Post-traumatic stress disorder and drug use disorder: examination of aetiological models in a Swedish population-based cohort

Abstracts from the NIH Office of Research on Women's Health 2018 Annual BIRCWH Meeting – Building Interdisciplinary Research Careers in Women's Health November 28, 2018

Substance use disorder (SUD) among women of reproductive age is a complex public health problem affecting a diverse spectrum of women and their families, with potential consequences across generations. The goals of this study were 1) to describe and compare the prevalence of patterns of injury requiring emergency department (ED) visits among SUD-positive and SUD-negative women and 2) among SUD-positive women, to investigate the association of specific categories of injury with type of substance used. This study was a secondary analysis of a large, multisource health care utilization data set developed to analyze SUD prevalence, and health and substance abuse treatment outcomes, for women of reproductive age in Massachusetts, 2002 through 2008. Sources for this linked data set included diagnostic codes for ED, inpatient, and outpatient stay discharges; SUD facility treatment records; and vital records for women and for their neonates. Injury data (ICD-9-CM E-codes) were available for 127,227 SUD-positive women. Almost two-thirds of SUD-positive women had any type of injury, compared to 44.8% of SUD-negative women. The mean (±SD) number of events also differed (2.27 ± 4.1 for SUD-positive women vs. 0.73 ± 1.3 for SUD-negative women, p < 0.0001). For four specific injury types, the proportion injured was almost double for SUD-positive women (49.3% vs 23.4%), and the mean (±SD) number of events was more than double (0.72 ± 0.9 vs. 0.26 ± 0.5, p < 0.0001). The numbers and proportions of motor vehicle incidents and falls were significantly higher in SUD-positive women (22.5% vs. 12.5% and 26.6% vs. 11.0%, respectively), but the greatest differences were in self-inflicted injury (11.5% vs. 0.8%; mean ± SD events = 0.19 ± 0.9 vs. 0.009 ± 0.2, p < 0.0001) and purposefully inflicted injury (11.5% vs 1.9%, mean ± SD events = 0.18 ± 0.1 vs. 0.02 ± 0.2, p < 0.0001). In each of the injury categories that we examined, injury rates among SUD-positive women were lowest for alcohol disorders only and highest for alcohol and drug disorders combined. Among 33,600 women identified as using opioids, 2,132 (6.3%) presented to the ED with overdose. Multiple overdose visits were common (mean ± SD = 3.67 ± 6.70 visits). After adjustment for sociodemographic characteristics, psychiatric history, and complex/chronic illness, SUD remained a significant risk factor for all types of injury, but for the suicide/self-inflicted injury category, psychiatric history was by far the stronger predictor. The presence of SUD increases the likelihood that women in the 15- to 49-year age group will present to the ED with injury. Conversely, women with injury may be more likely to be involved in alcohol abuse or other substance use. The high rates of injury that we identified among women with SUD suggest the utility of including a brief, validated screen for substance use as part of an ED injury treatment protocol and referring injured women for assessment and/or treatment when scores indicate the likelihood of SUD.

Post-traumatic stress disorder (PTSD) and substance use disorder (SUD) are highly co-occurring and evidence for the optimal ways of treating PTSD in SUD patients is mixed. Our aim was to compare three different PTSD treatments, each added simultaneously to SUD treatment, with SUD treatment alone in patients with co-occurring SUD-PTSD. These PTSD treatments were: Prolonged Exposure (PE), Eye Movement Desensitization and Reprocessing (EMDR) and Imagery Rescripting (ImRs). A single-blind 4-arm randomized controlled trial with follow-up at 3months. Two addiction treatment centers in the Netherlands, providing intra- and extramural care. 209 patients with SUD and co-morbid PTSD were included [mean age 37.5 (standard deviation, SD = 11.99), female sex = 46.4%, mean Clinically Administered PTSD Scale (CAPS) score = 37.35 (SD = 9.28)]. Participants were randomized to either simultaneous SUD + PE (n = 53), SUD + EMDR (n = 50), SUD + ImRs (n = 55) or to SUD treatment only (n = 51), with the active PTSD treatments consisting of 12 sessions each within 3months. Standard protocols were used. The primary outcome was clinician-administered PTSD symptom severity as measured by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (CAPS-5) at 3month follow-up. Secondary outcomes included loss of PTSD diagnosis, full remission of PSTD and SUD-severity, also recorded at 3months. Compared with SUD only, the mean differences in CAPS-5 score were B = -5.41 [95% confidence interval (CI) = 10.88, 0.05, P = 0.052] for SUD + PE, B = -7.97 (95% CI = -13.57, -2.37, P = 0.006) for SUD + EMDR and B = -10.03 (95% CI = -15.29, -4.77, P < 0.001) for SUD + ImRs. When adjusted for baseline covariates, mean differences were B = -5.81 (95% CI = -11.48, -0.15, P = 0.044) for SUD + PE, B = -8.85 (95% CI = -14.60, -3.10, P = 0.003) for SUD + EMDR and B = -10.75 (95% CI = -15.94, -5.56, P = <0.001) for SUD + ImRs. No between-group differences in SUD outcomes were found. Among people with co-occurring substance use disorder (SUD) and post-traumatic stress disorder (PTSD), trauma-focused PTSD treatment as add-on to SUD treatment appears to be effective in decreasing PTSD severity compared with manualized SUD only treatment and does not appear to increase SUD severity.

Objectives: Concurrent substance use disorder (SUD) and posttraumatic stress disorder (PTSD) occur at high rates and are typically associated with poor treatment outcomes in both sexes. However, women have a propensity to cope with increased negative affect via substance use in comparison to men; thus, it is important to elucidate the sex-specific bidirectional relationships between SUD and PTSD to improve our understanding of concurrent SUD/PTSD in men and women. Methods: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-Wave 3; n = 36,309), the present study evaluated the impact of sex on the relationship between past-year SUDs (new, remitted, ongoing), including alcohol and drug use, and retrospective transitions in new vs. absent and ongoing vs. remitted diagnoses of PTSD. Additionally, the impact of sex was explored in models examining past year PTSD (new, remitted, ongoing) and retrospective transitions in new vs. absent and ongoing vs. remitted diagnosis of SUDs. Diagnostic transitions were based on retrospective reporting. Results: Results indicated that new, remitted, and ongoing SUDs increase the likelihood of new PTSD diagnoses (OR range = 2.53–8.11; p < 0.05). Among individuals with ongoing drug use disorders (DUD), there were greater odds of ongoing PTSD (OR = 2.10, p < 0.01). When examining the relationship reciprocally, new, remitted, and ongoing PTSD increased the likelihood of new SUDs (OR range = 2.50–8.22; p < 0.05), and ongoing PTSD increased the likelihood of ongoing SUD and DUD (OR = 1.40, 1.70, respectively; p < 0.05). Sex-specific analyses revealed that the relationship between PTSD and SUDs varies between sexes, particularly among women. For instance, women with new PTSD had higher odds of SUDs, and women with ongoing PTSD were almost 2.5 times more likely to have an ongoing DUD. Women with a new PTSD diagnosis were more likely to be diagnosed with a new SUD (OR = 3.27) and an ongoing DUD (OR = 3.08). Conclusions: Results indicate a bidirectional relationship between PTSD and SUD that is in many instances larger in women. Thus, illustrating potential sex-specific differences in underlying mechanisms implicated in SUD/PTSD, warranting additional research.

The authors aim to delineate cognitive dysfunction associated with posttraumatic stress disorder (PTSD) by evaluating a well-defined cohort of former World War II prisoners of war (POWs) with documented trauma and minimal comorbidities. The authors studied a cross-sectional assessment of neuropsychological performance in former POWs with PTSD, PTSD with other psychiatric comorbidities, and those with no PTSD or psychiatric diagnoses. Participants who developed PTSD had average IQ, while those who did not develop PTSD after similar traumatic experiences had higher IQs than average (approximately 116). Those with PTSD performed significantly less well in tests of selective frontal lobe functions and psychomotor speed. In addition, PTSD patients with co-occurring psychiatric conditions experienced impairment in recognition memory for faces. Higher IQ appears to protect individuals who undergo a traumatic experience from developing long-term PTSD, while cognitive dysfunctions appear to develop with or subsequent to PTSD. These distinctions were supported by the negative and positive correlations of these cognitive dysfunctions with quantitative markers of trauma, respectively. There is a suggestion that some cognitive decrements occur in PTSD patients only when they have comorbid psychiatric diagnoses.

To determine the relations between obstructive sleep apnea (OSA) diagnosis, the likelihood of being diagnosed with a psychological condition, among obese veterans, after accounting for severity of obesity and the correlated nature of patients within facility. We hypothesized that (1) individuals with a diagnosis of OSA would be more likely to receive a diagnosis of a (a) mood disorder and (b) anxiety disorder, but not (c) substance use disorder. Cross-sectional retrospective database review of outpatient medical records between October 2009 and September 2010, conducted across all 140 Veterans Health Administration (VHA) facilities. The entire VA Health Care System. Population-based sample of veterans with obesity (N = 2,485,658). Physician- or psychologist-determined diagnosis of psychological conditions including mood, anxiety, and substance use disorders. Using generalized linear mixed modeling, after accounting for the correlated nature of patients within facility and the severity of obesity, individuals with a diagnosis of sleep apnea had increased odds of receiving a mood disorder diagnosis (OR = 1.85; CI = 1.71-1.72; p < 0.001), anxiety disorder diagnosis (OR = 1.82; CI = 1.77-1.84; p < 0.001), but not a diagnosis of substance use disorder. Among obese veterans within VA, OSA is associated with increased risk for having a mood and anxiety disorder, but not substance use disorder, with the strongest associations observed for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In addition, this relation remained after accounting for severity of BMI.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that may develop after exposure to traumatic events. Substance use disorder (SUD) is a behavioural disorder in which the use of one or more substances is associated with heightened levels of distress, clinically significant impairment of functioning, or both. PTSD and SUD frequently occur together. The comorbidity is widely recognised as being difficult to treat and is associated with poorer treatment completion and poorer outcomes than for either condition alone. Several psychological therapies have been developed to treat the comorbidity, however there is no consensus about which therapies are most effective.

Although there is a high degree of comorbidity between posttraumatic stress disorder (PTSD) and drug use disorders, little is known about causal relationships between PTSD, exposure to traumatic events, and drug use disorders. In a longitudinal study in southeast Michigan, 1007 adults aged 21 to 30 years were initially assessed in 1989 and were followed up 3 and 5 years later, in 1992 and 1994. Psychiatric disorders according to DSM-III-R criteria were measured by the National Institute of Mental Health Diagnostic Interview Schedule. To take into account temporal sequencing, the associations between PTSD, traumatic events, and drug use disorders were analyzed by using Cox proportional hazards models with time-dependent covariates. Posttraumatic stress disorder signaled an increased risk of drug abuse or dependence (hazards ratio, 4.5; 95% confidence interval, 2.6-7.6, adjusted for sex), whereas exposure to traumatic events in the absence of PTSD did not increase the risk of drug abuse or dependence. The risk for abuse or dependence was the highest for prescribed psychoactive drugs (hazards ratio, 13.0; 95% confidence interval, 5.3-32.0). There was no evidence that preexisting drug abuse or dependence increased the risk of subsequent exposure to traumatic events or the risk of PTSD after traumatic exposure. The results suggest that drug abuse or dependence in persons with PTSD might be the inadvertent result of efforts to medicate symptoms, although the possibility of shared vulnerability to PTSD and drug use disorders cannot be ruled out.

Posttraumatic stress disorder (PTSD) is often conceptualized from a fear conditioning perspective given individuals with PTSD demonstrate a reduced ability to inhibit fear even under safe conditions as compared to those without PTSD. The self-medication hypothesis suggests that individuals with PTSD often develop substance use disorders (SUDs) as an attempt to mitigate trauma-related distressing emotions. This investigation examined this hypothesis in a sample 214 participants, of which 81 did not meet criteria for either PTSD or SUDs (No diagnosis Control group); 33 met criteria for lifetime PTSD, but not SUDs (PTSD only group); 54 met criteria for lifetime SUDs, but not PTSD (SUDs only group); and 46 met lifetime criteria for both disorders (PTSD+SUDs group). PTSD was assessed using the modified PTSD Symptoms Scale (mPSS), SUDs were assessed using the Structured Clinical Interview for DSM-IV-TR (SCID). The startle magnitude was assessed using electromyography (EMG) of the eyeblink muscle in response to an acoustic startle probe. Fear-potentiated startle (FPS) was analyzed by comparing startle magnitude at baseline to startle during a fear conditioned stimulus. Results showed that PTSD significantly increased startle responses. However, there was a significant effect of SUDs on fear-potentiated startle to the danger signal, in that those who met criteria for SUDs had reduced fear compared to those who did not. The individuals who had co-morbid PTSD and SUDs did not differ from the Control group. Findings indicate that SUDs may attenuate exaggerated fear responses associated with PTSD. Consistent with the self-medication hypothesis, results suggest that substance use may co-occur with PTSD because it reduces heightened fear load and may allow normalized function in traumatized individuals.

Two predominant phenotypic models of causality exist to explain the high co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD): the self-medication and susceptibility models. Population-based longitudinal studies that simultaneously examine both models are needed. Thus, the goal of the present study is to test these models using the Swedish National Registries. Registries were used to conduct longitudinal Cox proportional hazard models (n ≈ 1.5 million) and cross-lagged panel models (N ≈ 3.8 million) with follow-up periods of ~23 years. Covarying for cohort and socioeconomic status, Cox proportional hazards model results found strong support for the self-medication model. Results showed that PTSD predicted increased risk for AUD among both men (HR = 4.58 [4.42, 4.74]) and women (HR = 4.14 [3.99, 4.30]), significantly more so for men (interaction HR = 1.11 [1.05, 1.16]). Support was also found for the susceptibility model, although the effects were lower in magnitude than those for the self-medication model. AUD increased risk for PTSD among men (HR = 2.53 [2.47, 2.60]) and women (HR = 2.06 [2.01, 2.12]), and significantly more so for men (interaction term HR = 1.23 [1.18, 1.28]). Cross-lagged model results of simultaneously testing both models found support for bidirectionality. The PTSD-to-AUD paths and the AUD-to-PTSD paths were of modest effect for men and women. The results from both complementary statistical approaches demonstrate that the models of comorbidity are not mutually exclusive. Although the Cox model results evidenced more support for the self-medication pathway, the cross-lagged model results suggest that the prospective relationships between these disorders are nuanced across development.

Anxiety disorders such as posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are increasingly recognized as comorbid disorders in children with bipolar disorder (BPD). This study explores the relationship between BPD, PTSD, and SUD in a cohort of BPD and non-BPD adolescents. We studied 105 adolescents with BPD and 98 non-mood-disordered adolescent controls. Psychiatric assessments were made using the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiologic Version (KSADS-E), or Structured Clinical Interview for DSM-IV (SCID) if 18 years or older. SUD was assessed by KSADS Substance Use module for subjects under 18 years, or SCID module for SUD if age 18 or older. Nine (8%) BPD subjects endorsed PTSD and nine (8%) BPD subjects endorsed subthreshold PTSD compared to one (1%) control subject endorsing full PTSD and two (2%) controls endorsing subthreshold PTSD. Within BPD subjects endorsing PTSD, seven (39%) met criteria for SUD. Significantly more SUD was reported with full PTSD than with subthreshold PTSD (chi(2) = 5.58, p = 0.02) or no PTSD (chi(2) = 6.45, p = 0.01). Within SUD, the order of onset was BPD, PTSD, and SUD in three cases, while in two cases the order was PTSD, BPD, SUD. The remaining two cases experienced coincident onset of BPD and SUD, which then led to trauma, after which they developed PTSD and worsening SUD. An increased rate of PTSD was found in adolescents with BPD. Subjects with both PTSD and BPD developed significantly more subsequent SUD, with BPD, PTSD, then SUD being the most common order of onset. Follow-up studies need to be conducted to elucidate the course and causal relationship of BPD, PTSD and SUD.

Reintegration Problems and Treatment Interests Among Iraq and Afghanistan Combat Veterans Receiving VA Medical Care

Substance use disorder (SUD) frequently co-occurs with posttraumatic stress disorder (PTSD). Feelings of shame and guilt are associated with either disorder but have not been studied in patients with both disorders. Index trauma characteristics are associated with PTSD severity and trauma-related shame. This study examines the effects of trauma-related guilt and shame, and index trauma on SUD and PTSD severity in a clinical sample of individuals with co-occurring SUD and PTSD. Participants were SUD-treatment-seeking patients with co-occurring PTSD (N = 209) who completed the Clinician-Administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders (DSM-5; CAPS-5), Alcohol Use Disorder Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), Trauma-Related Guilt Inventory (TRGI) and Trauma-Related Shame Inventory (TRSI). Regression analyses examined the predictive values of PTSD severity, trauma-related guilt, and shame on alcohol and drug use problems, and the predictive values of trauma-related guilt and shame on PTSD severity. One-way ANOVA and follow-up t-tests examined the effects of index trauma on PTSD severity and trauma-related shame. PTSD severity was significantly associated with drug use disorder (DUD) severity and showed a curvilinear relationship to alcohol use disorder (AUD) severity. Trauma-related guilt was not significantly associated with SUD severity, while trauma-related shame was significantly associated with DUD severity (but not AUD severity). Both trauma-related guilt and shame were significantly associated with PTSD severity; however, only trauma-related shame showed an independent association. Interpersonal (especially sexual) index traumas were associated with increased trauma-related guilt and shame, while childhood index traumas were associated with increased PTSD severity. Trauma-related guilt and shame might be important focus points in PTSD treatment, but for SUD problems, this study only showed an association between trauma-related shame and drug use problems. Trauma-related shame seems to be a more important treatment focus point than trauma-related guilt in the treatment of PTSD. It becomes particularly relevant for interpersonal index traumas (especially sexual trauma). Childhood traumas require attention in SUD-PTSD co-occurrence, given the higher severity of PTSD.

This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV-r) in treating patients with coronavirus disease-2019 (COVID-19) and substance use disorders (SUDs). This study included two cohorts: the first examined patients with SUDs, with and without a prescription for NMV-r, while the second compared patients prescribed with NMV-r, with and without a diagnosis of SUDs. SUDs were defined using ICD-10 codes, related to SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders (TUD). Patients with underlying SUDs and COVID-19 were identified using the TriNetX network. We used 1:1 propensity score matching to create balanced groups. The primary outcome of interest was the composite outcome of all-cause hospitalization or death within 30 days. Propensity score matching yielded two matched groups of 10 601 patients each. The results showed that the use of NMV-r was associated with a lower risk of hospitalization or death, 30 days after COVID-19 diagnosis (hazard ratio (HR), 0.640; 95% confidence interval (CI): 0.543-0.754), as well as a lower risk of all-cause hospitalization (HR, 0.699; 95% CI: 0.592-0.826) and all-cause death (HR, 0.084; 95% CI: 0.026-0.273). However, patients with SUDs had a higher risk of hospitalized or death within 30 days of COVID-19 diagnosis than those without SUDs, even with the use of NMV-r (HR, 1.783; 95% CI: 1.399-2.271). The study also found that patients with SUDs had a higher prevalence of comorbidities and adverse socioeconomic determinants of health than those without SUDs. Subgroup analysis showed that the benefits of NMV-r were consistent across most subgroups with different characteristics, including age (patients aged ≥60 years [HR, 0.507; 95% CI: 0.402-0.640]), sex (women [HR, 0.636; 95% CI: 0.517-0.783] and men [HR, 0.480; 95% CI: 0.373-0.618]), vaccine status (vaccinated <2 doses [HR, 0.514; 95% CI: 0.435-0.608]), SUD subtypes (alcohol use disorder [HR, 0.711; 95% CI: 0.511- 0.988], TUD [HR, 0.666; 95% CI: 0.555-0.800]) and Omicron wave (HR, 0.624; 95% CI: 0.536-0.726). Our findings indicate that NMV-r could reduce all-cause hospitalization and death in the treatment of COVID-19 among patients with SUDs and support the use of NMV-r for treating patients with SUDs and COVID-19.

Management of Mental Health Disorders, Substance Use Disorders, and Suicide in Adults with Spinal Cord Injury: Clinical Practice Guideline for Healthcare Providers.