eMedicine Specialties > Psychiatry > Addiction

Opioid Abuse: Treatment & Medication

Author: William J Meehan, MD, Chief Resident in Clinical Research, Department of Psychiatry, University of Massachusetts Memorial Medical Center, University of Massachusetts Medical School
Coauthor(s): Steven A Adelman, MD, Director, Behavioral Health and Addiction Medicine, Harvard Vanguard Medical Associates
Contributor Information and Disclosures

Updated: Jul 31, 2009

Treatment

Medical Care

Acute opioid-related disorders that require medical management include opioid intoxication, opioid overdose, and opioid withdrawal. Issues pertaining to treatment of chronic opioid abuse include opioid agonist therapy (OAT), psychotherapy, and treatment of acute pain in patients already on maintenance therapy.

Opioid intoxication

General supportive measures for opioid intoxication are as follows:

• Assess patient to clear airway.
• Provide support ventilation, if needed.
• Assess and support cardiac function.
• Provide IV fluids.
• Frequently monitor the vital signs and cardiopulmonary status until the patient has cleared opioids from the system.
• Give IV naloxone if necessary. Naloxone is a specific opiate antagonist with no agonist or euphoriant properties. When administered intravenously or subcutaneously, it rapidly reverses the respiratory depression and sedation caused by heroin intoxication.

Opioid overdose

• Naloxone is effective in treating acute overdose and is first-line treatment.
• Because overdoses usually occur in the presence of other people and because medical care is often not sought or is sought too late, at-home naloxone programs have been piloted in several countries. This is a controversial treatment that raises concerns about condoning heroin use, discouraging medical care, and producing side effects that cannot be managed at home. However, the efficacy of these pilot programs should be carefully monitored, as the potential for reducing mortality is high.

Opioid maintenance therapy

Pharmacologic therapy for heroin addiction has focused on ameliorating withdrawal symptoms and reducing cravings. By replacing heroin with legally obtained opioid agonists, many risk factors of the drug-abusing lifestyle can be mitigated.

• Methadone maintenance therapy⁵ (MMT) has been the standard of care for more than 30 years. However, the recent advent of buprenorphine maintenance therapy (BMT) is changing the landscape of treatment for opioid-dependent patients.⁶
  • Methadone
    • Methadone, a long-acting synthetic opioid agonist, can be dosed once daily and replaces the necessity for multiple daily heroin doses. As such, it stabilizes the drug-abusing lifestyle, reducing criminal behaviors, and also reducing needle sharing and promiscuous behaviors leading to transmission of HIV and other diseases.
    • Methadone is a highly regulated Schedule II medication, only available at specialized methadone maintenance clinics. It is estimated that established methadone clinics can accommodate only 15-20% of US heroin addicts.
    • Methadone clinics often generate controversy in communities fearful of addicts in various stages of recovery. In addition, some patients are unable to travel to clinics, and others will not enter MMT because of fear of stigmatization. Clearly other options would be beneficial for treatment of chronic opioid abuse.
  • Buprenorphine
    • Buprenorphine is a mu-opioid partial agonist that, like methadone, suppresses withdrawal and cravings. However, the property of partial agonism confers a "ceiling effect," at which higher doses of buprenorphine cause no additional effects. This ceiling effect affords a wider margin of safety than methadone, which can be lethal in overdose. The increased safety of buprenorphine has allowed it to become available by prescription as a Schedule III medication.
    • Buprenorphine has been combined with naloxone⁷ in a 4:1 ratio (Suboxone) in order to alleviate concerns that the sublingual tablet would be dissolved and injected by addicts. Naloxone is an opioid antagonist that is poorly absorbed sublingually and orally but is well-absorbed intravenously. As a result, an opioid-dependent patient injecting buprenorphine/naloxone will suffer a withdrawal syndrome secondary to naloxone's occupation of mu-opioid receptors.
    • Office-based treatment of opioid addiction is now possible with BMT.⁸ Physicians wishing to prescribe buprenorphine must meet several criteria, including requirements outlined in the Drug Abuse Treatment Act of 2000. However, physicians who do not meet these criteria can take an 8-hour training course to become certified to prescribe buprenorphine. Currently, physicians are limited to 30 buprenorphine patients, but this restriction may soon be lifted.
• LAAM: Historically, l-alpha-acetylmethadol (LAAM) has also been used for opioid-dependence maintenance pharmacotherapy. However, LAAM is associated with prolonged QT interval, and several cases of cardiac arrhythmia and death have been reported. Therefore, LAAM was recently removed from the market in the European Union and was given a black box label by the FDA.
• Cochrane reviews: Several Cochrane Database Systematic Reviews about the efficacy of opioid agonist therapy have been published in recent years. While all of these reviews stress the need for larger, multicenter, randomized clinical trials of longer duration, some conclusions can be drawn from existing data.
  • A review of Cochrane reviews found that high-dose MMT (60-109 mg/d) is more effective in retaining patients in treatment than low-dose MMT (1-59 mg/d). Moreover, methadone at flexible doses was more effective in retaining patients in treatment (RR, 1.23) than buprenorphine. A second systematic review of databases found that low-dose methadone (20 mg/d) was less effective than buprenorphine (2-8 mg/d) and that high-dose methadone (>50-65 mg/d) was more effective than buprenorphine (2-8 mg/d).
  • Another Cochrane review found that oral substitution treatment was associated with significant reductions in heroin injection and needle sharing, as well as a decrease in patients with multiple sexual partners and a reduction in exchanges of sex for drugs or money.⁹ Importantly, these changes were correlated with reductions in cases of HIV infection.
  • A recent randomized, placebo-controlled trial suggested that an injectable, sustained-release form of naltrexone (Depotrex) increased retention of patients in treatment for opioid abuse.¹⁰ Further studies are necessary to evaluate the efficacy of this treatment modality.

Opiate withdrawal

• Opiate withdrawal is generally considered less likely to produce severe morbidity or mortality compared with barbiturates and benzodiazepines. Safe withdrawal from opioids is termed detoxification and can be performed as outpatient or inpatient therapy, depending upon the following: presence of comorbid medical and psychiatric problems, availability of social support, and polydrug abuse.
• Methadone, buprenorphine, and alpha-2 agonists, such as clonidine and lofexidine, are commonly used pharmacologic methods of detoxification. The use of methadone and buprenorphine is based on the principle of cross-tolerance in which one opioid is replaced with another and then slowly withdrawn. Alpha-2 agonists appear to be most effective in suppressing autonomically mediated signs and symptoms of abstinence¹¹ , but they are less effective for subjective symptoms.
• Two recent Cochrane reviews compared the efficacy of alpha-2 adrenergic agonists to methadone or buprenorphine for management of withdrawal.^12,13 Patients experienced decreased side effects and stayed in treatment longer using tapered methadone compared to the alpha-2 agonists clonidine or lofexidine.
  • Buprenorphine was associated with fewer adverse effects than clonidine, and patients were more likely to complete withdrawal with buprenorphine compared with clonidine. Moreover, a second multicenter randomized trial demonstrated that buprenorphine-naloxone was more effective than clonidine for opioid detoxification.
  • Buprenorphine was equally effective as methadone for withdrawal completion, but withdrawal symptoms appeared to resolve more quickly with buprenorphine.
• In summary, data to date suggest that buprenorphine and methadone are more effective than alpha-2 agonists, such as clonidine, for opioid detoxification, with buprenorphine associated with a shorter duration of withdrawal symptoms. However, all of these medications are effective, and the choice may depend in part on availability.
• Kunoe et al described use of an investigational naltrexone implant in 56 abstinence-oriented patients who completed inpatient treatment for opioid dependence compared with patients who received usual care instead of the implant. The implant group had an average 45 days less heroin use and 60 days less opioid use than the usual care group over a 6-month period (P <0.05). The naltrexone implant significantly reduced opioid use compared with usual care.¹⁴
• Psychotherapies and support groups: Detoxification alone, without ongoing treatment, is not adequate to manage patients.¹⁵
  • Patients in methadone programs often benefit from cognitive behavioral, supportive, or analytical-oriented psychotherapies if they are added to standard drug counseling.
  • Cognitive behavior psychotherapy primarily focuses on the patient's thoughts and behaviors. Cognitive behavior–based models are widely used in drug rehabilitation programs. Cognitive behavior theories were aimed at substance abuse beginning in the mid 1980s. The techniques used help patients acquire specific skills for resisting substance use and teach coping skills to reduce problems related to drug use. Two major cognitive behavior theories of substance abuse are the following:
    • Relapse prevention: Based on the work of Marlatt and Gordon, important relapse prevention concepts and techniques include identification and avoidance of high-risk situations, understanding the chain of decisions leading to drug use, and changing one's lifestyle.
    • Cognitive therapy of substance abuse: Developed by Beck and colleagues, cognitive therapy of substance abuse is based on the concept that drug abusers engage in complex behaviors and thought processes, such as positive and negative drug-related beliefs and spontaneous flashes related to drug use before giving in to the actual drug use.
  • Dynamic psychotherapy is based on the concept that all symptoms arise from underlying unconscious psychological conflicts. The major goal of this therapy is to help the patient become aware of these conflicts and develop more adaptive coping mechanisms and healthier methods of resolving intrapsychic conflict.
  • Group therapy is argued to be especially effective because it can target the social stigma attached to having lost control of a substance. The presence of other group members who acknowledge having similar problems can provide support and be therapeutic in developing alternative methods of maintaining abstinence.
  • Aversion therapy involves pairing aversive stimuli to cognitive images of opioid use and conversely conjuring images of socially appropriate behaviors such as employment, education, and nondrug behavior.
• Narcotics Anonymous (NA): In 1947, NA was formed in Lexington, Ky. NA is based on principles similar to those of Alcoholics Anonymous (AA), including progression through 12 steps of recovery. Some patients have difficulty engaging in the AA-NA approach to recovery; however, these programs do help some people and can provide much needed support for those attempting abstinence.
• Acute pain management for patients receiving OAT: As more patients with opioid addiction receive OAT, physicians will encounter OAT patients with acute pain syndromes. It is important that acute pain be adequately treated in these patients.¹⁶
  • Common misconceptions
    • OAT provides analgesia: Maintenance methadone or buprenorphine does not provide sustained analgesia. Although methadone and buprenorphine are potent analgesics, the analgesic properties last only 4-8 hours, while the medications are dosed every 24-48 hours.
    • Use of opioid analgesia may cause addiction relapse: No evidence indicates that exposure to opioid analgesics during acute pain increases relapse rates. In fact, evidence suggests that the stress of unrelieved pain can trigger relapse.
    • The combination of OAT and other opioids may cause respiratory depression: This is a theoretical risk that is not supported by clinical or empirical experience. Tolerance to respiratory and CNS depressant effects occurs rapidly and reliably.
  • Recommendations
    • Reassure patients that their addiction histories will not prevent adequate pain management, and discuss plans in a nonjudgmental manner.
    • Verify methadone and buprenorphine doses with clinics or prescribing physicians, and inform these physicians of any benzodiazepines or opioids given that may be detected on urine drug screening.
    • Aggressively treat pain with conventional opioid analgesics. Opioid cross-tolerance often necessitates higher opioid analgesic doses at shorter intervals.
    • Use continuous scheduled dosing orders rather than as-needed orders.
  • For patients receiving methadone maintenance therapy: Continue methadone maintenance dose and add short-acting opioid analgesics.
  • For patients receiving buprenorphine maintenance therapy: Pain management with opioids is complicated by the high affinity of buprenorphine for the mu receptor. This affinity may cause buprenorphine to compete with opioid analgesics at mu receptors. As buprenorphine's rate of dissociation from mu receptors is highly variable, naloxone should be available, and consciousness and respiration should be closely monitored.
  • Several options are possible, and the most effective approach will be determined with increasing clinical experience:
    • Continue BMT and titrate a short-acting opioid analgesic to effect.
    • Divide buprenorphine dose to 6-8 hours to take advantage of its short-acting analgesic properties.
    • Discontinue BMT, implement opioid analgesia, and restart BMT when opioid analgesia is no longer necessary.
    • In the hospitalized patient, discontinue BMT, initiate MMT, and add short-acting opioids to treat pain. Have naloxone at bedside. Convert back to BMT prior to discharge from hospital.

Medication

The goals of pharmacotherapy are to treat the addiction of the chemical substances that cause them.

Opioid analgesics

Two uses for opioid analgesics are as follows: (1) Oral substitution therapy or maintenance therapy or opioid agonist therapy (OAT) refers to substitution of an oral opioid for injected heroin, with the goal of reducing harmful behaviors associated with heroin use. (2) Detoxification, or controlled withdrawal with the goal of abstinence, is based on the principle of cross-tolerance in which one opioid is replaced with another and then slowly withdrawn.

Methadone (Dolophine)

Inhibits ascending pain pathways, diminishing the perception of and response to pain. There are inpatient facilities and a few, specialized, licensed, outpatient, drug treatment programs that provide opioid detoxification using methadone. Also a preferred agent for opioid agonist maintenance. Some experts feel that laboratory measures of plasma levels should be used to adjust the dose and that 400 ng/mL seems sufficient to stop craving and drug hunger.
Benefits include good treatment retention, psychosocial adjustment, and reduced criminal activity.

Buprenorphine (Subutex)

Partial opioid agonist and potent antagonist, is a potent analgesic that can be administered once a day to block withdrawal symptoms. A dose of 0.6-1.2 mg/d of buprenorphine tapered over 3 days is found superior to a 5 day clonidine regimen in controlling early withdrawal symptoms. Proposed as an alternative to methadone for heroin detoxification and maintenance.
Used sublingually for the initial detoxification treatment of opioid addiction. Produces agonist/antagonist effects at the opioid mu receptor. The agonist effect is limited by a ceiling effect (ie, higher doses [>12-16 mg] do not produce more analgesia). The sublingual product is called Subutex.
8 mg SL is comparable to 30-60 mg oral methadone on suppressing heroin use and subject retention; in low doses, produces morphinelike effects but reaches its ceiling at about 12 mg; has abuse potential, but this potential is low compared with other opioids

Buprenorphine and naloxone (Suboxone)

Used sublingually for the maintenance detoxification treatment (unsupervised phase) of opioid dependence following induction with sublingual buprenorphine (Subutex). Contains both buprenorphine (an opiate agonist/antagonist) and the opiate antagonist naloxone. Naloxone has been added to guard against intravenous abuse of buprenorphine by individuals physically dependent on opiates.

Antidotes for opioids

Inhibit opioid effects by inhibiting opioid agonists at receptor sites.

Naltrexone (ReVia)

Used in combination with clonidine for rapid (4-5 d) detoxification.
Very effective long-acting opioid antagonist that was thought to be an ideal maintenance agent because it blocks receptor sites and, hence, opioid reinforcing properties. However, clinical results are not very promising when compared with methadone maintenance. Craving may continue during naltrexone maintenance. For groups of patients such as health care professionals or business executives for whom external incentives to stay away from drugs are important, naltrexone therapy has been very effective.

Naloxone (Narcan)

Pure opioid antagonist. Used to reverse opioid intoxication.
If patients do not respond to multiple doses of naloxone, consider alternative causes of unconsciousness. Need of ongoing substance abuse treatment should be established while caring for overdose.

Alpha 2 adrenergic agonists

Used primarily for the treatment of hypertension.

Clonidine (Catapres)

May reduce norepinephrine release. In opioid withdrawal, seems to be most effective in suppressing autonomically mediated signs and symptoms of abstinence but less effective for subjective symptoms.
Used in higher doses for detoxification than for treating hypertension. Benzodiazepine may be beneficial as adjuvant therapy for muscle cramps and insomnia. Clonidine also has anticraving effect for opioids. Clonidine in combination with naltrexone, which is a potent long-acting narcotic antagonist, also is referred to be as rapid detoxification. This approach is designed to shorten the time course of withdrawal to 5 d. Clonidine alone and in combination has been demonstrated to be feasible in primary care settings as an outpatient.
Treatment is initiated after confirmation of physical dependence by naloxone challenge test.

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