contraindicated. Although research now supports integrated treatment models, it is understandable that sequential models evolved and have been perpetuated. Some of the reasons for this include a shortage of child and adolescent psychiatrists with training in addictions; shortages of addiction clinicians with substantial psychiatric training; separate provider networks for mental health and substance treatment services; and poor third-party payer coverage for integrated treatment services. Although coordinated treatment of co-occurring disorders in adolescents provides significant clinical advantage, it is often unavailable because of inadequacies in the health delivery system.

The dearth of research related to pharmacological treatment of addiction in adolescents results in part from the traditional exclusion of addicted adolescents from clinical trials evaluating the safety and efficacy of medications, even when prescribed for psychiatric illnesses. Until very recently, virtually nothing was known about the safety and effectiveness of these medications in adolescents with substance dependence or the potential for adverse interactions of medications with drugs of abuse. Clinicians were therefore reluctant to use medications to treat psychiatric disorders in substance-abusing adolescents, often referring such youth for substance treatment before considering treatment of comorbidity. This reluctance to use pharmacotherapy is often cited as one reason for poorer treatment outcomes in dually diagnosed adolescents, as untreated psychiatric illness significantly diminishes the likelihood of successful substance treatment. The risks of treatment must be balanced with risks associated with not treating psychiatric comorbidity. Recent controlled clinical trials have begun to extricate clinicians from this therapeutic conundrum by demonstrating the safety and efficacy of some medications used to treat the most common psychiatric comorbidities, including bipolar disorder, ADHD, and depression (Geller et al., 1998; Lohman et al., 2002; Riggs et al., 2001).

Attention-Deficit Hyperactivity Disorder

Pharmacotherapy with psychostimulants is considered the first-line treatment for ADHD in children and adolescents without substance dependence. Only one controlled medication trial has been conducted in adolescents with ADHD and substance dependence. In this study, 69 out-of-treatment adolescents with conduct disorder, substance dependence, and ADHD were recruited from the community and randomized to receive either placebo or pemoline (a low-abuse potential psychostimulant). Results showed that pemoline had similar safety and efficacy for ADHD in nonabstinent adolescents to that reported in adolescents without substance dependence. Despite its efficacy for ADHD, pemoline did not reduce substance use or conduct problems when specific treatment for substance dependence was not provided. Although no patients in this trial developed serious side effects or elevations in liver enzymes, recent concerns about the rare but serious potential for liver toxicity with pemoline have led to recommendations for frequent monitoring of liver enzymes (Safer, Zito, & Gardner, 2001; Willy, Manda, Shatin, Drinkard, & Graham, 2002). This restriction has diminished the clinical feasibility of using pemoline in outpatient settings. Nonetheless, pemoline is still considered an important treatment option for ADHD in settings requiring the use of medications with low-abuse potential (e.g., substance abuse treatment programs) and once-per-day dosing regimens. The stimulants used for ADHD have good efficacy but a relatively high-abuse potential and have been placed in schedule II psychostimulants (e.g., methylphenidate, dextroamphetamine; Klein-Schwartz, & McGrath, 2003).

Fortunately, newer medications with low abuse liability, such as bupropion and atomoxetine, have been developed and shown to be effective for ADHD in adults and adolescents without substance dependence (Barrickman et al., 1995; Michelson et al., 2002; Riggs, Leon, Mikulich, & Pottle, 1998; Spencer et al., 2002; Wilens et al., 2001). Although no controlled trials have been conducted, preliminary data indicate that these medications are sufficiently safe to be considered in treating ADHD in dually diagnosed adolescents. Bupropion has also been shown to be effective in treating both ADHD and depression in adolescents and adults without substance dependence (Daviss et al., 2001). Clinicians may therefore wish to consider bupropion as a first-line treatment in adolescents who have substance dependence, ADHD, and depression, again with the caveat that there are no controlled trials in adolescents with substance dependence (Riggs et al., 1998).

Bipolar Disorder

Pharmacotherapy with mood stabilizers (e.g., lithium, valproic acid, carbamazepine) is the first-line treatment for bipolar disorder in ado lescents without substance dependence. Only one controlled trial (lithium vs. placebo) has been conducted in adolescents with bipolar disorder and substance dependence (Geller et al., 1998). In this study, lithium had a relatively good safety profile and was shown to be effective in stabilizing mania or hypomania in adolescents with substance dependence, many of whom were not abstinent during the trial (Geller et al., 1998). Although there was a somewhat greater decline in substance use in the lithium-treated group than in those who received placebo, the pharmacological treatment of bipolar disorder did not effectively treat substance dependence in the absence of specific substance treatment. The available data would support treating bipolar disorder only in the context of concurrent treatment for substance dependence in dually diagnosed adolescents. No data are yet available from controlled trials about the safety or efficacy of other mood stabilizers in dually diagnosed adolescents.

Depression

In standard practice, adolescents with major (severe) depression would receive both psychotherapy and pharmacotherapy, whereas those with mild or moderate symptoms might be given a trial of psychotherapy alone before considering medications. When medications are used, selective serotonin reuptake inhibitors (SSRIs; specifically fluoxetine and paroxetine) are considered first-line medication choices for adolescent depression without comorbid substance dependence (Emslie et al., 1997). No adequately powered controlled trials of SSRIs have yet been completed in depressed adolescents with substance dependence. Preliminary data from an ongoing randomized, controlled trial of fluoxetine for depression in 120 depressed and addicted adolescents indicate that fluoxetine appears to have a very good safety profile even in nonabstinent adolescents with polydrug abuse (Lohman et al., 2002). Since this trial is not yet completed, no data are yet available on the efficacy of fluoxetine for depression, although preliminary data from open trials and a small controlled trial indicate some promise for the efficacy of SSRIs for depression in adolescents with substance dependence (Deas & Thomas, 2001; Riggs, Mikulich, Coffman, & Crowley, 1997). Clinically, the SSRIs are currently considered by many adult and adolescent addiction psychiatrists to be the first-line medication choice for depression co-occurring with substance dependence (Deas & Thomas, 2001; Lohman et al., 2002; Riggs et al., 1997). If ADHD is also present, bupropion may be a first-line choice, as mentioned above. These recommendations must be regarded as provisional, since no antidepressant medications have yet demonstrated safety and efficacy in a conclusive controlled, clinical trial with adolescents with substance dependence. Moreover, there is currently a controversy over the possibility that all SSRIs, except fluoxetine, may increase the risk of suicide in adolescents. This issue is thoroughly discussed in Chapter 2, which deals with depression in adolescence.

Tricyclic antidepressants are relatively contraindicated for the treatment of depression or ADHD in adolescents with substance dependence. These agents have significant anticholinergic and cardiac side effects, a relatively high potential for adverse interactions with substances of abuse, and considerable danger of causing death if an overdose should occur (Wilens, Spencer, Biederman, & Schleifer, 1997).

Anxiety Disorders

Cognitive-behavioral therapies, often used in combination with SSRI medications, are considered standard treatment for a variety of anxiety disorders (including obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder [PTSD]) in adolescents without substance dependence. While SSRI treatment for adolescent anxiety disorders that are comorbid with substance dependence has not yet been well studied, the data support their relatively good safety profile in treating depression in adolescents with substance dependence. Furthermore, the high rates of co-occurring depression with anxiety disorders suggest that clinicians may wish to consider SSRIs in dually diagnosed adolescents with anxiety disorders. Good target symptoms for SSRIs include the management of sleep problems, de pressive symptoms, intrusive memories, and hyperarousal symptoms often associated with PTSD (Davies, Gabbert, & Riggs, 2001; Lohman et al., 2002). Benzodiazepines are contraindicated for anxiety disorders in patients with substance dependence because of their well-known abuse potential.

Pharmacotherapy in Adolescents: Special Considerations in Treating Comorbidity

If the adolescent has a comorbid disorder for which medication is being considered (e.g., ADHD, major depression), abstinence is ideal before initiating medication for comorbidity. However, abstinence is not a realistic goal for many adolescent patients. Clinicians must therefore weigh the risk of potential drug–medication interactions against the risk that the untreated psychiatric illness will thwart treatment engagement or precipitate early dropout. Once the adolescent is engaged in substance abuse treatment, both urine drug screening and self-report should indicate either abstinence or significant reduction in substance use, although it is often necessary to tolerate some ongoing alcohol or cannabis use. The mental health professional or psychiatrist should then develop a plan for regular drug abuse monitoring (e.g., urine toxicology, breath alcohol) and for information exchange regarding compliance with substance treatment, urine toxicology results, target symptom response, and emergence of adverse side effects. When initiating medications, the patient should be compliant with at least weekly therapy sessions. Our clinical experience suggests benefit from motivational enhancement therapy coupled with CBT and an empathic, encouraging therapeutic style. Such an approach typically leads to successful medication stabilization for comorbidity during the first month of treatment. Early treatment of a psychiatric disorder can be critically important in facilitating treatment engagement and retention during the initial months of substance abuse treatment.

The following principles also may be helpful when using medications to treat comorbid disorders concurrently with substance dependence. First, when medication is indicated, consider medications with good safety profiles, low-abuse liability, and once-per-day dosing, if possible. Second, use a single medication if at all possible. Third, provide the patient and family with education about the potential for adverse interactions of medications with substances of abuse and the need for abstinence or reduced substance use to ensure safety and efficacy. Fourth, establish mechanisms to closely monitor medication compliance (initially weekly), adverse effects, target symptom response, and ongoing substance use (using both self-report and urine drug screening). Fifth, monitor compliance with regular substance treatment (generally, individual or family counseling at least weekly) and regular urine drug screening (if not the primary substance abuse treatment provider). Sixth, monitor patient treatment motivation and target symptom response as well as behavior changes and psychosocial functioning throughout treatment. If substance abuse or target symptoms of the comorbid disorder do not significantly improve within the first 2 months after initiating treatment, or if there is evidence of escalation in drug abuse or clinical deterioration, consider several options. First, evaluate the medication efficacy and change the medication. Second, reassess the diagnostic formulation (e.g., bipolar vs. unipolar depression). Third, increase the treatment intensity (frequency or level of care). Adherence to these principles should facilitate pharmacotherapy in adolescents who frequently have comorbid Axis I psychiatric disorders with their substance dependence. Medications primarily targeted at the substance dependence, such as bupropion or NRT for nicotine dependence, might also be considered, but behavior treatments should be tried first for most adolescents with primary substance dependence and no other Axis I psychopathology.