Opioid Use by Adolescents: Prevention and Pharmacotherapy

2015

Non-Opioid-Dependent Teens

Primary Prevention

When prescribing opioid medications, clinicians should provide anticipatory guidance. Teens and parents should be advised that although pain medications are highly effective and safe when used as prescribed, they are also highly addictive and can be dangerous when misused. Parents should monitor use to ensure that medications are always used as directed. Any leftover medication should be discarded by returning it to the pharmacy. Medications should never be shared or given to anyone other than the patient for whom the prescription was written.

Pain medication can be safe for use even in patients with substance use disorders, and pain should not be left untreated because of a history of substance abuse or dependence. However, in these situations clinicians should require increased supervision and monitoring to avoid misuse. Parents should be asked to hold, dispense, and observe all medication doses. When treating chronic pain the clinician should insist on the patient receiving all prescriptions from a single prescriber, open communication among all treating physicians, and use of a single pharmacy to fill all prescriptions. A parent should bring in remaining medication for a pill count at every visit. Early refills should be avoided ().

Brief Advice

Adolescents who misuse opioids but do not have a substance use disorder may respond to brief counseling and advice. In these cases, the clinician should recommend that the adolescent discontinue use of prescription opioid medications entirely, and briefly discuss the risk of progressing to opioid dependence with continued use because of the addictive potential of opioids. An assessment for pain should be conducted if appropriate, and the adolescent should be seen again for a follow-up health visit.

Brief Intervention

Adolescents with a diagnosis of opioid abuse but not dependence may benefit from a relatively brief intervention. Motivational techniques that 1) encourage teens to consider the negative consequences they have experienced related to their drug use and 2) explore their ambivalence regarding continued use may be particularly helpful (). These teens should be followed closely to ensure that they are able to achieve and maintain abstinence or to refer them for more intensive treatment if they progress to opioid dependence.

Opioid-Dependent Teens

Adolescents with a diagnosis of opioid dependence require long-term treatment to keep them in stable recovery. Treatment should be comprehensive, and tailored to particular needs; no single approach is suitable for all individuals. Brief opioid detoxification, unless followed by an intensive rehabilitation program or a long-term therapeutic community program, is associated with very high rates of relapse. Similarly, standard drug-free outpatient counseling has minimal efficacy in both adolescents and adults. Few teens at this point in the course of opioid dependence will be able to remain drug free without ongoing treatment, and providing treatment to young patients may present an opportunity to prevent commonly associated biopsychosocial and medical comorbidities. In most cases, effective treatment for dependent adolescents should include opioid agonist therapy in conjunction with evidence-based behavioral therapies. Buprenorphine has added an important new option for the treatment of these high-risk patients.

Role of Pharmacotherapy for Opioid Dependence

A large body of evidence has demonstrated that pharmacotherapy is effective in treating opioid-dependent adults, both for detoxification and for long-term maintenance (). Few medication studies have included adolescents, but accumulating evidence suggests that opioid agonist therapy can be effective in reducing relapse rates in adolescent populations by stabilizing neurochemistry, ameliorating withdrawal, and curbing cravings (). However, there is little consensus regarding the optimal length of buprenorphine treatment for adolescents. Before describing the use of buprenorphine in adolescents, we review other pharmacotherapy options.

Short-term pharmacotherapy (detoxification). Detoxification refers to the medical management of symptoms of withdrawal (see “Clinical Use of Buprenorphine”). Due to the pharmacological properties of opioids, recurrent use results in upregulation of the µ opioid receptor, intercellular and intracellular dysregulation, activation of the dopamine-based reward system, and development of dependence. If opioid use is discontinued abruptly, adolescents with opioid dependence may experience unpleasant withdrawal symptoms, which is often the precipitating event that brings them into treatment (). Otherwise-healthy adolescents can tolerate withdrawal without serious medical consequences, although the unpleasant symptoms may lead to relapse to opioid use for symptomatic relief. Inpatient detoxification and medical management of withdrawal symptoms should be offered to all patients who meet criteria for opioid dependence. For adolescents in opioid withdrawal with underlying medical conditions, such as diabetes or cystic fibrosis, or with significant psychiatric comorbidity, inpatient detoxification is the standard of care.

Detoxification protocols for adults are well established, and similar protocols can be used for teens. Medication options include brief inpatient treatment with clonidine, methadone, or buprenorphine, or a more gradual outpatient buprenorphine taper. Clonidine is a centrally active α2-adrenergic blocker that decreases sympathetic outflow. It has been used to decrease symptoms associated with opioid withdrawal; it does not bond to the opioid receptor and its abuse potential is limited. A randomized controlled trial conducted among 13- to 18-year-olds with opioid dependence compared clonidine detoxification with bu-prenorphine detoxification. The buprenorphine group had significantly greater retention in treatment (72% vs. 39%), significantly less opioid use (64% vs. 32% of urine samples tested negative for opioids), and significantly greater retention in care after detoxification (61% vs. 5%) (). These findings, which are comparable to findings of similar detoxification trials in adults, suggest that buprenorphine is clinically more effective than clonidine for the detoxification treatment of opioid dependence. There are no published studies comparing methadone to buprenorphine for detoxification treatment of adolescents. Adolescents should only be discharged from a medical detoxification program once a plan for continued care is in place ().

Long-term pharmacotherapy. Treatment options include methadone, buprenorphine, and naltrexone. An overview of buprenorphine is provided in this section, and specifics of initiating buprenorphine treatment are discussed later in this chapter, in the section “Buprenorphine Treatment in Adolescents.”

Methadone maintenance. Patients with opioid dependence may be treated with long-term agonist therapy with the goal of reducing cravings, decreasing relapse rates, and improving overall functioning. Methadone and buprenorphine are currently the only two opioid agonist therapies available in the United States. Methadone maintenance has long been a mainstay of treatment for opioid-dependent adults, although access to treatment is limited (). In 2000, Congress passed the Drug Addiction Treatment Act, which permits office-based buprenorphine treatment, thus expanding options and access to opioid agonist therapy (see “Opioid Dependence in America”). Buprenorphine presents several advantages over methadone for the treatment of adolescents, including an improved safety profile and reduced potential for misuse. However, the treatment of opioid-dependent adolescents presents specific challenges to providers because limited evidence-based research for treatment exists.

Methadone is a full agonist of the µ opioid receptor. It has a long half-life, which allows for steady-state dosing without the peaks and troughs associated with euphoria and withdrawal. Methadone maintenance therapy improves functioning, decreases heroin use as evidenced by urine drug testing, leads to reductions in criminal activity, increases treatment retention and employment status, decreases the risk of spreading highly transmissible diseases, and reduces mortality associated with opioid dependence by approximately two-thirds in adult cohorts. Although methadone has been approved for use in adolescents younger than age 18 for detoxification, it can only be prescribed for maintenance therapy through specially licensed clinics, which limits its availability for those seeking treatment. Federal regulations limit methadone maintenance treatment to individuals with at least 1 year of dependence, making methadone less accessible to younger users with shorter histories of dependence. Furthermore, U.S. Department of Health and Human Services guidelines specify that methadone clinics cannot accept patients younger than age 18 for maintenance treatment unless they have undergone two unsuccessful attempts at short-term detoxification or drug-free treatment within a 12-month period, and have obtained parental consent.

Buprenorphine. Buprenorphine is a Schedule III, synthetic partial µ opioid receptor agonist and an antagonist at the κ opioid receptor. Because of its mixed partial agonist-antagonist profile, it has several advantages, including a greater margin of safety than full µ agonists, a less intense abstinence syndrome with fewer autonomic symptoms, lower abuse potential, and an improved safety profile with limited potential for overdose. The agonist activity of buprenorphine has a ceiling effect, and therefore causes less respiratory depression than full agonists (although deaths due to respiratory suppression have been reported when used in combination with alcohol, benzodiazepines, or other central nervous system depressant drugs) (see “General Opioid Pharmacology,” and “Efficacy and Safety of Buprenorphine”). Buprenorphine has a higher affinity for opioid receptors than full agonists and displaces full agonists, causing rapid and severe withdrawal symptoms if given to a patient who is dependent on a full µ opioid agonist. When used as maintenance therapy, buprenorphine provides a µ opioid blockade that diminishes a patient’s ability to become intoxicated with other opioids while the µ receptors are saturated (). Because buprenorphine has a long half-life of 24–60 hours, most patients can be maintained with 8–16 mg daily, which can be given in single or divided doses. Physicians who have received a special waiver from the U.S. Food and Drug Administration (FDA) can prescribe buprenorphine in an office-based setting, which reduces stigma and expands treatment access for adolescents ().

Buprenorphine is as efficacious as methadone in adults dependent on opioids when equi-effective doses of these medications are provided. It has been approved as opioid agonist therapy for patients ages 16 years and older who meet DSM-IV-TR criteria for opioid dependence. Unlike the federal regulations for methadone maintenance treatment, there is no requirement to document a 1-year history of dependence. This permits the treatment of younger individuals with shorter histories of opioid dependence, a major benefit when treating adolescents. The optimal length of treatment is unknown, although recent evidence suggests that teens can benefit from buprenorphine maintenance therapy. Woody et al. () recently published a randomized cohort study of 152 treatment-seeking adolescents ages 15–21 years who met DSM-IV-TR criteria for opioid dependence. Participants were randomly assigned to receive either 14-day opioid detoxification or 12 weeks of opioid agonist therapy. Patients who received 12 weeks of buprenorphine treatment reported less use of opioids and other illicit substances, had fewer opioid-positive urine test results, and were retained in the study longer. These differences disappeared after medications were discontinued.

Naltrexone. Naltrexone is a µ opioid receptor antagonist with high affinity for the receptor (). Oral naltrexone has been approved by the FDA for the treatment of both alcohol and opioid dependence, although clinical experience in opioid-dependent patients has been rather disappointing. Many physicians are reluctant to prescribe naltrexone for opioid dependence due to poor patient compliance and high treatment attrition rates. However, a sustained-release depot formulation of naltrexone has received FDA approval for the treatment of alcohol dependence, and a heightened interest has developed for its potential use in treating opioid dependence as well (). There is no published research on the efficacy of naltrexone for opioid dependence in adolescent patients.

Buprenorphine Treatment in Adolescents

Preliminary evaluation. Before beginning opioid agonist therapy, all adolescents should have a complete evaluation including a thorough substance use history assessment; medical, mental health, vocational, and psychosocial history assessments; and a physical examination. The treating clinician must address or refer the patient for treatment of any active problems that would interfere with long-term recovery. All patients should be tested for HIV infection, hepatitis B, hepatitis C, and other infectious diseases as indicated. Symptoms of mild depression or inattention may improve with abstinence and can be monitored if not debilitating. However, all patients should be screened for more significant co-occurring psychiatric symptoms, and comorbidities should be treated simultaneously. Homelessness or living with an active drug user presents special challenges; patients without a stable home and guardian should be referred to social services for support. School dropout and unemployment rates are high among adolescents with opioid dependence and should be addressed as soon as the patient is stable in order to improve long-term outcomes.

Setting treatment goals. The optimal length of treatment with opioid substitution therapy has not been scientifically determined, and the risks of long-term exposure to buprenorphine on the still-developing adolescent brain are unknown. Clinicians should therefore discuss the length of treatment with patients, and when appropriate, parents or guardians. Although there is little published evidence, in our clinical practice we recommend that adolescents continue to take buprenorphine until they have been abstinent from illicit opioid use for at least 1 year before considering discontinuation. This approach is consistent with DSM-IV-TR criteria for “opioid dependence in full sustained remission, on replacement therapy,” given that relapse rates for other addictions tend to fall sharply over the course of the first year of abstinence and then begin to level off. Buprenorphine should then be slowly tapered to avoid withdrawal symptoms and/or resurgence of cravings. After buprenorphine is tapered to discontinuation, clinicians should continue to follow adolescents clinically and with drug testing for an extended period to monitor for relapse.

The treatment contract. After completing a thorough assessment, the clinician should establish a set of expectations for adolescents beginning bu-prenorphine treatment. A written contract may be helpful (). On beginning treatment, adolescents should agree to abstain from all substances including alcohol, which can be dangerous in combination with buprenor-phine. All patients who receive buprenorphine treatment should be monitored with random drug tests to assure that they are taking their medication and to monitor for use of opioids, alcohol, or other illicit substances. Patients who are unable to achieve abstinence from substances other than opioids should be referred for complementary treatment. Office-based buprenorphine treatment may need to be stopped if a patient is unable to stop using alcohol or sedatives. We recommend that all adolescents with opioid dependence enter counseling to help them identify and avoid triggers for drug use, to learn healthy mechanisms for relieving stress, and to learn other life skills. Some individuals will also need specific counseling to address other issues such as depression, anxiety, and anger.

Clinicians treating adolescents should take advantage of the availability of parents or guardians for authority and structure whenever possible. As with treatment-seeking adults who benefit from family involvement, parental participation may improve adolescent treatment adherence, allow for prompt intervention when a relapse occurs, and minimize diversion risk ().

Getting started: the initial buprenorphine dose. Adolescents should be advised not to use opioids before buprenorphine induction — about 12–24 hours depending on the half-life of their drug of choice (see “Clinical Use of Buprenorphine”). Buprenorphine therapy may be started at home if a patient (along with a parent or guardian) can be taught to reliably monitor signs of withdrawal and wait until withdrawal has progressed enough to avoid inducing precipitated withdrawal. However, we recommend observed induction for all adolescent patients to give the clinician the opportunity to assess and quantify signs of withdrawal, to teach the teenager to take medications sublingually, to teach a parent or guardian how to observe a medication dose, and to answer questions.

Adolescents should be followed closely to monitor for side effects and continued cravings until they are taking a stable dose of buprenorphine. Because of the long half-life of buprenorphine, a single daily dose is effective, although many adolescents prefer divided doses to mimic previous drug use patterns. All patients should be warned to avoid driving for the first few weeks of taking the medication because drowsiness has been reported as a side effect of buprenorphine.

Buprenorphine and Pregnant Patients

Buprenorphine is listed as a category C medication in the United States and to date no studies are available to support its safety and efficacy during pregnancy. Methadone continues to be the only FDA-approved medication for maintenance treatment in pregnancy, and buprenorphine monotherapy should be used only if the potential benefit outweighs the risk to the fetus. Neonates should be closely monitored for neonatal abstinence syndrome or signs of respiratory depression, due to buprenorphine’s ability to cross the placental barrier. Similarly, breast-feeding is not advised because buprenorphine is excreted in breast milk in concentrations similar to those found in maternal serum. Further studies are needed to evaluate the true effect of buprenorphine in infants.