Abstract
Background.
Concurrent and/or simultaneous use of opioids and benzodiazepines has been associated with increased risk of accident and injury, as well as with co-occurring psychopathology.
Objectives.
The purpose of the present study was to explore potential correlates of simultaneous opioid and benzodiazepine use in a small community, including perceived risk, positive screens for psychiatric symptoms, and opioid-related consequences.
Methods.
A sample of 267 participants were recruited from a medication treatment provider that serves a small Midwestern community. Multinomial logistic regression was used to explore demographic and mental health correlates associated with self-reports of past-year simultaneous use. Zero-inflated Poisson regression was used to explore past-year consequences associated with reported simultaneous benzodiazepine and opioid use.
Results.
Intentional simultaneous use of opioids and benzodiazepines was associated with greater anxiety and depression symptoms, greater likelihood of a positive PTSD screen, and low self-perceived risk of simultaneous use. Individuals reporting opioid/benzodiazepine simultaneous use were also more likely to report opioid-related consequences.
Conclusions.
Results highlight the importance of assessing and treating simultaneous opioid/benzodiazepine co-use, as well as relevant comorbidities.
Keywords: opioids, benzodiazepines, depression, anxiety, PTSD
Introduction
Concurrent use (i.e., use of more than one substance within a short period of time, on separate occassions1,2) and/or simultaneous use (e.g., using more than one substance at in such a way that the effects overlap) of opioids and benzodiazepines presents several risks, many of which result from benzodiazepines heightening the respiratory depressant effects of opioids3. Higher rates of overdose have been observed among individuals co-prescribed opioids and benzodiazepines4,5, and in 2017 and 2018, benzodiazepines were found to be present in 32.5% of opioid overdose deaths in the US6. Benzodiazepines7 and opioids8 have also both been associated with increased risk of motor vehicle accident, and risk may be exacerbated following co-use. Additionally, each of these substances can have severe withdrawal symptoms9,10.
Despite these risks, and despite awareness that combining these medications poses a high level of risk11,12, previous work suggests that concurrent use of opioids and benzodiazepines or sedatives is common. Studies of administrative health claims5 and laboratory databases13 in the United States have found that among individuals with opioid prescriptions, around 17% had an overlapping benzodiazepine prescription5 and 19% provided positive urine screens for non-prescribed benzodiazepines13. Results from national surveysa suggest that anywhere from 11.3% to 16.4% of those with an opioid use disorder (OUD) have a sedative or tranquilizer use disorder14,15.
Concurrent use of benzodiazepines among individuals who use heroin has been associated with poorer psychological and physical health16, and alleviation of negative affect has also been cited as a motive for use17. Previous work suggests that anxiety disorders15,18,19, depressive symptoms15,20, posttraumatic stress disorder (PTSD)15,18,19, and bipolar disorder19 are associated with a concurrent sedative prescription18–20, or participant reported sedative use15–17 among individuals who use opioids regularlyb. Other work suggests that relationships between opioid/sedative co-use and anxiety21,22 and sedative use and depressive symptoms15 may only be present in women. Unfortunately, nonmedical benzodiazepine use during methadone treatment has been associated with increased risk of treatment discontinuation23, limiting opportunities to access other evidence-based treatments for co-occurring psychopathology. Older adults, who are more likely to have physical health conditions and may be more likely to access opioids24 and/or sedatives25 through a prescription, are at a particularly high risk for concurrent nonmedical use of opioids and sedatives26. Among older adults, concurrent use of opioids and sedatives has been linked to increased risk of suicidal ideation27.
One strength of the existing literature is that concurrent use has been investigated in a diverse range of populations, ranging from populations with chronic pain on chronic opioid therapy, those in treatment for OUD, and national community samples. However, limited attention has been given to clinics outside of large urban settings, despite evidence that the opioid epidemic has been devastating for nonurban areas28. Lack of availability of medication treatment and long travel times to clinics remain a barrier to evidence-based treatment in rural areas29, and travel time in rural areas has been cited as a barrier towards continuity of care for substance use disorder treatment generally30. Opioid/benzodiazepine simultaneous use is of particular relevance for individuals living in small communities given the overdose risk of opioid/benzodiazepine simultaneous use; as the time for emergency medical services to arrive may be longer in rural settings31.
Additionally, it is possible that correlates of simultaneous use differ by rural-urban status. Previous work suggests that rural-urban status moderates the association between socioeconomic disadvantage and heroin overdose; in rural areas (but not urban areas), low educational attainment was associated with greater odds of heroin overdose, whereas in urban areas (but not rural areas) poverty and unemployment were associated with heroin overdose32. Additionally, sex differences in mood and anxiety disorders have been observed in residents of urban areas, but not in rural areas33. Rates of psychiatric symptoms and nonmedical opioid use are generally similar across the rural-urban continuum, though urban areas have a higher prevalence of nonmedical benzodiazepine use34,35. However, it remains unknown whether correlates of simultaneous opioid/benzodiazepine use differ by rural-urban status.
The aims of the present study were to examine correlates of simultaneous benzodiazepines and opioid use in a sample of patients receiving medication treatment for OUD, and to examine consequences associated with simultaneous use. It was expected that opioid/benzodiazepine simultaneous use would be associated with a greater number of opioid-related consequences, lower self-perceived risk, and greater reporting of anxiety, depression, and PTSD symptoms on screening measures.
Method
Participants
Respondents were 267 individuals who were receiving medication treatment (i.e., methadone or buprenorphine) for OUD in a small Midwest community.
Procedure
Clinical staff introduced the study to all patients. Participants were eligible to enroll in the study regardless of how long they had been in treatment. Research staff obtained informed consent after a discussion with participants. Participants completed a computer-based survey at the clinic. Assistance was provided to participants who had difficulty with technology, reading, or vision. Surveys took approximately 20 minutes to complete. Participants were compensated with a $20 Meijer gift card. All study procedures were approved by the Wayne State University institutional review board.
Measures
Demographics.
Participants reported their gender, age, education, and race/ethnicity. Gender included response options for “male”, “female”, and “other”, though no participants reported a gender other than male or female. Age was included as a continuous variable.
Opioid/Benzodiazepine Simultaneous Use.
To examine whether participants purposively combined opioids and benzodiazepines, participants responded to the following question: “Have you ever used opioids in combination with benzodiazepines? (i.e., Have you ever used opioids and benzodiazepines in such a way that the effects overlapped?)”. Response options included “Yes, in the Past Year”, “Yes, in my lifetime”, and “Never”. Because even prescribed benzodiazepines can pose certain risks when use simultaneously with opioids, we did not differentiate between medical and nonmedical use.
Opioid Consequences.
An adapted version of the Heroin Use Consequences Questionnaire (HUC)36 was used to examine consequences related to opioid use. Items are included in Table 2. Because patients at the clinic have a history using heroin, prescription opioids, or their combination, the word “heroin” was changed to “opioid” for the current study. Because most patients were not enrolled in school, three items assessing school-related consequences (i.e., Factor 3: High at school, Missed School, Suspended or Expelled) were not included. Response options included “Yes, in the past year”, “In my lifetime, but prior to the past year”, and “Never”.
Table 2.
Correlates of Past-year Consequences (Zero-inflated Poisson Regressions)
| Factor 1: Acute Health Problems | Factor 2: Employment-Related Problems | Factor 4: Impulse Control and Psychosocial Functioning | Factor 5: Long-term health-related/ neurological problems | |||||
|---|---|---|---|---|---|---|---|---|
| Logit Model | Poisson Model | Logit Model | Poisson Model | Logit Model | Poisson Model | Logit Model | Poisson Model | |
| B (SE) | B (SE) | B (SE) | B (SE) | B (SE) | B (SE) | B (SE) | B (SE) | |
| PTSD | ||||||||
| Past-year simultaneous use | −1.39 (0.62)* | 0.26 (0.33) | −0.24 (0.47) | 0.29 (0.22) | −1.94 (0.71)* | 0.22 (0.11)* | −1.27 (0.59)* | 0.27 (0.22) |
| Simultaneous use prior to past year | −0.12 (0.40) | 0.10 (0.29) | 0.35 (0.43) | −0.13 (0.30) | −0.10 (0.33) | 0.02 (0.13) | −0.91 (0.80) | −0.38 (0.36) |
| Sex | 0.07 (0.36) | 0.04 (0.20) | 0.85 (0.52) | 0.17 (0.31) | 0.35 (0.33) | −0.17 (0.10) | 0.40 (0.51) | −0.03 (0.24) |
| Age | −0.02 (0.02) | −0.01 (0.01) | 0.05 (0.03)* | −0.01 (0.02) | 0.00 (0.02) | −0.01 (0.01) | −0.02 (0.03) | −0.01 (0.01) |
| PTSD Symptoms | −0.48 (0.41) | 0.14 (0.24) | −0.99 (0.64) | −0.11 (0.45) | −0.75 (0.36)* | 0.16 (0.10) | −2.19 (0.84)* | −0.04 (0.27) |
| DEPRESSION | ||||||||
| Past-year simultaneous use | −1.38 (0.60)* | 0.29 (0.31) | −0.50 (0.47) | 0.24 (0.21) | −1.96 (0.71)* | 0.23 (0.11)* | −1.39 (0.61)* | 0.20 (0.24) |
| Simultaneous use prior to past year | −0.10 (0.39) | 0.12 (0.28) | 0.26 (0.41) | −0.19 (0.28) | −0.09 (0.33) | 0.02 (0.13) | −0.53 (0.56) | −0.26 (0.30) |
| Sex | 0.06 (0.37) | 0.04 (0.21) | 0.64 (0.37) | 0.11 (0.21) | 0.33 (0.33) | −0.15 (0.10) | 0.36 (0.49) | 0.02 (0.25) |
| Age | −0.01 (0.02) | −0.01 (0.01) | 0.07 (0.02)* | −0.01 (0.01) | 0.01 (0.02) | −0.01 (0.01) | 0.02 (0.03) | −0.01 (0.01) |
| Depressive symptoms | −0.11 (0.10) | 0.01 (0.06) | −0.00 (0.09) | 0.01 (0.05) | −0.19 (0.08)* | 0.03 (0.02) | −0.33 (0.14)* | 0.04 (0.06) |
| ANXIETY | ||||||||
| Past-year simultaneous use | −1.59 (0.65)* | 0.13 (0.30) | −0.57 (0.48) | 0.10 (0.22) | −1.84 (0.68)* | 0.23 (0.11)* | −1.83 (1.35) | 0.02 (0.30) |
| Simultaneous use prior to past year | −0.20 (0.39) | 0.01 (0.26) | 0.18 (0.42) | −0.30 (0.28) | −0.06 (0.33) | 0.02 (0.13) | −0.52 (0.58) | −0.28 (0.31) |
| Sex | 0.18 (0.39) | 0.12 (0.22) | 0.69 (0.39) | 0.12 (0.21) | 0.38 (0.33) | −0.16 (0.10) | 0.67 (0.64) | 0.15 (0.28) |
| Age | −0.02 (0.02) | −0.02 (0.01) | 0.07 (0.02)* | −0.00 (0.01) | 0.01 (0.02) | −0.01 (0.01) | 0.01 (0.02) | −0.01 (0.01) |
| Anxiety symptoms | −0.01 (0.11) | 0.11 (0.07) | 0.02 (0.09) | 0.10 (0.05) | −0.21 (0.08)* | 0.02 (0.03) | −0.18 (0.27) | 0.19 (0.15) |
denotes p-value < .05. The logit part of the ZIP model examines the probability of endorsing 0 consequences, the Poisson model examines relationships between IVs and the count distribution.
Posttraumatic Stress Disorder Symptom Screening.
The Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) was used to screen clients for potential PTSD among patients who reported experiencing a traumatic event (examples included: serious accident or fire, a physical or sexual assault or abuse, an earthquake or flood, a war, seeing someone be killed or seriously injured, having a loved one die through homicide or suicide). Participants who endorsed experiencing a traumatic event completed five yes/no items (e.g., “in the past month, have you been constantly on guard, watchful, or easily startled?”). Continuous scores range from 0 to 5. A cut-point of four was used to classify patients as meeting criteria for probable PTSD diagnosis37. Individuals who had not experienced a traumatic event were coded as having screened negative.
Anxiety Symptom Screening.
The Generalized Anxiety Disorder 2-Item Scale (GAD-2)38 was used to screen participants for symptoms of anxiety. Participants were given the prompt: “Over the last two weeks, how often have you been bothered by the following problems:” 1) Feeling nervous anxious or on edge, and 2) Not being able to stop or control worrying. Scores on this measure range from 0 to 6.
Depressive Symptom Screening.
The Patient Health Questionaire-2 (PHQ-2)39 was used to screen participants for probable depression. Participants were given the prompt: “Over the last two weeks, how often have you been bothered by the following problems?”: 1) Little interest or pleasure in doing things, and 2) Feeling down, depressed or hopeless. Scores on this measure range from 0 to 6.
Perceived Risk of Mixing Opioids and Benzodiazepines.
Participants were asked: “How much do people risk harming themselves physically or in other ways if they mix prescription pain relievers with benzodiazepines (e.g., Xanax, Valium, Ativan, Klonopin)?” The wording of the first half of the question was adapted from the National Survey of Drug Use and Health40, although that survey does not ask about perceived risk of mixing substances. Similar to other studies11, the four response options (1 = No risk, 2 = Slight risk, 3 = Moderate risk, 4 = Great risk) were recoded into “Great Risk” vs. “Other” due to the small number of individuals who did not recognize that mixing opioids and benzodiazepines posed a great risk.
Data Analysis
Data were analyzed using SPSS version 2541 and Mplus version 8.6 with Monte Carlo integration42. Assumptions were checked and determined to be met. Full information maximum likelihood was used to account for the small amount of missing data (1.1–5.6% on each variable). Descriptive statistics were examined for all study variables. Next, zero-inflated Poisson (ZIP) regression was used to examine relationships between past-year consequences (outcome) and simultaneous use (in the past year, and prior to the past year), when controlling for co-occurring positive screens for mental health and demographic characteristics. A zero-inflated Poisson model yields two regressions; the logit model examines the probability of having a “0” response (vs. all other responses), and the Poisson model examines relationships between predictors (i.e., simultaneous use, mental health, demographics) and the count dependent variable (i.e., consequences). We then explored the relationship between lifetime simultaneous use and lifetime consequences (outcome), when controlling for demographic characteristics. Lifetime consequences were more commonly reported in the sample and were not zero-inflated; thus, Poisson models (i.e., not zero-inflated Poison models) were used for this analysis.
Next, multinomial logistic regressions were examined to explore whether each mental health screen was associated with opioid/benzodiazepine simultaneous use. The outcomes in the multinomial regressions included 1) Simultaneous opioid/benzodiazepine use in the past year, 2) Simultaneous opioid/benzodiazepine use in respondent’s lifetime, prior to the past year, and 3) Never engaged in simultaneous use. First, individuals who never engaged in simultaneous use were used as the reference group. Next, to compare individuals who engaged in simultaneous use in the past year to individuals who engaged in simultaneous use prior to the past year, we re-ran regressions with individuals who engaged in past-year simultaneous use as the reference group. Mental health screens were entered into separate regressions due to high levels of overlap between the conditions. Age, gender, and perceived risk of combining substance were included as covariates in each regression. To explore potential moderating effects of gender, an interaction term between gender and each mental health condition was added to each model after exploring main effects.
Results
Descriptive Information
Descriptive information about the sample is presented in Table 1. The majority of participants enrolled in treatment prior to the past year. Approximately one-third of participants screened positive for PTSD. Respondents also reported high levels of depression and anxiety symptoms on screening measures; the mean scores for depression and anxiety symptomology were 2.46 and 2.77, respectively. While the majority of the sample (71.9%) recognized that opioid/benzodiazepine simultaneous use posed a great risk, rates of reported simultaneous use were relatively common; 39.3% reported lifetime opioid/benzodiazepine simultaneous use and 14.6% reported past year simultaneous use.
Table 1.
Sample Characteristics
| Variable | N (%) or M(SD) |
|---|---|
| Gender | |
| Male | 105 (39.3%) |
| Female | 157 (58.8%) |
| Missing | 5 (1.9%) |
| Race/Ethnicity | |
| Non-Hispanic White | 222 (83.1%) |
| Non-Hispanic African American/Black | 12 (4.5%) |
| Non-Hispanic Asian/Pacific Islander | 2 (0.7%) |
| Non-Hispanic Native American/Alaska Native | 3 (1.1%) |
| Non-Hispanic Multiracial | 13 (4.9%) |
| Hispanic | 9 (3.4%) |
| Missing | 6 (2.2%) |
| Age – Mean (SD) | 38.51 (9.99) |
| Earned High School Degree/GED | 203 (76.0%) |
| Enrolled in treatment during past year | 51 (19.1%) |
| Screened Positive for PTSD | 91 (34.1%) |
| PHQ-2 (Depression, Range = 0–6) | 2.46 (2.04) |
| GAD-2 (Anxiety, Range = 0–6) | 2.77 (2.01) |
| Total Opioid Consequences | 3.29 (3.74) |
| Perceived Great Risk in Simultaneous use of Benzodiazepines and Opioids | 192 (71.9%) |
| Simultaneous use | |
| Simultaneous Opioids and Benzodiazepine use in past year | 39 (14.6%) |
| Simultaneous use of Opioids and Benzodiazepine use prior to past year | 105 (39.3%) |
| No history of simultaneous use of opioids and benzodiazepines | 118 (44.2%) |
| Missing | 5 (1.9%) |
Opioid Consequences Associated with Opioids and Benzodiazepines Simultaneous use
Opioid-related consequences associated with reporting intentionally combining substances in the past year are presented in Table 2. Individuals reporting past-year opioid/benzodiazepine simultaneous use were less likely to report no past-year opioid-related consequences, including acute (e.g., overdose, visiting the emergency room, accident) and long-term health-related consequences (e.g., memory loss), and consequences related to psychosocial functioning and impulsivity (e.g., financial and family problems). Past-year simultaneous use was also related to the number of impulse control and psychosocial functioning consequences endorsed, but was not related to the number of acute or long-term health problems endorsed. The groups did not differ on work-related problems. Opioid/benzodiazepine simultaneous use prior to the past year was not associated with past-year consequences or lifetime acute health problems, but was associated with greater likelihood of reporting lifetime employment-related problems (B = 0.28, p < .001), problems with impulse control and psychosocial functioning (B = 0.23, p = .025), and long-term health-related neurological problems (B = 0.30, p < .001).
Mental Health Correlates of Opioid and Benzodiazepine Simultaneous use
Results of the multinomial regressions are presented in Table 3. Participants who considered opioid/benzodiazepine simultaneous use to be a “great risk” were less likely to have reported past-year opioid/benzodiazepine simultaneous use in each regression. Those with higher levels of current anxiety on a symptom screen, higher levels of current depression on a symptom screen, and individuals who screened positive for PTSD were more likely to have reported purposely combining opioids and benzodiazepines in the past year. No variables were related to combined benzodiazepine and opioid use prior to the past year.
Table 3.
Odds of Opioid/Benzodiazepine Simultaneous Use
| MODEL 1: PTSD | |||
|---|---|---|---|
| Variable | B (SE) | p value | OR (95% CI) |
| Simultaneous use in past year | |||
| Age | −0.04 (0.02) | .120 | 0.97 (0.92, 1.01) |
| Female | 0.14 (0.40) | .716 | 1.16 (0.53, 2.51) |
| Positive PTSD Screen | 1.15 (0.41) | .005* | 3.16 (1.42, 7.08) |
| Perceived Great Risk in Simultaneous use | −1.35 (0.42) | .003* | 0.29 (0.13, 0.65) |
| Simultaneous use prior to past year | |||
| Age | −0.01 (0.01) | .356 | 0.99 (0.96, 1.01) |
| Female | 0.25 (0.28) | .364 | 1.29 (0.75, 2.23) |
| Positive PTSD Screen | −0.05 (0.30) | .880 | 0.96 (0.53, 1.73) |
| Perceived Great Risk in Simultaneous use | −0.27 (0.33) | .406 | 0.76 (0.40, 1.48) |
| MODEL 2: Depression | |||
| Simultaneous use in Past Year 1 | |||
| Age | −0.06 (0.02) | .013* | 0.95 (0.91, 0.99) |
| Female | 0.17 (0.39) | .664 | 1.19 (0.55, 2.55) |
| Depressive symptoms | 0.21 (0.09) | .014* | 1.24 (1.04, 1.47) |
| Perceived Great Risk in Simultaneous use | −1.02 (0.41) | .013* | 0.36 (0.16, 0.80) |
| Simultaneous use Prior to Past Year 1 | |||
| Age | −0.01 (0.01) | .384 | 0.99 (0.96, 1.02) |
| Female | 0.25 (0.28) | .362 | 1.29 (0.75, 2.22) |
| Depressive symptoms | −0.01 (0.07) | .772 | 0.99 (0.86, 1.14) |
| Perceived Great Risk in Simultaneous use | −0.29 (0.33) | .386 | 0.75 (0.40, 1.43) |
| MODEL 3: Anxiety | |||
| Simultaneous use in Past Year 1 | |||
| Age | −0.05 (0.02) | .020* | 0.95 (0.91, 0.99) |
| Female | 0.14 (0.39) | .728 | 1.15 (0.53, 2.48) |
| Anxiety symptoms | 0.27 (0.09) | .004* | 1.31 (1.09, 1.57) |
| Perceived Great Risk in Simultaneous use | −1.08 (0.41 | .009* | 0.34 (.15, 0.77) |
| Simultaneous use Prior to Past Year 1 | |||
| Age | −0.01 (0.01) | .369 | 0.99 (0.96, 1.01) |
| Female | 0.24 (0.28) | .387 | 1.27 (0.74, 2.20) |
| Anxiety symptoms | 0.02 (0.07) | .769 | 1.02 (0.89, 1.17) |
| Perceived Great Risk in Simultaneous use | −0.28 (0.33) | .397 | 0.76 (0.40, 1.44) |
Reference = Never engaged in simultaneous use. Mental health conditions were entered into separate regressions due to high levels of overlap between the conditions.
Next, individuals with past-year opioid/benzodiazepine simultaneous use were used as the reference group to directly compare individuals reporting past-year and lifetime (but not past-year) use of opioids/benzodiazepines. Results suggested that individuals reporting opioid/benzodiazepine simultaneous use prior to the past year reported lower anxiety symptoms (B = −.25, p = .007), lower depression symptoms (B = −0.22, p = .013), and lower likelihood of screening positive for PTSD (B = −1.20, p = .004) relative to individuals reporting past-year benzodiazepine use. Individuals reporting opioid/benzodiazepine simultaneous use prior to the past year tended to report greater perceived risk of mixing the two substances relative to individuals reporting past-year opioid/benzodiazepine simultaneous use (Bs > .80, ps < .046 in anxiety and PTSD models); however, this relationship was not significant in the regression controlling for co-occurring depressive symptoms (B = 0.73, p = .065).
Gender Differences in Psychiatric Co-morbidity and Opioid/Benzodiazepine Simultaneous Use
When an interaction term between gender and mental health was added to each model, all interactions were nonsignificant (ps > .183). Thus, moderation was not considered further.
Discussion
The purpose of the present study was to explore correlates of self-reported opioid/benzodiazepine simultaneous use among patients with OUD. Results indicated that current anxiety, depression, and PTSD symptoms were associated with reporting past year simultaneous use. Results suggest that individuals reporting simultaneous use were also more likely to report past-year opioid-related consequences. Opioid and benzodiazepine simultaneous use is associated with greater risk of overdose, accident, and treatment discontinuation.
Results from the present study suggest that anxiety symptoms, depression symptoms, and screening positive for PTSD were associated with reporting intentional co-use opioids/benzodiazepine simultaneous use, consistent with work by others15,18,19. Interestingly, current, but not lifetime, simultaneous use was associated with current mental health symptoms, and individuals reporting past-year simultaneous use were more likely to endorse current symptomology than those reporting simultaneous use prior to the past year. This suggests that it may be worthwhile for future studies to test whether simultaneous use emerges as a consequence of anxiety, depression, or PTSD. However, we can only draw limited conclusions with our cross-sectional data, as it is unclear whether the mental health symptoms associated with simultaneous use reflect a motive for use, a consequence of use, or both. Future work should examine motives for simultaneous opioid/benzodiazepine use, such as whether simultaneous use reflects attempts to alleviate negative affect or achieve positive reinforcement. Longitudinal or daily diary studies may be particularly useful in further disentangling these relationships.
Individuals who reported combining substances in the past year were more likely to have experienced certain opioid-related consequences, including acute and long-term health problems, as well as psychosocial impairment. Harm reduction strategies to minimize associated risks may be beneficial in treatment. Providers may want to encourage individuals engaged in high risk use to avoid engaging in risky behaviors (e.g. driving) after intentionally combining substances, avoid using alone, and have Narcan available. The association between a positive PTSD screen and anxiety or depression symptoms and past year simultaneous use suggest prevention and harm reduction efforts may be particularly important for those with co-occurring mental health and opioid use issues. Using evidence-based approaches for co-occurring PTSD and substance use43 or anxiety and substance use44 have been found to be effective at reducing symptoms, and may be useful when used in combination with other treatment. Interventions to reduce harm associated with simultaneous use should be tested for efficacy across diverse populations.
Several limitations associated with this study should be noted. Although the ratio of events to variables in the present study was acceptable45, the portion of the sample that reported simultaneous use was relatively small. Data from this study was also drawn from a single clinic, and may not generalize to other settings. Patients newer to treatment, who did not have take-home privileges, and had to come to the clinic daily may have been more likely to be recruited, and may be overrepresented. Additionally, participants self-reported on their simultaneous use; we did not review urine screen records. Finally, the present study focused on simultaneous use of particular substances (i.e., opioids and benzodiazepines). Thus, it is unclear whether the results reflect specific consequences and correlates associated with opioid and benzodiazepine simultaneous use, or reflect the fact that individuals with more severe OUD are more likely to engage in polysubstance use. Further, the simultaneous use question did not differentiate between medical and nonmedical use. Future work should examine how individuals who engaged in simultaneous opioid and benzodiazepine use accessed these medications (e.g., through a prescription, through a family member). Finally, although the screening measures used in the present study have been shown to have excellent psychometric properties and are consistent with brief measures often used in triage in time and resource-limited clinic settings, future work should also more thoroughly explore whether results replicate among individuals meeting full diagnostic criteria.
Nonetheless, the present study is among the first to examine correlates of intentionally using substances in such a way that the effects overlap. Results suggest that harm reduction, psychoeducation, and cognitive behavioral treatments that integrate both potential comorbid conditions (anxiety, PTSD) and substance use are important areas for future work. Exploring motives for simultaneous use is also an important area for future work. Findings from the current study suggest that efforts to better understand and intervene with individuals engaged in simultaneous use of substances may prevent a range of serious consequences.
Funding details:
This study was supported by the Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment, Rockville, MD under Grant #: 6H79TI080228-02M001 (Recipient: State of Michigan Department of Health and Human Services) and the National Institute on Drug Abuse under Grant #: T32DA007209.
Footnotes
Disclosure Statement: The authors declare no conflicts of interest.
Some individuals in these national surveys who met criteria for sedative or tranquilizer use disorder were using benzodiazepines; however, a broader range of substances that produce depressant or anxiolytic effects (e.g., barbiturates, non-benzodiazepines hypnotics, anxiolytics) were considered in these studies.
Some studies cited here examined benzodiazepine prescriptions or use as the outcome, whereas other studies examined prescriptions or use of a broader range of sedatives (including benzodiazepines).
Data availability statement:
The data that support the findings of this study are available from the corresponding author, [JDE], upon reasonable request.
References
- 1.Earleywine M, Newcomb MD. Concurrent versus simultaneous polydrug use: Prevalence, correlates, discriminant validity, and prospective effects on health outcomes. Exp Clin Psychopharmacol. 1997;5(4):353–364. [DOI] [PubMed] [Google Scholar]
- 2.Substance Abuse and Mental Health Services Administration (SAMHSA): Treating Concurrent Substance Use Among Adults. SAMHSA Publication No. PEP21-06-02-002. Rockville, MD: National Mental Health and Substance Use Policy Laboratory. Substance Abuse and Mental Health Services Administration, 2021. [Google Scholar]
- 3.Gudin JA, Mogali S, Jones JD, Comer SD. Risks, management, and monitoring of combination opioid, benzodiazepines, and/or alcohol use. Postgrad Med. 2013;125(4):115–130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Stein BD, Mendelsohn J, Gordon AJ, Dick AW, Burns RM, Sorbero M, Shih RA, Liccardo Pacula R. Opioid analgesic and benzodiazepine prescribing among Medicaid-enrollees with opioid use disorders: The influence of provider communities. J Addict Dis. 2017;36(1):14–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: Retrospective analysis. BMJ. 2017;356–363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Gladden RM, O’Donnell J, Mattson CL, Seth P. Changes in opioid-involved overdose deaths by opioid type and presence of benzodiazepines, cocaine, and methamphetamine—25 states, July–December 2017 to January–June 2018. MMWR Morb Mortal Wkly Rep. 2019;68(34):737–744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Rapoport MJ, Lanctôt KL, Streiner DL, Bédard M, Vingilis E, Murray B, Schaffer A, Shulman KI, Herrmann N. Benzodiazepine use and driving: a meta-analysis. J Clin Psychiatry. 2009;70(5):663–673. [DOI] [PubMed] [Google Scholar]
- 8.Chihuri S, Li G. Use of prescription opioids and motor vehicle crashes: A meta-analysis. Accid Anal Prev. 2017;109:123–131. [DOI] [PubMed] [Google Scholar]
- 9.Tyrer P, Murphy S, Riley P. The benzodiazepine withdrawal symptom questionnaire. J Affect Disord. 1990;19(1):53–61. [DOI] [PubMed] [Google Scholar]
- 10.Wesson DR, Ling W. The clinical opiate withdrawal scale (COWS). J Psychoactive Drugs. 2003;35(2):253–259. [DOI] [PubMed] [Google Scholar]
- 11.Ellis JD, Resko SM, Kollin R, Lister JJ, Agius E. Public perceptions of risks associated with mixing opioid pain-relievers with alcohol and benzodiazepines. Subst Use Misuse. 2020;55(7):1189–1193. [DOI] [PubMed] [Google Scholar]
- 12.Frank D, Mateu-Gelabert P, Guarino H, Bennett A, Wendel T, Jessell L, Teper A. High risk and little knowledge: overdose experiences and knowledge among young adult nonmedical prescription opioid users. Int J Drug Policy. 2015;26(1):84–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.McClure FL, Niles JK, Kaufman HW, Gudin J. Concurrent use of opioids and benzodiazepines: evaluation of prescription drug monitoring by a United States Laboratory. J Addict Med. 2017;11(6):420–426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Votaw VR, Witkiewitz K, Valeri L, Bogunovic O, McHugh RK. Nonmedical prescription sedative/tranquilizer use in alcohol and opioid use disorders. Addict Behav. 2019;88:48–55. [DOI] [PubMed] [Google Scholar]
- 15.Ellis JD, Pittman BP, McKee SA. Co-occurring opioid and sedative use disorder: Gender differences in use patterns and psychiatric co-morbidities in the United States. J Subst Abuse Treat. 2020:108012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Darke S, Ross J, Mills K, Teesson M, Williamson A, Havard A. Benzodiazepine use among heroin users: Baseline use, current use and clinical outcome. Drug Alcohol Rev. 2010;29(3):250–255. [DOI] [PubMed] [Google Scholar]
- 17.Vogel M, Knöpfli B, Schmid O, Prica M, Strasser J, Prieto L, Wiesbeck GA, Dürsteler-MacFarland KM. Treatment or “high”: benzodiazepine use in patients on injectable heroin or oral opioids. Addict Behav. 2013;38(10):2477–2484. [DOI] [PubMed] [Google Scholar]
- 18.Gressler LE, Martin BC, Hudson TJ, Painter JT. Relationship between concomitant benzodiazepine-opioid use and adverse outcomes among US veterans. Pain. 2018;159(3):451–459. [DOI] [PubMed] [Google Scholar]
- 19.Yarborough BJ, Stumbo SP, Stoneburner A, Smith N, Dobscha SK, Deyo RA, Morasco BJ. Correlates of benzodiazepine use and adverse outcomes among patients with chronic pain prescribed long-term opioid therapy. Pain Med. 2019;20(6):1148–1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Saunders KW, Von Korff M, Campbell CI, Banta-Green CJ, Sullivan MD, Merrill JO, Weisner C. Concurrent use of alcohol and sedatives among persons prescribed chronic opioid therapy: Prevalence and risk factors. J Pain, 2012;13(3), 266–275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Hearon BA, Calkins AW, Halperin DM, Kathryn McHugh R, Murray HW, Otto MW. Anxiety sensitivity and illicit sedative use among opiate-dependent women and men. The Am J Drug Alcohol Abuse. 2011;37(1):43–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.McHugh RK, Votaw VR, Bogunovic O, Karakula SL, Griffin ML, Weiss RD. Anxiety sensitivity and nonmedical benzodiazepine use among adults with opioid use disorder. Addict Behav. 2017;65:283–288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.White WL, Campbell MD, Spencer RD, Hoffman HA, Crissman B, DuPont RL. Patterns of abstinence or continued drug use among methadone maintenance patients and their relation to treatment retention. J Psychoactive Drugs. 2014;46(2),114–122. [DOI] [PubMed] [Google Scholar]
- 24.Schepis TS, McCabe SE, Teter CJ. Sources of opioid medication for misuse in older adults: results from a nationally representative survey. Pain. 2018;159(8):1543–1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Schepis TS, McCabe SE. Prescription tranquilizer/sedative sources for misuse in older adults. Subst Use Misuse. 2019;54(11):1908–1912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Maree RD, Marcum ZA, Saghafi E, Weiner DK, Karp JF. A systematic review of opioid and benzodiazepine misuse in older adults. Am J Geriatr Psychiatry. 2016;24(11):949–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Schepis TS, Simoni‐Wastila L, McCabe SE. Prescription opioid and benzodiazepine misuse is associated with suicidal ideation in older adults. Int J Geriatr Psychiatry. 2019;34(1):122–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Mack KA, Jones CM, Ballesteros MF. Illicit drug use, illicit drug use disorders, and drug overdose deaths in metropolitan and nonmetropolitan areas—United States. Am J Transplant. 2017;17(12):3241–3252. [DOI] [PubMed] [Google Scholar]
- 29.Lister JJ, Weaver A, Ellis JD, Himle JA, Ledgerwood DM. A systematic review of rural-specific barriers to medication treatment for opioid use disorder in the United States. Am J Drug Alcohol Abuse. 2020;46(3):273–88. [DOI] [PubMed] [Google Scholar]
- 30.Garnick DW, Horgan CM, Acevedo A, Lee MT, Panas L, Ritter GA, Campbell K. Rural Clients’ Continuity Into Follow‐Up Substance Use Disorder Treatment: Impacts of Travel Time, Incentives, and Alerts. J Rural Health. 2020;36(2):196–207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Mell HK, Mumma SN, Hiestand B, Carr BG, Holland T, Stopyra J. Emergency medical services response times in rural, suburban, and urban areas. JAMA Surg. 2017;152(10):983–984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Pear VA, Ponicki WR, Gaidus A, Keyes KM, Martins SS, Fink DS, Rivera-Aguirre A, Gruenewald PJ, Cerdá M. Urban-rural variation in the socioeconomic determinants of opioid overdose Drug Alcohol Depend 2019;195:66–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Diala CC, Muntaner C. Mood and anxiety disorders among rural, urban, and metropolitan residents in the United States. Community Ment. Health J 2003;39(3):239–52. [DOI] [PubMed] [Google Scholar]
- 34.Centers for Disease Control and Prevention. 2019. Annual Surveillance Report of Drug-Related Risks and Outcomes — United States Surveillance Special Report. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. Published November 1, 2019. Accessed from https://www.cdc.gov/drugoverdose/pdf/pubs/2019-cdc-drug-surveillancereport.pdf. [Google Scholar]
- 35.Czeisler M, Lane R, Petrosky E, et al. Mental health, substance use, and suicidal ideation during the COVID-19 pandemic—United States, June 24–30, 2020. Morb Mortal Wkly Rep. 2020;69(32):1049–1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Moses TE, Woodcock EA, Lister JJ, Lundahl LH, Greenwald MK. Developing a scale of domains of negative consequences of chronic heroin use. Addict Behav. 2018;77:260–266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Prins A, Bovin MJ, Kimerling R, Kaloupek DG, Marx BP, Pless Kaiser A, & Schnurr PP (2015). Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) [Measurement instrument]. Available from https://www.ptsd.va.gov. [DOI] [PMC free article] [PubMed]
- 38.Kroenke K, Spitzer RL, Williams JB, Monahan PO, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007;146(5):317–325. [DOI] [PubMed] [Google Scholar]
- 39.Kroenke K, Spitzer RL, Williams JB, Löwe B. An ultra-brief screening scale for anxiety and depression: The PHQ–4. Psychosomatics. 2009;50(6):613–621. [DOI] [PubMed] [Google Scholar]
- 40.Center for Behavioural Health Statistics and Quality. (2014). 2015 National Survey on Drug Use and Health (NSDUH) (English Version). Rockville, MD: Substance Abuse and Mental Health Services Administration. [Google Scholar]
- 41.IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. [Google Scholar]
- 42.Muthén LK and Muthén BO (1998–2017). Mplus User’s Guide. Eighth Edition. Los Angeles, CA: Muthén & Muthén. [Google Scholar]
- 43.Fareed A, Eilender P, Haber M, Bremner J, Whitfield N, Drexler K. Comorbid posttraumatic stress disorder and opiate addiction: a literature review. J Addict Dis. 2013;32(2):168–179. [DOI] [PubMed] [Google Scholar]
- 44.McHugh RK. Treatment of co-occurring anxiety disorders and substance use disorders. Harv Rev Psychiatry. 2015;23(2):99–111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165(6):710–718. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author, [JDE], upon reasonable request.