Extended-release buprenorphine in pregnancy.

BACKGROUND AND OBJECTIVES: The relative safety and efficacy of monthly extended-release buprenorphine (XR-BUP) has not been fully evaluated in pregnant persons. METHODS: Case report of two pregnant individuals receiving XR-BUP while pregnant. RESULTS: Both patients had positive experiences and healthy infants. DISCUSSION AND CONCLUSIONS: Sparse data regarding the use of XR-BUP in pregnant patients limits shared decision-making. Additional evidence will support the growing population of pregnant patients exposed to XR-BUP. SCIENTIFIC SIGNIFICANCE: Positive patient experiences using XR-BUP during pregnancy have been previously unreported. This report will contribute to discussions of risks and benefits for future patients using XR-BUP during pregnancy.

Association between psychosocial factors and co-morbid cigarette smoking and alcohol use in a population experiencing homelessness.

The prevalence of combustible cigarette smoking in populations experiencing homelessness in the United States is five times that of the general population. The psychosocial well-being of persons who smoke and experience homelessness is poorer if such persons also use alcohol heavily. The PTQ2 study was a randomized clinical trial among persons experiencing homelessness who were also current smokers and heavy alcohol consumers. Secondary data analysis of the PTQ2 baseline data was conducted to examine associations among psychosocial variables (anxiety, depression, hopelessness, social network size), heaviness of smoking (cigarettes/day) and alcohol consumption (drinking days/month), and duration and frequency of homelessness. Among the 420 participants, the majority were male (75%), black (70%) and non-Hispanic (94%) with a mean age of 46.6 years (SD = 11.6).  Bivariate analyses show that heaviness of smoking was positively correlated with social network size (r = 0.16, p = .001). Heaviness of drinking was positively correlated with the MINI anxiety score (r = 0.13, p = .009) and marijuana use (median total number of drinks in past 30 days among those who used marijuana in past 30 days vs. did not use: 50 vs. 24, p < .0001), and associated with frequency of homelessness (median total number of drinks in past 30 days among those experiencing homelessness once vs. >1 time: 30 vs. 44, p = .022). The findings highlight the psychosocial factors that warrant consideration when addressing heavy smoking and alcohol consumption in persons experiencing homelessness.

Resting State Hypoconnectivity of Reward Networks in Binge Eating Disorder.

The clinical presentation of binge eating disorder (BED) and data emerging from task-based functional neuroimaging research suggests that this disorder may be associated with alterations in reward processing. However, there is a dearth of research investigating the functional organization of brain networks that mediate reward in BED. To address this gap, 27 adults with BED and 21 weight-matched healthy controls (WMC) completed a multimodel assessment consisting of a resting functional magnetic resonance imaging scan, behavioral tasks measuring reward-based decision-making (i.e., delay discounting and reversal learning), and self-report assessing clinical symptoms. A seed-based approach was employed to examine the resting state functional connectivity (rsFC) of the striatum (nucleus accumbens [NAcc] and ventral and dorsal caudate), a collection of regions implicated in reward processing. Compared with WMC, the BED group exhibited lower rsFC of striatal seeds, with frontal regions mediating executive functioning (e.g., superior frontal gyrus [SFG]) and posterior, parietal, and temporal regions implicated in emotional processing. Lower NAcc-SFG rsFC was associated with more difficulties with reversal learning and binge eating frequency in the BED group. Results suggest that hypoconnectivity of striatal networks that integrate self-regulation and reward processing may promote the clinical phenomenology of BED. Interventions for BED may benefit from targeting these circuit-based disturbances.

The relationship between the INTERMED patient complexity instrument and Level of Care Utilisation System (LOCUS).

OBJECTIVE: To investigate the concurrent and criterion validity of two independently developed measurement instruments, INTERMED and LOCUS, designed to improve the treatment and clinical management of patients with complex symptom manifestations. METHODS: Participants (N = 66) were selected from hospital records based on the complexity of presenting symptoms, with tripartite diagnoses across biological, psychiatric and addiction domains. Biopsychosocial information from hospital records were submitted to INTERMED and LOCUS grids. In addition, Global Assessment of Functioning (GAF) ratings were gathered for statistical analyses. RESULTS: The product moment correlation between INTERMED and LOCUS was 0.609 (p = .01). Inverse zero-order correlations for INTERMED and LOCUS total score and GAF were obtained. However, only the beta weight for LOCUS and GAF was significant. An exploratory principal components analysis further illuminated areas of convergence between the instruments. CONCLUSIONS: INTERMED and LOCUS demonstrated shared variance. INTERMED appeared more sensitive to complex medical conditions and severe physiological reactions, whereas LOCUS findings are more strongly related to psychiatric symptoms. Implications are discussed.

Pilot study of the effects of lisdexamfetamine on cocaine use: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Amphetamine analogs have been demonstrated to have some efficacy in reducing use in cocaine dependent individuals. However, these agents also have potential for abuse. Lisdexamfetamine (LDX), a lysine+dextroamphetamine formulation, has been approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and as a prodrug, has less abuse potential. OBJECTIVE: This pilot study sought to evaluate the safety, tolerability, and efficacy of LDX as a candidate treatment for cocaine dependence. METHODS: A randomized, double-blind, placebo-controlled parallel group study served to evaluate LDX in 43 cocaine-dependent individuals: (1) placebo (PBO; 0mg, n=21), (2) LDX (70mg, n=22). Participants received medication for 14 weeks. Cocaine use was determined based on urine analysis for benzoylecgonine (BE; a cocaine metabolite). RESULTS: Retention rates were higher though not significantly different in the PBO (71.4%) than the LDX condition (57.1%). Compared to those in the PBO condition, those receiving LDX were more likely to report experiencing (ps<0.05) diarrhea (45.5% vs. 14.3%), headaches (45.5% vs. 9.5%), and anxiety (31.8% vs. 4.8%). No differences in medication conditions were observed for blood pressure, heart rate, or body weight. In the randomized sample, no differences in cocaine use were seen. Those receiving LDX reported significantly less craving for cocaine than participants receiving PBO. CONCLUSIONS: LDX did not significantly reduce cocaine use compared to PBO in the randomized sample.

Extended-Release Mixed Amphetamine Salts vs Placebo for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cocaine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Adult attention-deficit/hyperactivity disorder (ADHD) is prevalent but often unrecognized, in part because it tends to co-occur with other disorders such as substance use disorders. Cocaine use disorder is one such disorder with high co-occurrence of ADHD. OBJECTIVE: To examine whether treatment of co-occurring ADHD and cocaine use disorder with extended-release mixed amphetamine salts is effective at both improving ADHD symptoms and reducing cocaine use. DESIGN, SETTING, AND PARTICIPANTS: Thirteen-week, randomized, double-blind, 3-arm, placebo-controlled trial of participants meeting DSM-IV-TR criteria for both ADHD and cocaine use disorder conducted between December 1, 2007, and April 15, 2013, at 2 academic health center substance abuse treatment research sites. One hundred twenty-six adults diagnosed as having comorbid ADHD and cocaine use disorder were randomized to extended-release mixed amphetamine salts or placebo. Analysis was by intent-to-treat population. INTERVENTIONS: Participants received extended-release mixed amphetamine salts (60 or 80 mg) or placebo daily for 13 weeks and participated in weekly individual cognitive behavioral therapy. MAIN OUTCOMES AND MEASURES: For ADHD, percentage of participants achieving at least a 30% reduction in ADHD symptom severity, measured by the Adult ADHD Investigator Symptom Rating Scale; for cocaine use, cocaine-negative weeks (by self-report of no cocaine use and weekly benzoylecgonine urine screens) during maintenance medication (weeks 2-13) and percentage of participants achieving abstinence for the last 3 weeks. RESULTS: More patients achieved at least a 30% reduction in ADHD symptom severity in the medication groups (60 mg: 30 of 40 participants [75.0%]; odds ratio [OR] = 5.23; 95% CI, 1.98-13.85; P < .001; and 80 mg: 25 of 43 participants [58.1%]; OR = 2.27; 95% CI, 0.94-5.49; P = .07) compared with placebo (17 of 43 participants [39.5%]). The odds of a cocaine-negative week were higher in the 80-mg group (OR = 5.46; 95% CI, 2.25-13.27; P < .001) and 60-mg group (OR = 2.92; 95% CI, 1.15-7.42; P = .02) compared with placebo. Rates of continuous abstinence in the last 3 weeks were greater for the medication groups than the placebo group: 30.2% for the 80-mg group (OR = 11.87; 95% CI, 2.25-62.62; P = .004) and 17.5% for the 60-mg group (OR = 5.85; 95% CI, 1.04-33.04; P = .04) vs 7.0% for placebo. CONCLUSIONS AND RELEVANCE: Extended-release mixed amphetamine salts in robust doses along with cognitive behavioral therapy are effective for treatment of co-occurring ADHD and cocaine use disorder, both improving ADHD symptoms and reducing cocaine use. The data suggest the importance of screening and treatment of ADHD in adults presenting with cocaine use disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00553319.

Using the INTERMED complexity instrument for a retrospective analysis of patients presenting with medical illness, substance use disorder, and other psychiatric illnesses.

BACKGROUND: The financial and treatment challenges of complex patients must be addressed with adequate assessment and evaluation. The INTERMED complexity instrument (INTERMED) has been developed for this purpose, but to date has not been used retrospectively. The current study represents a retrospective validity investigation of INTERMED with patients with substance use disorder comorbid with other psychiatric and medical conditions (triple diagnoses). Such patients were expected to generate high complexity scores on the INTERMED instrument. METHODS: Information on 66 patients with triple diagnoses was submitted to the INTERMED complexity grid. These data were subjected to cluster analysis and other analytic procedures. RESULTS: Total INTERMED scores reflected elevated complexity for patients with triple diagnoses. As a group, they represented a single cluster of complex patients. CONCLUSIONS: The validity of the INTERMED complexity assessment was corroborated in relation to retrospective data. In addition to elevations in the biological domain that hospital personnel typically confront, findings related to coping deficiencies and problems in living conditions were noteworthy in requiring comprehensive interventions.

Changes in resting functional connectivity during abstinence in stimulant use disorder: a preliminary comparison of relapsers and abstainers.

BACKGROUND: Previously identified resting functional connectivity (FC) differences in individuals with stimulant use disorder (SUD) suggest an imbalance in neural regions that mediate behavioral aspects relevant to addiction such as emotion regulation and reward processing. There is a need to further investigate these differences across time between those that relapse and those that do not. This is the first longitudinal study of recently abstinent SUD (SUD-RA) that identifies specific FC changes in subsequent relapsers (vs abstainers). We hypothesized that (1) subsequent relapsers (vs abstainers) will show lower FC of emotion regulation regions and higher FC of reward processing regions and (2) FC differences would be more evident across time. METHODS: We examined resting FC in 18 SUD-RAs (8 females, age: M=22.05 ± 2.64) and 15 non-substance abusing controls (NSAC; 5 females, age: M=24.21 ± 5.76) at Time 1 (abstinent ∼5 weeks). Fourteen NSAC and 12 SUD-RAs were re-examined at Time 2 (abstinent ∼13 weeks). With seed-based FC measures, we examined FC differences between SUD-RAs that abstained or relapsed over the subsequent 6 months. RESULTS: Relapsers (vs abstainers) had higher FC between (1) nucleus accumbens (NAcc) and left frontopolar cortex (FPC), (2) NAcc and posterior cingulate gyrus and (3) subgenual anterior cingulate and left FPC at Time 1. Relapsers (vs abstainers) showed larger reduction in FC strength within these regions across time. CONCLUSIONS: Resting FC reduction found in relapsers (vs. abstainers) from 5 to 13 weeks of abstinence may be a biological marker of relapse vulnerability. These preliminary findings require replication with larger sample sizes.

Context-processing abilities in chronic cocaine users.

Cocaine dependence is a particularly severe problem in the United States, resulting in broad economic and personal costs. Significant evidence of generalized cognitive deficits associated with cocaine dependence has been reported. Two studies evaluated whether context processing, the processes involved in representing and maintaining information regarding the context of one's environment, might be seen as a process-specific deficit that may explain some aspects of the broader cognitive deficits associated with cocaine dependence. Study 1 used the expectancy variant of the AX task to assess this ability; Study 2 employed the Dot Pattern Expectancy task. Significant between-groups differences were found in each study for d'-context, a comparison of AX hits and BX misses; these results indicated significant between-groups differences in context-processing ability. In Study 1, significant between-groups a priori contrasts of AY versus BX trials indicated the likelihood of a specific deficit in context processing in the cocaine group; however, this contrast was not significant in Study 2. Overall, the results of these studies support the theory of impaired context-processing ability associated with cocaine misuse. However, these results do not allow for the interpretation of a process-specific deficit in context-processing ability. Future research targeted at investigating aspects of this context-processing impairment associated with cocaine misuse can shed light on the specificity of this deficit.

Treating individuals with social anxiety disorder and at-risk drinking: phasing in a brief alcohol intervention following paroxetine.

Paroxetine alone is not sufficient to decrease alcohol use in socially anxious alcoholics seeking anxiety treatment. We tested the hypothesis that adding a brief-alcohol-intervention (BI) to paroxetine would decrease alcohol use. All subjects (N=83) had a diagnosis of social anxiety disorder, endorsed drinking to cope with anxiety, were NIAAA-defined at-risk drinkers, and were randomized to either paroxetine alone, or paroxetine plus BI. Both groups showed significant improvement in both social anxiety severity (F(5,83)=61.5, p<0.0001) and drinking to cope (e.g. F(4,79)=23, p<0.0001) and these two constructs correlated with each other (B=3.39, SE=0.696, t(71)=4.88, p<0.001). BI was not effective at decreasing alcohol use (e.g. no main effect of group, all p values >0.3). Paroxetine decreased social anxiety severity in the face of heavy drinking and decreasing the anxiety was related to a concurrent decrease in coping related drinking. BI was not effective at decreasing drinking or drinking to cope.

Frontal hyperconnectivity related to discounting and reversal learning in cocaine subjects.

BACKGROUND: Functional neuroimaging studies suggest that chronic cocaine use is associated with frontal lobe abnormalities. Functional connectivity (FC) alterations of cocaine-dependent individuals (CD), however, are not yet clear. This is the first study to our knowledge that examines resting FC of anterior cingulate cortex (ACC) in CD. Because ACC is known to integrate inputs from different brain regions to regulate behavior, we hypothesized that CD will have connectivity abnormalities in ACC networks. In addition, we hypothesized that abnormalities would be associated with poor performance in delayed discounting and reversal learning tasks. METHODS: Resting functional magnetic resonance imaging data were collected to look for FC differences between 27 CD (5 women, age: M = 39.73, SD = 6.14 years) and 24 control subjects (5 women, age: M = 39.76, SD = 7.09 years). Participants were assessed with delayed discounting and reversal learning tasks. With seed-based FC measures, we examined FC in CD and control subjects within five ACC connectivity networks with seeds in subgenual, caudal, dorsal, rostral, and perigenual ACC. RESULTS: The CD showed increased FC within the perigenual ACC network in left middle frontal gyrus, ACC, and middle temporal gyrus when compared with control subjects. The FC abnormalities were significantly positively correlated with task performance in delayed discounting and reversal learning tasks in CD. CONCLUSIONS: The present study shows that participants with chronic cocaine-dependency have hyperconnectivity within an ACC network known to be involved in social processing and "mentalizing." In addition, FC abnormalities found in CD were associated with difficulties with delay rewards and slower adaptive learning.

Increased mortality in bulimia nervosa and other eating disorders.

OBJECTIVE: Anorexia nervosa has been consistently associated with increased mortality, but whether this is true for other types of eating disorders is unclear. The goal of this study was to determine whether anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified are associated with increased all-cause mortality or suicide mortality. METHOD: Using computerized record linkage to the National Death Index, the authors conducted a longitudinal assessment of mortality over 8 to 25 years in 1,885 individuals with anorexia nervosa (N=177), bulimia nervosa (N=906), or eating disorder not otherwise specified (N=802) who presented for treatment at a specialized eating disorders clinic in an academic medical center. RESULTS: Crude mortality rates were 4.0% for anorexia nervosa, 3.9% for bulimia nervosa, and 5.2% for eating disorder not otherwise specified. All-cause standardized mortality ratios were significantly elevated for bulimia nervosa and eating disorder not otherwise specified; suicide standardized mortality ratios were elevated for bulimia nervosa and eating disorder not otherwise specified. CONCLUSIONS: Individuals with eating disorder not otherwise specified, which is sometimes viewed as a "less severe" eating disorder, had elevated mortality risks, similar to those found in anorexia nervosa. This study also demonstrated an increased risk of suicide across eating disorder diagnoses.

Psychiatric consultation and substance use disorders.

BACKGROUND: A substantial number of patients in general hospitals will evince substance abuse problems but a majority is unlikely to be adequately identified in the referral-consultation process. This failure may preclude patients from receiving effective interventions for substance use disorders. OBJECTIVES: 1. To evaluate all referred patients for possible substance use disorders. 2. To ascertain the degree of convergence between patients referred for chemical problems and the corresponding DSM diagnosis. 3. To compare demographic data for substance abusing patients and referrals not so classified. 4. To evaluate conditions concomitant with substance use disorders. METHOD: Consecutive one-year referrals (524) to consultation-liaison psychiatric services were scrutinized for chemically-related problems by psychiatric consultants. RESULTS: Of the referrals, 176 met criteria for substance use disorders (SUD) (57% alcohol; 25% other drugs; 18% both alcohol and other drugs). Persons diagnosed with SUD tended to be younger, male, non-Caucasian, unmarried, and unemployed. They were more likely to be depressed, have liver and other gastrointestinal problems, and to have experienced traumatic events; they also tended to have current financial difficulties. Most were referred for SUD evaluation by personnel in general medicine and family practice. Following psychiatric consultation, SUD designated patients were referred mainly to substance abuse treatment programs. The only variable related to recommended inpatient versus outpatient services for individuals with SUD was the Global Assessment of Functioning Axis (GAF) with persons having lower estimated functioning more likely to be referred for inpatient interventions. CONCLUSIONS: These data are similar to the results of past studies in this area. Unlike previous investigations in the domain of consultative-liaison psychiatry, financial stressors and specific consultant recommendations were included in data gathering. Although the results are encouraging in that individuals with SUD were identified and potentially sent for appropriate treatment, the likelihood is that many patients with SUD remain unrecognized and do not receive necessary consultative and treatment services.

Brain macrostructural and microstructural abnormalities in cocaine dependence.

RATIONALE: Two previous studies have utilized diffusion tensor imaging (DTI) to examine microstructural integrity in cocaine abuse and found evidence of brain abnormalities in white matter. OBJECTIVE: Using anatomical magnetic resonance imaging (MRI), DTI, and clinical evaluation, the macrostructural and microstructural correlates of cocaine abuse were investigated. METHODS: Twenty-one men and women (mean age 42.5 and mean 18.9 years of cocaine use) and 21 age/gender-matched controls were included. Fractional anisotropy (FA) was measured in frontal white matter ROIs. Gray and white matter volumes in superior and inferior frontal regions were compared. RESULTS: DTI data revealed that cocaine users had lower FA than controls, specifically in inferior frontal white matter. FA differences were not seen in other areas. Significant volumetric differences were not seen, but both gray and white matter inferior frontal volumes trended toward smaller in the cocaine group. The data suggested that duration of use was associated with decreased gray and white matter volumes. FA and gray matter volume were correlated in cocaine users. CONCLUSIONS: Both macrostructural and microstructural abnormalities were seen in a group of cocaine abusers. Length of cocaine use was associated with severity of the brain abnormalities. Future studies of white matter tissue integrity are warranted including examination of the relationship between DTI measures and traditional volumetric measures.

Simulation of drug use and urine screening patterns.

Urine drug screens are used extensively in substance-abuse treatment, especially methadone maintenance treatment programs, as well as criminal-justice and clinical research settings. While positive urinalysis generally indicates drug use, no information is provided about the context or pattern of use. A computer generated model was created to examine the influence of drug use patterns and drug screen schedules upon urine test results. The results indicate that (1) when urine testing is performed at a rate of eight times per year, the probability of testing positive in a given month is little better than 50-50 even for daily use, (2) infrequent drug use is difficult to detect regardless of drug testing frequency, and (3) the benefits of more frequent drug testing are greatest with moderate drug use. The data presented provide a guide for clinicians to match drug screen schedules to frequency or pattern of suspected drug use.

Course and Severity of Substance Abuse in Women with Comorbid Eating Disorder.

The objective of this study is to ascertain whether the course and severity of Substance Abuse among female patients with comorbid Substance Related Disorder and Eating Disorder (SRD-ED) is similar to or different from the course and severity of SRD among female patients with Substance Related Disorder but no Eating Disorder (SRD). Subjects were voluntary patients, obtained in two addiction programs located within departments of psychiatry in two state university medical centers, and included 66 women with SRD-ED and 211 women with SRD. Data were collected on demography, course and severity of SRD, and associated biomedical conditions. SRD-ED patients were significantly younger and more apt to be single, more highly educated, living with family and friends, employed, and of higher socioeconomic status. SRD-ED and SRD patients were more similar than different on most indicators of course and severity, although several clinical differences prevailed. These clinical differences were primarily ascribed to age. In most respects, patients with comorbid SRD-ED manifest course and severity of SRD similar to patients with SRD. Demographic differences between the two groups can mostly be ascribed to the younger mean age of SRD-ED patients rather than to the comorbid ED. Some biomedical problems are related to the specific consequences of ED.