Important note: Information in this article was accurate in July 2002. The state of the art may have changed since the publication date.
Since 1989, approximately one-third of all AIDS cases in the United States have been among active or former injection drug users (IDUs) [MMWR June 01, 2001 / 50(21);430-434]. Although the major risk factor for HIV infection in the United States among men is same-sex contact, the major risk factor among women with AIDS is either IDU or heterosexual contact with an injection drug user [CDC, HIV/AIDS Surveillance Report 2002;13]. Once HIV enters any IDU population, the virus can spread very quickly. For example, in the Northeast of the United States, where injection drug use is prominent, the prevalence of HIV among IDUs entering drug treatment centers from the period of 1998-1997 was 28% compared to only 3% in the West [CDC National Serosurveillance, 1993-1997]. It has been estimated that at least 55% of the patients seen in the Johns Hopkins AIDS Service (JHAS) in Baltimore are injection drug users.
Injection drug users engage in two behaviors that put them at risk for HIV infection: needle sharing and having multiple injection partners. However, substance abuse can play a major role in HIV transmission even among non-injection drug users. Addiction and high-risk sexual behavior have been linked across a wide range of settings. For example, women who use crack cocaine are more likely to engage in unprotected sex in exchange for money or drugs [Edlin BR, et al. N Engl J Med 1994 Nov 24;331(21):1422-7; Astemborski J, et al., Am J Public Health 1994 Mar;84(3):382-7]. Men who use crack cocaine are more likely to engage in unprotected anal sex with casual male contacts [deSouza CT, et al. J Acquir Immune Defic Syndr 2002 Jan 1;29(1):95-100]. Alcohol intoxication has been associated with high-risk sexual behavior as well as more needle sharing among drug users [Stein MD, J Subst Abuse Treat 2000 Jun;18(4):359-63, Rees V, J Subst Abuse Treat 2001 Oct;21(3):129-34].
Even though it is evident that a high proportion of IDUs are infected with HIV, there has been little research on how to improve treatment accessibility and outcome in this population. It is estimated the approximately 80% of IDUs in the United States are not in drug treatment [National Association of State Alcohol and Drug Abuse Directors, unpublished data]. Adherence to treatment in this population is difficult because of the high prevalence of psychiatric, cognitive and social problems. This article will examine the nature of drug addiction, its interaction with HIV and psychiatric co- morbidities, assessment and screening of the drug user, and the types of treatments that may be useful for these patients.
A Model for Understanding Addiction
The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) divides substance use disorders into two main categories: substance dependence and substance abuse.
In order to satisfy the criteria for substance dependence, an individual must have at least three of the following criteria:
According to the DSM-IV criteria, tolerance and withdrawal are not sufficient or even necessary to make a diagnosis
of substance dependence. Compulsive cannabis use, for example, can occur in the absence of significant tolerance or withdrawal symptoms. Likewise, surgical patients can experience tolerance and withdrawal from opioid pain medications without showing signs of compulsive use.
Substance abuse is defined by one of the following criteria:
To better understand the nature of habitual substance use, various models of addiction have been developed. Currently, the most popular model for understanding substance addiction is to view it as a chronic disease, akin to diabetes or asthma, in which behavioral interventions and treatment compliance play a part in controlling a lifelong illness [Leshner AI, Hosp Practice 1997:6-8; McLellan AT, et al. JAMA 2000 Oct 4;284(13):1689-95]. Although the medical paradigm has done much to lessen the stigma and has resulted in improved treatment services, it is inadequate in that it fails to address the importance of psychosocial and cognitive learning variables in addiction. On the JHAS Psychiatry Service, we have used a “motivated behavior” model for understanding addiction [McHugh PR, The Perspectives of Psychiatry]. This model takes into account the individual’s free will, biological drive, and conditioned learning, which interact to produce addictive behavior.
All motivated behaviors (eating, sleeping, and sex) are driven, in part, by biological mechanisms. In the case of addiction, abused substances have been found to cause increased levels of dopamine in the nucleus accumbens, a part of the mesolimbic dopamine system found in the ventral tegmental area of the brain. These structures are among the most primitive areas of the brain and are powerful motivators when stimulated. Animals will perform a task (such as a lever press) several thousand times in order to receive an electrical or chemical stimulus to the nucleus accumbens. This biological “reward system” is modulated not only by dopamine but also by opioid receptors. Cocaine and stimulants directly cause elevated levels of dopamine, while alcohol and opiates increase the firing rate of dopaminergic neurons by acting on opioid receptors.
Conditioned learning shapes behavior by way of psychological and environmental variables. Society can also play a role in initiating and sustaining addiction. This was convincingly illustrated in a study of 898 U.S. servicemen enlisted in Vietnam, where 21% were addicted to heroin while in Vietnam, but only 1% remained addicted upon their return to the U.S. [Robins LN, Arch Gen Psychiatry 1975 Aug;32(8):955-61]. Easy access to opiates in Southeast Asia and a culture of opiate use may have been factors contributing to the high rate of heroin use.
Learning is also shaped by reinforcers provided by the drug itself. In the earlier stage of addiction, the “high” or euphoria provided by the drug serves as the positive reinforcer. In later stages, negative reinforcement becomes more important as the addict develops tolerance to the drug. Long-term heroin addicts continue to use the drug not because it makes them “high” but to avoid withdrawal sickness.
A highly conditioned behavior eventually becomes more stereotypical and compulsive in nature. Moreover, environmental cues can trigger “cravings” or urges to use the drug in a Pavlovian fashion. This is best illustrated in nicotine dependence, when smokers experience strong cravings when performing activities usually associated with cigarette smoking. In short, addiction results when biological mechanisms and environmental conditioning combine to produce a new “drive” or hunger to use drugs without the normal checks and balances that usually keep natural drives under control.
Finally, choice involves the free will of the individual to initiate and continue using the drug. While it is true that choice becomes narrower as addiction progresses, it is by choice that an individual enters treatment resulting in a lifestyle change.
Ongoing substance abuse has grave medical implications for HIV-infected individuals. Many physical symptoms of HIV infection overlap with those of substance abuse and withdrawal, including malaise, fatigue, weight loss, fever, diarrhea and night sweats. The accumulation of medical sequelae from chronic substance use may accelerate HIV infection itself. HIV-seropositive IDUs, for example, are at higher risk for developing bacterial infections such as pneumonia, sepsis, soft tissue infections and endocarditis than seronegative drug users [Selwyn PA, et al. N Engl J Med 1992 Dec 10;327(24):1697-703]. Tuberculosis and hepatitis C infection are found more commonly in this population as well [O’Connor PG, et al. N Engl J Med 1994 Aug 18;331(7):450-9]. Because high-risk sexual behavior and drug use are often linked, these patients are also at risk for contracting and spreading a variety of STDs.
Neurological symptoms due to HIV infection and substances of abuse can overlap. For instance, both AIDS dementia and drug intoxication can present with apathy, disorientation, aggression, and an altered level of consciousness. Drug withdrawal can present with seizures and neurovegetative symptoms, as can opportunistic infections of the CNS. With respect to medical treatment, HIV-infected active IDUs tend to be less compliant with medical appointments, medications, and in obtaining regular laboratory testing [Arici C, et al. HIV Clin Trials 2002 Jan-Feb;3(1):52-7]. Substance use is associated with poor antiretroviral medication adherence, resulting in higher viral loads and lower CD4 cell counts [Lucas GM, et al. AIDS 2002 Mar 29;16(5):767-74].
Because the HIV-infected patient is likely to be on a variety of antiretroviral medications and prophylactic agents for opportunistic infections, the clinician must be especially mindful of interactions between these medications and methadone treatment. Decreased plasma levels of methadone can occur with concurrent administration of ritonavir, nelfinavir, efavirenz, and nevirapine, necessitating adjustments in methadone dosage if withdrawal symptoms occur [Gourevitch MN, Mt Sinai J Med 2000 Oct-Nov;67(5-6):429-36]. Medications used to treat opportunistic infections and seizures such as rifampin, phenytoin, phenobarbital, and carbam-azepine can also cause decreased methadone levels.
Concurrent Psychiatric Disorders
The term “dual diagnosis” refers to a patient who has both a drug use disorder and another psychiatric disorder; “triple diagnosis” refers to a dual diagnosis patient who also has HIV. Such patients are over-represented in treatment settings because of their symptom severity and chronicity. In a study of 50 new entrants to the JHAS, 44% of the patients had a diagnosis of current or previous substance use disorder, and 24% of those patients had both a comorbid primary psychiatric diagnosis and substance use disorder [Lyketsos CG, et al. Int J Psychiatry Med 1994;24(2):103-13]. Personality disorders, especially antisocial personality disorder, are commonly found in the substance abusing population. Although the DSM-IV uses a categorical approach to diagnosing personality disorders in which patients need to meet a certain set of criteria to qualify for a diagnosis, it is often more helpful to view personality traits as existing along a continuum. Thus, more or less of a particular personality trait can predict habitual adaptive or maladaptive responses to life circumstances.
One model that we use on the JHAS Psychiatry Service depicts personality as existing around the axes of stability-instability and introversion-extroversion [see Hutton, Hopkins HIV Rep 2001 Nov;13(6):5-7]. The combination of the personality traits of instability and extroversion are often seen in patients being treated in the HIV clinic. Persons with extreme traits of instability have very strong and reactive emotional responses that tend to be overpowering, easily taking control of the person’s judgment and behavior. Persons with extreme traits of extroversion have emotional responses that are quick and changeable, focused in the present, and tend to be predominantly reward-seeking rather than harm-avoiding. These traits are generally found in the so-called cluster B personality disorders in the DSM-IV (antisocial, borderline, narcissistic, and histrionic), which can be found in as many as 49% of all substance abusers [Kokkevi A, et al. Addict Behav 1998 Nov-Dec;23(6):841-53].
Unstable extroversion has important implications for the HIV-infected addict. Not only do these traits result in a vulnerability to addiction and other risky behaviors that predispose to HIV infection, but they also pose significant barriers to treatment. These patients tend to act on strong, impulsive feelings rather than on carefully considered treatment instructions. Their behavior will tend to be driven by the transient, immediate rewards of drugs rather than by their lasting future consequences. Such patients tend to become bored easily. They tend to “want what they want when they want it” rather than when it may be good for them. Studies have shown that drug users with a diagnosis of antisocial personality disorder are more likely to engage in HIV risk behaviors such as needle sharing and injection drug use [Brooner RK, et al. Am J Psychiatry 1993:140:309] and to have a greater number of sexual partners [Kelley JL, J Subst Abuse Treat 2000 Jul;19(1):59-66]. They are also less likely to stop high-risk sexual behaviors after being educated about HIV prevention [Comptom WM, et al. Drug Alcohol Depend 2000 Mar 1;58(3):247-57]. It is critical to identify such personality vulnerabilities in this patient population, because they can have a profound effect on treatment engagement and prognosis.
Mood disorders, especially major depressive disorder, are also found in these patients, with studies estimating a prevalence of 15% to 30% [Ahmad B, et al. J Pak Med Assoc 2001 May;51(5):183-6; Brooner BK, et al. Arch Gen Psychiatry 1997 Jan;54(1):71-80]. Diagnosing affective disorders in drug users can be difficult and even controversial. This controversy stems from the problem of determining the causal or even chronological relationship between drug disorders and affective disorders. In making the diagnosis of a primary mood disorder, it often becomes necessary to observe the patient over a period of abstinence, ideally in a confined environment. Careful consideration should be given to whether the symptoms are isolated or whether they meet the full criteria for a major depressive syndrome. The temporal relationship of symptoms to substance use should also be considered. Patients with a family history of psychiatric disorders are more likely to have a comorbid psychiatric diagnosis than those who do not. Finally, collateral informants such as family members and friends who have knowledge of a patient’s premorbid functioning can be invaluable in determining the longitudinal course of a patient’s symptoms.
The importance of identifying affective disorders early on lies not only in their own well-known sequelae, including suicide, but also in their complex interactions with addiction. Depression is associated with worsening of addiction and resistance to treatment. Depressed patients are also more difficult to engage in and maintain in treatment given their anergy, hopelessness, and negativism. Given the high prevalence of overlapping addictive and affective disorders in clinical settings, as well as the poor prognosis associated with untreated affective disorders, a treatment approach should necessarily emphasize simultaneous and equal treatment of both entities.
Because of societal stigma attached to both substance abuse and HIV, a patient may be reluctant to disclose information in an initial evaluation. Forming a close therapeutic alliance is the first step to effective history taking. If necessary, it can be spread out over several sessions. The clinician should take a nonjudgmental and empathetic approach to interviewing the patient and move from more comfortable topics of discussion (employment, family, friends, hobbies) before introducing questions about drug use and sexual behavior. Confidentiality should be assured, as in other types of medical settings. In many cases collateral sources of information can be helpful in eliciting accurate histories. These may include old medical records,
family members, friends, and health care providers (both previous and current).
A careful substance abuse history should contain specific information not only about the type of substances used but also about routes of administration, duration, frequency of use, date of first use, most recent use, and the highest/usual amount used of each drug. The patient should also be asked about periods of abstinence and relapse and the respective conditions surrounding each one.
A drug treatment history should also be obtained, including the types and period of detoxification, outpatient drug treatment, methadone maintenance, attendance at AA/NA meetings, and residential drug treatment. This information is helpful in ascertaining which methods of treatment may have been helpful in the past and which treatment modalities have failed.
To assess patients for drug dependency, questions related to drug craving, loss of control of drug use, withdrawal symptoms, medical complications, and impairment in psychosocial functioning should be explored with patients. A simple screening tool for alcoholism is the CAGE questionnaire, which has a 75% sensitivity and 96% specificity for two or more positive answers [Bush B, et al. Am J Med 1987 Feb;82(2):231-5]. CAGE is a mnemonic for:
A complete physical examination should include a careful search for physical evidence of drug abuse, including injection marks, scars, burns, nasal septum erosion or perforation, skin abscesses, cellulitis, and soft-tissue infection. Stigmata of alcohol abuse include hepatosplenomegaly, ascites, and physical trauma. A careful neurological assessment, including a complete mental status examination is essential in order to assess for the presence of both substance intoxication and the neuropsychiatric manifestations of AIDS.
The initial and often most daunting task of treating the addict is engagement and induction of the patient role. The general rule is that addicts and treatment providers begin with differing agendas—addicts tend to come to treatment settings seeking comfort and immediate crisis relief, whereas physicians and other health providers look at long term goals of improvement in a patient’s health and overall functioning. One of the clinician’s initial goals should be to gradually bring the patient’s attitudes in line with the treatment plan.
An important first step is to identify where the patient is in terms of his or her motivation to change. Addiction experts use a “transtheoretical stages of change” model to evaluate a patient’s motivational state [Prochaska JD, et. al. Psychotherapy: Theory, Research, and Practice 1982;19:276-88]. A patient is viewed as progressing through several different stages:
The most difficult task faced by most clinicians is in moving a patient from a precontemplative or contemplative stage to an action stage. Change is more effective and sustained when the patient is able to verbalize self-motivational statements that indicate readiness to enter treatment (“I’ve got to do something about this problem.”). A technique known as “motivational interviewing,” developed by Miller and Rollnick, uses five main techniques to help the patient resolve ambivalence about needing treatment:
Once a patient has decided to change his or her addictive behavior, the clinician’s role is to then help the patient decide on a plan and to facilitate entry into treatment. This can include helping the patient make phone calls to treatment facilities, working out a child care plan for single mothers, or arranging transportation from the patient’s home to the treatment site.
In order for intoxicated patients to understand and process the cognitive steps needed for recovery, detoxification is the first step. Many HIV-infected substance abusers benefit from a brief hospital stay to stabilize their psychiatric and medical co-morbidities and to give them respite from the social chaos that is often such a prominent part of their lives. This is usually accomplished by either slowly tapering the drug of dependence or using a cross-dependent drug that has a similar pharmacological mechanism of action.
Alcoholics are detoxified through the use of a long-acting benzodiazepine, such as diazepam (Valium) or chlordiazepoxide (Librium). Patients who have liver abnormalities or are more prone to delirium can be detoxified using oxazepam (Serax), which has no active metabolites. Detoxification from short-acting benzo-diazepines such as lorazepam (Ativan), alprazolam (Xanax) can be accomplished by converting the patient to an equivalent dosage of a longer acting benzodiazepine, such as clonazepam, or by using a phenobarbital taper. Opioid dependent individuals are commonly detoxified through a methadone or buprenorphine taper. Clonidine, an alpha-2 adrenergic agonist, can be used alone or adjunctively to alleviate the autonomic symptoms of heroin withdrawal.
Many patients with HIV and addictions often have comorbid psychiatric conditions, which need to be treated in order to maximize treatment compliance. Conditions such as major depression, bipolar disorder, and schizophrenia are best managed pharmacologically and if necessary, a psychiatric referral should be made early in the course of treatment. Because these patients tend to have multiple medical complications, it is important to remember to start psychotropic medications at low dosages and to titrate slowly to minimize the risk of developing adverse side effects and delirium.
Disorders of personality are managed with cognitive-behavioral psychotherapy. Unstable extroverts may sabotage treatment by engaging in staff splitting, doctor shopping, general noncompliance and manipulative behavior. Therapy should help the patient focus on thoughts instead of feelings and should emphasize rewards resulting from the desired behavior. Firm limit setting and a devotion to consistency on the part of all health care providers involved are essential. To this end, the treatment staff should work on a documented treatment plan with clear goals agreed upon by all. The treatment plan should be reviewed with the patient at the initiation of treatment so that he understands clearly what is expected of him and what he can expect from his treatment providers if these goals are adhered to.
Long-term treatment is necessary for patients to begin the process of lifestyle change and recovery. Treatment settings can be inpatient, outpatient, or a combination of the two. Whether a patient can be maintained on an inpatient or outpatient basis depends on the availability of social supports in the community, presence of medical and/or psychiatric comorbidities, likelihood of relapse, number of previous failed treatment attempts, and the need for inpatient medical monitoring for withdrawal symptoms.
An integrated approach to treatment is most effective because the complexity of this patient population makes it especially vulnerable to recidivism. To this end a “one-stop shopping” model is needed to maintain treatment engagement. Thus, a treatment center catering to HIV infected addicts should ideally include medical providers, psychiatrists, social workers, housing counselors, and day care workers on site. Directly observed therapy of antiretroviral and psychotropic medications at substance abuse treatment facilities can improve adherence and compliance. This has proven to be successful in a number of JHAS patients who also attend the 911 Broadway Center (a Hopkins-based outpatient substance abuse treatment facility), where medications are administered to patients when they arrive for their daily methadone treatment or substance abuse groups.
It is important to remember that addiction treatment is “active” rather than “passive” and entails transforming previously held beliefs, attitudes, and personal identity into a new way of life. To this end, group therapy is a necessary part of all substance abuse treatment. In group therapy, the more experienced members of the group provide both confrontation and support for the newly initiated member. Group support also provides the newly recovering addict with a hopeful view of the benefits to be achieved with recovery. A commitment to a community of recovery protects the patient from the influences of the drug community and provides the patient with new bonds that help maintain a sense of purposefulness and hopefulness.
The individual health care provider can assist the patient during this phase of recovery by helping the patient identify and avoid triggers to possible relapse and increasing the patient’s sense of self-efficacy and ability to cope without drugs. It is important to realize that relapse is often the rule and not the exception, and plans should be in place for early intervention. Random urine and serum drug toxicology screens and Breathalyzer tests can be used to monitor a patient’s continued abstinence. When a relapse or “slip” does occur, the health care provider should immediately facilitate the patient’s re-entry into drug treatment before old patterns of behavior become reestablished.
Pharmacological treatments should be seen as enhancements to the overall treatment plan and not as a replacement for them. For example, studies have shown that in the treatment of alcohol dependence, naltrexone in conjunction with supportive and coping skills therapy was much more effective than treatment with naltrexone alone [O’Malley SS, et al. Arch Gen Psychiatry 1992 Nov;49(11):881-7]. Likewise, patients had better outcomes in methadone treatment when they had access to regular counseling, on-site psychiatric/medical services, and family therapy [McLellan AT, et al. JAMA 1993 Apr 21;269(15):1953-9].
In alcoholics, disulfiram can be very effective. It is taken once daily at dosages from 250 mg to 500 mg and causes a very unpleasant reaction when alcohol is ingested due to the build up of acetaldehyde in the body. Symptoms include nausea, flushing, headaches and hypotension. Liver enzymes should be monitored because of the risk of hepatotoxicity. Another medication, which has been more recently available to clinicians, is naltrexone administered at dosages of 50 to 100 mg/day. Naltrexone has been shown to reduce alcohol cravings and the subjective feeling of alcohol intoxication [Volpicelli JR, et al. Arch Gen Psychiatry 1992 Nov;49(11):876-80; Volcipelli JR, et al. J Clin Psychiatry 1995;56(suppl 7):39-44; Swift RM, J Clin Psychiatry 1995;56 Suppl 7:24-9].
In opiate dependent individuals, pharmacotherapy includes both opioid agonist and antagonist medications. Methadone is the opioid agonist most often used for maintenance treatment and has been very effective in reducing the spread of HIV. This medication is usually given to the patient at varying dosages from 40 to 100 mg daily; however, patients tend to do best at dosages above 60 mg/day. The medication is administered daily under supervision until the patient has established a pattern of abstinence, at which time take-home dosages are allowed. Buprenorphine, a partial agonist, is currently being considered for FDA approval for sublingual administration and may be a useful alternative to methadone. Naltrexone is an opioid antagonist that has a high affinity for blocking mu receptors. The medication blocks the euphoric effects of opioids when taken at dosages of 50 to 100 mg/day. Before the medication is started, the patient must have been abstinent from opioids for a period of time, usually 5-10 days, because it precipitates rapid withdrawal in individuals who still have opioids in their system. As with disulfiram, liver function tests must be monitored because of the risk of hepatotoxicity.
Working with the HIV-infected substance abuser is a challenging and often frustrating task. An integrated treatment team approach consisting of medical providers, psychiatrists, substance abuse counselors, therapists and social workers is essential in unraveling and addressing the variety of problems these patients face which make them vulnerable to nonadherence. Early identification and rapid accessibility to treatment is essential in improving both their mental and physical well-being and in halting further spread of HIV.
Jeffrey H. Hsu, M.D. is an Instructor in the Department of Psychiatry, Johns Hopkins University, School of Medicine.
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