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. Author manuscript; available in PMC: 2024 Aug 1.
Published in final edited form as: AIDS Care. 2021 Feb 4;35(8):1173–1180. doi: 10.1080/09540121.2021.1876838

Post-Traumatic Stress Disorder and Risky Opioid Use among Persons Living with HIV and Chronic Pain

Elenore Bhatraju 1, Jane M Liebschutz 2, Sara Lodi 3, Leah S Forman 4, Marlene C Lira 5, Theresa W Kim 5, Jonathan Colasanti 6, Carlos del Rio 6, Jeffrey H Samet 5,7, Judith I Tsui 1
PMCID: PMC8333265  NIHMSID: NIHMS1664509  PMID: 33535800

Abstract

Persons with HIV (PWH) experience chronic pain and Post-Traumatic Stress Disorder (PTSD) at higher rates than the general population, and more often receive opioid medications to treat chronic pain. A known association exists between PTSD and substance use disorders, but less is known about the relationship between PTSD and risky opioid use among PWH taking prescribed opioid medications. In this observational study of PWH on long-term opioid medications for pain we examined associations between PTSD symptom severity based on the Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5, response range 0–80) and the following outcomes : 1) risk for opioid misuse (COMM score ≥13); 2) risky alcohol use (AUDIT score ≥8); 3) concurrent benzodiazepine prescription; and 4) morphine equivalent dose. Among 166 patients, 38 (23%) had a PCL-5 score over 38, indicating high PTSD symptom burden. Higher PCL-5 score (per 10 point difference) was associated with increased odds of opioid misuse (aOR 1.55; 95%CI: 1.31–1.83) and risky drinking (aOR: 1.28;1.07–1.52). No significant association was observed between PCL-5 score and benzodiazepine prescriptions or morphine equivalent dose. These findings suggest that when addressing alcohol and opioid use in PWH on long term opioid therapy, attention to PTSD symptoms is especially important given the higher risk for risky alcohol and opioid use among patients with this common comorbid condition.

Introduction:

Opioids continue to contribute to high levels of morbidity and mortality in the United States (Hedegaard, 2020). While the rates of opioid prescriptions overall have started to decrease or plateau (Guy et al., 2017), substantial numbers of patients remain on long-term opioid therapy for chronic pain. These patients may be at high risk for opioid-related adverse outcomes including development of opioid use disorder. People living with HIV (PWH) are more likely to receive opioids for chronic pain, and at higher doses than uninfected individuals (Edelman et al., 2013; Merlin et al., 2016; Silverberg et al., 2012).

Post-traumatic stress disorder (PTSD) and chronic pain are each more prevalent among PWH compared to the general population. Meta-analyses have estimated a PTSD prevalence range from 7% to 74% among PWH depending on the population studied, compared with 7 to 10% in the general population (Sherr et al., 2011). Chronic pain has been estimated to be present in 55 to 85% of PWH (Dahlhamer et al., 2018; Miaskowski et al., 2011; Parker et al., 2014), compared to 20% among the general population.

The overlap between PTSD and chronic pain is substantial in the general patient population (Bilevicius et al., 2018; Brennstuhl et al., 2015). Among those with chronic pain in the general population, PTSD is associated with greater risk of illicit opioid use (Meier et al., 2014; Schwartz et al., 2006), development of opioid use disorder (Hassan 2017), and increased risk of fatal and non-fatal overdose compared to those without PTSD ((Hassan et al., 2017; Shorter et al., 2015). Among PWH, PTSD symptoms are linked to lower antiretroviral medication adherence, additional psychiatric co-morbidity and substance use disorders (Ebrahimzadeh et al., 2019; Fellows et al., 2015; Spies et al., 2012; Yiaslas et al., 2014). Much of the literature examining PTSD and opioids is focused on VA populations (Hawkins et al., 2019; Hawkins et al., 2013). Although among PWH there is literature demonstrating the risks associated with PTSD as a whole, less is known about PTSD symptom severity and high risk substance use behaviors such as risky alcohol consumption and opioid medication misuse (Centers for Disease Control and Prevention, 2018; Gudin et al., 2013; Jones CM et al., 2014; Witkiewitz & Vowles, 2018). It is also not known whether PTSD severity is associated with prescribing patterns such as co-prescribed benzodiazepine and opioid medications and higher morphine equivalent dose, which also confer risk of overdose (Jones et al., 2012; Park et al., 2015; Sun et al., 2017).

This study aims to better characterize the association between PTSD symptom severity and specific high-risk substance use behaviors and prescribing patterns among PWH prescribed opioid medications for chronic pain. Among a sample of PWH with chronic pain who were on long-term opioid therapy, this study examines the associations between PSTD symptom burden and the following four risk factors for overdose (two patient behaviors and two provider controlled factors): 1) risk for opioid misuse; 2) risky alcohol use; 3) concurrent benzodiazepine prescription; and 4) higher prescribed opioid dose (Gudin et al., 2013).

Methods:

Study design

These analyses were conducted using data from a pragmatic clinical trial of a collaborative care intervention to improve opioid prescribing among clinicians in HIV clinics (Samet et al., 2020) (NCT02564341, NCT02525731). The study design and protocol have previously been described in detail (Lira et al., 2019). Briefly, the Targeting Effective Analgesia in Clinics for HIV (TEACH) study included a cluster randomized controlled trial (RCT) testing a collaborative care intervention for HIV providers to improve the management of long term opioid therapy among PWH, and a parallel observational cohort of PWH receiving long term opioid therapy. This study utilized data from the observational patient cohort which enrolled PWH from two HIV clinics in Atlanta and Boston from September 2015 to December 2016.

Study participants and procedures

The study inclusion criteria included the following: age ≥18 years; living with HIV; fluent in English; and receiving long-term opioid therapy defined as ≥3 opioid prescriptions written at least 21 days apart during the preceding 6 months. A list of candidate participants was created through screening electronic medical record systems. Patients were contacted at the time of a clinical encounter and offered enrollment in the observational cohort study. Data were collected at baseline and 12 months. Research staff collected study variables by administering participant surveys and by reviewing electronic medical records. Institutional Review Boards of Boston University Medical Campus, Emory University and the Grady Memorial Hospital Research Oversight Committee approved this study.

Independent Variable

The main independent variable of interest was level of PTSD symptom severity, measured through the PTSD Checklist for DSM-5 (PCL-5). The PCL-5 is a 20-question screening survey scored from 0–80 with higher scores indicating more severe symptoms. A score of 31–33 or higher is indicative of probable PTSD, however a higher cutoff score of 38 may be used in certain populations with high rates of trauma, such as the participants in this study (Weathers et al., 2013). For the descriptive analyses, we used a cutoff of 38 for the PCL-5 to create a dichotomous comparison between those with higher vs. lower PTSD symptom burdens at baseline. For the main statistical analyses we evaluated the PCL-5 score as a continuous variable. A change of 10 points is recommended as a threshold for clinically meaningful change (Using the PTSD Checklist (PCL), 2012), and therefore was selected as the unit of measurement.

Dependent Variables/Outcomes

We examined each of the following high risk outcomes: 1) opioid misuse defined as COMM score ≥13; 2) risky alcohol use defined as AUDIT score ≥8; 3) ongoing benzodiazepine prescription defined as any prescription other than a one-time dose; and 4) prescribed morphine equivalent dose as a continuous variable. These outcomes were selected based on research demonstrating that they are risk factors for adverse opioid related outcomes including overdose (Bohnert et al., 2011; Meltzer et al., 2011; Park et al., 2016).

The Current Opioid Misuse Measure (COMM) score is calculated based on results of a 17-item self-administered patient questionnaire. A score of 9 is often used as a cutoff for risky use. However, we used a higher cutoff of 13 because in primary care studies a score of 13 has sensitivity and specificity of 77% for identifying current opioid use disorder (Meltzer et al., 2011). The Alcohol Use Disorders Identification Test (AUDIT) is a 10-question research assistant administered patient assessment. A score of 8 or higher is indicative of harmful or hazardous drinking (Higgins-Biddle & Babor, 2018; Saunders et al., 1993).

Benzodiazepine prescriptions were identified through each hospital’s electronic medical record (EMR). We excluded single benzodiazepine prescriptions (e.g., written prior to a procedure). Morphine equivalent doses were calculated using the documented prescribed opioids in the EMR and analyzed as a continuous variable.

Other Characteristics

Other descriptive data collected from baseline study assessments included: age; gender; sexual orientation; race; marriage employment and housing status; incarceration history; HIV risk factors; HCV co-infection; number and duration of opioid pain medications; substance use disorders (Integrated Addiction Severity Index [ASI] and Texas Christian University scale [TCU]); depressive symptoms (Center for Epidemiologic Studies Depression Scale [CESD]); and percent of HIV medications taken in the past 30 days (visual scale) (Herge WM et al., 2013; Institute of Behavioral Research, 2020; McLellan et al., 1980; National Institute on Drug Abuse, 2013).

Statistical analysis

Descriptive statistics of baseline characteristics were used to describe the study population and were presented both overall and stratified by baseline PCL-5 score ≥38 (Table 1).

Table 1:

Characteristics of patients living with HIV on long term opioid therapy for chronic pain stratified by PTSD Symptom Severity*

Overall (n=166) PTSD Score ≥38 (n=38) PTSD Score <38 (n=128)
Age (Median, IQR) 55 49.22 – 59.13 53, 46.94 – 57.60 55, 49.66 – 59.23
Gender
 Male 65.1% (108) 50.0% (19) 69.5% (89)
 Female 34.3% (57) 47.4% (18) 30.5% (39)
 Other 0.6% (1) 2.6% (1) 0.0% (0)
Race
 White 18.7% (31) 15.8% (6) 19.5% (25)
 African American/Black 72.3% (120) 76.3% (29) 71.1% (91)
 Other 9.0% (15) 7.9% (3) 9.4% (12)
Hispanic 9.0% (15) 10.5% (4) 8.6% (11)
Employment Status
 Working/Student/Other 22.9% (38) 18.4% (7) 24.2% (31)
 Looking for work/Unemployed 1.8% (3) 0.0% (0) 2.3% (3)
 Retired 3.6% (6) 7.9% (3) 2.3% (3)
 Disabled, perm/temp 71.7% (119) 73.7% (28) 71.1% (91)
Married 29.5% (49) 13.2% (5) 34.4% (44)
Sexual Orientation
 Heterosexual 67.5% (112) 71.1% (27) 66.4% (85)
 Gay/Lesbian/Queer/Homosexual 22.9% (38) 26.3% (10) 21.9% (28)
 Bisexual 9.0% (15) 2.6% (1) 10.9% (14)
 Other 0.6% (1) 0.0% (0) 0.8% (1)
Own or rent home/apartment 84.9% (141) 71.1% (27) 89.1% (114)
Has spent time in jail, past year 8.4% (14) 5.3% (2) 9.4% (12)
Smoker 54.8% (91) 63.2% (24) 52.3% (67)
HIV Risk Factor
 MSM + IDU 5.4% (9) 5.3% (2) 5.5% (7)
 MSM only 25.3% (42) 23.7% (9) 25.8% (33)
 IDU only 12.0% (20) 13.2% (5) 11.7% (15)
 Presumed heterosexual + blood 7.8% (13) 10.5% (4 7.0% (9)
 Presumed heterosexual only 49.4% (82) 47.4% (18) 50.0% (64)
HCV Co-infection 31.9% (53) 23.7% (9) 34.4% (44)
Risky Alcohol Use (AUDIT>=8) 15.1% (25) 23.7% (9) 12.5% (16)
Substance Use Disorder (non-alcohol) 19.3% (32) 31.6% (12) 15.6% (20)
No. of Opioid Pain Medications (Median, IQR) 1, 1 – 2 1, 1 – 1 1, 1 – 2
Duration of Rx Opioid Use, years (Median, IQR) 5.0, 2.0 – 10.0 5.0, 2.0 – 10.0 5.0, 2.0 – 10.0
Morphine Equivalent Dose, last 60 days (Median, IQR) 15.5, 3.9 – 38.50 11.7, 0.3 – 32.0 16.3, 6.1 – 42.0
Aberrant Use (COMM≥13) 22.9% (38) 47.4% (18) 15.6% (20)
Depression (CESD≥16) 41.0% (68) 81.6% (31) 28.9% (37)
Prescribed Benzos (≥ 14 doses) 13.3% (22) 21.1% (8) 10.9% (14)
Percent HIV medication taken, last 30 days (Median, IQR) 100, 95 – 100 100, 90 – 100 100, 98 – 100
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*

PTSD symptom severity based on the Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5), response range 0–80 with higher scores reflecting greater PTSD symptom severity.

We used all available data from both baseline and follow-up visits to evaluate the association between PTSD symptom severity (PCL-5 score) and the dichotomous outcomes (COMM score≥13, AUDIT≥8, and benzodiazepine prescription) using separate generalized estimating equation (GEE) logistic regression analyses for each outcome to account for within subject correlation. We evaluated the association between PCL-5 and the continuous outcome, morphine equivalent dose of opioid therapy using multivariable GEE linear regression. As sensitivity analyses, given the non-normal distribution, we also ran a median regression model with bootstrap confidence intervals for this outcome. Spearman correlation coefficients were estimated and no variables with correlations greater than 0.4 were included in regression models. Models were adjusted for the following characteristics defined a-priori: age; gender; and study-related variables, namely the study arm (intervention, control, or cohort only) and study visit (baseline, 12-months).

Analyses were conducted using the statistical package SAS 9.4 (SAS Institute, Inc. NC, USA).

Results:

Participants (n=166) had the following baseline PCL-5 scores: 38 (23%) had high PCL-5 scores; and 128 (77%) had low scores (i.e., below 38). The overall mean (±SD) and median (IQR) for PCL-5 scores were 21 (±18) and 16 (7–33), respectively.

Compared with participants with low PCL-5 scores, patients with PCL-5 ≥38 were different in the following ways: more likely to be female (47 vs 31%); less likely to be married (13 vs 34%); less likely to have stable housing (71 vs 89%); more likely to have a diagnosis of a substance use disorder (32 vs 16%); and more likely to have high depressive symptoms scores (82 vs 29%) and high COMM scores (47 vs 16%) compared to patients with low PTSD symptom severity (Table 1).

Table 2 shows results from the logistic and linear regression models using PCL-5 score as a continuous exposure variable, measured in 10-point units. Associations between PCL-5 and measures of high-risk substance use behaviors were similar between adjusted and unadjusted models. Adjusted models show that a 10 point increase in the PCL-5 score is significantly associated with 55% increased odds of having a COMM ≥13 (aOR=1.55 (95% CI: 1.31, 1.83)), and is also associated with 28% increased odds of risky alcohol use based on an AUDIT score ≥8 (aOR=1.28 (95% CI: 1.07, 1.52). No significant association was observed between PCL-5 score and receipt of benzodiazepine prescriptions (aOR=1.01 (95% CI: 0.84, 1.22)) and no significant difference in mean morphine equivalent dose was observed between groups (β=−1.41 (95% CI: −3.44, 0.62)). Results from a sensitivity analysis using median regression were not substantively different: PCL-5 score was not significantly associated with morphine equivalent dose.

Table 2.

Association between PCL-5 score and high-risk opioid use and behaviors of patients living with HIV on long term opioid therapy for chronic pain: results from logistic and linear regression models*

OR Unadjusted (95% CI) p-value OR Adjusted** (95% CI) p-value
Current Opioid Misuse Measure (≥13) 1.54 (1.31, 1.82) <0.0001 1.55 (1.31, 1.83) <0.0001
Risky Alcohol Use per AUDIT (≥8) 1.27 (1.07, 1.50) 0.0055 1.28 (1.07, 1.52) 0.0064
Prescribed Benzodiazepines 1.03 (0.87, 1.22) 0.7258 1.01 (0.84, 1.22) 0.8845
β-Estimate (95% CI) p-value β-Estimate Adjusted (95% CI) p-value
Morphine Equivalent Dose Over Past 60 Days −1.78 (−3.99, 0.44) 0.1158 −1.41 (−3.44, 0.62) 0.1735
Morphine Equivalent Dose Over Past 60 Days *** −0.85 (−2.07, 0.36) 0.1672 −0.97 (−1.99, 0.06) 0.0645
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*

Based on 10-point increase in PCL 5 scores

**

Adjusted for age, gender, study arm (intervention, control, or cohort only) and study visit (baseline or follow up).

***

Results show beta estimate from median regression rather than a linear regression model

Discussion:

In this study of PWH prescribed opioids for chronic pain, higher PCL-5 scores were associated with higher risk of opioid misuse and risky alcohol consumption, two substance use behaviors that increase the risk of overdose. We did not detect an association between higher PTSD symptom severity and the two provider controlled factors: likelihood of being prescribed benzodiazepines or higher doses of prescribed opioids for pain.

It is notable that nearly a quarter of this cohort had a PCL-5 score of 38 or above, consistent with a probable PTSD diagnosis. This is similar to prior studies showing a high prevalence of PTSD among PWH (Israelski et al., 2007; Machtinger et al., 2012; Martin & Kagee, 2011), and adds new insights on the specific population of PWH with chronic pain on long term opioid therapy. Among this cohort, persons with high PTSD symptom severity were more likely to be female and to have a drug use disorder, also consistent with the medical literature (Beckerman & Auerbach, 2011; Machtinger et al., 2012). We were able to show that patients with higher PTSD symptom burden were at higher risk of misusing their prescribed opioids, based on the COMM prediction tool.

It is important to identify the association between PTSD symptom severity and indicators of high risk substance use behaviors because patients with comorbid PTSD and substance use disorder tend to have more severe symptoms of both conditions, compared to those who have either one alone (Jacobsen et al., 2001). In a 2007 study of 509 primary care patients, 23% were determined to have active PTSD while only 11% of those had a documented diagnosis in their chart, showing that PTSD is under recognized in primary care settings (Liebschutz et al., 2007). A trauma informed approach is increasingly seen as a fundamental aspect of the care of all people but especially vulnerable populations (SAMSHSA, 2014). Given the high prevalence of both PTSD and chronic pain among PWH, and the known association among non-HIV patients between PTSD and overdose risk (Shorter et al., 2015, Bilevicious 2018, Seal 2012,), it is important for providers to increase awareness of PTSD as a risk factor when considering long term opioid therapy. The findings from this study underscore the need to be attentive to trauma history. The findings raise the possibility that reducing PTSD symptom severity could reduce opioid misuse and risky alcohol use, although this would require further research as our work shows an association but not causality.

The number of patients who received ongoing prescriptions (>1 dose) for benzodiazepines was 13.3% in this cohort overall. Among patients with high PTSD symptom severity, 21% (8/38) received benzodiazepine prescriptions, however they were not statistically more likely to be prescribed benzodiazepines compared to the low PCL-5 score group. Benzodiazepines have historically been prescribed at high rates for PTSD (Hawkins et al., 2015), but systematic reviews have now shown them to be ineffective in the long term, with risk outweighing any short term benefit (Guina et al., 2015), and studies estimate that up to 30% of unintentional overdose deaths involving opioids also involve benzodiazepines (Sun et al., 2017; Webster, 2010).

The distribution of opioid doses in this cohort was significantly skewed towards lower doses: the overall median dose was 15.5 morphine mg equivalents per day with no significant difference between PTSD symptom severity groups. This dose of opioids is lower than previous studies of similar populations (Edelman et al., 2013; Seal et al., 2012), and may again reflect changing prescribing habits based on substantial literature demonstrating increased overdose risk with higher opioid doses (Dowell et al., 2016; Seal et al., 2012).

This study has several limitations. The study utilizes PCL-5 scores, but not DSM-V criteria-based diagnosis of PTSD. However, the PCL-5 score gives us a potentially more nuanced picture of the patients’ current symptom burden, with scores ranging from 0–80. The primary outcome of opioid misuse is based on a risk score (COMM) for opioid misuse rather than actual documented episodes of opioid misuse. However, the COMM score has been shown to reliably predict the presence of opioid use disorder in the primary care setting (Meltzer et al., 2011). Data were collected from patients in two urban, academic medical centers and results may not be generalizable to other clinical settings where persons with HIV receive care. Lastly, this was a cross sectional study, which makes it difficult to identify a potential causal pathway between PTSD symptom severity and increased opioid risk.

In summary, this study demonstrated that a high-level of PTSD symptoms were prevalent among PWH and chronic pain on long term opioid therapy, and that high PTSD symptom severity was closely associated with high risk opioid and alcohol use behaviors, but not associated with opioid dose or receipt of benzodiazepine prescriptions. Given this population’s elevated likelihood of high risk substance use behaviors, specifically opioid and alcohol use, providers should be attentive to assessing patients with chronic pain on long term opioid therapy for PTSD, and be prepared to offer additional resources to tailor treatment plans if this common comorbid diagnosis is identified. Whether decreasing PTSD symptom severity may lead to lower risk of opioid and alcohol misuse is also a question for further research.

Funding Support:

This study was supported by the National Institute on Drug Abuse (R01DA037768). Dr. Samet and Dr Lodi received support from the Providence/Boston Center for AIDS Research (CFAR - P30AI042853). Dr Del Rio receives support from the center for AIDS Research at Emory University (CFAR- P30AI050409) Dr. Tsui reports additional support from P30AI027757.

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