Abstract
Objective:
Substance use among individuals receiving prescription opioids for pain may be associated with poorer functioning. The purpose of this study was to examine whether the use of substances (ie, alcohol, marijuana, or tobacco) among individuals prescribed opioids for pain management was associated with pain, psychiatric disorders, and opioid misuse.
Methods:
Patients with non-cancer pain and a new opioid prescription were recruited from 2 health systems. Participants (N = 827) completed measures regarding pain severity, pain interference, psychiatric symptoms, and substance use.
Results:
Substance use was common with 58.0%, 26.2%, and 28.9% reporting alcohol, tobacco, and marijuana use, respectively. The use of tobacco or marijuana was associated with poorer functioning. Those with tobacco use had greater pain severity, interference, number of pain sites, and concern for opioid misuse, and were more likely to have probable depression, anxiety, and posttraumatic stress disorders. Participants reporting marijuana use were more likely to have higher concerns for opioid misuse scores and probable depression, anxiety, and posttraumatic stress disorders. Use of alcohol was associated with lower pain severity and interference and fewer number of pain sites.
Conclusion:
Substance use is common among individuals receiving prescription opioids. Some types of substance use may be related to poorer opioid, pain, and psychiatric functioning. Clinicians prescribing opioids for pain management should assess for substance use, including tobacco, and be aware of the association with poorer functioning. Interventions could target pain, psychiatric symptoms, and substance use simultaneously to optimize outcomes for individuals with pain and substance use.
Keywords: alcohol, marijuana, opioids, pain, psychiatric disorders, substance use, tobacco
The Centers for Disease Control and Prevention estimates that over 50 million U.S. adults experience chronic pain (ie, pain lasting most days for at least 3 mo).1 Historically, opioids were widely prescribed for the treatment of chronic pain in the United States.2 Both pain and opioid use are linked to psychiatric symptoms. As many as half of individuals with chronic pain experience comorbid depression or anxiety, and pain severity is positively correlated with psychiatric symptoms.3–6 Similar findings are seen for opioids and psychiatric symptoms. Those receiving opioids for chronic pain management exhibit increased symptoms of anxiety and depression, and the risk for depression increases with the frequency of opioid use.7,8
In addition to increased psychiatric symptoms among those receiving prescription opioids, other substance use (ie, alcohol, marijuana, and tobacco) is common.9–12 Individuals using opioids who also have alcohol misuse tend to have poorer outcomes such as greater severity of psychiatric symptoms, increased risk for overdose, greater likelihood of substance misuse or substance use disorders, and greater pain severity.9,12–16 However, there is limited data on any alcohol use. Given the increase in adverse events with any alcohol use with opioids,17 it is important to understand how any alcohol use among those prescribed opioids is associated with psychiatric and pain-related outcomes. Individuals who use marijuana with opioids also have poorer outcomes with regard to symptoms of anxiety and depression, substance misuse, and pain-related functioning (ie, pain severity, pain interference, and pain self-efficacy).11,18 Similarly, those using tobacco with prescription opioids are significantly more likely to experience opioid misuse or develop an opioid use disorder.10,19
Taken together, individuals using another substance (ie, alcohol, marijuana, or tobacco) while receiving prescription opioids appear to be at greater risk for adverse outcomes. However, prior studies have not examined the association of multiple types of substance use with opioids, while also examining both psychiatric and pain variables.9–16,19 To have a comprehensive understanding of substance use and the potential impact (ie, association with pain and psychiatric functioning), there is a need to examine various types of substance use (ie, alcohol, marijuana, and tobacco) among a single sample of individuals prescribed opioids for pain management to compare and contrast findings between substances. This knowledge would also be helpful in guiding safer opioid prescribing and identifying those who may especially benefit from multidisciplinary care. The purpose of this study was to examine the prevalence of substance use among individuals prescribed opioids for pain management and whether alcohol use, cannabis use, or tobacco use were associated with pain severity, pain interference, psychiatric disorders, and opioid misuse.
METHODS
Participants and Procedure
This study was part of a prospective longitudinal project that examined individuals who recently initiated a prescription opioid.20,21 Patients were recruited from 2 health systems (Henry Ford Health in Detroit, Michigan and Saint Louis University in Missouri) and were eligible to enroll if they had non-cancer pain and recently initiated a new period of 30-90 day opioid use (ie, no opioid use in the 3 mo before the current opioid prescription). Potentially eligible individuals were identified from electronic health records at each respective health system on a weekly basis and eligibility was confirmed through a brief screen (ie, currently using an opioid for pain; non-cancer treatment). Patients who consented to participate completed measures through Research Electronic Data Capture, a web-based platform, or with a trained interviewer by phone. The present study uses baseline data from 1047 participants who consented; complete data were available for 827 participants (see Supplemental Table 1 for missing data, Supplemental Digital Content 1, http://links.lww.com/CJP/B171). We previously conducted a sensitivity analysis within this project where we used multiple imputations to address missing values and the results were the same.22
Measures
Demographic Variables
Participants reported on age, sex, race, and marital status.
Opioid Variables
Opioid variables included daily vs. non-daily opioid use, high dose daily morphine milligram equivalent (MME) dose ( ≥ 50 vs < 50 MME), and concerns about opioid misuse. Participants were asked to respond on the number of days each week they use the prescribed opioid (ie, 0 to 7 d). Those who endorsed 7 days per week were considered to have “daily use” whereas < 7 was considered “non-daily use.” Concerns about opioid misuse were measured with the “concerns” subscale of the Prescription Opioids Difficulties Scale (example item: “I have worried that I might be dependent on or addicted to opiate pain medicines”).23 Scores can range from 0 to 28, and higher scores on this subscale indicate greater concern regarding opioid misuse.
Substance Use
Participants reported on alcohol, tobacco, and marijuana use. Alcohol use was measured with the first question of the Alcohol Use Disorder Identification Test, regarding how often alcohol has been consumed over the past year.24 Participants were considered to have alcohol use if they reported alcohol use (ie, “monthly or less,” or more frequently). This definition was used to measure any alcohol use because most work has focused on alcohol misuse, and the other substances are measured as any use. Tobacco use was assessed with the question “Do you now smoke cigarettes every day, some days, or not at all?” Participants were considered to have tobacco use if they reported currently smoking cigarettes every day or some days. Participants were considered to have marijuana use if they reported the last use was within the past year. Other substance use was also queried; however, because of the low endorsement of stimulants (n = 18) and heroin (n = 1), these were not included in analyses.
Pain Variables
Pain severity, pain interference, and the number of pain sites were assessed with the Brief Pain Inventory.25 Four items assessed the severity of pain on a 0 (no pain) to 10 scale (pain as bad as you can imagine): worst pain in the last 30 days, least pain in the last 30 days, average pain, and current pain. Pain severity was the average of these 4 items. Pain interference was also rated on a 0 (does not interfere) to 10 scales (completely interferes) with regard to the level of interference that the pain had on activities of daily living in the past 30 days. The ratings were averaged across 7 activities of daily living for a total score (general activity, mood, walking ability, normal work, relationships, sleep, and enjoyment of life). Participants also reported on the areas of the body (up to 17 sites) where they experience pain. Participants responded to whether they had persistent, bothersome pain in the following sites: head, neck, shoulder, upper back, lower back, arm, elbow, wrist, hand, buttocks, hip, chest, abdomen/pelvis, leg, knee, ankle, and feet. The number of pain sites reported was totaled, with the total ranging from 0 to 17.
Psychiatric Disorders
Participants were categorized into whether they had probable depression, generalized anxiety disorder, or posttraumatic stress disorder (PTSD). The “semi-structured assessment for the genetics of alcoholism” was used to assess symptoms of depression over the past year.26 The semi-structured assessment for the genetics of alcoholism is a semistructured instrument designed to measure Diagnostic and Statistical Manual of Mental Disorders-IV criteria diagnoses (including depression) through lay-administered interviews. This measure was adapted for self-administration and we programmed skip patterns in the web-based survey based on participants’ responses. Participants were considered to have depression based on Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a major depressive episode. The Generalized Anxiety Disorder-7 (GAD-7) was used to assess symptoms of anxiety.27 The GAD-7 consists of 7 items and assesses the frequency of experiencing each anxiety-related symptom from 0 (not at all) to 3 (nearly every day). Participants were considered to have probable anxiety when the total score of all items was 10 or greater. The Primary Care PTSD Screen was used to screen for major symptom domains of PTSD.28 Participants responded to whether they experienced a traumatic event (yes/no), and if so, responded to whether they experienced symptoms associated with the prior traumatic event over the past month (yes/no). Participants were considered to have probable PTSD if they endorsed 3 or more of the 5 symptom domains.
Analyses
Descriptive statistics and frequencies were conducted for all variables. Bivariate analyses (independent samples t tests and χ2 analyses) were conducted to determine the association between each substance use variable and pain, opioid, and psychiatric variables. Unadjusted and adjusted logistic regression models were constructed to assess the association between each substance use variable and opioid variables both before and after adjusting for covariates described above (ie, demographics, pain variables, and psychiatric disorders). Analyses were first conducted among participants with complete data. Analyses were also performed using multiple imputations to address missing values. Because findings were similar (Supplemental Table 2, Supplemental Digital Content 2, http://links.lww.com/CJP/B172), the results reported are among those with complete data.
RESULTS
Patient Characteristics
The characteristics and percentages of substance use among the 827 included participants are presented in Table 1. Participants were primarily female and white with a mean age of ~53 years. Most patients endorsed using at least 1 additional substance (tobacco, alcohol, or marijuana) in addition to their prescription opioid; only about a quarter of patients were not using any tobacco, alcohol, or marijuana. The most common type of substance use was alcohol (58%), with more than half of the participants reporting alcohol use. Use of marijuana and tobacco were also relatively common, with approximately a quarter of participants reporting use of each of these substances. Nearly one-third of participants endorsed using 2 or more substances (31.6%) and 7.5% endorsed using all 3 substances.
TABLE 1.
Participant Characteristics and Types of Substance Use Among Individuals Receiving Prescription Opioids (N = 827)
| n (%) | |
|---|---|
| Demographics | |
| Age (mean, SE) | 52.9 (0.4) |
| Race | |
| White | 593 (71.7) |
| Black | 199 (24.1) |
| Other | 35 (4.2) |
| Sex | |
| Female | 550 (66.5) |
| Male | 277 (33.5) |
| Relationship status | |
| Married/living with partner | 423 (51.2) |
| Widow/divorced/separated | 248 (30.0) |
| Never married | 156 (18.9) |
| Substance use | |
| Alcohol | 480 (58.0) |
| Tobacco | 217 (26.2) |
| Marijuana | 239 (28.9) |
| Co-substance use | |
| No other substance use | 214 (25.9) |
| Alcohol only | 254 (30.7) |
| Tobacco only | 61 (7.4) |
| Marijuana only | 37 (4.5) |
| Alcohol and tobacco | 59 (7.1) |
| Alcohol and marijuana | 105 (12.7) |
| Tobacco and marijuana | 35 (4.2) |
| Alcohol, tobacco, and marijuana | 62 (7.5) |
| Opioid variables | |
| Daily opioid | 569 (68.8) |
| MME ≥ 50 | 146 (17.7) |
| Opioid misuse concern score (mean, SE) | 3.0 (0.2) |
| Pain variables | |
| Continuous pain interference (mean, SE) | 6.8 (0.07) |
| Continuous pain severity (mean, SE) | 5.9 (0.06) |
| Total pain sites (mean, SE) | 6.2 (0.1) |
| Psychiatric disorders | |
| Depression | 191 (23.1) |
| Anxiety | 180 (21.8) |
| PTSD | 146 (17.7) |
MME indicates morphine milligram equivalent; PTSD, posttraumatic stress disorder.
Psychiatric Disorders
The presence of a probable psychiatric disorder was common among participants, including depression (23.1%), anxiety (21.8%), and PTSD (17.7%; Table 1). Those who reported the use of tobacco or marijuana versus those not using were more likely to have depression, anxiety, and PTSD (Table 2). The presence of psychiatric disorders was not associated with alcohol use.
TABLE 2.
Associations of Substance Use and Pain and Psychiatric Variables Among Individuals Receiving Prescription Opioids
| Alcohol use (n = 480) | No alcohol use (n = 347) | P | Tobacco use (n = 217) | No tobacco use (n = 610) | P | Marijuana use (n = 239) | No marijuana use (n = 588) | P | |
|---|---|---|---|---|---|---|---|---|---|
| Pain variables | |||||||||
| Pain interference (mean, SE) | 6.6 (0.1) | 7.0 (0.1) | 0.02 | 7.2 (0.1) | 6.6 (0.1) | <0.001 | 6.9 (0.1) | 6.7 (0.09) | 0.18 |
| Pain severity (mean, SE) | 5.8 (0.08) | 6.1 (0.09) | <0.001 | 6.3 (0.1) | 5.8 (0.1) | <0.001 | 6.0 (0.1) | 5.9 (0.07) | 0.23 |
| Total pain sites (mean, SE) | 5.7 (0.2) | 6.8 (0.2) | <0.001 | 7.0 (0.2) | 5.9 (0.2) | <0.001 | 6.5 (0.2) | 6.0 (0.2) | 0.14 |
| Opioid variables | |||||||||
| Daily opioid; n (%) | 314 (65.4) | 255 (73.5) | 0.01 | 168 (77.4) | 401 (65.7) | 0.001 | 172 (72.0) | 397 (67.5) | 0.21 |
| MME > 50; n (%) | 89 (18.5) | 57 (16.4) | 0.43 | 43 (19.8) | 103 (16.9) | 0.33 | 50 (20.9) | 96 (16.3) | 0.12 |
| Opioid misuse concern score (mean, SE) | 2.9 (0.2) | 3.2 (0.2) | 0.21 | 4.0 (0.4) | 2.7 (0.2) | 0.002 | 3.8 (0.3) | 2.7 (0.2) | 0.004 |
| Psychiatric disorders | |||||||||
| Current depression; n (%) | 113 (23.5) | 78 (22.5) | 0.72 | 65 (30.0) | 126 (20.7) | 0.005 | 76 (31.8) | 115 (19.6) | <0.001 |
| Anxiety; n (%) | 94 (19.6) | 86 (24.8) | 0.07 | 68 (31.3) | 112 (18.4) | <0.001 | 67 (28.0) | 113 (19.2) | 0.005 |
| PTSD; n (%) | 81 (16.9) | 65 (18.7) | 0.49 | 55 (25.3) | 91 (14.9) | <0.001 | 56 (23.4) | 90 (15.3) | 0.006 |
MME indicates morphine milligram equivalent; PTSD, posttraumatic stress disorder.
Opioid Use and Pain-related Variables
Individuals with alcohol use had lower pain interference, lower pain severity, and fewer number of pain sites compared with those without alcohol use, whereas those with tobacco use had higher pain interference, higher pain severity, and a greater number of pain sites compared with those without tobacco use (Table 2). Marijuana use was not associated with pain variables.
Those using tobacco or marijuana were more likely to have higher opioid misuse concerns scores; alcohol use was not associated with concerns with opioid misuse scores (Table 2). Females with alcohol use (OR = 0.66; CI: 0.47, 0.92), tobacco use (OR = 0.70; CI: 0.50, 0.97), and marijuana use (OR = 0.68; CI: 0.49, 0.96) were less likely to report daily opioid use compared with males. Sex was not significantly associated with high-dose daily MME. Participants using alcohol with prescription opioids were less likely to be using opioids daily, whereas those using tobacco were more likely to have daily opioid use (Table 3). There was no association between marijuana and the likelihood of daily opioid use. The use of alcohol, marijuana, or tobacco was not associated with daily MME dose.
TABLE 3.
Predicting Opioid Use Characteristics by Alcohol, Tobacco, or Marijuana
| Daily opioid use |
MME ≥ 50 |
|||
|---|---|---|---|---|
| Model 1; OR (95% CI) | Model 2; OR (95% CI) | Model 1; OR (95% CI) | Model 2; OR (95% CI) | |
| Alcohol | 0.68 (0.50-0.92)* | 0.72 (0.52-0.98)* | 1.16 (0.80-1.67) | 1.19 (0.82-1.74) |
| Tobacco | 1.79 (1.25-2.56)* | 1.60 (1.09-2.34)* | 1.22 (0.82-1.81) | 1.04 (0.68-1.60) |
| Marijuana | 1.24 (0.89-1.72) | 1.16 (0.82-1.65) | 1.36 (0.93-1.98) | 1.27 (0.85-1.90) |
Model 1 was unadjusted. Model 2 was adjusted for demographics, pain variables, and psychiatric disorders reported in Table 1.
P < 0.05
MME indicates morphine milligram equivalent; OR, odds ratio.
DISCUSSION
Findings from this study suggested that the use of other substances (ie, alcohol, tobacco, and/or marijuana) is common among individuals prescribed opioids for pain management. Though prior work has suggested that a substantial proportion of individuals with prescription opioids may engage in other substances, studies have typically only measured one other type of substance.9–12 As such, this study extends upon prior work and suggests that ~3 of 4 patients recently receiving prescription opioids reported past-year substance use, and oftentimes, using multiple types of substances raising potential concern about co-use of opioids and other substances.
Results also suggested that the use of tobacco or marijuana among those with an opioid prescription was associated with poorer functioning. Similar to previous studies, this study found that those with tobacco or marijuana use have greater concerns regarding opioid misuse.10,11,19 Previous work has found that individuals with pain who use tobacco report a greater number of pain sites and higher pain severity.29 The current study confirmed these findings and also found that tobacco use may associated with greater pain interference as well. It is possible that smoking could lead to greater pain sensitivity, which could explain the association between smoking and daily opioid use.30 In addition, tobacco and marijuana use are often associated with psychiatric diagnoses in the general population,31,32 and our findings suggest that this is also true among those receiving opioids for pain management. It is possible that substance use, including opioids, could lead to increased psychiatric symptoms.8,33 Nevertheless, the relationship between substance use and psychiatric disorders is likely bidirectional, and cessation of substances could lead to improved psychiatric symptoms.31
Although tobacco and marijuana appeared to be associated with poorer pain functioning, alcohol use was associated with better pain functioning (ie, lower pain severity, lower pain interference, and fewer number of pain sites). Though the difference between those using and not using alcohol may not be clinically meaningful, there are several potential explanations for these findings. First, the current study examined any alcohol use, whereas others have examined the severity of use.34 Alcohol, when used occasionally, may have a pain-dampening effect, which could explain why current alcohol use may be associated with better functioning.34,35 Similarly, some past work has found that alcohol problems, but not the amount consumed, were associated with a greater number of painful medical conditions, particularly in men.36 It may be that associations with greater pain emerge primarily among individuals engaged in problematic alcohol use. Second, those who are “too sick” (ie, high levels of pain and disability from pain), may be less likely to consume alcohol, as those with health conditions are more likely to discontinue alcohol use.37 Finally, given that participants have a new period of opioid prescription, it is also possible that opioid use and alcohol use do not overlap for some participants. Providers may have discussed the dangers of using alcohol with opioids and patients could be adhering to prescribing instructions and could be reporting on alcohol use before initiating the opioid.
Although this study contributes to the knowledge regarding the association between substance use with prescription opioids on pain and psychiatric functioning, it is important to acknowledge its limitations. First, a significant limitation is that the exact timing of substance use was not assessed. Because alcohol and marijuana use were assessed over the previous year, it is possible that participants did not use these at the same time as their recent (ie. 30 to 90 d) opioid prescription. In addition, it is not known whether participants were using the substances together or separately (ie, on different days), which could have an impact on the findings. It is also possible that not all substance use was captured. Patients using other substances may have been less likely to participate in this study, or among those who did participate, substance use may have been minimized or was not reported. Finally, because of the small group sizes for those reporting the use of 2 or all 3 substances, additional analyses could not be conducted.
The results of this study have important implications. Clinicians prescribing opioids for non-cancer pain management should be aware that past-year substance use is commonly reported among those receiving prescription opioids. Clinicians could routinely assess for other types of substance use, including alcohol, tobacco, and marijuana. When other substance use is identified, clinicians could provide education to patients regarding the association with poorer functioning and encourage decreasing other substance use. For example, although physicians may discuss the risks of overdose risk related to alcohol use while taking opioids, clinicians can also discuss the association with increased psychiatric symptoms and poorer pain functioning among those with tobacco and marijuana use. Clinicians may also want to consider the risks and benefits of prescribing opioids for pain management when other substance use is present, especially when concerns regarding opioid misuse are expressed. In addition, findings suggest that a multidisciplinary approach among those with other types of substance use could be especially useful. Future work could investigate whether interventions can target pain, psychiatric symptoms, and substance use simultaneously to optimize outcomes for individuals with pain and substance use.
Supplementary Material
ACKNOWLEDGMENTS
The authors thank the study participants for their time and effort. We also thank the research assistants who contributed to recruiting participants and conducting phone surveys.
This work was supported by the National Institute on Drug Abuse (R01DA043811). R.W.C. was supported by the National Institute on Alcohol Abuse and Alcoholism (K23AA029729). The remaining authors declare no conflict of interest.
Footnotes
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website, www.clinicalpain.com.
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