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.

Effects of Oxytocin Administration on Cue-Induced Craving in Co-occurring Alcohol Use Disorder and PTSD: A Within-Participant Randomized Clinical Trial.

BACKGROUND: Individuals with alcohol use disorder (AUD) are much more likely to meet criteria for posttraumatic stress disorder (PTSD) than the general population. Compared to AUD alone, those with comorbid AUD-PTSD experience worse outcomes. Prior literature suggests that oxytocin, a hypothalamic neuropeptide, may be effective in the treatment of both AUD and PTSD when administered intranasally, although specific mechanisms remain elusive. METHODS: Forty-seven male patients with comorbid AUD-PTSD were administered intranasal oxytocin in a randomized, double-blind, dose-ranging (20 IU, 40 IU, and matched placebo), within-participant design with study visits at least 1 week apart. A cue-induced craving paradigm was conducted using each participant's preferred alcoholic beverage versus a neutral water cue. Self-reported alcohol craving and heart rate (HR) were recorded and analyzed using linear mixed-effect models. RESULTS: While alcohol cues significantly induced self-reported craving and increased HR compared to neutral water cues, neither dosage of oxytocin compared to placebo reduced self-reported cue-induced alcohol craving nor cue-induced changes in HR in patients with PTSD-AUD. CONCLUSIONS: These preliminary findings suggest that oxytocin does not affect cue-induced craving. Our results contribute to an ever-growing field of research investigating the effects of intranasal oxytocin on the symptoms of substance use disorders and will help further refine methodology and streamline future inquiries in this area.

An electronic intervention to improve safety for pain patients co-prescribed chronic opioids and benzodiazepines.

BACKGROUND: Co-prescribing opioids and benzodiazepines increases overdose risk. A paucity of literature exists evaluating strategies to improve safety of co-prescribing. This study evaluated an electronic intervention to improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines at 3 and 6 months. METHODS: A prospective cohort study was conducted from December 2015 through May 2016 at San Francisco Veterans Affairs Health Care System. A clinical dashboard identified 145 eligible patients prescribed chronic opioids and benzodiazepines. Individualized taper and safety recommendations were communicated to prescribers via electronic medical record progress note and encrypted e-mail at baseline. Primary outcome was number of patients co-prescribed chronic opioids and benzodiazepines. Secondary outcomes included daily dose of opioids and benzodiazepines and number prescribed ≥100 mg morphine equivalent daily dose. Safety outcomes included number with opioid overdose education and naloxone distribution, annual urine drug screening, annual prescription drug monitoring program review, and signed opioid informed consent. Linear mixed models and generalized estimating equations were used to examine within-group change in outcomes between baseline and 3 and 6 months. RESULTS: Among the 145 patients, mean (standard deviation) age was 62 (11) years and 91.7% (133/145) were male. Number co-prescribed significantly decreased from 145/145 (100%) at baseline to 93/139 (67%) at 6-month follow-up (odds ratio [OR] = 0.53, 95% confidence interval [CI]: 0.34-0.81, P = .003). Mean opioid and benzodiazepine doses significantly decreased from 84.61 to 65.63 mg (95% CI: 8.32-27.86, P < .001) and from 16.10 to 13.45 mg (95% CI: 1.6-3.9, P < .001), respectively, from baseline to 6-month follow-up. Patients prescribed ≥100 mg morphine equivalent daily dose significantly decreased from 39/145 (26.8%) at baseline to 26/139 (18.7%) at end of study (OR = 0.59, 95% CI: 0.44-0.78, P < .001), and patients with opioid overdose education and naloxone distribution significantly increased from 3/145 (2.1%) at baseline to 46/139 (33.1%; OR = 23.4, 95% CI: 7.61-71.99, P < .001) by the end of study. Number of patients with annual urine drug screening tended to increase from 123/145 (84.8%) at baseline to 132/145 (91.4%) by the end of study (OR = 1.89, 95% CI: 0.95-3.76, P = .07), and there were no significant changes across time in numbers of patients with annual prescription drug monitoring program review or signed opioid informed consent. CONCLUSIONS: Electronic interventions may provide an effective strategy to improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines.

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.

Cognitive-behavioral therapy in depressed primary care patients with co-occurring problematic alcohol use: effect of telephone-administered vs. face-to-face treatment-a secondary analysis.

This secondary analysis of a larger study compared adherence to telephone-administered cognitive-behavioral therapy (T-CBT) vs. face-to-face CBT and depression outcomes in depressed primary care patients with co-occurring problematic alcohol use. To our knowledge, T-CBT has never been directly compared to face-to-face CBT in such a sample of primary care patients. Participants were randomized in a 1:1 ratio to face-to-face CBT or T-CBT for depression. Participants receiving T-CBT (n = 50) and face-to-face CBT (n = 53) were compared at baseline, end of treatment (week 18), and three-month and six-month follow-ups. Face-to-face CBT and T-CBT groups did not significantly differ in age, sex, ethnicity, marital status, educational level, severity of depression, antidepressant use, and total score on the Alcohol Use Disorders Identification Test. Face-to-face CBT and T-CBT groups were similar on all treatment adherence outcomes and depression outcomes at all time points. T-CBT and face-to-face CBT had similar treatment adherence and efficacy for the treatment of depression in depressed primary care patients with co-occurring problematic alcohol use. When targeting patients who might have difficulties in accessing care, primary care clinicians may consider both types of CBT delivery when treating depression in patients with co-occurring problematic alcohol use.

Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis.

BACKGROUND: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). METHODS: Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. RESULTS: Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. CONCLUSIONS: Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.

Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia: a randomized, placebo-controlled pilot trial.

Alcohol and nicotine dependence are common in schizophrenia. Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers. The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia. Outpatients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week, double-blind, randomized, placebo-controlled trial. Alcohol use and smoking were assessed using self-report (Timeline Follow-Back) and biological measures. Adverse events were recorded. Changes in the number of standard drinks per week and cigarettes per week were compared in the 2 groups. Because of safety concerns or loss to follow-up, of 55 patients enrolled, only 10 started study medication, 5 each on varenicline and placebo. Gastrointestinal adverse effects, such as severe abdominal pain, limited study completion to only 4 subjects. Number of standard alcoholic drinks consumed per week decreased by [mean (SD)] 16.6 (20.1) in the varenicline group and by 2.4 (27.4) in the placebo group. Mean (SD) number of cigarettes smoked per week decreased by 66 (65) in the varenicline group and by 47 (77) in the placebo group. Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability (gastrointestinal adverse effects) limiting retention. There was no increased number of serious neuropsychiatric adverse events in the varenicline group. Based on this small sample, concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline.

Team-based learning exercise efficiently teaches brief intervention skills to medicine residents.

BACKGROUND: Evaluations of substance use screening and brief intervention (SBI) curricula typically focus on learner attitudes and knowledge, although effects on clinical skills are of greater interest and utility. Moreover, these curricula often require large amounts of training time and teaching resources. This study examined whether a 3-hour SBI curriculum for internal medicine residents utilizing a team-based learning (TBL) format is effective for SBI skills as measured by a standardized patient (SP) assessment. METHODS: A waitlist-controlled design was employed. RESULTS: Twenty-four postgraduate year 2 (PGY-2) and PGY-3 residents participated in a SP assessment prior to the TBL session (waitlist control group) and 32 participated in a SP assessment after the TBL session (intervention group). The intervention residents demonstrated better brief intervention skills than waitlist control residents, but there were no differences between the groups in screening and assessment skills. Residents receiving the TBL curriculum prior to the SP assessment reported increased confidence in all SBI skills. CONCLUSION: Findings indicate that a brief educational intervention can improve brief intervention skills. However, more intensive education may be needed to improve substance use screening and assessment.

Effects of buprenorphine on opioid craving in comparison to other medications for opioid use disorder: A systematic review of randomized controlled trials.

BACKGROUND: Craving is a distressing symptom of opioid use disorder (OUD) that can be alleviated with medications for OUD (MOUD). Buprenorphine is an effective MOUD that may suppress craving; however, treatment discontinuation and resumed opioid use is common during the early phases of treatment. More information on the craving response through the high-risk period of initiating buprenorphine may provide meaningful information on how to better target craving, which in turn may enhance outcomes. This systematic review investigated buprenorphine doses and formulations on craving during the induction and maintenance phases of treatment, and for context also compared the craving response to other MOUD (i.e., methadone, extended-release naltrexone [XR-NTX]). METHODS: PubMed, PsycInfo, Embase, and Cochrane Central databases were searched for randomized trials of buprenorphine versus placebo, various buprenorphine formulations/doses, or other MOUD that included a measure of opioid craving. RESULTS: A total of 10 studies were selected for inclusion. Buprenorphine and buprenorphine/naloxone (BUP/NAL) were each associated with lower craving than placebo over time. Craving was greater among those prescribed lower versus higher buprenorphine doses. In comparison to other MOUD, buprenorphine or BUP/NAL was linked to greater craving than methadone in 3 of the 6 studies. BUP/NAL was associated with greater reported craving than XR-NTX. DISCUSSION: Craving is reduced over time with buprenorphine and BUP/NAL, although other MOUD may provide greater reductions in craving. Although there is currently considerable variability in the measurement of craving, it may be a valuable concept to address with individuals receiving MOUD, especially early in treatment.

N-acetylcysteine for smoking cessation among dual users of tobacco and cannabis: Protocol and rationale for a randomized controlled trial.

BACKGROUND: Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared environmental cues reinforcing use may make tobacco smoking cessation more difficult. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's potential efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. To date, no RCT has examined NAC for smoking cessation among dual users of tobacco and cannabis. METHOD: In a double-blind, placebo-controlled RCT, we will examine NAC for smoking cessation among dual users of tobacco and cannabis. Sixty adult cigarette-cannabis co-users are randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups receive 8 weekly cognitive behavioral therapy sessions addressing smoking cessation and cannabis reduction. Outcomes are assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette craving, nicotine dependence, and use; and cannabis craving and use. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes. CONCLUSION: Results will inform smoking cessation treatment among dual users of tobacco and cannabis. CLINICALTRIALS: gov Identifier: NCT04627922.

Using standardized patients to evaluate screening, brief intervention, and referral to treatment (SBIRT) knowledge and skill acquisition for internal medicine residents.

Comprehensive clinical competency curricula for hazardous drinking and substance use disorders (SUDs) exists for medical students, residents, and practicing health care providers. Evaluations of these curricula typically focus on learner attitudes and knowledge, although changes in clinical skills are of greater interest and utility. The authors present a pre-post clinical skill evaluation of a 10-hour screening, brief intervention, and referral to treatment (SBIRT) curriculum for hazardous drinking and SUDs for primary care internal medicine residents using standardized patient examinations to better determine the impact of SBIRT training on clinical practice. Residents had large improvements in history taking, substance use screening skills, SUD assessment and diagnostic skills, and in SBIRT knowledge, including documentation, systems, and diversity issues. Residents made moderate improvements in brief intervention skills. Future SBIRT curricular evaluations would ideally include a controlled comparison with larger samples from multiple institutions.

The Impact of Exercise and Virtual Reality Executive Function Training on Cognition Among Heavy Drinking Veterans With Traumatic Brain Injury: A Pilot Feasibility Study.

Executive function (EF) underlies self-control deficits in alcohol use disorder (AUD) and traumatic brain injury (TBI). Cognitive training is a promising adjunctive treatment targeting TBI- and AUD- related cognitive dysfunction. However, major limitations related to compliance and generalizability in the field of cognitive training exist. Physical activity is associated with enhanced cognitive performance across several executive functions and may enhance the benefits of cognitive training. Virtual reality provides multisensory embodied experiences which are likely to engage brain networks more efficiently than standard cognitive training systems, ultimately resulting in greater near- and far-transfer effects. This pilot study aimed to obtain feasibility data and a preliminary assessment of an enriched virtual reality (VR) EF training (EFT) intervention combined with exercise (NCT03786276). Using an 8-week randomized adaptive design study, 30 AUD treatment seeking U.S. Veterans completed nine sessions of exercise-only (n = 15) or gameplay control (n = 15) over 3 weeks, followed by a week-4 repeat assessment in Phase 1. Twenty-three participants completed and moved onto Phase II, where they completed up to nine sessions of VR-EFT plus exercise and completed a week-8 end-of-study assessment. Primary outcomes included feasibility to retain participants, usability, and satisfaction of using VR-EFT. Secondary and exploratory outcomes included within group assessment of change in cognitive function, alcohol use, alcohol craving, and post-concussive symptoms among the three treatment conditions.VR-EFT was feasible with moderate usability and high acceptability ratings.The most common VR-related adverse effect was motion sickness (n = 2/16, 12.5%). The VR-EFT condition was associated with significant improvement in inhibition-switching and visual scanning (both p < 0.05) during Phase II. Exercise-only was associated with significant improvements in cognitive inhibition, cognitive flexibility, reductions in alcohol craving, and number of standard alcohol drinks per week (all p ≤ 0.05). The gaming-control condition was associated with improvement in cognitive flexibility and visuospatial immediate recall (both p < 0.05) during Phase 1. Recruitment and retention of U.S. veterans with AUD and TBI into an exercise plus VR-EFT intervention is feasible, but technological barriers may impact usability. VR-EFT was associated with improvement in executive function domains that were targeted in as little as 3-week and nine sessions of VR-EFT exposure. Results are promising and indicate the need for a larger controlled investigation to assess the efficacy of VR-EFT to enhance treatment outcomes among AUD treatment-seeking U.S. veterans with co-occurring AUD and TBI. Clinical Trial Registration: www.ClinicalTrials.gov, Identifier: NCT03786276.

Impact of Alcohol Use, Traumatic Stress, and Cigarette Smoking on Cognitive Functioning in Veterans With Co-occurring Alcohol Use Disorder and Posttraumatic Stress Disorder.

INTRODUCTION: Alcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD. MATERIALS AND METHODS: U.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition. RESULTS: Smoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers. CONCLUSIONS: Overall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers.

Psychiatric and substance use disorders among methadone maintenance patients with chronic hepatitis C infection: effects on eligibility for hepatitis C treatment.

We set out to describe the prevalence and severity of psychiatric and substance use disorders (SUDs) in methadone maintenance treatment (MMT) patients with chronic hepatitis C virus (HCV) infection and to measure the impact on HCV-treatment eligibility. Psychiatric disorders, SUDs, and HCV-treatment eligibility were assessed in 111 MMT patients prior to a controlled trial of HCV treatment. Lifetime and current diagnosis rates, respectively, were: any non-SUD Axis I disorder: 82% and 57%, any mood disorder: 67% and 35%, any anxiety disorder: 63% and 22%, any psychotic disorder: 11% and 9%. Antisocial personality disorder was present in 40%. A total of 56% met criteria for current SUDs. A total of 66% received psychiatric medications prior to HCV treatment; over half were receiving antidepressants. Despite psychiatric and substance use comorbidity, only 15% of patients were ineligible for HCV treatment: 10% due to failure to complete the evaluation, and 5% due to psychiatric severity. Substance use did not lead to ineligibility in any participant. Multiple logistic regression showed the Beck Depression Inventory contributed significantly to predicting HCV treatment eligibility. Most MMT patients were eligible [corrected] for HCV treatment despite current SUD and non-SUD diagnoses. Depression severity may be a more significant predictor of HCV treatment eligibility than is substance use.

Predictors of smoking severity in patients with schizophrenia and alcohol use disorders.

The goal of the present study was to identify predictors of smoking severity in patients with schizophrenia and co-occurring alcohol use disorders (AUD). Our hypothesis was that negative symptoms of schizophrenia, severity of depression, male gender, drinking severity, and recreational drug use were associated with increased smoking. Clinical data, including demographic variables, alcohol and substance use severity, psychiatric medications, severity of depression, positive and negative symptoms of schizophrenia were analyzed in a cohort of 90 patients with schizophrenia or schizoaffective disorder and AUD. Eighty-eight percent of participants were smokers, they smoked an average of 15 cigarettes/day. Zero-inflated negative binomial (ZINB) regression analyses demonstrated that alcohol use severity, gender, and severity of negative symptoms were not predictive of the number of cigarettes smoked. Smoking severity was positively related to Caucasian race, psychosis severity (Positive and Negative Syndrome Scale [PANSS] general score), and medications (conventional antipsychotics). Subjects who used recreational drugs smoked less. In summary, severe, treatment resistant schizophrenia, and conventional antipsychotic treatment is associated with heavy smoking in patients with schizophrenia and AUD regardless of gender or alcohol use.

Working memory and alcohol demand relationships differ according to PTSD symptom severity among veterans with AUD.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid with complex and often unclear associations. Working memory deficits may represent a shared mechanism implicated in emotion regulation and control over impulsive alcohol use. Here we test whether PTSD symptoms and working memory correlated with performance on a behavioral economic assessment of alcohol demand. 113 veterans (mean age 51 years; 89% male) completed an Alcohol Purchase Task (APT) and were assessed for PTSD, alcohol use, and working memory. We examined the interaction of PTSD symptoms and working memory on four indices of alcohol demand measured from the APT; specifically, we used separate models to test whether associations between working memory and intensity (consumption at $0), Omax (maximum expenditure), Pmax (price at maximum expenditure), and elasticity (price sensitivity), differed as a function of PTSD symptoms. In a model controlling for hazardous drinking, average drinking levels, age, sex, marital status, occupation, and education, we observed a significant interaction between PTSD symptoms and working memory on elasticity, whereby greater working memory capacity was associated with greater elasticity for veterans with lower PTSD symptoms. Follow-up analyses regarding specific PTSD symptom domains indicated that this effect was strongest for avoidance symptoms. Taken together, working memory abilities correlated with subjective valuations of alcohol in a laboratory setting for veterans with less severe PTSD symptoms. This work highlights the conditions under which working memory may be a potential target for interventions geared toward reducing alcohol use in veterans with co-occurring PTSD and AUD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial.

The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.

Pilot study of extended-release lorcaserin for cocaine use disorder among men who have sex with men: A double-blind, placebo-controlled randomized trial.

OBJECTIVE: To determine if men who have sex with men (MSM) with cocaine use disorder (CUD) and actively-using cocaine could be enrolled and retained in a pharmacologic intervention trial of lorcaserin-a novel 5-HT2cR agonist-and determine the degree to which participants would adhere to study procedures. METHODS: This was a phase II randomized, double-blind, placebo-controlled pilot study with 2:1 random parallel group assignment to daily extended-release oral lorcaserin 20 mg versus placebo (clinicaltrials.gov identifier-NCT03192995). Twenty-two of a planned 45 cisgender MSM with CUD were enrolled and had weekly follow-up visits during a 12-week treatment period, with substance use counseling, urine specimen collection, and completion of audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps and self-report. This study was terminated early because of an FDA safety alert for lorcaserin's long-term use. RESULTS: Eighty-six percent completed the trial, with 82% of weekly study follow-up visits completed. Adherence was 55.3% (lorcaserin 51.6% vs. placebo 66.2%) by MEMS cap and 56.9% (56.5% vs. placebo 57.9%) by self-report and did not differ significantly by treatment assignment. Intention-to-treat analyses (ITT) did not show differences in cocaine positivity by urine screen between the lorcaserin and placebo groups by 12 week follow-up (incidence risk ratio [IRR]: 0.96; 95%CI = 0.24-3.82, P = 0.95). However, self-reported cocaine use in timeline follow-back declined more significantly in the lorcaserin group compared to placebo (IRR: 0.66; 95%CI = 0.49-0.88; P = 0.004). CONCLUSION: We found that it is feasible, acceptable, and tolerable to conduct a placebo-controlled pharmacologic trial for MSM with CUD who are actively using cocaine. Lorcaserin was not associated with significant reductions in cocaine use by urine testing, but was associated with significant reductions in self-reported cocaine use. Future research may be needed to continue to explore the potential utility of 5-HT2cR agonists.

Pharmacological approaches to methamphetamine dependence: a focused review.

Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.