Substance Use Treatment Modalities for HIV-Infected Substance Users
Posted January 2008
Clinicians should be familiar with the substance use treatment programs and services available in their communities.
This chapter addresses treatments for the use of heroin, cocaine, amphetamines, and benzodiazepines; treatment for alcohol use is addressed in Clinical Management of Alcohol Use and Abuse in HIV-Infected Patients. Pharmacotherapies and psychosocial treatments are discussed, although the latter are often not substance specific. For a discussion of general issues related to the diagnosis and treatment of psychiatric disorders with comorbid substance use in HIV-infected individuals, see Mental Health Disorders Among Substance-Using HIV-Infected Patients.
For information regarding management of substance use treatment during hospitalization, see Care of the Hospitalized HIV-Infected Substance User.
II. SELECTING THE INITIAL SUBSTANCE USE TREATMENT MODALITY
Clinicians should discuss treatment options with substance-using patients and should ask which treatment options they prefer.
Clinicians should inquire about use of multiple substances and should consider the full spectrum of the patient’s drug use when discussing treatment options with the patient.
Several treatment options may be appropriate for a patient with an identified substance use problem. Clinicians should strongly consider the patient’s preference when selecting initial treatment modalities because the patient’s motivation to participate is critical to success. For example, some patients may wish to receive treatment outside of their own communities, where they are less likely to be recognized. Patients with multiple comorbidities may benefit from drug-free programs that offer on-site HIV-related medical and psychiatric services.
The use of multiple drugs (polydrug use), including alcohol, either at the same time or distinctly, is common among substance-using patients. Patients may discontinue the use of one drug while continuing the use of others. Clinicians and patients may need to discuss alternative treatment modalities targeted toward the substance(s) that the patient is still using.
The Patient Placement Criteria of the American Society of Addiction Medicine (ASAM) are the most comprehensive and evidence-based guidelines for matching patients to specific treatment modalities. Clinicians should consult this resource for guidance on selecting the best treatment alternatives for specific patients.
III. TREATMENT FOR OPIOID DEPENDENCE
Clinicians should offer agonist treatment for patients who are opioid-dependent and unable to discontinue use.
Clinicians should only use naltrexone as a second choice to agonist (methadone or buprenorphine) treatment to treat opioid dependence in HIV-infected patients.
Two classes of medications interact with opioid receptors and are used to treat opioid dependence:
- Agonists: methadone (full agonist); buprenorphine (partial agonist)
- Antagonists: naltrexone
Table 1 outlines the prescribing regulations for each of these medications.
|Table 1: Prescribing Regulations for Medications Used to Treat Opioid Dependence|
For information regarding interactions with these drugs, refer to Drug-Drug Interactions Between ARV Agents, Medications Used in Substance Use Treatment, and Recreational Drugs.
A. Methadone Maintenance
Methadone, the most extensively studied pharmacologic treatment for heroin addiction, is a synthetic, orally administered opioid. Methadone is used to treat opioid dependence and does not treat use of or dependence on cocaine, benzodiazepines, or alcohol. The goals of methadone maintenance are as follows:
- To prevent symptoms of opioid withdrawal
- To eliminate the craving for opioids
- To block the effects of opioids if they are taken
In the United States, only clinicians who work in a methadone maintenance treatment program, or who have received federal waivers for office-based prescribing, are permitted to prescribe methadone for treatment of opioid dependence. To minimize the number of methadone doses that patients take with them after a visit, regulations stipulate that, at the start of treatment, patients must attend clinic frequently to receive doses (5 to 6 days per week). As patients achieve stability in treatment, their mandated clinic attendance is reduced, with weekly attendance possible after 1 year of stability in treatment. The structured nature of methadone treatment programs can serve as a barrier to treatment for some opioid-dependent patients, whereas others benefit from the frequent communication and support that such programs provide. Despite discomfort with various aspects of methadone maintenance treatment among many clinicians and patients, it remains one of the best studied and most effective medical therapies.
1. Dosing and Duration of Methadone Treatment
Methadone treatment is usually initiated at 30 to 40 mg once daily, with gradual but steady increases until the patient reports a clinical comfort level and results of urine screening are free of other opioids. Most patients require 80 to 120 mg of methadone to stop using and craving opioids; a few patients require higher doses, and others respond to lower doses.1 New York State has been granted a federal waiver that allows clinicians to prescribe up to 200 mg without restriction; doses >200 mg/day require approval through a simple process. High methadone doses can be given to stop the craving for heroin, but some patients remain reluctant to receive such a dose for the following reasons:
- Desire to continue to experience some effect from heroin, while using methadone to reduce symptoms of craving and withdrawal
- Fear of discomfort associated with potential involuntary detoxification—particularly if at risk of losing benefits or going to prison
- Pressure from others to discontinue methadone maintenance treatment
Methadone maintenance is not a cure and is most effective as a long-term treatment. Most patients (80-90%) who discontinue methadone maintenance will relapse to opioid use. Nevertheless, some patients may prefer to enroll in methadone treatment with the expectation that they will be tapered off methadone within months. Programs of short-term methadone treatment (typically 2-18 months, often referred to as methadone-to-abstinence programs) may be attractive to patients wishing to be opioid free, despite the risks of relapse following cessation of treatment. Patients near or at the end of a methadone maintenance program can be offered ongoing treatment or participation in an alternative treatment modality, as indicated.
2. Efficacy and Safety of Methadone Treatment
Most patients will stop using opioids when they receive sufficient doses of methadone.2 However, some patients continue to use opioids even during methadone treatment. For these patients, methadone maintenance may help them use less heroin and use less often. By helping opioid users gain greater control of their use, methadone maintenance may decrease harmful behaviors, HIV risk behaviors,3 and overdose (see Table 2).
|Table 2: Benefits of Methadone Treatment|
Some clinicians, as well as patients, have misconceptions about the safety of methadone (see Table 3). To date, no long-term adverse sequelae of methadone maintenance have been identified.7 The most common adverse effects of methadone maintenance are constipation and increased sweating. Because of its relatively long half-life, excessively rapid dose escalation at the beginning of methadone treatment can put patients at risk for overdose. High doses of methadone have been associated with uncommon instances of torsade de pointes.8
|Table 3: Misconceptions and Truths About Methadone|
3. Role of Counseling During Methadone Maintenance
Patients are required to receive substance use counseling in order to receive medication in methadone maintenance programs.
Patients are required by New York Code Rules and Regulations (NYCRR) Part 828 to receive substance use counseling in order to receive medication in methadone maintenance programs. Although the specific elements of counseling that are helpful have not been clearly established, the importance of psychosocial support has been demonstrated.11 Honest and open communication is critical to effective treatment. Some substance use treatment programs may restrict patients’ privileges when treatment guidelines are not met. Because effective counseling can be of substantial benefit, patients need to be able to discuss their behaviors freely with counseling staff without concern for programmatic sanctions.
For counseling considerations, see Working With the Active User, which includes strategies to enhance effective patient-provider communication, including motivational interviewing and brief interventions.
B. Buprenorphine Treatment
Buprenorphine is an important new therapeutic option for treating opioid addiction. It is a semisynthetic opioid that is a partial opioid agonist administered in a sublingual lozenge formulation (see Table 4).
|Table 4: Buprenorphine: Available Formulations|
|* The buprenorphine/naloxone combination is preferable because the risk of its misuse by crushing and injection is diminished by the naloxone, which is active only when injected, not when ingested orally.|
Because of its improved safety profile, federal regulations permit trained, registered clinicians to prescribe buprenorphine for the treatment of opioid dependence in general office-based settings. Patients’ ability to receive treatment for opioid dependence in a general primary care setting, and to pick up their medication in their pharmacy, may be appealing to individuals who do not want to receive methadone treatment or who have received methadone treatment in the past and are interested in a different treatment modality. Therefore, clinicians treating opioid-dependent patients are encouraged to register as buprenorphine prescribers (see Table 5 for requirements). Nurse practitioners (NPs) and physician assistants (PAs) cannot write prescriptions for buprenorphine. However, with on-site MD collaboration/supervision, some practices use NPs and PAs to manage every other aspect of buprenorphine treatment.
Appendix VI includes further guidance for clinicians who are interested in prescribing buprenorphine.
|Table 5: Clinician Requirements for Buprenorphine Licensure|
1. Dosing and Duration of Buprenorphine Treatment
Buprenorphine has a ceiling effect, which means that the agonist effect
increases with the dose but plateaus at a moderate dosage. For many patients, the correct dose of buprenorphine may be selected in the first 1 or 2 days during the induction. Most patients stabilize on a daily dose of 12 to 24 mg. Because of the ceiling effect, the maximum suggested dose is 32 mg. Some patients are comfortable on as little as 2 to 4 mg/day. Clinicians may need to encourage patients to increase the dose to one which not only alleviates withdrawal but also extinguishes opioid craving. The frequency of follow-up visits for a patient initiating buprenorphine should be individualized and discussed with the patient, but is generally not less often than monthly.
The literature on methadone clearly indicates that a significant majority of patients who discontinue methadone will relapse to illicit drug use.12 The same result likely applies to discontinuation of buprenorphine treatment. Experience suggests that most long-term opioid-dependent persons with a history of many relapses will require long-term treatment. Among shorter-term users, it is likely that some will need long-term treatment, whereas others will taper and do well without medication.13
2. Efficacy and Safety of Buprenorphine Treatment
Flexible dosing of buprenorphine and methadone has been found to be highly effective in reducing heroin use.14 Although the relative efficacy of buprenorphine and methadone has not yet been precisely defined, the ability to offer in-office or home induction makes buprenorphine an appealing treatment option for many patients who may not otherwise access pharmacotherapy for their opioid dependence. A 2006 evaluation of buprenorphine office-based treatment showed that at 6-month follow-up, 81% of patients had abstained from opioids, and 59% had abstained from all drug use.15
In high doses, buprenorphine can actually block the effects of full opioid agonists and will precipitate symptomatic withdrawal when taken by an opioid-dependent person with a full agonist in his/her bloodstream. For this reason, patients need to be in moderate withdrawal before initiating buprenorphine treatment; patients in moderate withdrawal will experience relief of withdrawal symptoms upon initiation of buprenorphine treatment. The most widely used formulation (Suboxone) is mixed with naloxone, which has no significant activity when taken sublingually but is active when injected.16 Thus, if the medication is injected, the user will either experience withdrawal if dependent, or experience an attenuated effect if not dependent. If buprenorphine is withdrawn abruptly, the withdrawal symptoms are thought to be less severe than those experienced with methadone or heroin.
The clinical significance of the partial agonist quality of bupre-norphine is its ceiling effect. The likelihood of respiratory depression from overdose is very low. Buprenorphine-related deaths from overdose have been reported in France17,18; however, all were among patients who were misusing benzodiazepines, most often by injection, or benzodiazepines plus alcohol. Patients are less likely to suffer fatal overdoses with buprenorphine than with methadone.19
Reports have also indicated elevated serum liver enzyme levels and subclinical hyperlactatemia, but the clinical relevance of these findings is unclear. Buprenorphine is metabolized by the hepatic enzyme system P450 3A4; therefore, clinicians should be alert to the possibility of interactions with inhibitors, such as NNRTIs, PIs, azoles, and macrolides, and inducers, such as phenobarbital, carbamazepine, phenytoin, and rifampicin. Contraindications for prescribing buprenorphine are listed in Table 6.
|Table 6: Contraindications and Precautions for Prescribing Buprenorphine|
3. Role of Counseling During Buprenorphine Maintenance
Counseling and other support resources should be made available to all patients treated with buprenorphine.
Patients who decline counseling services should be maintained on buprenorphine if otherwise medically appropriate.
Counseling and other psychosocial support is strongly encouraged during buprenorphine treatment. Support can be in the form of self-help groups, HIV support services, harm-reduction centers, and other community resources. Although many studies have shown that counseling is associated with better outcomes, an optimal level of counseling remains unclear.21 Poor access to counseling or refusing to receive counseling is rarely a medical reason for discontinuing medication, given the likelihood of relapse to illicit opioids. However, as with other medications, if the patient appears to be deriving no benefit from the medication or there is evidence of diversion, the clinician may stop prescribing buprenorphine and refer the patient to other sources of care for opioid dependence. Other sources of care can be found on the Office of Alcoholism and Substance Abuse Services website at www.oasas.state.ny.us.
C. Naltrexone Treatment
Clinicians should only use naltrexone as a second choice to agonist (methadone or buprenorphine) treatment to treat opioid dependence in HIV-infected patients. Strong supports should be in place to maximize adherence and treatment retention.
Clinicians should not prescribe oral naltrexone until patients are opioid-free for 3 to 4 days.
Clinicians should not prescribe oral naltrexone for patients with acute hepatitis or liver failure.
Naltrexone is an opioid antagonist that is orally administered daily. Although it blocks the effects of opioids, it does not affect craving.
Oral naltrexone is not a highly recommended therapy for the following reasons:
- It has a very low retention rate
- Concern about its safety in the setting of liver disease
- It blocks the analgesic effects of opioid agonists and should be discontinued 72 hours prior to elective surgery
- There is an elevated risk of fatal overdose upon discontinuation of oral naltrexone therapy22
In opioid-dependent persons (i.e., daily users of heroin or prescription opioids), naltrexone will precipitate withdrawal and should not be used until the patient is opioid-free for 3 to 4 days. High doses of naltrexone can cause hepatocellular injury and should not be administered to patients with acute hepatitis or liver failure.
D. Medication-Assisted Opioid Withdrawal
Clinicians should not initiate medication-assisted opioid withdrawal in opioid-dependent pregnant women. Rather, opioid-dependent pregnant women should be referred for treatment in a methadone maintenance treatment program.
Medication-assisted withdrawal, often referred to as “detoxification,” is often offered as an initial intervention for heroin-using patients. This process involves medical relief for physical withdrawal symptoms associated with discontinuation of opioid use. Medication-assisted withdrawal is not generally considered an effective long-term treatment for addiction, although it can be used to aid transition to such treatment.
Acute “detoxification” in an opioid-dependent pregnant woman can result in withdrawal syndrome and thus threaten the pregnancy. Instead, pregnant women should be referred for opiate agonist treatment.
IV. TREATMENT FOR STIMULANT AND SEDATIVE DEPENDENCE
Despite numerous trials and continuing investigations, no pharmacotherapy has been approved for treatment of cocaine use,23 which presents a major challenge to both the user and the clinician. Many people are able to reduce or stop using cocaine, although few behavioral therapies have been shown to have any substantial effect on these outcomes. The treatment modalities listed in Section V: Nonpharmacologic Treatment Modalities may provide guidance for determining treatment options.
Some studies have been performed on nonpharmacologic and pharmacologic treatments of methamphetamine dependence in the non-HIV-infected population.24 Studies of cognitive behavioral therapy and contingency management have shown reduction in stimulant use.25,26 Bupropion, modafinil, and baclofen have shown some utility as pharmacotherapy to treat methamphetamine dependence.27-29
The treatment modalities listed in Section V: Nonpharmacologic Treatment Modalities may provide guidance for determining treatment options.
Benzodiazepines are prescription drugs with sedating properties that are often abused by substance users. They may be used to enhance the effect of other sedatives, to attenuate the effect of stimulants, to reduce symptoms of withdrawal, or to relieve anxiety. Dependence may develop from recreational use, iatrogenic use, or both. Withdrawal can include the following symptoms:
- Depressed mood
- Sleep disturbance
- Hypersensitivity to touch
- Paranoid reaction
- Seizures (less common, rarely fatal)
Detoxification is usually accomplished by tapering treatment, which can be accelerated in the inpatient setting; it can also be accomplished gradually in an outpatient setting.30 Few data exist on the rates of abstinence following withdrawal. A prolonged abstinence syndrome may occur, but few studies have assessed this.
V. NONPHARMACOLOGIC TREATMENT MODALITIES
A. Twelve-Step Programs
Twelve-step programs include Alcoholics Anonymous (AA), Narcotics Anonymous (NA), Crystal Meth Anonymous (CMA), and Cocaine Anonymous (CA). Twelve-Step programs are based on a series of principles and associated actions, or “steps.” Participants share substance-related problems and experiences at meetings while working through the steps of the program. Although many people report 12-step groups as being tremendously helpful and effective, findings from empirical studies vary regarding the efficacy of self-help programs. Clinicians should inform patients about 12-step programs and be supportive of their participation in them.
Acupuncture is offered in many settings, most commonly as simplified auricular acupuncture to diminish symptoms of craving. Needles are inserted in several points in the patient’s ear at least several times per week. A 1997 NIH Consensus Statement found sufficient evidence to suggest that this procedure may be a helpful adjunct to other forms of substance use treatment31; however, subsequent studies found no difference among 4-point auricular acupuncture, sham acupuncture, and relaxation for cocaine users,32 or among 4-point auricular acupuncture, symptom-based acupuncture, and standard substance use treatment for alcohol abuse.33
VI. SUBSTANCE USE TREATMENT SETTINGS
The range of settings available for HIV-infected patients seeking substance use treatment are similar to those for non-HIV-infected patients, with the exception of certain services offered in HIV-specific facilities, such as dedicated nursing homes and other residences (see Table 7).
Most settings for substance use treatment will admit patients who are using illicit substances or alcohol (as opposed to requiring a period of abstinence prior to entry). Ambulatory treatment is commonly referred to as chemical-dependency treatment. There are two common residential treatment modalities: 1) rehabilitation, which typically lasts for 28 days; and 2) therapeutic community participation, which typically lasts for a year or more. Childcare, family, or job responsibilities may present significant obstacles to participation in residential treatment.
|Table 7: Treatment Settings for Substance Use|
VII. COMMUNICATION AND CONFIDENTIALITY
Clinicians should inform substance-using HIV-infected patients of the laws governing confidentiality of both HIV status and substance use treatment.
Clinicians should obtain written consent from the patient before communicating with substance use treatment programs.
Primary care clinicians should communicate with substance use treatment programs to ensure optimal care for substance-using patients. Programs in which substance use treatment, medical care, and psychiatric care are co-located or closely linked may facilitate communication between providers across disciplines. Communication among all providers and the patient may help prevent adverse drug interactions, such as interactions between drugs used to treat HIV infection and drugs used to treat substance use (see Appendices XI and XII). Disclosure of all medical conditions may also enable substance use treatment programs to individualize treatment plans.
Some patients are uncomfortable with their substance use treatment program knowing their medical history and/or their primary care provider knowing their substance use treatment information. Primary care clinicians should stress that open and honest communication can help ensure better medical care; however, it is important to recognize that communication regarding patients’ participation in substance use treatment is closely regulated by federal confidentiality laws. Written consent from the patient is required for exchange of information between providers.
For detailed information regarding patient confidentiality, refer to the Substance Abuse and Mental Health Services Administration’s website HIPAA: What It Means for Mental Health and Substance Abuse Services.
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