Substance use disorders in adolescents with psychiatric comorbidity: When to screen and how to treat

Medication to alleviate withdrawal symptoms. Some patients may find the physical discomfort and psychological dis­tress associated with substance withdrawal so intolerable that to avoid it they continue to use drugs or alcohol. Medication to treat withdrawal symptoms and agonist treat­ments can be used to alleviate discomfort and distress associated with withdrawal. Agonist treatments, such as methadone and buprenorphine, bind to the same receptors as the target substance, which allows the patient to shift to controlled use of a prescribed substitute. Agonist treatments are used for short detoxifi­cation and over longer periods of time for maintenance treatment. Methadone, which decreases craving and withdrawal symptoms from opiates by binding to the μ-opiate receptor and blocking other sub­stances from binding, is frequently used for detoxification and maintenance treat­ment in adults. There is limited data on methadone substitution therapy for adolescents in the United States.¹⁶ Methadone maintenance for adolescents in the United States is restricted to severe cases of opioid use disorder. Federal guidelines specify that adolescents age <18 can only receive methadone if they have had 2 unsuccess­ful detoxification attempts or outpatient psychosocial treatments and have met DSM criteria for an opioid use disorder for 1 year.¹⁷

Buprenorphine is a partial μ-opiate receptor agonist that is FDA-approved for use in adolescents age ≥16 with opioid dependence. Although a waiver from the U.S. Drug Enforcement Administration is required to prescribe buprenorphine, it generally can be administered in outpa­tient settings with relative ease compared with methadone.

Marsch et al¹⁸ examined the efficacy of buprenorphine compared with clonidine for detoxification over 1 month in 36 ado­lescents with opioid dependence. Clonidine is an α-2 adrenergic agonist that often is used during detoxification from opioids.¹⁹ Although both buprenorphine and cloni­dine relieved withdrawal symptoms, a significantly higher percentage of patients receiving buprenorphine completed treat­ment (72%) compared with those taking clonidine (39%) (P < .05).¹⁸ Detoxification with buprenorphine also was associated with a higher percentage of negative urine drug screens (64% vs 32%, P = .01), and those receiving buprenorphine were more likely to continue on naltrexone mainte­nance for continued medication-assisted treatment after detoxification compared with those randomized to clonidine.

Woody et al²⁰ compared use of buprenor­phine/naloxone for opioid detoxification vs short-term maintenance. Patients age 16 to 21 were randomized to detoxification over 2 weeks vs stabilization and maintenance for 9 weeks and taper over 3 weeks. Maintenance treatment with buprenorphine/naloxone was associated with less opioid use, less injection drug use, and less need for addic­tion treatment outside of that received through the study compared with detoxifica­tion treatment. When buprenorphine/nalox­one was discontinued both the detoxification and maintenance groups had high rates of positive urine toxicology screens at 1-year follow up (mean 48% to 72%). These data suggests maintenance with buprenorphine/ naloxone for adolescents and young adults is more effective than short-term detoxifi­cation for stabilizing opioid use disorders, although optimal treatment duration is unclear. Clinically, it is important to continue buprenorphine/naloxone maintenance until the patient has stabilized in recovery and has acquired coping skills to manage urges, crav­ings, and psychological distress (eg, anger, stress) that often arise during a slow taper of agonist treatment.

Antagonist treatment to block the effect of substance use
As an opioid receptor antagonist, naltrex­one is effective for treating opioid use dis­order because it blocks the action of opioids. Fishman et al²¹ published a descriptive series of 16 adolescents and young adults followed over 4 months who received the injectable depot preparation (extended-release) nal­trexone while in residential treatment, and then discharged to outpatient care. Most patients who received extended-release nal­trexone remained in outpatient treatment (63%) and reduced their opioid use or were abstinent at 4 months (56%). One barrier to naltrexone treatment is the need to be absti­nent from opioids for 7 to 10 days to prevent precipitated opioid withdrawal. Therefore, naltrexone is a good option for adolescents who present for treatment early and are not physiologically dependent on opioids or are receiving treatment in a structured environ­ment after detoxification, such as residential treatment or sober living.

Aversive agents to diminish substance use. Aversive agents produce an unpleas­ant reaction when a target substance is consumed. Disulfiram is prototypic aver­sive agent that prevents the breakdown of acetaldehyde, a toxic metabolite of alcohol. Patients who drink alcohol while taking disulfiram may experience adverse effects, including tachycardia, shortness of breath, nausea, dizziness, and confusion. There have been 2 studies examining the efficacy of disulfiram in adolescents with alcohol use disorder. Niederhofer et al²² found that disulfiram treatment significantly increased cumulative abstinence in a small RCT (P = .012). In another small randomized, open-label, 3-month study of adolescents who received disulfiram or naltrexone in addition to weekly psychotherapy, disul­firam was superior to naltrexone in mean days abstinent from alcohol, 84 days vs 51 days, respectively (P = .0001).²³ Often adolescents are not willing to adhere to disulfiram because they are concerned about the aversive reaction when combined with alcohol use. Consider prescribing disulfiram for adolescents who are about to go “on pass” from a therapeutic school or residen­tial SUD treatment center and will be return­ing to an environment where they may be tempted to use alcohol.