Patrick G. O'Connor

Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

UNLABELLED Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related policies. PERSPECTIVE Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.

Use of Opioid Medications for Chronic Noncancer Pain Syndromes in Primary Care

AbstractOBJECTIVES: To define the spectrum of chronic noncancer pain treated with opioid medications in 2 primary care settings, and the prevalence of psychiatric comorbidity in this patient population. We also sought to determine the proportion of patients who manifested prescription opioid abuse behaviors and the factors associated with these behaviors. DESIGN: A retrospective cohort study. SETTING: A VA primary care clinic and an urban hospital-based primary care center (PCC) located in the northeastern United States. PATIENTS: A random sample of VA patients (n=50) and all PCC patients (n=48) with chronic noncancer pain who received 6 or more months of opioid prescriptions during a 1-year period (April 1, 1997 through March 31, 1998) and were not on methadone maintenance. MEASUREMENTS: Information regarding patients’ type of chronic pain disorder, demographic, medical, and psychiatric status, and the presence of prescription opioid abuse behaviors was obtained by medical record review. MAIN RESULTS: Low back pain was the most common disorder accounting for 44% and 25% of all chronic pain diagnoses in the VA and PCC samples, respectively, followed by injury-related (10% and 13%), diabetic neuropathy (8% and 10%), degenerative joint disease (16% and 13%), spinal stenosis (10% and 4%), headache (4% and 13%) and other chronic pain disorders (8% and 22%). The median duration of pain was 10 years (range 3 to 50 years) in the VA and 13 years in the PCC sample (range 1 to 49 years). Among VA and PCC patients, the lifetime prevalence rates of psychiatric comorbidities were: depressive disorder (44% and 54%), anxiety disorder (20% and 21%), alcohol abuse/dependence (46% and 31%), and narcotic abuse/dependence (18% and 38%). Prescription opioid abusive behaviors were recorded for 24% of VA and 31% of PCC patients. A lifetime history of a substance use disorder (adjusted odds ratio [OR], 3.8; 95% confidence interval [CI], 1.4 to 10.8) and age (adjusted OR, 0.94; 95% CI, 0.89 to 0.99) were independent predictors of prescription opioid abuse behavior. CONCLUSIONS: A broad spectrum of chronic noncancer pain disorders are treated with opioid medications in primary care settings. The lifetime prevalence of psychiatric comorbidity was substantial in our study population. A significant minority of patients manifested prescription opioid abusive behaviors, and a lifetime history of a substance use disorder and decreasing age were associated with prescription opioid abuse behavior. Prospective studies are needed to determine the potential benefits as well as risks associated with opioid use for chronic noncancer pain in primary care.

Three Methods of Opioid Detoxification in a Primary Care Setting: A Randomized Trial

Opioid-dependent persons (for example, those who take heroin) may seek treatment for substance abuse from their primary care physicians [1]. Treatment options include counseling and such pharmacologic therapies as 1) maintenance with opioid agonists [for example, methadone or LAAM] or 2) detoxification followed by maintenance with an opioid antagonist (naltrexone) or by psycho-therapy alone [2]. Opioid maintenance has been demonstrated to effectively decrease drug use [3]. However, maintenance with opioids is highly restricted by federal regulations and may be difficult to access for many patients [4, 5]. Although approaches other than opioid maintenance may be less effective, detoxification followed by ongoing treatment may be a reasonable alternative for patients ineligible for or unable to access maintenance treatment. The extent to which primary care physicians can initiate treatment may improve access to treatment for opioid dependence [5, 6]. Methadone detoxification is safe and efficacious; however, as occurs with methadone maintenance, federal regulations restrict its use to specially licensed programs [4, 7]. Detoxification with clonidine or rapid detoxification with combined clonidine and naltrexone [8-10] may be suitable for primary care settings [6]. In a previous study of detoxification in a primary care setting [6], combined clonidine and naltrexone was more successful than clonidine alone; however, methodologic limitations (nonrandom assignment and nonblinded assessment) make it difficult to draw definitive conclusions about the efficacy of the protocols [6]. Rapid detoxification has the advantage of bringing patients through withdrawal more quickly, although patients require close observation on day 1 because of severe withdrawal symptoms [6, 9]. Buprenorphine (a partial micro-opioid receptor agonist with mixed agonist-antagonist properties) may be more effective in alleviating withdrawal symptoms than is clonidine [11] and, when combined with rapid detoxification [12], may reduce the severity of withdrawal symptoms observed in patients who receive clonidine and naltrexone. Our objective was to compare three protocols for opioid detoxification in a primary care setting: clonidine, combined clonidine and naltrexone, and buprenorphine. We hypothesized that combined clonidine and naltrexone would result in more successful detoxification than clonidine alone and that buprenorphine would be as effective as and have fewer withdrawal symptoms than the combined agents alone. Methods The site of the study was the Central Medical Unit, a free-standing primary care clinic staffed by internists and nurse practitioners who provide medical care for substance abusers enrolled in programs affiliated with the Yale Substance Abuse Treatment Unit (SATU) [13]. The Central Medical Unit offers a full range of adult primary care services, including preventive care, chronic disease management, and urgent care. Trial participants were recruited by word of mouth and referral from intake coordinators of SATU-affiliated programs (for example, methadone waiting lists). Participants had to be opioid dependent and 18 to 50 years of age; participants could not be enrolled in a drug treatment program and must have had sufficient social support (such as safe transportation and a residence) for outpatient detoxification. Exclusion criteria were pregnancy, reactions to study medications, medical conditions potentially exacerbated by detoxification (for example, uncontrolled hypertension), contraindications to naltrexone (for example, severe chronic hepatitis or pain that required narcotic treatment), and psychiatric conditions that indicated the need for intensive services (for example, depression with suicidal ideation). All participants had medical and substance use evaluation at baseline, including standardized rating of withdrawal symptoms (24 symptoms were rated on a scale of 0 to 3) [14]. Detoxification started on a Monday (day 1). Participants had daily visits with primary care providers except on the weekend (days 6 and 7), and medications were dispensed at each visit to manage withdrawal symptoms until the next visit [6]. In the clonidine protocol, participants received 0.1 to 0.2 mg of clonidine every 4 hours as needed to control withdrawal symptoms from days 1 through 7 [6]. Detoxified participants were given a full opioid-blocking dose of naltrexone (50 mg) on day 8. In the combined clonidine and naltrexone protocol, participants received clonidine on a similar schedule and 12.5 mg of naltrexone on day 1, 25 mg on day 2, and 50 mg on day 3 [6]. In the buprenorphine protocol, participants received 3 mg of buprenorphine sublingually on days 1 through 3 and then clonidine as described plus 25 mg of naltrexone on day 4 and 50 mg on day 5. The following adjuvant medications were available for participants in all three treatment groups on an as-needed basis: oxazepam for insomnia and cramps, ibuprofen or ketorolac for muscle cramps, and prochlorperazine for nausea [6]. No other drug-treatment services were provided during detoxification. Participants were randomly assigned to a treatment group, and staff and patients were blinded to the protocols. Study medications were prepared so that participants received either active or placebo preparations of all medications. The primary outcome of our trial was successful detoxification, which was achieved when a participant received an opioid-blocking dose (50 mg) of naltrexone. Secondary outcomes were treatment retention for 8 days and daily scores of withdrawal symptoms. All participants who completed detoxification were referred for naltrexone maintenance. Participants who did not complete detoxification and those who had opioid relapse were referred to community treatment programs for opioid dependence (for example, methadone maintenance programs). Differences in the means of continuous variables were calculated by using the Student t-test. Chi-square statistics were used to evaluate differences in proportions. Results We screened 202 patients, 25 of whom were ineligible because of insufficient social support, comorbid medical or psychiatric conditions, or other reasons. Of the remaining 177 participants, 15 (5 per group) did not show on day 1 (all 15 were lost to follow-up); thus, 162 patients participated in the trial. Fifty-five patients were randomly assigned to receive clonidine, 54 to receive combined clonidine and naltrexone, and 53 to receive buprenorphine. The groups had no substantial differences in sociodemographic and clinical features (Table 1). Table 1. Baseline Characteristics of Study Participants Sixty-five percent of participants in the group receiving clonidine (36 of 55) successfully completed detoxification compared with 81% (44 of 54) in the group receiving clonidine and naltrexone (P = 0.06) and 81% (43 of 53) in the group receiving buprenorphine (P = 0.07). Because the day of protocol completion varied among the groups, we compared retention at day 8, which represented a uniform time point (that is, the first day on which participants in all three protocols had completed detoxification). Retention did not differ significantly among the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. The daily mean symptom severity scores for participants in each group are shown in the (Figure 1). Participants assigned to the combined clonidine and naltrexone group had more severe withdrawal symptoms early in detoxification. Participants assigned to the buprenorphine group had a significantly lower mean overall withdrawal symptom score (13.2 8.4) than did those in the clonidine and naltrexone group (17.6 9.3; t = 2.42; P = 0.016) and those in the clonidine group (17.8 10.3; t = 2.56; P = 0.01). The mean peak withdrawal symptom score (the highest score achieved by each patient during detoxification) was also lower for those receiving buprenorphine (22.3 12.3) than for those receiving clonidine and naltrexone (28.0 13.1; t = 2.66; P = 0.03) or clonidine (29.9 14.9; t = 2.96; P = 0.004). Figure 1. Mean scores for withdrawal symptoms by detoxification day. asterisk Discussion Given the high rates of relapse associated with illicit opioid use, new approaches that enhance access to treatment merit investigation. Office-based practices have been advocated as a site for methadone maintenance [5, 15], but methadone is not currently available for use in such settings [4, 5, 7, 16]. Although methadone in tapered doses may be the most effective approach to opioid detoxification, this agent is also unavailable to primary care physicians [7, 16]. Opioid detoxification in a primary carre setting with referral to ongoing drug treatment may be a suitable approach for patients who cannot access, are inappropriate for, or do not want opioid maintenance. In our study, eligible participants were randomly assigned to treatment groups, with double-blind measures implemented to minimize staff and participant expectations. In a previous study [6], participants were allowed to select their protocol group, thereby raising the possibility of selection bias. In the present study, the differential for success between the group receiving clonidine and the group receiving clonidine and naltrexone (81% compared with 65%) was not as dramatic as previously observed [6]. Although combined clonidine and naltrexone may be modestly superior to clonidine alone for successful detoxification, the effectiveness of the protocols after 8 days of retention was similar. In fact, participants who received clonidine alone were observed to be somewhat more likely than those receiving clonidine and naltrexone to have retention after 8 days. These differences in findings for protocol completion and 8-day retention may be attributable to clinical characteristics of the withdrawal protocols (for example, more s

A brief intervention reduces hazardous and harmful drinking in emergency department patients.

STUDY OBJECTIVE Brief interventions have been shown to reduce alcohol use and improve outcomes in hazardous and harmful drinkers, but evidence to support their use in emergency department (ED) patients is limited. The use of research assessments in studies of brief interventions may contribute to uncertainty about their effectiveness. Therefore we seek to determine (1) if an emergency practitioner-performed Brief Negotiation Interview or a Brief Negotiation Interview with a booster reduces alcohol consumption compared with standard care; and (2) the impact of research assessments on drinking outcomes using a standard care-no-assessment group. METHODS We randomized 889 adult ED patients with hazardous and harmful drinking. A total of 740 received an emergency practitioner-performed Brief Negotiation Interview (n=297), a Brief Negotiation Interview with a 1-month follow-up telephone booster (Brief Negotiation Interview with booster) (n=295), or standard care (n=148). We also included a standard care with no assessments (n=149) group to examine the effect of assessments on drinking outcomes. Primary outcomes analyzed with mixed-models procedures included past 7-day alcohol consumption and 28-day binge episodes at 6 and 12 months, collected by interactive voice response. Secondary outcomes included negative health behaviors and consequences collected by telephone surveys. RESULTS The reduction in mean number of drinks in the past 7 days from baseline to 6 and 12 months was significantly greater in the Brief Negotiation Interview with booster (from 20.4 [95% confidence interval {CI} 18.8 to 22.0] to 11.6 [95% CI 9.7 to 13.5] to 13.0 [95% CI 10.5 to 15.5]) and Brief Negotiation Interview (from 19.8 [95% CI 18.3 to 21.4] to 12.7 [95% CI 10.8 to 14.6] to 14.3 [95% CI 11.9 to 16.8]) than in standard care (from 20.9 [95% CI 18.7 to 23.2] to 14.2 [95% CI 11.2 to 17.1] to 17.6 [95% CI 14.1 to 21.2]). The reduction in 28-day binge episodes was also greater in the Brief Negotiation Interview with booster (from 7.5 [95% CI 6.8 to 8.2] to 4.4 [95% CI 3.6 to 5.2] to 4.7 [95% CI 3.9 to 5.6]) and Brief Negotiation Interview (from 7.2 [95% CI 6.5 to 7.9] to 4.8 [95% CI 4.0 to 5.6] to 5.1 [95% CI 4.2 to 5.9]) than in standard care (from 7.2 [95% CI 6.2 to 8.2] to 5.7 [95% CI 4.5 to 6.9] to 5.8 [95% CI 4.6 to 7.0]). The Brief Negotiation Interview with booster offered no significant benefit over the Brief Negotiation Interview alone. There were no differences in drinking outcomes between the standard care and standard care-no assessment groups. The reductions in rates of driving after drinking more than 3 drinks from baseline to 12 months were greater in the Brief Negotiation Interview (38% to 29%) and Brief Negotiation Interview with booster (39% to 31%) groups than in the standard care group (43% to 42%). CONCLUSION Emergency practitioner-performed brief interventions can reduce alcohol consumption and episodes of driving after drinking in hazardous and harmful drinkers. These results support the use of brief interventions in ED settings.

Long-Term Treatment with Buprenorphine/Naloxone in Primary Care: Results at 2-5 Years

To examine long-term outcomes with primary care office-based buprenorphine/naloxone treatment, we followed 53 opioid-dependent patients who had already demonstrated six months of documented clinical stability for 2-5 years. Primary outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases, and adverse events. Thirty-eight percent of enrolled subjects were retained for two years. Ninety-one percent of urine samples had no evidence of opioid use, and patient satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment occurred. We conclude that select opioid-dependent patients exhibit moderate levels of retention in primary care office-based treatment.

TREATMENT OF HEROIN DEPENDENCE WITH BUPRENORPHINE IN PRIMARY CARE

Buprenorphine is an effective treatment for heroin dependence. The feasibility and potential efficacy of buprenorphine with brief counseling in primary care is unknown. We enrolled 14 heroin dependent patients in a 13-week clinical trial using thrice weekly buprenorphine along with brief counseling in the primary care center of an urban medical center. Primary outcomes included urine toxicology and treatment retention. Opioid-positive urine toxicology tests reduced over the 13-week period from 95 to 25% (p<0.05). Eleven patients (79%) had greater than or equal to one week of opioid-free urine toxicologies. Nine patients (64%) had greater than or equal to three weeks of opioid-free urine toxicologies. Eleven patients (79%) were retained through the maintenance phase. We conclude that buprenorphine maintenance is feasible in a primary care setting.

Physician impairment by substance abuse.

Physician impairment by substance abuse represents a significant challenge to physicians, patients, and society as a whole. Although data is sparse, the prevalence of alcohol and illicit drug abuse among physicians is probably similar to that of the general population, while abuse of prescription drugs may be more prevalent. From a medicolegal standpoint, these issues are managed mostly at the state level and substance abuse is of increasing interest to credentialling organizations such as hospitals and managed care organizations. A variety of concrete steps can be taken to identify physicians with substance abuse problems and treatment approaches have been designed specifically for impaired physicians. With improved attention to the problem of physician impairment by substance abuse, the well-being of both physicians and their patients can be enhanced.

Human immunodeficiency virus infection in intravenous drug users: A model for primary care

PURPOSE Intravenous drug users (IVDUs) often encounter barriers to primary care. To improve access, we developed a primary care clinic--Central Medical Unit (CMU)--for substance abusers in drug treatment. We report outcomes for services offered to IVDUs with human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS During 1990, 24% (120 of 509) of IVDUs eligible for CMU were HIV positive. Diagnostic therapeutic and preventive goals for IVDUs with HIV infection were evaluated for acceptance and compliance by chart review for these 120 patients. RESULTS On admission, 65% (78 of 120) of patients reported having no source of primary care, 64% (77 of 120) were male, and 77% (92 of 120) were in methadone maintenance. All were screened for tuberculosis, syphilis, and hepatitis; 94% (15 of 16) of eligible patients accepted tuberculosis prophylaxis and 83% (5 of 6) accepted syphilis treatment, but only 36% (5 of 14) accepted hepatitis B vaccine. Of those who accepted therapy, 87% (13 of 15) were compliant with tuberculosis prophylaxis, and 100% (5 of 5) were compliant with syphilis treatment. Influenza vaccine was accepted by 49% (59 of 120) and pneumococcal vaccine by 81% (97 of 120). Ninety-eight percent (118 of 120) accepted T-cell testing: 61% had T-helper counts less than 500/mm3 and 25% were less than 200/mm3. Of those eligible, 89% (70 of 79) accepted antiretroviral therapy, and 100% (35 of 35) accepted Pneumocystis carinii pneumonia prophylaxis. Six-month compliance rates for these therapies were 84% (59 of 70) and 77% (27 of 35), respectively. CONCLUSION By offering primary care services with drug treatment, the CMU model may be an effective way of providing access to primary care for HIV-infected IVDUs and for facilitating compliance.

HIV infection and cocaine use in methadone maintained and untreated intravenous drug users

In a survey of 424 intravenous drug users (IVDUs) of whom 107 were currently enrolled in a methadone maintenance program (MMP), we assessed risk behaviors for Human Immunodeficiency Virus (HIV) transmission and conducted HIV testing. We found that African Americans were over-represented in the HIV infected group and under-represented in the methadone maintenance treatment group. Furthermore, subjects in current methadone maintenance treatment reported fewer drug injections in the last 30 days, a reduced speedball (a heroin/cocaine mixture) injection frequency and reduced total cocaine and injected cocaine use. HIV infected subjects reported 20% more cocaine use and injected cocaine use than HIV negatives. However, this difference was due to African Americans reporting more cocaine use and at the same time being over-represented in the HIV infected group. Stratified analysis by ethnicity found significant MMP effects for all ethnic groups, but only one significant HIV status effect, and this was limited to African Americans. Cocaine injection frequency in African Americans was significantly higher for the HIV infected versus non-infected subjects. We conclude that i.v. cocaine use is a risk factor associated with HIV infection and that methadone maintenance treatment is associated with reducing this risk factor. Furthermore, African American cocaine users are at great risk for HIV infection, and increased efforts for engagement in treatment are necessary.

Integrating Addiction Medicine Into Graduate Medical Education in Primary Care: The Time Has Come

Substance use disorders create an enormous burden of medical, behavioral, and social problems and pose a major and costly public health challenge. Despite the high prevalence of substance use and its consequences, physicians often do not recognize these conditions and, as a result, provide inadequate patient care. At the center of this failure is insufficient training for physicians about substance use disorders. To address this deficit, the Betty Ford Institute convened a meeting of experts who developed the following 5 recommendations focused on improving training in substance abuse in primary care residency programs in internal medicine and family medicine: 1) integrating substance abuse competencies into training, 2) assigning substance abuse teaching the same priority as teaching about other chronic diseases, 3) enhancing faculty development, 4) creating addiction medicine divisions or programs in academic medical centers, and 5) making substance abuse screening and management routine care in new models of primary care practice. This enhanced primary care residency training should represent a major step forward in improving patient care.