Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial.

Importance: Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment. Objective: To determine whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing vs usual care. Participants included 676 clinicians and 1944 patients. Participants were enrolled from 22 Department of Veterans Affairs medical centers from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were those with MDD who were initiating or switching treatment with a single antidepressant. Exclusion criteria included an active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications. Interventions: Results from a commercial pharmacogenomic test were given to clinicians in the pharmacogenomic-guided group (n = 966). The comparison group received usual care and access to pharmacogenomic results after 24 weeks (n = 978). Main Outcomes and Measures: The co-primary outcomes were the proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization and remission of depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) (remission was defined as PHQ-9 ≤ 5). Remission was analyzed as a repeated measure across 24 weeks by blinded raters. Results: Among 1944 patients who were randomized (mean age, 48 years; 491 women [25%]), 1541 (79%) completed the 24-week assessment. The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7% compared with 25.7%, 54.6%, and 19.7% in the usual care group. The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47 to 5.39]; P < .001) and no/moderate vs substantial interaction (OR, 2.08 [95% CI, 1.52 to 2.84]; P = .005) (P < .001 for overall comparison). Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care (OR, 1.28 [95% CI, 1.05 to 1.57]; P = .02; risk difference, 2.8% [95% CI, 0.6% to 5.1%]) but were not significantly higher at week 24 when 130 patients in the pharmacogenomic-guided group and 126 patients in the usual care group were in remission (estimated risk difference, 1.5% [95% CI, -2.4% to 5.3%]; P = .45). Conclusions and Relevance: Among patients with MDD, provision of pharmacogenomic testing for drug-gene interactions reduced prescription of medications with predicted drug-gene interactions compared with usual care. Provision of test results had small nonpersistent effects on symptom remission. Trial Registration: ClinicalTrials.gov Identifier: NCT03170362.

Depression in Female Veterans Returning from Deployment: The Role of Social Factors.

Objective: Women are serving in the armed forces and deployed to areas of conflict in increasing numbers. Problems such as depressive symptoms and risks related to combat exposure can have negative effects on adjustment following service; understanding the relationship between these problems may contribute to strategies providers can use to facilitate healthy adjustment after deployment. The purpose of this study is to examine social factors as they relate to mental health adjustment, namely depressive symptoms among female veterans who served in Iraq and Afghanistan as part of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OND). We hypothesized that combat exposure would predict higher levels of depressive symptoms and that social support would moderate the relationship between combat exposure and depression. Methods: In a cross-sectional design, 128 female Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans completed an online survey about combat experience, social support, depression, demographic characteristics, and behavioral health symptom history. We conducted multiple regression analyses to examine linear and moderating relationships. Results: There was no significant relationship between combat exposure and depression; social support did not significantly moderate the relationship between combat exposure and depression. However, higher levels of social support and financial comfort were significantly related to lower levels of depression. Conclusion: This study highlights the role of social factors, specifically social support and perceived financial status, as potential barriers to healthy emotional readjustment following deployment. These findings suggest that it may be beneficial for mental health providers to screen female veterans and refer them to appropriate services to reduce financial stressors and strengthen their use of social support. More research should continue to examine more fully the impact of combat exposure on female service members' mental health and work to isolate the factors most strongly related to depression.

Telephone-based management of chronic pain in older adults in an integrated care program.

OBJECTIVE: Few studies have explored behavioral strategies for managing chronic pain in older adults. Pain Care Management (PCM) is a telephone-based behavioral intervention for chronic pain. The present study examined chronic pain characteristics among older adults and tested the delivery of PCM as an adjunct to depression and anxiety care management. METHODS: Participants were drawn from a state-sponsored program offering care management services to community members aged 65 and older who were prescribed a psychotropic medication by a primary care provider. Chronic pain information was collected for all participants in the state program (N = 250) and treatment outcome data were collected for a subset with significant chronic pain. Eighty participants with high chronic pain interference were offered PCM and compared to 80 participants with chronic pain who received monitoring only on depression, anxiety, and pain interference outcomes. RESULTS: Chronic pain was identified in 14% of older adults newly prescribed a psychotropic medication. Compared to monitoring only, PCM participants had higher odds of seeing a reduction of 2 or more points in pain interference at 6 months. Pain care management participants' anxiety scores significantly decreased over the study period. CONCLUSIONS: Older adults treated with psychotropic medications often also experience chronic pain that interferes with daily activities. A telephone-based care management intervention is acceptable and feasible with an older community-based population and can lead to improvements in anxiety symptoms and interference from chronic pain. Further research will help to refine interventions that may help improve symptoms and increase functioning with this population.

The impact of service-connected disability and therapist experience on outcomes from prolonged exposure therapy with veterans.

OBJECTIVE: Although prolonged exposure therapy (PE) has been shown to be effective in treating posttraumatic stress disorder (PTSD), a sizable minority do not benefit. Examining patient and therapist characteristics that impact treatment outcome may improve treatment delivery and identify individuals who are less likely to respond to treatment or are at risk to prematurely discontinue treatment. The current study uses a sample from a large urban Veterans' Affairs (VA) hospital to build on a previous report that identified correlates of treatment outcome for Veterans who received PE. METHOD: Two hundred eighty-seven veterans completed measures of PTSD, depression, and quality of life at the beginning and end of treatment. Veterans' service-connected disability rating, therapist experience, benzodiazepine prescription, and traumatic brain injury diagnosis were investigated as predictors of treatment outcome in linear regression analyses. RESULTS: Results showed that Veterans with a service-connected disability for a mental health condition had smaller treatment gains than those without service connection (p < .01). Additionally, results showed that patients treated by certified PE therapists had larger treatment gains than those treated by noncertified PE therapists (p < .01). Finally, younger age and therapist certification were associated with dropout from treatment (p < .05). CONCLUSION: Veterans treated by PE-certified therapists and Veterans who were not service-connected for a mental health condition fared better in treatment. Results suggest that additional study of both the national effort to train VA clinicians in PE and the impact of service connection on PTSD treatment outcome may be helpful for future research. (PsycINFO Database Record

Reductions in Alcohol Craving Following Naltrexone Treatment for Heavy Drinking.

AIMS: The role of craving for alcohol as a response to alcohol treatment is not well understood. We examined daily diary ratings of craving over the course of 28 days among individuals participating in an inpatient substance abuse treatment program. METHODS: Participants were alcohol dependent patients (n = 100) in the Hazelden residential treatment program who were offered and agreed to take naltrexone and an age- and gender-matched comparison group (n = 100) of alcohol-dependent patients in the same program who declined the offer of treatment with naltrexone. Changes in craving over time were compared between the two groups. RESULTS: The naltrexone-treated group reported a more rapid decrease in craving than the usual care group. CONCLUSIONS: The change in the trajectory of craving is consistent with prior reports suggesting that craving reduction is a mechanism of naltrexone's efficacy in treating alcohol dependence. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in their craving, consistent with a primary target of many addiction treatment programs. SHORT SUMMARY: Craving ratings by 100 residential patients taking naltrexone for alcohol dependence were compared to ratings by 100 patients who did not take naltrexone. Craving for alcohol decreased more rapidly in the patients taking naltrexone. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in craving, which may benefit treatment efforts.

The Moderating Role of Perceived Social Support on Alcohol Treatment Outcomes.

OBJECTIVE: This study examined the extent to which perceived social support is related to longitudinal treatment outcomes among heavy drinkers randomized to a brief, telephone-based care management intervention versus standard care. METHOD: This is a secondary analysis of data from a randomized trial comparing an enhanced, brief alcohol intervention to standard care. Participants comprised 136 male, heavy drinkers (mean age = 57.3 years) receiving primary care at Corporal Michael J. Crescenz Veterans Affairs Medical Center clinics. Participants in the intervention arm received a telephone-based care management intervention focused on helping patients reduce their alcohol use. Primary measures included the Timeline Followback method for number of heavy drinking days and the Multidimensional Scale of Perceived Social Support for self-reported baseline social support. RESULTS: Although there was no significant main effect for baseline perceived social support on number of heavy drinking days over time, there was a significant three-way interaction (Perceived Social Support × Randomization Group × Time). Specifically, among patients reporting high support, those randomized to the intervention arm experienced significantly greater declines in number of heavy drinking days over time. Conversely, among patients reporting low support, those randomized to standard care experienced more improvement over the course of followup. CONCLUSIONS: Perceived social support may be related to differential outcomes depending on whether patients are in care management or standard care. For those receiving brief intervention, certain therapy techniques may mobilize pre-existing social resources and/or enhance the ability for patients to use their social supports, suggesting the need for replication and further research in understanding this interaction.

Outcomes of Prolonged Exposure therapy for veterans with posttraumatic stress disorder.

Prolonged Exposure (PE) is an evidenced-based psychotherapy for posttraumatic stress disorder (PTSD) that is being disseminated nationally within the U.S. Department of Veterans Affairs (VA) with promising initial results. Empirical evidence, however, regarding the effectiveness of PE for treatment of PTSD in military veterans is limited. Building on previous treatment outcome research, the current study investigated the effectiveness of PE in a diverse veteran sample. One-hundred fifteen veterans were enrolled in PE at an urban VA medical center and its surrounding outpatient clinics. PTSD and depression symptoms as well as quality of life were measured before and after treatment. Several baseline patient characteristics were examined as predictors of treatment response. Eighty-four participants completed treatment. Participants experienced a 42% reduction in PTSD symptoms, a 31% reduction in depression symptoms, and an increase in quality of life following PE. Veterans not prescribed psychotropic medication reported greater PTSD symptom reduction than veterans prescribed such medication. The implications of these results for treatment programs targeting PTSD in veterans are discussed.

Subsyndromal posttraumatic stress disorder symptomatology in primary care military veterans: treatment implications.

Subsyndromal posttraumatic stress disorder (PTSD) is highly prevalent in Veterans Affairs Medical Centers' primary-care clinics and is associated with significant impairment. We used a cross-sectional design to examine PTSD symptoms and depressive disorders endorsed by two cohorts of Veterans meeting less than full PTSD criteria who presented to primary care at the Philadelphia VA Medical Center (i.e., those from Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) and non-OEF/OIF/OND Veterans). The Philadelphia VA Behavioral Health Lab (BHL) assessed 141 Veterans who screened positive for subsyndromal PTSD. Avoidance was endorsed significantly less often than arousal in the total group. When the groups were split by cohort era, higher levels of avoidance and lower levels of arousal were reported in the non-OEF/OIF/OND group than the OEF/OIF/OND group. Comorbid depression was present in 43.9% of the total group with no significant differences between groups. Exposure-based treatments for PTSD offered in specialty mental health clinics target avoidance symptoms. Because the endorsement of avoidance symptoms was low in both of the cohorts that were studied this may not be the most effective treatment target for Veterans with subsyndromal PTSD receiving treatment in primary care settings. For these Veterans, treatments that target reexperiencing and arousal symptoms and/or comorbid depression may be more effective.

Treatment of posttraumatic stress disorder in U.S. combat veterans: a meta-analytic review.

Among U.S. veterans who have been exposed to combat-related trauma, significantly elevated rates of posttraumatic stress disorder (PTSD) are reported. Veterans with PTSD are treated for the disorder at Veterans Affairs (VA) hospitals through a variety of psychotherapeutic interventions. Given the significant impairment associated with PTSD, it is imperative to assess the typical treatment response associated with these interventions. 24 studies with a total sample size of 1742 participants were quantitatively reviewed. Overall, analyses showed a medium between-groups effect size for active treatments compared to control conditions. Thus, the average VA-treated patient fared better than 66% of patients in control conditions. VA treatments incorporating exposure-based interventions showed the highest within-group effect size. Effect sizes were not moderated by treatment dose, sample size, or publication year. Findings are encouraging for treatment seekers for combat-related PTSD in VA settings.

Implications of participant self-selection for generalizability: who participates in smoking laboratory research?

The generalizability of data from laboratory smoking studies using volunteer samples is debatable. We tracked potential participants from first contact with research staff through screening to study completion. We found that a minority of individuals were ultimately enrolled in the study. Failure to enroll was as often a function of participant lack of attendance at the laboratory as a function of ineligibility. With some exceptions, groups of potential participants were similar regarding demographic characteristics and substance use history. These findings support the generalizability of the sample and highlight the importance of documenting details of study eligibility and participation. The study's limitations are noted.

Motivational enhancement therapy for high-risk adolescent smokers.

The majority of regular adult smokers begin smoking in adolescence and there is a clear need for youth-targeted smoking cessation interventions. The present randomized, controlled trial tested the effectiveness of motivational enhancement therapy (MET) to reduce smoking among 81 adjudicated adolescents. Participants received either MET or an education control. Smoking abstinence, quantity, and frequency were assessed at 1 and 6 months post treatment. Results suggest that although between-group differences on outcome measures were not significant at follow-up, smoking behavior decreased in both groups with approximately 10% achieving 1-month smoking abstinence at 6-month follow-up. Furthermore, participant response to MET varied by level of alcohol use and impulsivity such that participants with lower levels of alcohol use and impulsivity had significantly greater response to MET. In contrast, participants who endorsed higher rates of alcohol use and impulsivity responded better to the control than the MET condition. Results suggest that MET may be an effective intervention for some adolescent smokers but may be contraindicated for adolescents who have concomitant problems with alcohol use or impulsivity.

Smoking cessation and alcohol abstinence: what do the data tell us?

Cigarette smoking and nicotine dependence commonly co-occur with alcohol dependence. However, treatment for tobacco dependence is not routinely included in alcohol treatment programs, largely because of concerns that addressing both addictions concurrently would be too difficult for patients and would adversely affect recovery from alcoholism. To the contrary, research shows that smoking cessation does not disrupt alcohol abstinence and may actually enhance the likelihood of longer-term sobriety. Smokers in alcohol treatment or recovery face particular challenges regarding smoking cessation. Researchers and clinicians should take these circumstances into account when determining how best to treat these patients' tobacco dependence.

A psychometric evaluation of the Smoking Consequences Questionnaire-Adult in smokers with psychiatric conditions.

Rates of smoking among individuals with psychiatric conditions are much greater than those seen in the general population, yet little is known about the psychometric properties of commonly used instruments that assess smoking-related variables among smokers with psychiatric conditions. The present study examined the factor structure and psychometric characteristics of the Smoking Consequences Questionnaire-Adult (SCQ-A; Copeland, Brandon, & Quinn, 1995, Psychological Assessment, 7, 484-494) among smokers with psychiatric conditions. A confirmatory factor analysis of the instrument indicated that the factor structure derived by the instrument's authors provided an adequate fit to the data. In addition, many of the 10 subscales of the SCQ-A demonstrated adequate internal consistency as assessed by Cronbach's alpha as well as adequate test-retest reliability over the course of 1 week. Based on the data derived from this sample, the SCQ-A has adequate psychometric properties for applications involving smokers with psychiatric conditions.

Tobacco and alcohol use as an explanation for the association between externalizing behavior and illicit drug use among delinquent adolescents.

The prevalence and persistence of adolescent substance use and abuse is a national health issue, and substance use among adolescents is frequently comorbid with other psychiatric disorders. Most studies in this area utilize samples of middle or high school students or from inpatient settings. Less is known about substance use and psychiatric comorbidity among delinquent adolescents. The present study examined data from two cohorts of juvenile offenders collected over a 2-year period (n = 245, n = 299). Participants reported frequency of cigarette, alcohol, marijuana, and other substance use. Participants' parents completed a measure of behavior problems. Path analyses suggested that parental reports of externalizing problems were significantly related to self-reported substance use while parental reports of internalizing problems were not. Results also suggested that smoking and alcohol use act as mediators between externalizing problems and marijuana and other drug use. Although there were some mean differences by gender, the pattern of relationships amongst the variables did not differ by gender. Implications of the findings and future directions are discussed.