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.

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.

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.

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.