Temporal dynamics of symptom change among veterans receiving an integrated treatment for posttraumatic stress disorder and substance use disorders

Christal L. Badour, Julianne C. Flanagan, Nicholas P. Allan, Amanda K. Gilmore, Daniel F. Gros, Therese Killeen, Kristina J. Korte, Delisa G. Brown, Kateryna Kolnogorova, Sudie E. Back

Research output: Contribution to journalArticlepeer-review

Abstract

The present study examined temporal patterns of symptom change during treatment for comorbid posttraumatic stress disorders (PTSD) and substance use disorders (SUDs). We hypothesized that PTSD symptom severity would predict subsequent-session substance use and that this association would be particularly strong among patients who received an integrated treatment versus SUD-only treatment. Participants were 81 United States military veterans with current PTSD and an SUD who were enrolled in a 12-week, randomized controlled trial examining the efficacy of an integrated treatment called Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) compared with cognitive behavioral relapse prevention therapy (RP). Lagged multilevel models indicated that PTSD symptom improvement did not significantly predict the likelihood of next-session substance use (likelihood of use: B = 0.03, SE = 0.02, p =.141; percentage of days using B = -0.02, SE = 0.01, p =.172. Neither substance use, B = 1.53, SE = 1.79, p =.391, nor frequency of use, B = 0.26, SE = 0.50, p =.612, predicted next-session PTSD symptom severity in either treatment condition. Stronger associations between PTSD symptoms and next-session substance use were expected given the self-medication hypothesis. Additional research is needed to better understand the temporal dynamics of symptom change as well as the specific mediators and mechanisms underlying symptom change.

Original languageEnglish
Pages (from-to)546-558
Number of pages13
JournalJournal of Traumatic Stress
Volume35
Issue number2
DOIs
StatePublished - Apr 2022

Bibliographical note

Funding Information:
The authors would like to acknowledge support from the National Institute on Drug Abuse (NIDA; R01DA030143: Sudie E. Back; R25DA020537: Sudie E. Back, Kathleen T. Brady; K12DA035150: Christal L. Badour; K23DA042935: Amanda K. Gilmore), National Institute on Alcohol Abuse and Alcoholism (K23AA023845: Julianne C. Flanagan; R01 AA025086‐03S1: Sudie E.Back), the Department of Veteran Affairs (VA) (CX000845: Daniel F. Gros), NIDA and Office of Research on Women's Health in partnership with the Medical University of South Carolina (U54 DA016511: Delisa G. Brown), and resources at the Ralph H. Johnson VA Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of NIDA, NIAAA, National Institute of Mental Health, VA, or the U.S. Government. Sudie E. Back and Therese Killeen are co‐authors of the COPE therapy manuals. This study is registered at ClinicalTrials.gov (NCT01338506).

Funding Information:
The authors would like to acknowledge support from the National Institute on Drug Abuse (NIDA; R01DA030143: Sudie E. Back; R25DA020537: Sudie E. Back, Kathleen T. Brady; K12DA035150: Christal L. Badour; K23DA042935: Amanda K. Gilmore), National Institute on Alcohol Abuse and Alcoholism (K23AA023845: Julianne C. Flanagan; R01 AA025086-03S1: Sudie E.Back), the Department of Veteran Affairs (VA) (CX000845: Daniel F. Gros), NIDA and Office of Research on Women's Health in partnership with the Medical University of South Carolina (U54 DA016511: Delisa G. Brown), and resources at the Ralph H. Johnson VA Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of NIDA, NIAAA, National Institute of Mental Health, VA, or the U.S. Government. Sudie E. Back and Therese Killeen are co-authors of the COPE therapy manuals. This study is registered at ClinicalTrials.gov (NCT01338506). Despite mounting literature supporting the efficacy of integrated treatments for co-occurring PTSD and SUD (Back et?al., 2019; Badour et?al., 2017; Brady et?al., 2001; McCauley et?al., 2012; Mills et?al., 2012; Roberts et?al., 2016), important questions remain about how symptoms change during treatment and the potential mediators and mechanisms that may drive this change. The present study represents a first step toward this line of inquiry through the investigation of the temporal relations between changes in PTSD symptoms and substance use among veterans participating in an RCT comparing the efficacy of COPE, a trauma-focused, integrated treatment for PTSD and SUD, versus RP, a treatment that targets SUDs only. Consistent with the self-medication hypothesis, we expected that PTSD symptoms would predict subsequent-session substance use during treatment and that this association would be stronger among participants who received COPE. However, although the pattern of data was generally consistent with PTSD symptoms predicting next-session likelihood of use, the strength of this association was weak and nonsignificant, and there was no effect of PTSD symptoms on subsequent-session frequency of use. Moreover, although COPE resulted in significantly more PTSD symptom improvement compared with RP, such improvement did not correspond to larger symptom reductions, only comparable reduction, in substance use among individuals receiving COPE. If the primary mechanism of change in substance use behavior during COPE was the reduction of PTSD symptoms, we would have expected to observe a stronger association between PTSD symptom severity and subsequent-session substance use. There was also no evidence that (a) whether someone used substances or (b) the frequency of their use in a given week predicted PTSD symptoms at the next session. The self-medication hypothesis is one of the most widely accepted theories to explain the high comorbidity of PTSD and SUDs; however, important nuances undergirding this theory should be considered in the context of the present results. First, the self-medication hypothesis offers an explanation for the development of PTSD?SUD comorbidity, wherein trauma exposure and PTSD symptoms temporally precede and contribute to the onset or exacerbation of coping-related substance use to mitigate the distressing symptoms of PTSD. Repeated and increased substance use to obtain or maintain one's desired reduction in PTSD symptom?related distress can lead to long-term harmful substance use patterns, including the emergence of SUDs (Haller & Chassin, 2014; Hawn et?al., 2020). However, once PTSD?SUD comorbidity has been established, it is less clear if this self-medication process remains the best explanation for why the co-occurrence of these symptoms persists. The mutual maintenance hypothesis (Stewart et?al., 1998) is another theory that acknowledges there are likely multiple interacting risk factors that contribute to the development of comorbid PTSD and SUD. Once established, this theory suggests that PTSD and SUD maintain one another over time such that PTSD symptoms lead to the continued use of substances, and substance use leads to the maintenance or worsening of PTSD symptoms over time by interfering with trauma processing (Kaysen et?al., 2011; McFarlane et?al., 2009) and sensitizing reward and stress response systems in the brain (Mar?a-R?os & Morrow, 2020). The present findings appear counter to those expected by the self-medication hypothesis if, indeed, this hypothesis extends to understanding maintenance and treatment of PTSD/SUD comorbidity. Specifically, if a primary mechanism maintaining ongoing substance use is negative reinforcement obtained through a temporary reduction in distress associated with PTSD symptoms, PTSD symptom improvement should result in a reduced need for substance use, and a subsequent reduction of use should be observed. Further, we would expect the larger reduction in PTSD symptoms seen among participants who received COPE relative to RP to also lead to larger improvements in substance use. Similarly, if PTSD symptoms and substance use behavior are maintaining or exacerbating one another over time, in line with the mutual maintenance model, PTSD symptoms should be expected to predict subsequent substance use behavior, and vice versa, across the course of treatment. However, we failed to observe these expected associations when PTSD symptoms and substance use were assessed week-to-week. It is possible that session-to-session intervals are too brief to observe the expected prospective association between PTSD symptom improvement and subsequent substance use; however, in the parent trial for this study (Back et?al., 2019), differences in substance use frequency also failed to emerge as a function of treatment condition at posttreatment and 3- and 6-month follow-ups despite significantly larger improvements in PTSD symptoms during the treatment window among participants who received COPE versus those who received RP. It is notable that the present results diverge from those of a recently published trial of COPE versus Seeking Safety in veterans with PTSD and co-occurring alcohol use disorder, in which PTSD symptom severity was found to predict subsequent-session alcohol use, and vice versa, in both treatment conditions (Tripp et?al., 2020). Importantly, participants were included in the study by Tripp and colleagues based on the presence of PTSD or subclinical PTSD and alcohol use disorder comorbidity, whereas nearly 40% of participants in the present trial presented with at least one substance use disorder other than or in addition to alcohol use disorder. Moreover, in the present study, week-to-week associations between PTSD symptoms and substance use considered the use of all substances (i.e., alcohol and drugs), as polysubstance use was common. Despite the broad acceptance of the self-medication hypothesis as a leading explanation for PTSD/SUD comorbidity, most empirical studies that have tested this hypothesis have focused specifically on the link between PTSD and alcohol use, been limited by the use of cross-sectional designs, and relied on self-report measures of the tendency to engage in coping-related drinking rather than directly measuring proximal associations between PTSD symptoms and substance use behavior (Hawn et?al., 2020). This theory has also been critiqued based on evidence that the successful treatment of psychiatric symptoms among dual-diagnosis patients tends not to result in large, sustained improvements in substance use outcomes in the absence of addiction-focused treatment (Lembke, 2012). This is not to say that additional research on the potential role of the self-medication hypothesis is not warranted in comorbid PTSD and SUD. Indeed, the inconsistent findings emerging from the few studies that have considered the temporal association between PTSD symptoms and substance use during treatment (e.g., Hien et?al., 2010, 2018; Kackurkin et?al., 2016; Peirce et?al., 2010; Tripp et?al., 2020) underscore the need to better understand both the unique and shared mediators and mechanisms of change in these two symptom dimensions in response to single-disorder and integrated treatment protocols. Given the heterogeneity in presentation among patients with comorbid PTSD and SUDs, it is also likely that there are important moderators of change processes that need to be considered. For example, among individuals who report heavy or chronic use of substances that lead to physiological dependence, it may be that short-term fluctuations in PTSD symptom severity have less of an influence on substance use patterns compared with individuals who are not physiologically dependent on one or more substances. Moreover, the use of some illicit substances is likely restricted by the availability of access at a given time; thus, the use of some drugs might not be as directly tied to fluctuations in symptoms, as might be expected for alcohol. Finally, other significant stressors that frequently impact this population, such as housing and employment instability, interpersonal relationship conflict, and financial resource strain, may have a more robust influence on proximal substance use behavior during the course of treatment, compared to week-to-week fluctuations in PTSD symptoms. Ongoing stressors such as these are rarely considered in the context of examining the temporal relations between PTSD symptoms and substance use. The present findings represent an important next step aimed at understanding how integrated treatments may function differently than single-disorder protocols to improve the symptoms of both PTSD and SUDs. The use of an integrated treatment may simultaneously reduce the symptoms of both PTSD and SUDs, resulting in improvements in each disorder in the same amount of time when compared with treatment that focuses on one disorder only. Moreover, the present findings converge with a growing literature suggesting superior improvements in PTSD symptoms occur via trauma-focused integrated treatments compared to disorder-specific treatments for SUD, such as RP. However, considerable gaps remain in our understanding of (a) the temporal dynamics of PTSD and SUD symptom change, (b) the purported mediators that may account for observed symptom change, and (c) the specific mechanisms that drive both PTSD and substance use symptom change in each of these treatments. Such research is necessary to optimize treatment delivery to obtain the best results for individual patients. Although more research is needed on integrated treatments, the initial findings regarding safety, acceptability, and efficacy are promising, and integrated treatment is recommended in the U.S. Department of Veterans Affairs/Department of Defense Clinical Practice Guidelines (Ostacher & Cifu, 2019). Several study limitations should be noted. First, this study presents secondary analyses from a parent RCT that was adequately powered to detect group differences in primary outcomes of PTSD and substance change across 12 weeks of treatment. As such, this dataset was underpowered to conduct formal tests of mediation, and, thus, we were only able to address questions regarding the temporal ordering of symptom change. Future studies should consider recruiting adequate sample sizes or pooling samples across similar trials to conduct further investigations regarding mediators and mechanisms of change. In addition, the present sample consisted of veterans, most of whom were male, reported military-related trauma exposure, and had an alcohol use disorder alone or an alcohol use disorder plus at least one other drug use disorder. The current findings may differ among civilians or individuals who have primarily drug use disorders. Further, although there was some racial diversity in the current sample, there was limited ethnic diversity and not enough power to examine differences based on racial or ethnic group. Self-report measures were used, which are subject to various biases, including recall and social desirability. Although similar to those reported for other integrated treatments (Roberts et?al., 2016), the attrition rate in this study was relatively high. This patient population is characterized by significant challenges to treatment adherence, highlighting the need for additional research on effective implementation strategies to ensure that patients are able to access adequate doses of integrated therapies. Although participants were equally likely to complete treatment in either condition, the association between PTSD and SUD symptom change may differ among individuals who drop out of treatment prior to completion. The addition of a standalone PTSD arm or alternative integrated treatment to further investigate and improve the generalization of findings for integrated treatments should be considered to move this line of research forward. The present study was the first of which we are aware to investigate the week-to-week temporal dynamics of PTSD and SUD symptom change during an integrated treatment for PTSD and SUD versus treatment for SUD alone in a sample of military veterans with co-occurring PTSD and SUD. Although some PTSD symptom improvement emerged, predicting the next-session likelihood of substance use, but not the frequency of use, during the course of integrated treatment (COPE), this finding was weak and nonsignificant. Substance use also did not predict subsequent-session PTSD symptoms. The self-medication hypothesis would suggest stronger temporal associations between PTSD symptoms and subsequent-session substance use. Significant gaps remain regarding the field's understanding of how symptom change occurs during integrated versus single-disorder treatments. Note: The percentage of each group reporting any substance use at each session is based on the number of participants in the intent-to-treat sample (n = 54 in COPE; n = 27 in RP).PTSD = posttraumatic stress disorder; COPE = Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure; PCL-M = PTSD Checklist?Military Version; RP = relapse prevention; TLFB = timeline follow-back.

Publisher Copyright:
© 2021 International Society for Traumatic Stress Studies.

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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