Topiramate treatment of alcohol use disorder in veterans with posttraumatic stress disorder: a randomized controlled pilot trial.

BACKGROUND: The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders. METHODS: This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300 mg/d in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity. RESULTS: Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared with placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment. CONCLUSIONS: These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity-particularly hyperarousal symptoms. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated.

Trauma exposure predicts alcohol, nicotine, and drug problems beyond the contribution of PTSD and depression in patients with cardiovascular disease: data from the Heart and Soul Study.

BACKGROUND AND OBJECTIVES: This study examined the role of lifetime trauma exposure in a longitudinal study of adults with cardiovascular disease to determine the unique contribution of trauma exposure to risk for drug and alcohol problems and smoking. METHODS: Data were drawn from the Heart and Soul Study, a prospective cohort study designed to determine the mechanisms of associations between psychological factors and increased risk of cardiovascular events in high-risk patients (n = 1,022). RESULTS: Lifetime exposure to a higher number of trauma types predicted substance use outcomes beyond risk explained by PTSD and depression. In addition, across trauma types, interpersonal traumas were most strongly associated with substance use problems. CONCLUSIONS: Our results suggest that, though PTSD and depression play a role in the association between trauma exposure and substance use, many other factors also contribute; therefore focusing on these psychological comorbidities alone is not sufficient. SCIENTIFIC SIGNIFICANCE: The integration of mental health care and/or case management support with primary and specialty medical care may improve detection and treatment for patients with substance use and comorbid mental and physical health problems. Screening for trauma exposure is an important part of good clinical care.

Contingency management in community programs treating adolescent substance abuse: a feasibility study.

PROBLEM: Adolescent substance abuse remains a public health problem, and more effective treatment approaches are needed. PURPOSE: The study aims to determine the feasibility and preliminary effectiveness of implementing a cost-effective contingency management (CM) intervention in community substance abuse treatment for adolescents with marijuana use disorders. METHODS: Thirty-one adolescents with primary marijuana use disorder enrolled in a community treatment were randomized into either a prize-based CM intervention contingent when submitting negative urine drug screens (UDS) or a noncontingent control group. FINDINGS: There were no significant group differences in percent negative UDS, sustained negative UDS, or retention in treatment. CONCLUSIONS: CM was difficult to integrate into community treatment programs and did not seem to be an effective adjunct to standard community substance abuse treatment for adolescents with marijuana use disorders. Modifying the CM procedure for adolescents, changing staff attitudes toward CM, and/or combining CM with other evidence-based psychosocial treatment may improve outcomes.

Substance use disorders in Iraq and Afghanistan veterans in VA healthcare, 2001-2010: Implications for screening, diagnosis and treatment.

BACKGROUND: The prevalence and correlates of alcohol use disorder (AUD) and drug use disorder (DUD) diagnoses in Iraq and Afghanistan veterans who are new users of Department of Veterans Affairs (VA) healthcare nationwide has not been evaluated. METHODS: VA administrative data were used in retrospective cross-sectional descriptive and multivariable analyses to determine the prevalence and independent correlates of AUD and DUD in 456,502 Iraq and Afghanistan veterans who were first-time users of VA healthcare between October 15, 2001 and September 30, 2009 and followed through January 1, 2010. RESULTS: Over 11% received substance use disorder diagnoses: AUD, DUD or both; 10% received AUD diagnoses, 5% received DUD diagnoses and 3% received both. Male sex, age < 25 years, being never married or divorced, and proxies for greater combat exposure were independently associated with AUD and DUD diagnoses. Of those with AUD, DUD or both diagnoses, 55-75% also received PTSD or depression diagnoses. AUD, DUD or both diagnoses were 3-4.5 times more likely in veterans with PTSD and depression (p < 0.001). CONCLUSIONS: Post-deployment AUD and DUD diagnoses were more prevalent in subgroups of Iraq and Afghanistan veterans and were highly comorbid with PTSD and depression. Stigma and lack of universal screening may have reduced the number of DUD diagnoses reported. There is a need for improved screening and diagnosis of substance use disorders and increased availability of integrated treatments that simultaneously address AUD and DUD in the context of PTSD and other deployment-related mental health disorders.

Patterns and predictors of alcohol use in male and female urban police officers.

In a large sample of urban police officers, 18.1% of males and 15.9% of females reported experiencing adverse consequences from alcohol use and 7.8% of the sample met criteria for lifetime alcohol abuse or dependence. Female officers had patterns of alcohol use similar to male officers and substantially more than females in the general population. Critical incident exposure and posttraumatic stress disorder (PTSD) symptoms were not associated with level of alcohol use. Greater psychiatric symptoms were related to adverse consequences from alcohol use. There was a noteworthy gender by work stress interaction: greater routine work stress related to lower current alcohol use in female officers.

Community-dwelling cocaine-dependent men and women respond differently to social stressors versus cocaine cues.

UNLABELLED: There are likely to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Cocaine-dependent women are more likely to attribute relapse to negative emotional states and interpersonal conflict. Cocaine dependence has also been linked to dysregulation of stress response and the hypothalamic pituitary adrenal (HPA) axis which may differ between genders. Subjective and HPA-axis responses to a social evaluative stressor, the Trier Social Stress Test (TRIER), and in vivo cocaine-related cues were examined in the present study. RESULTS: There were no gender differences in magnitude of craving responses to the TRIER or the CUE. Both genders had a greater craving response to the CUE than to the TRIER, but the magnitude of the difference was greater for men than women (p=0.04). Cocaine-dependent subjects, compared to the control group, had significantly higher response throughout the TRIER (p<0.0001) and CUE (p<0.0001) testing sessions. There were no gender differences and no gender by cocaine interaction for ACTH responses to the TRIER, although women had lower baseline ACTH (p=0.049). On the CUE task, in contrast, female cocaine-dependent subjects had a more blunted ACTH response than did the other three groups (p=0.02). Female cocaine-dependent subjects also had a lower odds of a positive cortisol response to the TRIER as compared to the other three groups (OR=0.84, 95% CI=[0.02, 1.01]). During the CUE task, cocaine-dependent subjects had overall higher mean cortisol levels (p=0.0001), and higher odds of demonstrating a positive cortisol response to the CUE (OR=2.61, 95% CI=[1.11, 6.11]). No gender differences were found in ACTH responses to the CUE. The results are reviewed in the context of the existing literature on gender differences in cocaine dependence and potential implications for treatment are discussed.

Prescription opioid aberrant behaviors: a pilot study of sex differences.

OBJECTIVES: Patients who are prescribed opioids often display 1 or more aberrant prescription use behaviors (eg, requesting early refills, borrowing medication from family), which raise concern among healthcare professionals. Little is known about the sex differences in specific types of aberrant behaviors or sex-specific predictors of such behaviors. The current study is aimed to begin addressing this gap in the literature. METHODS: A battery of anonymous, self-report assessments was administered to 121 (49 men, 72 women) chronic pain patients enrolled in an outpatient pain management clinic. Most of the participants were white women with an average age of 51.6 years (SD=13.2). RESULTS: Significantly more men than women were taking a prescribed opioid (91.7% vs. 77.8%, P=0.05). Women were significantly more likely than men to hoard unused medication (67.6% vs. 47.7%, P=0.04) and to use additional medications to enhance the effectiveness of pain medication (38.8% vs. 20.0%, P=0.04). A trend toward men using alternative routes of administration (eg, crushing and snorting pills) more often than women was observed (8.9% vs. 1.5%, P=0.08). Among men, high rates of aberrant prescription use behaviors were associated with current alcohol use and the use of oxycodone and morphine. Among women, use of hydrocodone was associated with high rates of aberrant prescription use behaviors. DISCUSSION: Some aberrant prescription use behaviors are common among chronic pain patients and may be sex-specific. Predictors of aberrant prescription use behaviors may also differ by sex. Additional research is needed to help identify aberrant prescription use behaviors that best predict sex-specific risk for developing opioid abuse or dependence.

Response to corticotropin-releasing hormone infusion in cocaine-dependent individuals.

CONTEXT: Corticotropin-releasing hormone (CRH), through the hypothalamic pituitary adrenal axis and other brain stress systems, is involved in the emotional dysregulation associated with cocaine dependence. Little is known about the response of cocaine-dependent individuals to CRH administration. OBJECTIVE: The primary objective was to examine the hypothalamic-pituitary-adrenal axis and the subjective and physiologic response to CRH in cocaine-dependent individuals and controls. DESIGN: A case-control study. SETTING: Subjects were admitted to a General Clinical Research Center for testing and abstinence was verified with a urine drug screening. PARTICIPANTS: Participants were male controls (n = 23), female controls (n = 24), cocaine-dependent men (n = 28), and cocaine-dependent women (n = 25). Individuals with dependence on other substances (except caffeine or nicotine) or with major depression, posttraumatic stress disorder, bipolar disorder, or psychotic or eating disorders were excluded. INTERVENTION: Subjects received 1 microg/kg of CRH intravenously. MAIN OUTCOME MEASURES: Primary outcomes included plasma corticotropin levels, cortisol levels, and heart rate and subjective measurements. RESULTS: Cocaine-dependent individuals exhibited higher stress (P < .001) and craving for CRH compared with controls. A positive correlation (r(s) = 0.51; P < .001) between stress and craving was found in cocaine-dependent subjects. Intravenous CRH elevated heart rates in all groups; however, cocaine-dependent women demonstrated a significantly higher heart rate at all time points (P = .05). Women had higher cortisol responses to CRH (P = .03). No effect of cocaine status was observed. The corticotropin response to CRH was independent of sex and cocaine dependence. Cortisol and corticotropin were positively correlated in the controls and cocaine-dependent men, but not in cocaine-dependent women (r(s) = 0.199; P = .4). CONCLUSIONS: There is an increased subjective and heart rate response to CRH and a relationship between stress and craving in cocaine-dependent individuals. The lack of difference in hypothalamic pituitary adrenal axis response between the cocaine-dependent and control groups suggests that the heart rate and subjective responses in the cocaine group may be mediated by sensitization of nonhypothalamic stress-responsive CRH systems.

Treatment challenges associated with comorbid substance use and posttraumatic stress disorder: clinicians' perspectives.

A significant proportion of individuals with substance use disorders (SUDs) meet criteria for comorbid posttraumatic stress disorder (PTSD). This comorbidity confers a more complicated clinical presentation that carries with it formidable treatment challenges for practitioners. The current study examined sources of difficulty and gratification among clinicians (N = 423) from four national organizations who completed an anonymous questionnaire. As expected, the findings revealed that comorbid SUD/PTSD was rated as significantly more difficult to treat than either disorder alone. The most common challenges associated with treating SUD/PTSD patients included knowing how to best prioritize and integrate treatment components, patient self-destructiveness and severe symptomatology, and helping patients abstain from substance use. The findings increase understanding of SUD/PTSD treatment challenges, and may be useful for enhancing therapist training programs, supervision effectiveness, and designing optimal SUD/PTSD interventions.

Combat posttraumatic stress disorder, substance use disorders, and traumatic brain injury.

Among both civilian and veteran populations, substance use disorders (SUDs) and anxiety disorders frequently co-occur. One of the most common comorbid anxiety disorder is posttraumatic stress disorder (PTSD), a condition which may develop after exposure to traumatic events, such as military combat. In comparison with the general population, rates of both SUDs and PTSD are elevated among veterans. Recent data show that soldiers returning from Iraq and Afghanistan demonstrate high rates of co-occurring SUDs, PTSD, and traumatic brain injury. Careful assessment of these conditions is critical and may be complicated by symptom overlap. More research targeting integrated interventions for these conditions is needed to establish optimal treatments.

The influence of monetary compensation on relapse among addicted participants: empirical vs. anecdotal evidence.

Although common, the use of cash incentives to compensate drug-addicted participants is controversial. This is particularly true given concerns that cash incentives might precipitate relapse, as is commonly believed. The following investigation examined whether cash versus money order compensation differentially influenced drug use among 34 non-treatment-seeking, cocaine-dependent individuals. Consistent with past evidence, results did not suggest that form of compensation was associated with likelihood of continued cocaine use or dollar amount of cocaine consumed after participation. Findings do not support commonly held concerns that cash incentives increase the risk of relapse following research participation.

Early life trauma and sensitivity to current life stressors in individuals with and without cocaine dependence.

This study investigated the link between exposure to early life trauma, sensitivity to current daily stressors, and cocaine dependence. Individuals with (n = 105) or without (n = 53) cocaine dependence completed the Early Trauma Inventory and the Daily Hassles Scale. In comparison to controls, cocaine-dependent individuals reported almost twice as many daily hassles and perceived those hassles more negatively (p < .001). For participants with cocaine dependence, a significant relationship between exposure to early life trauma and negative perception of current daily hassles was observed (p < .01), whereas no such relationship was observed for participants without cocaine dependence. Adverse childhood events may lead to an altered view of the environment that contributes to increased irritability with daily life events among cocaine-dependent individuals.

Effects of gender and cigarette smoking on reactivity to psychological and pharmacological stress provocation.

We examined the influence of gender and smoking status on reactivity in two human laboratory stress paradigms. Participants were 46 (21 men, 25 women) healthy individuals who completed the Trier Social Stress Task (i.e., performed speech and math calculations in front of an audience) and a pharmacological stress provocation (i.e., administration of corticotrophin releasing hormone (CRH)) after an overnight hospital stay. Approximately half (53%) of the participants were smokers. Cortisol, adrenocorticotrophin hormone (ACTH), physiologic measures (heart rate, blood pressure), and subjective stress were assessed at baseline and at several time points post-task. Men demonstrated higher baseline ACTH and blood pressure as compared to women; however, ACTH and blood pressure responses were more pronounced in women. Women smokers evidenced a more blunted cortisol response as compared to non-smoking women, whereas smoking status did not affect the cortisol response in men. Finally, there was a more robust cardiovascular and subjective response to the Trier as compared to the CRH. Although preliminary, the findings suggest that women may be more sensitive than men to the impact of cigarette smoking on cortisol response. In addition, there is some evidence for a more robust neuroendocrine and physiologic response to acute laboratory stress in women as compared to men.

Sleep disturbances associated with posttraumatic stress disorder and alcohol dependence.

Sleep disturbances commonly appear in the context of both posttraumatic stress disorder (PTSD) and alcohol use disorders. Sleep symptoms typically reported among clinical populations include delayed sleep onset, poor sleep continuity, early morning awakening, and disturbed sleep architecture. The aim of the present study was to examine multiple forms of sleep disturbances among individuals with comorbid PTSD and alcohol dependence, PTSD only, alcohol dependence only, and a control group. Both PTSD and alcohol dependence diagnoses were associated with multiple forms of sleep disturbance, but comorbidity of the two disorders did not appear to increase the risk over and above either single disorder for reporting any of the sleep difficulties examined. As PTSD symptom severity increased, so did sleep latency, mid-sleep wakening, and early morning wakening. However, contrary to our hypothesis, no significant direct relationship between severity of alcohol use and sleep disturbances was revealed. These findings suggest a need for thorough assessment of sleep symptoms in patients presenting with PTSD or alcohol dependence.

Differences in early onset alcohol use and heavy drinking among persons with childhood and adulthood trauma.

We examined predictors for age at onset of first alcohol use and onset of heaviest alcohol use among men (n = 43) and women (n = 46) with alcohol dependence and PTSD, PTSD only, alcohol dependence only, and controls, with a particular focus on individuals with child versus adult trauma. Using analysis of variance procedures, results showed differences in onset of first alcohol use and heaviest drinking between childhood and adulthood trauma victims. These preliminary results indicate that behavioral mechanisms associated with alcohol use patterns between individuals with childhood and adulthood trauma are dissimilar, suggesting greater psychopathological consequences for individuals with childhood trauma.

Risk factors for suicidal behavior among a national sample of adolescents: implications for prevention.

Factors associated with suicidal ideation and attempts were examined among a national probability sample of adolescents. Sample prevalences of suicidal ideation and attempts were 24.3% and 3.3%, respectively, yielding weighted population prevalence estimates of 23.3% and 3.1%. Suicidal ideation was positively associated with female gender, age, family alcohol and drug problems, violence exposure, lifetime depression, and posttraumatic stress disorder (PTSD). Suicide attempts were associated with female gender, age, sexual and physical assault, lifetime substance abuse or dependence, PTSD, and depression. Implications for intervention and prevention are discussed.

Daily stressor sensitivity, abuse effects, and cocaine use in cocaine dependence.

This study highlights respondent sensitivity to daily hassles as it relates to situational cocaine use and perceived long-term effects of adverse events in childhood. Data were drawn from a larger study on stress reactivity in cocaine dependent individuals. Participants (n=104) were cocaine dependent men and women without comorbid posttraumatic stress disorder (PTSD). They completed the Early Trauma Inventory (ETI), the Daily Hassles Scale (DHS), the Inventory of Drug-Taking Situations (IDTS), and the Time-Line Follow-Back (TLFB; for 90 days prior to interview). There were no gender differences in the amount or frequency of cocaine use, although the patterns of use differed between male and female users. Overall, there were some associations in the patterns of cocaine use and sensitivity to daily hassles, particularly the use in response to conflict with others. Early negative life events were positively related to response to daily hassles, but current triggers were more relevant. Reactivity to cocaine cues was related to daily hassle sensitivity among women only. Limitations and implications of the findings are discussed.

Randomized controlled evaluation of an early intervention to prevent post-rape psychopathology.

A randomized between-group design was used to evaluate the efficacy of a video intervention to reduce post-traumatic stress disorder (PTSD) and other mental health problems, implemented prior to the forensic medical examination conducted within 72 h post-sexual assault. Participants were 140 female victims of sexual assault (68 video/72 nonvideo) aged 15 years or older. Assessments were targeted for 6 weeks (Time 1) and 6 months (Time 2) post-assault. At Time 1, the intervention was associated with lower scores on measures of PTSD and depression among women with a prior rape history relative to scores among women with a prior rape history in the standard care condition. At Time 2, depression scores were also lower among those with a prior rape history who were in the video relative to the standard care condition. Small effects indicating higher PTSD and Beck Anxiety Inventory (BAI) scores among women without a prior rape history in the video condition were observed at Time 1. Accelerated longitudinal growth curve analysis indicated a videoxprior rape history interaction for PTSD, yielding four patterns of symptom trajectory over time. Women with a prior rape history in the video condition generally maintained the lowest level of symptoms.

Triggers for cocaine and alcohol use in the presence and absence of posttraumatic stress disorder.

The present study compared high-risk triggers and substance use situations among 72 (34 men, 38 women) individuals with alcohol (AD) or cocaine dependence (CD), with or without comorbid PTSD. Consistent with the self-medication hypothesis, individuals with PTSD reported significantly greater use of substances in response to negative situations, such as unpleasant emotions and physical discomfort, as compared to individuals without PTSD. CD individuals were significantly more likely than AD individuals to report using in temptation situations, regardless of PTSD status. Also, CD individuals with PTSD reported greater use of cocaine during pleasant times with others, as compared to those without PTSD. The findings highlight the importance of addressing individual-specific high-risk situations in relapse prevention.