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. Author manuscript; available in PMC: 2021 Aug 7.
Published in final edited form as: Subst Use Misuse. 2020 Aug 7;55(13):2205–2212. doi: 10.1080/10826084.2020.1797807

Psychosocial and clinical risk factors associated with substance use in observational cohort of patients with sickle cell disease

J Deanna Wilson 1, Sophie Lanzkron 2, Lydia H Pecker 3, Shawn M Bediako 4, Dingfen Han 5, Mary Catherine Beach 5
PMCID: PMC8208322  NIHMSID: NIHMS1625387  PMID: 32762425

Abstract

Background:

Patients with Sickle cell disease (SCD) experience high rates of chronic pain, and have a high burden of mental health comorbidities shown to negatively influence health. There is limited research on substance use among individuals with SCD.

Objective:

The aim of this study is to measure the prevalence of substance use in patients with SCD and determine whether psychosocial or clinical risk factors are associated with substance use.

Methods:

This study was conducted as part of an observational study of patients with SCD at two academic medical centers. We asked participants (ages 15 and older) about lifetime use of heroin, cocaine, amphetamines, and marijuana/cannabis. We measured stigma, depression, urban life stress, pain catastrophizing, and asked about a brief pain inventory.

Results:

Of 258 participants, 24.9% (n=71) reported substance use. Marijuana was most common substance used (22.5%; n=65). The mean depressive score met criteria for positive screen amongst individuals who reported a history of substance use (mean 10.7(5.76)). Adjusting for age, sex, yearly family income, and education level, odds of substance use increased with higher levels of internalized stigma (aOR:1.38;95% CI: 1.07,1.77;p=0.012); higher urban life stress scores (aOR1.06; 95%CI:1.01,1.12;p=0.017) and higher pain catastrophizing scores (aOR:1.03;95% CI:1.01,1.06;p=0.008).

Conclusions:

Among individuals with SCD who endorse substance use, there was markedly more stress and distress with higher rates of depression and poorer quality of life. Interventions focusing on improving distress tolerance and coping to not only pain, but also social stressors, might reduce substance use.

Keywords: sickle cell anemia, substance-related disorders, depression, marijuana, health disparity

Introduction

Sickle cell disease (SCD) is among the most commonly inherited autosomal recessive disorders in the United States (McCavit, 2012) associated with significant morbidity and early mortality(Piel, Steinberg, & Rees, 2017). Patients with SCD experience significant health disparities (Wolfson, Sheree, Schrager, Kipke, & Coates, 2009). Individuals often have chronic pain, and also bear a high burden of mental health comorbidities, such as depression, that have been shown to negatively influence health. Substance use disorders are a mental health comorbidity with significant implications for both physical and mental well-being.

The discussion of substance use and substance use disorders in patients with SCD is complex. While there is evidence that rates of substance use are not greater in patients with SCD than the general population, research suggests healthcare providers often over-estimate and assume higher rates of substance use in patients presenting with SCD (C. Haywood, Jr. et al., 2014; Ruta & Ballas, 2016; Shapiro, Benjamin, Payne, & Heidrich, 1997; Zempsky, 2009). For example, over half of emergency room physicians believed over 20% of patients with SCD were “addicted” (Shapiro, Benjamin, Payne, & Heidrich, 1997); and false assumptions about high rates of substance use in patients with SCD have remained common over time (Ruta & Ballas, 2016). These false assumptions contribute to negative provider attitudes towards patients with SCD (Dorsey, Phillips, & Williams, 2001; Labbe, Herbert, & Haynes, 2005; Pack-Mabien, Labbe, Herbert, & Haynes, 2001; Zempsky, 2009), delays in timely administration of appropriate opioid analgesia, and assumptions of high rates of drug seeking behaviors or opioid misuse in patients with SCD (Green et al., 2003; Green & Hart-Johnson, 2010; Labbe et al., 2005; McCracken, Matthews, Tang, & Cuba, 2001; Zempsky, 2009). Some have suggested that under-treatment of pain may lead individuals with SCD to develop behavior that is misinterpreted as drug seeking or misuse, but which is a kind of ‘pseudoaddiction’ from poorly treated pain (Elander, Lusher, Bevan, & al, 2004; Lusher, Elander, Bevan, Telfer, & Burton, 2006). This is distinct from the self-medication hypothesis that individuals use drugs or alcohol to manage negative emotional or physical states.

Studies have found substance use among individuals with other chronic diseases are associated with poor disease self-management and worse health outcomes (Fox, Merrill, Chang, & Califano, 1995). Individuals with co-occurring substance use have higher utilization of health care resources (Ford, Trestman, Steinberg, Tennen, & Allen, 2004) and increased medical expenditures for chronic physical and mental health conditions (Clark, Samnaliev, & McGovern, 2009). Patients with SCD are a distinct population of patients among those with chronic disease, and even among those with chronic pain. Patients with SCD often experience lifelong bouts of recurrent, severe pain starting at early ages complicated by the development of chronic pain in adolescence or young adulthood (Piel et al., 2017). In addition, patients with SCD experienced high rates of perceived racial bias in medical settings (Wakefield, et al, 2017; Wakefield, et al, 2018), negative attitudes from healthcare providers (Freiermuth, et al, 2014), and implicit bias (Nelson & Hackman, 2013) that may make their experience of the healthcare system different than other patients with chronic pain syndromes, particularly if comorbid substance use is present. The healthcare interactions for patients with SCD and substance use may also be more complex as Brown, et al (2015) suggest it may not be the primary addiction only leading to increased hospitalization rates and length in patients with SCD, but different coping strategies leading to problematic interactions with the healthcare system (Brown, Weisberg, Balf-Soran, & Sledge, 2015).

Individuals using substances are also at elevated risk for complications associated with their chronic disease (Banerjea, Sambamoorthi, Smelson, & Pogach, 2007). Similarly in patients with SCD, depression diagnoses were associated with both higher acute and total health care costs (Adam et al., 2017; Hasan, Hashmi, Alhassen, Lawson, & Castro, 2003). Adults with SCD who reported depressed mood and anxiety had poorer physical and mental health quality of life and endorsed more daily pain and more opioid use than those without (Levenson et al., 2008). Pain catastrophizing refers to a negative orientation toward pain and relates to certain thoughts and feelings associated with pain (Sullivan, Bishop, & Pivik, 1995). In contrast to other chronic pain syndromes, pain catastrophizing in patients with SCD may be more prevalent, but it is not associated with increased healthcare utilization, intensity of pain, distress or interference from pain in daily life that are seen in other conditions (Citero, et al, 2007). Nonetheless, pain catastrophizing has been associated with an increase in use of short-acting opioids for patients with SCD (Finan, et al, 2018). In addition to depression and pain catastrophizing, which are relevant for patients with chronic pain syndromes, there is a rich body of literature describing the unique impact of SCD-related stigma on quality of life, health perception, stress, maladaptive coping behaviors, and health seeking behaviors (Bulgin, Tanabe, & Jenerette, 2018; Labore, Mawn, Dixon, & Andemariam, 2017).

There is limited research on the prevalence of substance use among individuals with SCD and the interplay that psychosocial factors, like stress, depression, internal stigma, and pain catastrophizing, and clinical factors, such as self-reported health status, have on substance use behavior (Ballas, 2017; Howard, Anie, Holdcroft, Korn, & Davies, 2005; Ruta & Ballas, 2016; Savage et al., 2016). Patients with SCD experience lifelong acute and chronic pain with risk of life-threatening complications from their disease state making them unique among other chronic pain syndromes. Research evaluating these relationships for patients with SCD is novel and important.

The first aim of this study was to measure the prevalence of substance use in subjects of the IMPORT study, an observational cohort study of patients with SCD 15 years and older who were followed at two urban, academic medical centers. Our second aim was to determine whether psychosocial or clinical risk factors are associated with substance use in this population, including if these relationships persisted independent of depression.

Materials and methods

Study design, subjects, and setting

This study was conducted as part of the IMPORT (Improving Patient Outcomes with Respect and Trust) Study, an observational cohort study of patients with SCD, based at two academic medical centers in the Baltimore and Washington, DC area. It was approved by Institutional Review Boards at both institutions. In order to participate in the study, participants had to be 15 years of age or older at time of enrollment, diagnosed with any sickle cell hemoglobinopathy (e.g. hemoglobin SS, hemoglobin SC), report no plan to relocate in three years, and report willingness to adhere to study procedures. Participants were recruited from waiting rooms in adult and pediatric SCD clinics at each of the two academic medical centers. We obtained consent from adult participants and parental consent and participant assent for participants less than 18 years of age.

Data collection procedures

At baseline, participants were asked to complete a 45-minute computer-assisted audio self-interview and were reimbursed $50 for their time. We collected data on substance use along with basic demographic information, psychosocial factors, health status, and health behaviors. Further details of the study, including data collection procedures, are described elsewhere (Bediako et al., 2016; C. Haywood, Jr. et al., 2014; C. Haywood et al., 2014; Haywood et al., 2013).

Study Variables

Substance Use

We asked about any lifetime use of heroin, cocaine, amphetamines, and marijuana/cannabis, defined as number of years that the respondent used 3 or more times per week, and whether the respondent had any use in the past 30 days.

Psychosocial Factors

We evaluated potential psychosocial risk factors for substance use using validated scales for internal stigma, depressive symptoms, urban life stress, and pain catastrophizing. Internal stigma was assessed with the eponymous subscale from the Measure of Sickle Cell Stigma (Bediako et al., 2016). The subscale measures feelings of self-worth or guilt related to having a diagnosis of sickle cell disease (Holloway, McGill, & Bediako, 2017). Participants responded to a series of statements, such as, “Having sickle cell makes me feel that I’m a bad person” and “I’m not as good as others because I have sickle cell.” They rated each statement on six-point scale, from 1, “completely false”, to 6, “completely true.” Responses were summed to give a composite score with higher levels suggesting more internal stigma.

To measure depressive symptoms, we used the 10-item Center for Epidemiologic Studies Depression Scale Revised (CESD-R-10) (Miller, Anton, & Townson, 2008). Individuals described how often they felt certain ways during the week using a five-point scale from 0, “rarely/none of the time,” to 4, “most/all of the time.” For example: “I felt that everything I did was an effort.” Any score equal to or above 10 is considered positive screen for depressive symptoms. This instrument has been validated in individuals with SCD (Laurence, George, & Woods, 2006).

The Urban Life Stress Scale is a 21-item scale evaluating stress related to various aspects of one’s life (Sanders-Phillips & Harrell, 1996). Individuals were asked how much stress they experienced during the past 5 months in different areas on a five point scale from, 0, “no stress at all (or not relevant to me),” to 4, “extreme stress, more than I feel I can handle.” Areas included, “money or finances,” “your neighborhood environment (e.g. safety, cleanliness, noise, pollution, graffiti),” and “relations with police (e.g. harassment, availability).”

The Pain Catastrophizing Scale evaluates the degree to which respondents evaluate certain thoughts and feelings associated with their pain (Sullivan et al., 1995). A sample item includes, “When I’m in pain, I worry all the time about whether the pain will end.” Participants noted their level of agreement with each of the items on a five-point scale, from 0, “not at all,” o 4, “all the time.” We computed a composite pain catastrophizing score that ranged from 0 to 52, where higher scores were indicative of greater catastrophizing.

Disease Severity

To assess SCD-related disease severity, we used the Brief Pain Inventory and a single item asking participants to rate their own health status, The Brief Pain Inventory evaluates frequency and quantity of pain and pain interference (Anderson, Syrjala, & Cleeland). Participants rated their pain on a scale from 0, no pain, to 10, pain as bad as you can imagine. Individuals rated their health in general, “how would you say your health is: excellent, very good, good, fair, and poor.

Covariates

We examined 4 patient characteristics as covariates as they are known to be associated with substance use: age, sex, annual household income (less than $10,000; $10,000 to $29,999; $30,000 to $49,999; $50,000 to $99,999; greater than $100,000) and maximal education level (high school or less, high school diploma or GED, some college, college, graduate or professional school). We reported race as a descriptive characteristic, but opted not to include this covariate in our model as the vast majority of our sample (greater than 97%) was African-American.

Statistical analyses

All analyses were conducted using the Stata 15.0 statistical software package (Statacorp, 2017). We used descriptive statistics to indicate our sample’s levels of substance use and their psychosocial, self-management and demographic characteristics. For our analyses, we defined any substance use as an affirmative answer to lifetime or current use of amphetamines, marijuana, heroin, or cocaine. We then evaluated the association of any substance use with the other sample characteristics (psychosocial and disease severity) using t-tests for continuous variables and Fisher’s exact test for categorical variables. A p-value of <= 0.05 was the threshold used to determine statistical significance in the bivariate and multivariable analyses.

We completed multivariate analyses looking at the association between each independent variable and the outcome of interest (any substance use) adjusting for age, sex, education, and income. We included age, sex, education and income in all multivariable models due to their importance in studies of substance use. We included all of the above covariates as well as depression and health status to further explore impact of internal stigma and pain catastrophizing on substance use. We assessed goodness-of-fit with the Hosmer-Lemeshow test.

Results

Demographics of study participants

Two-hundred and eight-five participants were included in this study: 46.3% were male. Characteristics of the study participants are shown in Table 1. The vast majority were African-American (97.5%). The mean (SD) age of participants was 34.6 (12.5) years. While the study sample included individuals across all income levels, over half of all individuals had incomes below $29,999 and over a quarter had incomes less than $10,000. Less than half had more education than a high school diploma.

Table 1.

Patients with sickle cell disease stratified by history of substance use.*

Total (N=285) No substance use (n=214) Any substance use (n=71) p-value
Age mean (SD) 34.6 (12.48) 24.2 (12.79) 35.9(11.5) 0.329
Gender n (%)
Male 132(46.32%) 87(40.65%) 45(63.38%) 0.001
Race n (%)
African-American, Black 278(97.54%) 208 (97.2%) 70 (98.59%) 1.00
White 1 (0.35%) 1 (0.47%) -
Other 6 (2.11)% 5 (2.34%) 1 (1.41%)
Annual income n (%)
Less than $10.000 64(25.7%) 40(21.74%) 24(36.92%) 0.11
$10,000 to $29,999 62(24.9%) 45(24.46%) 17(26.15%)
$30,000 to $49,999 51(20.48%) 39(21.2%) 12(18.46%)
$50,000 to $99,999 47(18.88%) 39(21.2%) 8(12.31%)
Greater than $100,000 25(10.04%) 21(11.41%) 4(6.15%)
Education n (%)
None or less than high school 45(16.07%) 27(12.86%) 18(25.71%) 0.018
High school diploma or GED 135(48.21%) 98(46.67%) 37(52.86%)
Some college 45(16.07%) 38(18.1%) 7(10%)
Bachelors or 4-year college 31(11.07%) 28(13.33%) 3(4.29%)
Graduate or professional school 24(8.57%) 19(9.05%) 5(7.14%)
Psychosocial factors
Internal stigma score† mean (SD) 1.9(1.17) 1.8(1.1) 2.2(1.29) 0.007
Depressive Symptom Scale‡
mean (SD) 8.9(6.13) 8.2(6.14) 10.7(5.76) 0.003
positive score (>=10), n (%) 107(39.93%) 70 (35.18%) 37 (53.62%) 0.01
Urban life stress score§ mean (SD) 16.6(12.09) 15.2(11.38) 20.6(13.28) 0.001
Pain catastrophizing scale|| mean (SD) 29(13.24) 27.6(13.42) 33.5(11.67) 0.001
Disease severity
Brief Pain inventory mean (SD)
Severity score 4.1(3.21) 3.9(3.19) 4.9(3.16) 0.025
Interference score 3.8 (2.53) 3.5 (2.50) 4.3 (2.51) 0.021
Self-reported health n (%)
Poor 25(8.8%) 20(9.39%) 5(7.04%) 0.062
Only fair 83(29.23%) 53(24.88%) 30(42.25%)
Good 121(42.61%) 93(43.66%) 28(39.44%)
Very Good 38(13.38%) 33(15.49%) 5(7.04%)
Excellent 17(5.99%) 14(6.57%) 3(4.23%)
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*

Any substance use as defined as current or lifetime use of amphetamines, cocaine, heroin, or marijuana. Compared no substance use and any substance use using t-tests for continuous variables and Fisher’s exact test for categorical variables.

†

Internal stigma scale rates statements on a six-point scale from 1, completely false, to 6, completely true. Higher scores suggest more internal stigma.

‡

The Center for Epidemiologic Studies Depression Scale (CESD-R-10) uses a ten item five-point scale from 0, rarely or none of the time to 4, most/all of the time. Higher scores equal more depressive symptoms as positive screen for depression is score greater than or equal to 10.

§

Urban life stress scale is 21-item scale rating on five-point scale from 0, no stress at all, to 4, extreme stress. Higher scores associated with greater reports of stress.

||

The scale uses a five-point scale from 0, not at all, to 4, all the time. Greater scores indicative of greater catastrophizing.

Brief pain inventory evaluates frequency and quantity of pain and pain interference. Higher scores indicate increased frequency and interference from pain.

Substance use prevalence

A minority of individuals reported any substance use in our sample (71 of 285; 24.9%). Table 2 displays the prevalence of lifetime and current substance use among our participants, by specific substances. The most commonly reported substance was marijuana with 22.5% (n=65) of the sample reporting marijuana use in their lifetime and 15% reporting use in the past 30 days (Table 2). Far fewer reported ever using heroin (3.13%), cocaine (3.83%) and amphetamines (4.2%).

Table 2.

Prevalence of substance use by type in patients with Sickle Cell Disease.

Number (percentage)
Non-prescribed Substances
Heroin
Lifetime use 9 (3.13)
Current use1 4 (1.39)
Cocaine
Lifetime use 11 (3.83)
Current use1 4 (1.39)
Amphetamines
Lifetime use 12 (4.2)
Current use1 9 (3.14)
Marijuana
Lifetime use 65 (22.65)
Current use1 43 (14.98)
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1

Current = endorsed yes to use in past 30 days.

Indicators of substance use

Bivariate associations of substance use with other participant characteristics are shown in Table 1. In terms of demographic characteristics, any substance use was associated with being male, with lower education, and with higher income but not with patient age. In terms of psychosocial characteristics, substance use was associated with higher rates of internalized stigma, increased depressive symptoms, urban life stress, and pain catastrophizing. Finally, in terms of clinical outcomes, substance use was associated with greater levels of pain and poorer overall health. The mean depressive symptom score amongst individuals who reported any history of substance use was 10.7 (SD5.76), which met criteria for positive depression screen.

Multivariable logistic regression analyses adjusting for age, sex, yearly family income, and educational level are shown in Table 3. Males were 2.5 times more likely to report having used substances (heroin, cocaine, marijuana, and/or amphetamines) than females (2.53; 95% CI: 1.45, 4.4; p=0.001). Higher income and higher levels of education were associated with 27% and 42% lower odds respectively of reporting substance use than those with lower levels (0.72; 95% CI: 0.58, 0.92; p=0.007 and 0.58; 95% CI: 0.29, 0.87; p=0.008). There were increased odds of substance use associated with higher rates of internalized stigma (1.38; 95% CI: 1.07, 1.77, p=0.012). Individuals were 6% more likely to have reported substance use for each one-unit increase in depressive symptoms and 3% more likely to report substance use for each one-unit increase in their urban life stress score (1.06; 95% CI: 1.01, 1.12; p=0.017 and 1.03; 95% CI: 1.01, 1.06; p=0.011) and pain catastrophizing score (1.03; 95% CI: 1.01, 1.06, p=0.008). Individuals were increasingly less likely to report substance use as they reported higher levels of health and while they were more likely to have reported slightly higher odds of using substances if they had more pain, this was not significant when adjusting for covariates.

Table 3.

Unadjusted and adjusted logistic regression models estimating odds of any substance use* for each of the SCD domains (N=246).

Unadjusted Analyses Adjusted Analyses2 Hosmer-Lemeshow Test
Odds Ratio 95% CI p-value Odds Ratio 95% CI p-value p-value
Psychosocial factors
Internal Stigma‡ 1.34 1.08, 1.67 0.009 1.38 1.07, 1.77 0.012 0.149
Depressive Symptom Score§ 1.07 1.02, 1.11 0.004 1.06 1.01, 1.12 0.017 0.162
Urban Life Stress Score|| 1.04 1.01, 1.06 0.002 1.03 1.01, 1.06 0.011 0.243
Pain Catastrophizing Scale 1.04 1.01,
1.06 0.002 1.03 1.01, 1.06 0.008 0.942
Clinical severity
Brief Pain Inventory#
Interference Score 1.1 1.01, 1.20 0.026 1.08 0.98, 1.19 0.114 0.648
Severity Score 1.13 1.02, 1.26 0.022 1.09 0.97, 1.24 0.151 0.596
Self-reported Health Status 0.67 0.5, 0.9 0.007 0.66 0.47, 0.93 0.017 0.154
Demographics
Age (years) 1.01 0.99, 1.03 0.328
Sex (male gender) 2.53 1.45, 4.4 0.001
Yearly family income 0.73 0.58, 0.92 0.007
Highest degree 0..58 0.39, 0.87 0.008
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*

Any substance use as defined as current or lifetime use of amphetamines, cocaine, heroin, or marijuana.

†

Adjusted for age, sex, yearly family income, and highest degree or diploma. Participants with missing variables excluded from the analyses. GOF: Goodness of Fit tested using Hosmer Lemeshow goodness of fit test. t

‡

Higher scores suggest more internal stigma.

§

Using the Center for Epidemiologic Studies Depression Scale (CESD-R-10) ten item five-point scale with higher scores associated with more depressive symptoms and a positive screen for depression is greater than or equal to 10.

||

Urban life stress scale is 21-item scale rating on five-point scale from 0, no stress at all, to 4, extreme stress. Higher scores associated with greater reports of stress.

The scale uses a five-point scale from 0, not at all, to 4, all the time. Greater scores indicative of greater catastrophizing.

#

Brief pain inventory evaluates frequency and quantity of pain and pain interference. Higher scores indicate increased frequency and interference from pain.

Multivariable logistic regression analyses adjusting for age, sex, yearly family income, and educational level, as well as, depressive symptom score and self-reported health status, showed a consistent but not statistically significant trend for internal stigma (1.26; 95% CI: 0.95, 1.68; p=0.103) and pain catastrophizing (1.03; 95% CI: 1.0, 1.06; p=0.07).

Discussion

The prevalence of substance use we found in participants with SCD is similar to the patterns of substance use we see in the general population. There are slightly more people than the national average who reported lifetime use of substances (Quality, 2015), although substance use was reported by a minority of the sample. The most commonly used substance in our study was marijuana with over one in five respondents reporting marijuana use in their lifetime and over one in seven reporting that they used it within the past 30 days, which are similar to rates found in other studies (Ballas, 2017; Howard et al., 2005; Kalu, O’Neal, Nwokolo, Diaz, & Owoyemi, 2016; Knight-Madden, Lewis, & Hambleton, 2006; Ruta & Ballas, 2016). The subset of patients who endorsed substance use also tended to report lower levels of economic resources and lower educational attainment, and experience greater levels of depressive symptoms, stress, and internalized stigma than those without substance use histories. Endorsing substance use in this case may be a surrogate or marker for untreated or unrecognized suffering in the clinical encounter.

Patients reported high rates of depressive symptoms with a mean score amongst those with a history of substance use meeting criteria for depression. Although less has been written about SCD, substance use and depression, the high comorbidity of SCD and depressive symptoms has been described, particularly in pediatric patients (JK, C, & E, 2016; Kessler et al., 1997; Sehlo & Kamfar, 2015).Depressive symptoms were significantly correlated with a history of substance use in our sample with SCD and this relationship likely reflects the high comorbidity of depression and substance use seen in the general population (Davis, Uezato, Newell, & Frazier, 2008). Untreated substance use can worsen depressive symptoms and can complicate treatment. In light of the growing push to screen for and treat depression in patients with SCD (Jonassaint, Jones, Leong, & Frierson, 2016), this work suggests we should consider substance use screening for patients with depression as comorbid substance use may worsen mood disorders and complicate treatment. Indeed, our findings showed that depressive symptoms mediated the relationship between pain catastrophizing and internal stigma on substance use. Untreated depressive symptoms may also separately influence ability to tolerate one’s pain and even how one feels about one’s disease.

Individuals endorsing substance use in our study report higher urban life stress and greater pain catastrophizing suggesting less capacity to cope with a host of negative emotional states and stressors, defined in the literature as distress tolerance (Leyro, Zvolensky, & Bernstein, 2010). They were more likely to report increased stress and distress with not only painful stimuli, but also with financial, relationship, and community stressors, like money, and family or community violence. Similarly, adjusted analyses suggest that it may not be quantity of pain predicting substance use, but the associated catastrophizing thoughts and beliefs related to pain or associated negative affective states, like depression, that increase the likelihood of substance use. Individuals with low distress tolerance, may be using substances to self-medicate or treat their distress. Research has shown a relationship between pain catastrophizing and increased short-acting opioid use for patients with SCD (Finan, 2018), but few have examined illicit substance use. Research has shown similar links between distress tolerance and substance misuse in a number of different patient populations, although this is the first to our knowledge looking at this relationship in patients with SCD (Buckner, Keough, & Schmidt, 2007; Galen, Henderson, & Coovert, 2001; Simons, Gaher, Correia, Hansen, & Christopher, 2005; Wilson et al., 2017).

In addition to external stressors, individuals who experienced high rates of internalized stigma, or low self-worth and guilt specifically resulting from the diagnosis of SCD were more likely to endorse substance use. The majority of research support the positive associations between SCD-related stigma, depressive symptoms (Jenerette, Brewer, Crandell, & Ataga, 2012), and pain (Cohen, Quintner, Buchanan, Nielsen, & Guy, 2011; Holloway et al., 2017; Waugh, Byrne, & Nicholas, 2014). Individuals with SCD who exhibited higher levels of stigma and depression were less adherent to medication, less likely to use preventive health services (Cooper, Corrigan, & Watson, 2003; Corrigan, Druss, & Perlick, 2014; Henderson, Evans-Lacko, & Thornicroft, 2013), and at increased risk of pain episodes requiring hospitalization (Jenerette et al., 2012). Internal stigma for other chronic disease states, such as HIV, has shown that even after adjusting for depressive symptoms, internal stigma seems to independently predict recreational substance use, such as hazardous alcohol use (Owens, et al, 2017) and has been viewed as an independent risk factor in these populations for substance use (Kulesza, et al, 2017). In our study, we found the relationship was attenuated by depressive symptoms suggesting internal stigma may influence substance use through development of negative affective states. Cognitive behavioral therapy has been shown to be effective at reducing both internal stigma and associated depressive symptoms for individuals with mental health diseases (Young, 2016) suggesting that this modality may be particularly useful treatment to target patients endorsing both. This research is novel in demonstrating the relationships between internalized stigma, depressive symptoms, and substance use and may suggest a pathway by which internalized stigma affects health outcomes and health behaviors.

Although the study is limited by its focus on patients with SCD in two urban health centers, it characterizes and provides information on a particularly vulnerable subset of patients with SCD. The observational and cross-sectional nature of the study makes it impossible to draw causal inferences about the relationship between various psychosocial characteristics and substance use behavior. As we analyzed substance use in aggregate, we are not able to examine the unique differences between different types of substance use or years of substance use. We also did not explicitly ask patients about why they may be using substances, such as for untreated pain or perceived health benefits. For example, the higher rates of substance use in males may reflect increased self-medication in a group known to have lower rates of allopathic health care receipt compared to women or it may be to do to higher rates of sensation-seeking behavior in men. It may also be that the true determinants of substance use disorder risk were not measured in the IMPORT study, for example, family history supporting a genetic vulnerability for substance use, a known risk factor. While we need additional longitudinal studies to further explore the directionality of these relationships, this study provides some important insight on the importance of identifying patients at psychosocial risk for substance use. In this study we asked about reported substance use, which remains a highly stigmatized topic. Participants may not have felt comfortable disclosing substance use and our findings may be an under-report on the true prevalence of substance use in these patients. Although we captured prevalence of certain substance use behaviors, we are unable to draw diagnostic conclusions about substance use disorders from this study.

Our findings demonstrate that while substance use is endorsed by a minority of patients with SCD, among the subset who endorse substance use, individuals report markedly more stress and distress with higher rates of depression and poorer quality of life. Marijuana use is the most common substance reported, which has important clinical implications as marijuana becomes more available as a result of changing laws across the US. Those who use substances reported increased distress and suggests that interventions that focus on improving distress tolerance and coping to not only pain, but also social stressors, might reduce substance use in this vulnerable group.

Acknowledgements

MCB was supported through the National Institute of Health (NIH) National Heart, Lung, and Blood Institute R01 HL088511 (nih.nhlbi.gov). MCB was supported by NIH National Institute on Drug Abuse K24 DA037804-01 (drugabuse.gov) and JDW was supported by NIH National Center for Advancing Translational Sciences KL2 TR001856 (nih.ncats.gov). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

Footnotes

Declaration of interest statement

None of the authors have any conflicts of interest to disclose.

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