Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection
Introduction
Hospitalization of opioid-dependent individuals for acute (as well as chronic) illness often interrupts their heroin use and can result in withdrawal. Untreated opioid withdrawal, aside from being very unpleasant, can confound medical assessment and increase patients' anxiety towards necessary medical procedures, resulting in conflicts with the healthcare team or in premature discharges against medical advice (with potentially harmful consequences). Although pharmacological treatments have been shown to minimize opioid withdrawal intensity in medically stable patients, their effects on withdrawal have not been evaluated in drug users hospitalized for an acute illness.
Of particular interest are hospitalized drug users infected with HIV, as injection drug use is a major cause of HIV transmission in the United States (Center for Disease Control, 1997, Karon et al., 2001). When HIV-infected drug users are hospitalized, they are brought in contact with healthcare professionals who could alleviate drug use withdrawal discomfort and possibly intervene in the cycle of drug use. Besides withdrawal-related discomfort during hospitalization, HIV-infected opioid users may experience additional pain from their underlying HIV-related illnesses (Breitbart et al., 1996, Breitbart et al., 1997, Rosenfeld et al., 1996). Neurologic changes associated with HIV progression may affect the response to opioid detoxification and perhaps even exacerbate pain from withdrawal-related conditions. For example, animal research has demonstrated that neuromediator changes underlying neuropathic pain are similar to those observed in opioid tolerance (Mao et al., 1995). This finding raises the question of whether intensity of HIV-related pain could be increased by opioid withdrawal and, thus, promote relapse to heroin use upon discharge. It is, therefore, important to assess the potential impact of opioid detoxification on pain syndromes and to develop standards of care that minimize suffering.
This study was designed to evaluate responses to three different opioid detoxification medications (clonidine, methadone, and buprenorphine) on withdrawal and pain measures while HIV-infected patients received treatment for their acute medical condition. Clonidine, an α2-noradrenergic agent, is a presynaptic inhibitor of norepinephrine release in the locus coeruleus with weak analgesic activity at the spinal level (Aghajanian, 1978, Gold et al., 1978, Gold et al., 1980, Guthrie, 1990, Striebel et al., 1993, Bischoff and Kochs, 1993), though the importance of this activity in opioid-dependent human is not known. Methadone, a μ-opioid agonist with pharmacological properties qualitatively similar to those of morphine, has been recommended for managing opioid dependence in the hospital setting (Perkins, 1970, Stimmel, 1997). Buprenorphine is a partial μ-opioid agonist analgesic that is 25–50 times more potent than morphine (Jaffe and Martin, 1990, Jasinski et al., 1978). All three medications have been tested in clinical trials for opioid detoxification and shown to be effective in suppressing opioid withdrawal in healthy opioid-dependent volunteers seeking treatment (Umbricht et al., 1999, Jasinski et al., 1985, Agren, 1986, Buccafusco, 1992, Cheskin et al., 1994, Nigam et al., 1993, O'Connor et al., 1997, Bearn et al., 1998, Bickel et al., 1988).
The outcome of opioid detoxification in HIV-infected individuals hospitalized for an acute medical condition has not been evaluated. We hypothesized that, while all three regimens would be effective among hospitalized HIV-infected persons, buprenorphine would be superior to clonidine and methadone because it has high receptor affinity, a long duration of action, and low intensity of withdrawal symptoms following abrupt discontinuation (Jasinski et al., 1978). Because of its partial agonist activity, buprenorphine causes little or no cardio-respiratory depression in opioid-tolerant individuals, even at high doses (Walsh et al., 1994, Preston et al., 2001) and, thus, may be the safest in medically compromised patients.
The objectives of this study were to compare the effectiveness of these three opioid detoxification methods on withdrawal and pain scores in HIV/AIDS patients during hospitalization for an acute medical condition. A subsidiary objective was to evaluate patterns of medical indication for opiate (morphine) administration during the detoxification and associated treatment outcome.
Section snippets
Patients and setting
Patients were admitted to the inpatient AIDS service of the Johns Hopkins Hospital, either through the emergency department or via the outpatient AIDS clinic. Within 18 h of admission, subjects were screened by questionnaire and urine toxicology for current heroin use and for evidence of physical dependence. Inclusion criteria were HIV seropositivity, age of at least 18, hospitalization for an acute medical illness, and current opioid dependence by self-report and physical examination.
Results
Sixty-three eligible heroin-dependent patients were enrolled in the study, and 21 were assigned to each treatment group. Data were available for 55 patients: three patients were dropped out after baseline before receiving any study medication, and five were excluded due to medication errors (e.g., staff administered open-label buprenorphine instead of “study (blinded placebo or active) buprenorphine”). Table 1 shows patients' characteristics at enrollment. There were no other significant
Discussion
The post-treatment improvements in this study suggest that opioid withdrawal was effectively accomplished by treatment with any one of the three regimens during hospitalization for medical reasons. Although relatively high at baseline, opioid withdrawal symptoms and pain ratings decreased during the 4-day study period. This interpretation, however, must be considered in light of the lack of a control group (for ethical reasons) and potential longitudinal reporting bias. The initiation of
Acknowledgements
The study was funded by the National Institute on Drug Abuse, Intramural Research Program. We thank Marcia Hoffman, Betsey Emilien, Michelle Dequina, and Neena Thomas for their expertise in data collection and data management, and Dr. David Epstein for his constructive review of the manuscript. We also thank the nursing staff of the Johns Hopkins Inpatient AIDS Service for their cooperation and unconditional support of the study, and the Osler Medical Service for physician support.
References (32)
- et al.
Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for inpatient opiate detoxification
Drug Alcohol Depend.
(1998) - et al.
Pain in ambulatory AIDS patients. I. Pain characteristics and medical correlates
Pain
(1996) - et al.
A comparison of pain report and adequacy of analgesic therapy in ambulatory AIDS patients with and without a history of substance abuse
Pain
(1997) Neuropharmacologic and behavioral actions of clonidine: interactions with central neurotransmitters
Int. Rev. Neurobiol.
(1992)- et al.
A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids
Drug Alcohol Depend.
(1994) The development of a short opiate withdrawal scale (SOWS)
Addict. Behav.
(1990)- et al.
Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions
Pain
(1995) - et al.
Buprenorphine in opiate withdrawal: a comparison with clonidine
J. Subst. Abuse Treat.
(1993) - et al.
Pain in ambulatory AIDS patients. II. Impact of pain on psychological functioning and quality of life
Pain
(1996) - et al.
Naltrexone shortened opioid detoxification with buprenorphine
Drug Alcohol Depend.
(1999)
Tolerance of locus coeruleus neurons to morphine and suppression of withdrawal response by clonidine
Nature
Clonidine treatment of the opiate withdrawal syndrome
Acta Psychiatr. Scand.
A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts
Clin. Pharmacol. Ther.
Alpha2 agonists in anaesthesia and intensive care medicine
Anaesthesiol. Intensivmed. Notfallmed. Schmerzther.
Update: trends in AIDS incidence, deaths, and prevalence—United States
MMWR
A comparison of three ways of measuring pain
Rheumatol. Rehabil.
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Present address: Sinai Hospital Addictions Recovery Program, Baltimore, MD 21215, USA.