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Ward 86 Management Recommendations

Management of HIV-Infected Patients Who Use Methamphetamine

Contributors: Paula J. Lum, MD, MPH
Jacqueline P. Tulsky, MD
John Baker, MD
Valerie Gruber, PhD, MPH

In industrialized countries and, increasingly, in resource-limited settings, stimulant use, especially the use of methamphetamine, is common among people infected with HIV and accounts for substantial morbidity and mortality. Methamphetamine use is a driving force in HIV transmission among men who have sex with men (MSM), more than doubling the probability both of engaging in high-risk sexual behavior and of acquiring sexually transmitted infections (including HIV and hepatitis C).

In addition to its acute effects on the sympathetic branch of the autonomic nervous system, methamphetamine and amphetamine are neurotoxic to the brain's dopaminergic and serotonergic circuits.(1) Methamphetamine use can be complicated by severe hypertension, arrhythmias, cardiomyopathy, pulmonary hypertension, rhabdomyolysis, acute renal failure, myocardial infarction, stroke, severe dental caries, dyskinesias, memory loss, mood disorders, and psychosis, in addition to debilitating acute and chronic withdrawal syndromes. In a recent and well-performed metaanalysis of studies examining the effects of chronic methamphetamine use on neuropsychiatric and neurologic function, the most frequently reported deficits were in episodic memory, executive function, and motor function, and the largest impairments were in episodic memory, executive functions, and information processing speed.(1) Given all these health effects, training in how to elicit a history of stimulant use, how to characterize the nature of stimulant use in the medical record, and tools and techniques to manage this disorder are important for providers who treat HIV-infected individuals and those at risk of acquiring HIV infection.

Common clinical signs of long-term methamphetamine use include:

  • Irritability, aggression, impulsivity, paranoia

  • Preoccupation with minutiae and details that can lead to compulsive repetitive behavior

  • Impaired sexual functioning

  • Skin picking, tactile hallucinations, and delusional parasitosis

Screening for Methamphetamine Use

  1. Asking HIV-infected patients and those at high-risk of acquiring HIV infection about drug use should be part of the every initial medical history. The following validated single-question drug screening tool helps the clinician determine which patients need further substance use assessment: "How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?" A response of just 1 or more is considered to be positive.(2) Those who screen positive with this question should be assessed for patterns/quantity of methamphetamine use and for a diagnosis of stimulant use disorder. (See Appendix for more details.)

  2. Since patients often experience shame about their substance use, questions about methamphetamine should be introduced matter-of-factly and nonjudgmentally (in the same manner one might present the rationale for colon cancer screening to a patient) in order to create a more productive working relationship and to reduce the stigma of substance use in an already heavily stigmatized patient population.

Treatment for Methamphetamine Use

  • For patients diagnosed with stimulant abuse (DSM-IV) or mild stimulant use disorder (DSM-5), brief counseling interventions during office visits may help them to reduce methamphetamine use or stop altogether. (See Appendix for specific DSM diagnostic criteria). For patients diagnosed with stimulant dependence (DSM-IV) or moderate-severe stimulant use disorder (DSM-5), higher levels of care are indicated, including intensive individual or group therapy, residential detoxification and treatment, and/or a trial of medication management (see below).

  • For patients who are not quite ready to make a change in their drug use, patient-centered counseling at office visits can be used to build motivation and strengthen commitment to change. Providers may find that conversations about change are most productive using Motivational Interviewing, "a collaborative conversation style for strengthening a person's own motivation and commitment to change."(3)

  • Once a patient demonstrates readiness and commitment to change, it's time to proceed to an action plan, which may include behavioral interventions, medical management, or referral to more specialized treatment. The choice depends on what the patient is ready for and what is clinically indicated for his/her degree of substance use.

  • Behavioral therapies are currently the only evidence-based treatment for stimulant use disorders. They can be resource intensive, and their cost-effectiveness has not been well characterized. The Matrix Model is one example of a proven effective treatment for stimulant dependence.(4) This intervention consists of engaging the patient in relapse-prevention groups, education groups, social-support groups, individual counseling, and urine and/or breath drug screening delivered over a 16-week period. Contingency management is another effective behavioral treatment. An example of a 12-week contingency management program in San Francisco that uses positive reinforcement to support people who choose to stop using methamphetamine without the use of groups or meetings can be found on the San Francisco AIDS Foundation website. A metaanalysis of 13 randomized trials of behavioral interventions has shown that high-intensity behavioral interventions such as cognitive behavioral therapy (CBT) combined with contingency management is more effective than CBT alone in reducing stimulant use.(5) For MSM, CBT that is tailored to MSM was found to have a greater effect than general CBT techniques. An example of a behavioral treatment program in San Francisco that offers harm reduction-based individual or group counseling for MSM who are using or trying to stop using stimulants can be found on the Stonewall Project website.

  • Medical therapy. Promising preliminary results have been seen in small trials testing mirtazapine, naltrexone, bupropion, and methylphenidate for the management of methamphetamine use.(6,7,8,9) These trials have had small sample sizes and relatively short-term follow-up, and they generally have been conducted in specific patient subgroups (eg, patients with less-severe dependence at baseline or MSM), limiting the generalizability of their findings. With the caveat that larger, definitive trials are required to establish efficacy, we currently think there are two medication-assisted treatment strategies worth considering. When added to behavioral therapies, the following medications may be efficacious for selected treatment-seeking patients with stimulant use disorders.

    1. Naltrexone is an opioid receptor antagonist that can partially modulate or blunt the reinforcing dopaminergic effects of methamphetamine and amphetamine. Naltrexone is well tolerated in patients who do not require opioids for medical reasons and is FDA approved for the treatment of alcohol and opioid use disorders. In a trial conducted in Sweden,(6) where amphetamine use is more prevalent than methamphetamine use, 80 treatment-seeking individuals who met DSM-IV criteria for amphetamine dependence were randomized to 12 weeks of double-blind naltrexone (50 mg/day) or placebo. All subjects received 60 minutes of individualized relapse prevention counseling weekly by a licensed psychologist. A significantly higher mean number of amphetamine-negative urine samples and higher continuous abstinence rates were observed in the group treated with naltrexone compared with the placebo group. Cravings and self-reported consumption also were lower in the naltrexone-treated group.

      Notably, the trial required a 2-week period of abstinence prior to enrollment. Similar to findings in alcohol research, a greater period of abstinence prior to initiating medication selects patients likely to achieve better outcomes. Thus, this study showed that naltrexone, when combined with weekly counseling, may be an effective medication for reducing methamphetamine relapse. Naltrexone can be initiated at a dosage of 25 mg once daily for the first week to reduce risk of its most common side effect, gastrointestinal distress, then increased to 50 mg once daily for a total of 12 weeks. Because hepatotoxicity can be an adverse effect of this drug, naltrexone should be used cautiously in patients who have laboratory evidence of hepatic impairment.

    2. Mirtazapine is a noradrenergic and specific serotonergic antidepressant that facilitates the release of norepinephrine, serotonin, and dopamine in the areas of the brain involved in drug reward, craving, and drug-seeking behavior.(7) Mirtazapine was tested in a 12-week randomized, placebo-controlled trial in 60 methamphetamine-dependent MSM(7); participants were instructed to take 15 mg nightly for 1 week and then 30 mg nightly for the remainder of the study. In addition to the medication, both treatment groups received 30 minutes of substance use counseling weekly and medication adherence counseling monthly. In the mirtazapine group, there were significantly fewer methamphetamine-positive urine specimens as well as a reduction in high-risk sexual behavior despite low medication adherence. A second randomized, controlled trial is currently under way to determine if mirtazapine's efficacy can be replicated in a larger study population and sustained over a longer period of time. We consider trying mirtazapine for those patients who are interested in promising pharmacotherapies and understand that its efficacy has been established only when combined with weekly substance use counseling. We use the same dosage and duration as was used in this small study. Of note, adverse effects of mirtazapine include somnolence, increased appetite, weight gain, dry mouth, and, very rarely, erectile dysfunction. Patients may appreciate that among antidepressants, mirtazapine has one of the lowest rates of sexual side effects.

  • Urine drug testing (UDT) for methamphetamine. With patient consent, testing urine for methamphetamine and amphetamine can be a useful method during either behavioral or medication treatment for documenting stimulant use in the prior 2-5 days. As a component of counseling or behavioral treatments, UDT may help patients reflect on their frequency or patterns of use. Urine drug testing also can provide the patient with a measurable goal to work toward (ie, increasing the number or ratio of confirmed methamphetamine-negative urine tests in a set time period). Of note, screening immunoassays for amphetamine and methamphetamine are highly cross-reactive; false positives can occur at our hospital laboratory with bupropion, trazodone, sildenafil, some bath salts, and other drugs. Confirmatory testing of positive results by liquid/gas chromatography and mass spectroscopy is therefore essential when using UDT in clinical practice.

  • Management of methamphetamine withdrawal and relapse prevention
    1. Patients who stop using methamphetamine may show the following symptoms of acute withdrawal: feelings of fatigue and unrest, irritability, long but troubled sleep, intense hunger, and moderate to severe depression. These symptoms may be observed up to 2 weeks after discontinuing use. Intense craving for methamphetamine may persist for weeks to months after stopping use.

    2. People who stop using methamphetamine experience a reduction in brain concentrations of dopamine that may reach their lowest point after several months of abstinence. The neurotoxic effects of methamphetamine on the brain's dopamine terminals have been associated with the significant loss of dopamine transporters (DAT) in the thalamus and striatum. Positron emission tomography studies conducted after short (<6 month) and protracted (12-17 month) abstinence periods have shown partial recovery of DAT metabolism in only some areas of the brain and were associated with improved motor and verbal memory tests; these improvements, however, may take a year or more to achieve.(10)

    3. Depression is a common feature during both acute and subacute withdrawal. Patients can benefit from being informed about this effect, as delayed-onset depression may increase the risk of relapse.

    4. Providers should develop a plan with each patient for addressing possible depression (eg, nutrition, exercise, psychiatric consultation, antidepressant therapy). Mental health and other support services may be important for months after abstinence begins.

  • Other considerations. For persons who use methamphetamine, auditory memory is more negatively impacted and (in those who quit) returns more slowly than visual memory. This may have important implications for HIV clinicians, who often share important information verbally. Providers should write down instructions, HIV treatment plans, and appointment dates; they should visually review treatment plans, schedules, and medications; and use medi-sets or pillboxes as adherence reminders.

  • Appendix. Assessment of methamphetamine use and diagnosis of stimulant use disorders for patients who screen positive for at-risk methamphetamine use.

    1. Assessment can provide a specific diagnosis and inform the type of treatment that is most appropriate for an individual. Assessment done in a patient-centered manner also can be therapeutic and create a context for brief intervention. The type and depth of assessment can vary depending on time constraints and patient presentation.

      1. We recommend starting with an open-ended, nonjudgmental question: "Using drugs affects people's health and lives differently. In the last year, how has using crystal meth affected you?"

      2. Ask about injecting drugs and patterns of injecting, because injecting drug use is associated with increased risk of addiction, infections, and higher levels of other drug-related problems.

        1. "Have you ever used a needle to inject a drug?"

        2. "Can you get enough sterile equipment to use a new syringe/rig for every injection?"

      3. In order to determine the most effective intervention or treatment, assess whether the patient meets DSM-IV criteria for stimulant "abuse" or "dependence," or DSM-5 diagnostic criteria for a diagnosis of "stimulant use disorder" (mild, moderate, severe).

        Stimulant Abuse (DSM-IV)
        • One or more abuse criteria within a 12-month period and no dependence diagnosis: 1) risk of bodily harm; 2) relationship trouble; 3) role failure; 4) run-ins with the law.

        • ICD-9 code 305.7, Amphetamine or related acting sympathomimetic abuse; ICD-10 code F15.1, Other stimulant abuse

        Stimulant Dependence (DSM-IV):
        • Three or more dependence criteria within a 12-month period: 1) tolerance; 2) withdrawal; 3) used larger amounts/longer; 4) repeated attempts to quit/control use; 5) much time spent using; 6) gave up other meaningful activities; 7) physical/psychological problems related to use.

        • ICD-9 code 304.4, Amphetamine and other psychostimulant dependence; ICD-10 code F15.2, Other stimulant dependence

        Stimulant Use Disorder (DSM-5):
        • Two or more of the following substance use disorder criteria within a 12-month period: 1) risk of bodily harm; 2) relationship trouble; 3) role failure; 4) tolerance; 5) withdrawal; 6) used larger amounts/longer; 7) repeated attempts to quit/control use; 8) much time spent using; 9) gave up other meaningful activities; 10) physical/psychological problems related to use; 11) craving.

        • Mild = 2-3; Moderate = 4-5; Severe ≥6 substance use disorder criteria

          • Mild: ICD-9 code 305.7, Amphetamine or related acting sympathomimetic abuse; ICD-10 code F15.1, Other stimulant abuse

          • Moderate or severe: ICD-9 code 304.4, Amphetamine and other psychostimulant dependence; ICD-10 code F15.2, Other stimulant dependence

    2. Assess for medical complications and medication interactions that can exacerbate health risks:

      1. Concurrent use of methamphetamines with sildenafil or other phosphodiesterase inhibitors has been associated with increased risk of STDs, especially syphilis as well as HIV transmission to high-risk HIV negatives

      2. Use of ritonavir, which can increase amphetamine levels

      3. ART nonadherence

    3. Elicit patients' perspectives about their use. They often can come up with plenty of reasons not to use.

    4. Provide patients with feedback on their screening and assessment--this can be a valuable tool for building motivation to change and assessing their readiness for change. Engage patients in an interactive discussion regarding the severity and the health implications of their use.

      • ELICIT: What do you think might be the medical recommendation regarding your meth use?

      • PROVIDE: You meet criteria for the diagnosis of a moderate stimulant use disorder. The best treatment for this problem is to cut down or stop altogether, and I'm willing to help.

      • ELICIT: What do you make of this? How does this affect your thinking about your use?

    5. At every follow-up visit, ask about recent methamphetamine use and its consequences. Explore patients' values and goals as a way of learning what motivates them. For patients who have stopped use, ask about cravings or triggers, how they managed them, and if they could use some extra support. Always look for opportunities to recognize, support, and encourage the patient's strengths and efforts. This is considered "strength-based" counseling--you reflect back to the patient their past achievements or current strengths that can help them in their situation now. It can be helpful to refer patients to social work, case management, or behavioral health providers who can continue these motivational conversations with patients and refer them the appropriate level of care for substance use disorders when patients are ready.

    References

    1. Scott JC, Woods SP, Matt GE, et al. Neurocognitive effects of methamphetamine: a critical review and meta-analysis. Neuropsychol Rev. 2007 Sep;17(3):275-97.
    2. Smith PC, Schmidt SM, Allensworth-Davies D, et al. A single-question screening test for drug use in primary care. Arch Intern Med. 2010 Jul 12;170(13):1155-60.
    3. Miller WR, Rollnick S. Motivational Interviewing: Helping People Change, 3rd ed. New York: Guilford Press; 2013.
    4. Rawson RA, Marinelli-Casey P, Anglin MD, et al; Methamphetamine Treatment Project Corporate Authors. A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence. Addiction. 2004 Jun;99(6):708-17.
    5. Colfax G, Santos GM, Chu P, et al. Amphetamine-group substances and HIV. Lancet. 2010 Aug 7;376(9739):458-74.
    6. Jayaram-Lindstrom N, Hammarberg A, Beck O, et al. Naltrexone for the treatment of amphetamine dependence: a randomized, placebo-controlled trial. Am J Psychiatry. 2008 Nov;165(11):1442-8.
    7. Colfax GN, Santos GM, Das M, et al. Mirtazapine to reduce methamphetamine use: a randomized controlled trial. Arch Gen Psychiatry. 2011 Nov;68(11):1168-75.
    8. Shoptaw S, Heinzerling KG, Rotheram-Fuller E, et al. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. Drug Alcohol Depend. 2008 Aug 1;96(3):222-32.
    9. Ling W, Chang L, Hillhouse M, et al. Sustained-release methylphenidate in a randomized trial of treatment of methamphetamine use disorder. Addiction. 2014 Sep;109(9):1489-500.
    10. Wang GJ, Volkow ND, Chang L, et al. Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence. Am J Psychiatry. 2004 Feb;161(2):242-8.