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).

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.

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.

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.

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.

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 depen dence. 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).

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.

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).

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