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The treatment of pain in patients with substance use disorders creates tensions for clinicians between undertreating pain and enabling opioid analgesic misuse.
To characterize prevalence and factors associated with aberrant opioid analgesic behaviors in a cohort of HIV infected individuals who are at high risk for opioid analgesic misuse.
We assessed pain and substance use disorders in a cross-sectional study that enrolled 296 participants from the Research on Access to Care in the Homeless (REACH) cohort, a community-based sample of indigent HIV-infected adults. We measured aberrant opioid behaviors, defined as major or minor depending on level of risk of harm to patients, using Audio Computer Assisted Technology (ACASI).
Most participants (91.2%) reported pain in the week prior to interview, with the majority of these experiencing severe pain (53.7%). Over two-thirds (69.2%) met criteria for a lifetime history of cocaine, amphetamine, or heroin/opioid use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). Over one-third of the sample (37.4%) had a history of aberrant opioid behavior within 90 days of interview. One-fifth (18.5%) had a history of “major” aberrant behaviors.
In this high risk population, severe pain is common and aberrant opioid behaviors are prevalent but not universal. As recommended by American Pain Society and American Academy of Pain Medicine guidelines, when prescribing opioid analgesics, clinicians must consider variation in the severity of aberrant behaviors, particularly aberrant behaviors that may represent undertreatment of pain.
As rates of both opioid analgesic prescriptions and opioid analgesic misuse rise [1, 2], clinicians experience increasing concerns about facilitating misuse . In order to reduce opioid misuse, the American Pain Society (APS) and American Academy of Pain Medicine (AAPM) recommend that clinicians perform a risk assessment for aberrant behaviors in all individuals who receive an opioid prescription [4–6]. While a number of screening tools for opioid misuse have been developed and tested [7, 8], a recent review noted that none can be recommended confidently for routine use . In the absence of available screening tools, clinicians must rely on relatively insensitive methods such a patient’s personal history of illicit substance use. These assessments may yield a high rate of false positive risk screens .
Patients with past illicit drug use and HIV disease are particularly at risk for both prescription opioid misuse and undertreatment of pain [9–19]. The prevalence of chronic pain among individuals with HIV disease ranges from 25% to 80% [20–22]. Clinicians face difficult decisions about which patients with pain who also have a personal history of illicit substance use or use disorders can be prescribed opioid analgesics safely. We identified only three studies that evaluated aberrant behaviors in this population [19, 23, 24]. All three studies provide evidence of positive associations between unrelieved pain and aberrant use of prescription opioid analgesics; however, none used Audio Computer Assisted (ACASI) technology to measure a comprehensive list of aberrant behaviors and focused on a high risk, community-based sample.
The Pain Study was designed to measure opioid analgesic misuse and aberrant behaviors in a high-risk, community-based cohort of HIV-infected indigent adults who have high rates of chronic nonmalignant pain (CNMP) and illicit substance use and who reside in an area known for the availability of non-medical prescription opioids .
The Pain Study co-enrolled participants from the Research on Access to Care in the Homeless (REACH) cohort, a community-based sample of homeless and marginally housed HIV-positive adults in San Francisco. The majority of this cohort was enrolled via systematic sampling [26–30]. Recruitment occurred at homeless shelters, free-meal programs, and single room occupancy hotels charging less than $600 per month.
Pain Study interviews took place at the UCSF Clinical and Translational Research Institute’s Tenderloin Clinical Research Center (TCRC), a university-affiliated, community-based research site. For the REACH study, interviewers conducted quarterly structured interviews including questions about sociodemographic characteristics, depression (Beck Depression Inventory) [31, 32], residential history, and past 90-day illicit substance and alcohol use. At each interview, participants underwent phlebotomy to assess CD4 count.
All REACH participants who came for an interview between September 2007 and June 2008 were invited to enroll in the Pain Study. The Pain Study baseline interview took place at the same visit or within one calendar week of the REACH study visit and involved a 45-minute interviewer-administered questionnaire with questions about pain, health service utilization, 90-day use of prescribed opioid analgesics and the medical use of analgesic medications.
Participants answered questions about aberrant opioid analgesic behavior using Audio Computer-Assisted (ACASI) technology to minimize response bias [33, 34]. To obtain valid diagnostic data regarding lifetime history of substance use disorder(s) including abuse and dependence, a trained interviewer conducted the Diagnostic Interview Schedule-IV (DIS-IV) alcohol and substance modules (full version for heroin/opiates, amphetamines, and cocaine/crack) [35, 36].
Participants were reimbursed $20 for participation in the baseline Pain Study Interview. The Institutional Review Board at UCSF approved the REACH and Pain Study protocols and instruments.
Participant characteristics included age at enrollment in the Pain Study, gender (man, woman, transgender), race (Black, White or other), educational attainment (<12th grade or ≥12th grade), monthly income, history of chronic homelessness (defined as having spent at least one year homeless since age 18), men who have sex with men, identification of a primary care provider, history of smoking nicotine cigarettes, type of health insurance (private, Medicare/Medicaid, Veterans’ benefits, or no insurance), prior year history of medical or mental health hospitalization, prior year history of ambulatory mental health services, history of incarceration in prison, and CD4 count nadir less than 200 since REACH cohort enrollment.
Participants were asked whether they experienced any pain or took any pain medicines in the past week. Those responding affirmatively rated their worst pain in the previous week using a 0 to 10 numeric rating scale from the Brief Pain Inventory  and indicated when their pain started (chronic pain defined as pain starting ≥ 6 months prior to the interview). A cut-point analysis was done  to classify pain as mild, moderate, or severe based on ratings of worst pain intensity in the past week. Scores of 0–4 represent mild, 5–7 moderate, and > 8 severe pain. Participants reported whether or not they had an opioid analgesic prescribed to them by a health care provider in the past 90 days and identified the specific opioids prescribed, using medication lists and photographs to assist recall. Analgesics were categorized as either short- or long-acting.
Participants were asked to report use of heroin, amphetamines, and cocaine/crack in the 90 days prior to interview. Lifetime histories of substance use disorders, including abuse and dependence, were determined for heroin/opiates, amphetamines, cocaine/crack and alcohol using the DIS-IV . For each substance, participants were categorized as having a history of a substance use disorder, a history of illicit drug use that did not qualify as a substance use disorder, or no history of illicit drug use. The DIS-IV provides valid measurement of DSM-IV substance use disorder diagnoses using a calculation based on multiple weighted questions throughout the interview . Substance use was defined with the DIS-IV question: "Which one of these have you used more than five times when they were not prescribed for you, or for longer than prescribed, to feel more active or alert, or to feel good or high?"
Passik et al. defined aberrant behaviors as any behaviors on the part of the patient that raise the possibility of abuse [23, 40–43]. For this study, an inventory of twenty opioid analgesic aberrant behaviors was developed based on a review of the literature and survey of clinicians’ experiences [23, 44–52]. Aberrant behaviors were classified into two groups to represent different levels of patient and societal risk associated with each behavior. “Major” aberrant behaviors were defined as behaviors that posed imminent risk to the patient or others for overdose or legal consequences (e.g., using opioid analgesics to “get high” or snorting, crushing, injecting, or smoking opioid analgesics). “Minor” aberrant behaviors were defined as those behaviors that posed less risk to the patient or others as well as behaviors that might be related to unrelieved pain or “pseudoaddiction” behaviors (e.g., saving unused prescribed opioid analgesics or using alcohol or other street drugs to augment the effect of opioid analgesics) [19, 53, 54]. Participants responded to yes/no questions using ACASI technology regarding occurrence of each behavior both in the past 90 days and over their lifetime.
To provide insight on individuals with active pain, we excluded individuals who reported no pain or analgesic use in the week prior to the interview. We stratified the population of those with recent pain by mild pain vs. moderate or severe pain. Using the Chi-square statistic and Fisher’s exact test, we compared patient demographics and substance use histories by pain severity (mild vs. moderate/severe). We described rates of concurrent use of illicit drugs and prescription opioids and rates of lifetime and 90-day aberrant behaviors. We conducted an additional analysis in which we included illicit substance use (heroin, cocaine or methamphetamine) used concurrently with a prescription opioid analgesic as a major aberrant behavior in the past 90 days. We performed bivariate comparisons with Fisher’s exact test to determine the relationship between 90-day aberrant opioid analgesic behaviors and: 1) pain history in the seven days prior to interview, 2) 90-day receipt of a prescription for opioid analgesics, and 3) 90-day use of illicit drugs. The data were analyzed using SAS software, Version 8 (SAS Institute, Inc., Cary, NC).
A total of 296 individuals completed the study interview; 270 (91.2%) reported pain or analgesic use in the past week and were included in the analysis. The sample had a mean age of 49.5 (standard deviation [SD] ±7.5). Nearly two-thirds (64.1%, n=173) were men and 7.8% were transgender (n=21, all men to women). The participants were predominantly Black (41.9%, n=113) and White (38.1%, n=103) (Table 1).
The majority of participants with pain reported moderate (38.1%, n=103) or severe (53.7%, n=145) pain. Chronic pain lasting six months or longer was present in 90.0% (n=243) of respondents. The mean worst pain intensity score was 7.45 (SD ±2.1). More than half (57.0%, n=154) described receiving a prescription for opioid analgesics. Of these 154, 59 (38.3%) reported receiving long-acting opioid analgesics.
One-third of respondents (33.0%, n=89) with recent pain reported use of heroin, cocaine or methamphetamine in the 90 days prior to interview; 5.6% (n=15) reported heroin use within 90 days. Approximately one-fifth (17.8%, n=48) of respondents described concurrent use of illicit drugs and prescribed opioids in the 90 days prior to the interview.
Among Pain Study respondents who completed the DIS-IV instrument and reported pain in the week prior to interview (n=260), 30.4% (n=79) met DSM-IV diagnostic criteria for lifetime heroin or opiate use disorder (e.g., abuse or dependence) based on the DIS-IV interview. All of these individuals reported a history of heroin use (i.e., none met criteria on the basis of non-medical use of prescription opioid analgesics alone). An additional 34 respondents (13.1%) reported heroin or non-medical prescription opioid use but did not qualify for a use disorder. Over one-third of participants (39.2%, n= 102) met the criteria for lifetime amphetamine abuse or dependence and an additional 20.0% (n=52) described use that did not qualify as a use disorder. Over half of respondents (55.0%, n= 143) met criteria for lifetime cocaine/crack use disorder, and an additional 22.7% (n=59) met criteria for use without qualifying for a use disorder. Less than a third of respondents (30.8%, n=80) had no history of heroin/opiate, amphetamine, or cocaine/crack use disorder.
Three-quarters of participants (73.3%, n=198) reported a lifetime history of at least one aberrant behavior. The mean number of lifetime aberrant behaviors among participants who reported any history of aberrant behaviors was 4.0 (SD ±3.3). Individuals with a history of major aberrant behavior (n=129) reported an average of 2.4 (SD ±1.6) major and 3.0 (SD ±1.9) minor aberrant behaviors. Of those who described a lifetime history of only minor behaviors (n=69), the mean number was 1.4 (SD ±0.9). Half of respondents (44.1%) described a lifetime history of both major and minor aberrant behaviors, whereas a quarter (25.6%) described a history of only minor aberrant behaviors.
The most frequently reported lifetime major behaviors were: used opioid analgesics “to get high” (34.4%); sold opioid analgesics (18.2%); and snorted, crushed, injected, or smoked opioid analgesics (17.0%). The most frequently reported minor behaviors were: saved prescribed opioid analgesics when finished using as prescribed (41.1%); drank alcohol or took street drugs with opioid analgesics to boost effects of opioid analgesics (31.5%); and borrowed opioid analgesics from another person (30.4%) (Table 2).
Approximately one-third (37.4%, n=101) reported a history of aberrant behavior within 90 days. Half of these individuals reported major aberrant behavior (18.5% of all respondents, n=50). Individuals who reported major aberrant behaviors in the past 90 days reported an average of 1.7 (SD ±1.2) major and 1.6 (SD±1.0) minor aberrant behaviors. When concurrent illicit substance and opioid analgesic use was included as an additional major aberrant behavior, an additional 31 respondents (30.0%, n=81) met criteria for major aberrant behavior within 90 days. Of those who described a past 90-day history of only minor aberrant behaviors (18.9 %, n=51), the mean number of minor behaviors was 1.3 (SD±0.7).
In bivariate analyses, we found that 13.6% (n=3) of those with mild pain reported either major or minor aberrant behaviors within 90 days, whereas 39.5% (n=98) of those with moderate or severe pain reported 90-day major or minor aberrant behavior (P=0.02). Major aberrant behaviors were reported by 4.6% (n=1) of those with mild pain compared to 19.8% (n=49) of those with moderate or severe pain (P=0.09). We found that 40.3% (n=91) of individuals reporting illicit drug use in the past 90 days also reported major or minor aberrant opioid behaviors in the past 90 days compared to 22.7% (n=10) of those who did not report recent illicit drug use (P=0.03). Major behaviors were reported by 21.7% (n=49) of those reporting recent illicit drug use compared to 2.3% (n=1) of those who denied illicit drug use (P <0.01). In addition, individuals who had received a prescription for opioid analgesics were more likely to report aberrant opioid analgesic behaviors. Approximately half (47.4%) of those reporting a prescription for opioid analgesics within 90 days reported either a major or minor aberrant behavior compared to 24.1% of those not receiving prescription opioid treatment (P <0.01). However, individuals reporting a prescription for opioid analgesics were no more likely to specifically report major aberrant behavior than those who had not received a prescription (18.8% vs. 18.1%, P=1.00).
Among individuals reporting a lifetime history of either major or minor aberrant behavior, individuals reporting major aberrant behaviors were significantly more likely to use illicit substances in the past 90 days (93.0%, n=120) compared to those with a lifetime history of only minor aberrant behavior (84.1%, n=58; P<0.01).
In this sample of adults with HIV infection and high rates of prior substance use disorders, aberrant opioid analgesic behaviors were common but not universal. Using a broader definition of aberrant behaviors than previously investigated and employing ACASI technology to strengthen the validity of responses, we found rates of aberrant behavior similar to those reported by patients in primary care settings and pain clinics despite the high risk profile of our sample [11, 45, 55]. Rates of lifetime illicit substance use in this sample were over 50% higher than those observed in the 2008 National Survey on Drug Use and Health, where fewer than half of respondents (49.3%) described lifetime illicit substance use (defined as nonmedical use of marijuana or hashish, cocaine, inhalants, hallucinogens, heroin or psychotherapeutics at least once) . In our study, considering only heroin, cocaine, and methamphetamine, over 80% of participants reported lifetime use of illicit substances. Moreover, over two-thirds of our study sample met criteria for a lifetime history of substance use disorders related to these substances. Most study participants reported both severe and chronic nonmalignant pain. Our finding of high rates of illicit substance use, substance use disorders, and both CNMP and severe pain highlight the need for clinicians to carefully balance the risks of misuse of prescription opioid analgesics and undertreatment of chronic pain in this population.
Tsao et al. found that patients with HIV disease in a nationally representative probability sample experienced more pain and distress and engaged in high rates of aberrant drug-related behaviors . Passik et al. have similarly examined aberrant drug-related behaviors in clinic-based HIV and non-HIV populations and found rates significantly lower than those observed in our cohort . We have built on this work with our examination of aberrant behavior in a cohort considered to be at high risk of opioid misuse behaviors. By employing a community-based sampling strategy of an indigent population, we enrolled a cohort of participants distinct from the populations studied in previous investigations of aberrant behavior. ACASI technology has been demonstrated to improve accuracy in survey response, and our work represents the first time this technology has been used to measure aberrant opioid analgesic behaviors. Using these methods, we have documented significant associations between increasing pain, recent illicit drug use, and receipt of a prescription for opioid analgesics and aberrant behavior.
Clinicians who treat high-risk patients with CNMP face the dilemma of trying to distinguish between aberrant behaviors associated with an opioid use disorder versus behaviors associated with unrelieved pain (i.e., “pseudoaddictive” behaviors) [19, 53, 54]. Treatment of pseudoaddiction requires that clinicians increase the intensity of therapy in order to extinguish aberrant behaviors [12, 57]. As recommended in the APS/AAPM guidelines , clinicians need to recognize variability in the seriousness of aberrant opioid analgesic behaviors. In our sample, individuals with a lifetime history of only minor aberrant behaviors represented a quarter of the study population and were significantly less likely to report illicit substance use compared to those with major aberrant behaviors.
Clinicians who observe aberrant behaviors may need to be aware that patient motivations for behaviors may reflect the desire to treat pain, to get high, or, in the case of hoarding, to avoid future pain or medication costs. Although all aberrant behaviors may require a change in opioid therapy, the direction of this change is dependent on whether behaviors represent addiction or pseudoaddiction.
Our data rely on self-reported behaviors and may be subject to response bias. However, our study design included several elements to minimize the likelihood of response bias including ACASI technology and use of a community-based research facility instead of a clinical site for interviews. In addition, participants were familiar with the interview site and had participated in previous interviews at the study site related to stigmatizing behaviors including illicit drug use [26–30]. Undertreatment is a known risk in HIV infected individuals and patients with a history of substance use disorders [10, 15–19]; however, we are unable to assess the effects of under-treatment in our sample because we did not measure adherence to prescribed therapy. Finally, although the study sample provides novel information concerning a community-based population at high risk for aberrant opioid analgesic behaviors, the REACH cohort is not representative of the general population of individuals using opioid analgesics or those with HIV disease.
Our findings support balanced attention to the presence of aberrant opioid behaviors as well as the high prevalence of moderate to severe chronic pain among indigent, HIV-infected patients. Future research exploring patients’ motivations for aberrant behaviors will help clinicians better assess the risks associated with prescribing opioid analgesics as well as minimize inappropriate discontinuation or withholding of prescription opioid analgesics.
Disclosures and Acknowledgments
Dr. Hansen was supported by the Robert Wood Johnson Foundation Clinical Scholars Program. Dr. Kushel, Dr. Miaskowski, Dr. Bangsberg, Mr. Guzman and Ms. Penko received support from NIDA R01DA022550; Drs. Kushel and Bangsberg received support from NIMH R01MH54907. This project was supported by NIDA R01DA022550, NIMH R01MH54907, and NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
The authors thank Greg Barnell, Rebecca Packard, Joyce Powell, Matt Reynolds, Paul Rueckhaus, and John Weeks for their assistance in interviewing Pain Study participants.
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This work was presented in poster format at the Society for General Internal Medicine Annual Meeting, Miami, FL, May 14, 2009.