IMPORTANCE Alcohol use disorder is one of the leading causes of disability worldwide. While effective pharmacological treatments exist, they are efficacious only in certain individuals, contributing to their limited use. Secondary analysis of clinical trial data suggests that a functional polymorphism (rs1799971, Asn40Asp) of the μ-opioid receptor gene (OPRM1) is associated with the risk of relapse to heavy drinking following treatment with the opioid antagonist naltrexone. OBJECTIVE To prospectively examine whether rs1799971 is predictive of naltrexone treatment response. DESIGN, SETTING, AND PARTICIPANTS We conducted a 12-week, double-blind, randomized clinical trial of naltrexone vs placebo in individuals with alcohol dependence (intent-to-treat analysis). Participants were randomly assigned to study treatment based on the presence of 1 or 2 copies of the Asp40 allele compared with those homozygous for the Asn40 allele (2 × 2 cell design). Recruitment occurred between January 2009 and September 2013. All participants were seen in an outpatient clinical setting. A convenience sample of participants (n = 221) was recruited from 5 sites. All participants met DSM-IV criteria for alcohol dependence, with no concurrent psychotic or manic symptoms, no use of concurrent psychotropic medications, and no current dependence on illicit substances. INTERVENTIONS The study drug was naltrexone (50 mg) given once daily or corresponding placebo. MAIN OUTCOMES AND MEASURES The primary study outcome measure was relapse to heavy drinking measured using the timeline follow-back method. RESULTS There was no evidence of a genotype × treatment interaction on the primary outcome of heavy drinking (P = .32). In the Asn40 group, the observed effect of naltrexone was similar to that in previous trials (odds ratio, 0.69; 95% CI, 0.41-1.18; P = .17), with a very small naltrexone effect in the Asp40 group (odds ratio, 1.10; 95% CI, 0.52-2.31; P = .80), contrary to the pattern expected a priori. A significant reduction in heavy drinking occurred across all groups (P = .001). Other drinking outcomes, and all secondary outcomes, demonstrated similar time effects, with no genotype × treatment interaction. CONCLUSIONS AND RELEVANCE The results of this study do not support the hypothesis that the Asp40 allele moderates the response to naltrexone treatment. It is premature to use the Asn40Asp polymorphism as a biomarker to predict the response to naltrexone treatment of alcohol dependence. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00831272
IMPORTANCE Established nosology identifies schizoaffective disorder as a distinct category with boundaries separating it from mood disorders with psychosis and from schizophrenia. Alternative models argue for a single boundary distinguishing mood disorders with psychosis from schizophrenia (kraepelinian dichotomy) or a continuous spectrum from affective to nonaffective psychosis. OBJECTIVE To identify natural boundaries within psychotic disorders by evaluating associations between symptom course and long-term outcome. DESIGN, SETTING, AND PARTICIPANTS The Suffolk County Mental Health Project cohort consists of first-admission patients with psychosis recruited from all inpatient units of Suffolk County, New York (72% response rate). In an inception cohort design, participants were monitored closely for 4 years after admission, and their symptom course was charted for 526 individuals; 10-year outcome was obtained for 413. MAIN OUTCOMES AND MEASURES Global Assessment of Functioning (GAF) and other consensus ratings of study psychiatrists. RESULTS We used nonlinear modeling (locally weighted scatterplot smoothing and spline regression) to examine links between 4-year symptom variables (ratio of nonaffective psychosis to mood disturbance, duration of mania/hypomania, depression, and psychosis) and 10-year outcomes. Nonaffective psychosis ratio exhibited a sharp discontinuity-10 days or more of psychosis outside mood episodes predicted an 11-point decrement in GAF-consistent with the kraepelinian dichotomy. Duration of mania/hypomania showed 2 discontinuities demarcating 3 groups: mania absent, episodic mania, and chronic mania (manic/hypomanic >1 year). The episodic group had a better outcome compared with the mania absent and chronic mania groups (12-point and 8-point difference on GAF). Duration of depression and psychosis had linear associations with worse outcome. CONCLUSIONS AND RELEVANCE Our data support the kraepelinian dichotomy, although the study requires replication. A boundary between schizoaffective disorder and schizophrenia was not observed, which casts further doubt on schizoaffective diagnosis. Co-occurring schizophrenia and mood disorder may be better coded as separate diagnoses, an approach that could simplify diagnosis, improve its reliability, and align it with the natural taxonomy.
Benzodiazepine use among older adults is common despite evidence for many potential risks. While treatment guidelines recommend short-term use of benzodiazepines, up to one-third of use is long term, which is most common among older adults. 1 To reduce benzodiazepine prescribing to older adults, one potential point for intervention is at the transition from new to long-term use, yet little is known about the factors that predict conversion to long-term use.
Background and Objectives: This study examined the relationship between distress tolerance and psychosocial changes among individuals participating in Mindfulness-Based Stress Reduction (MBSR). The objective of the analysis was to discern whether individuals with lower distress tolerance measured before MBSR showed larger reductions in perceived stress following MBSR. Design and Methods: Data were collected from a sample of convenience (n = 372) using a quasi-experimental design. Participants completed self-report measures immediately prior to course enrollment and following course completion. Results: Perceived stress, distress tolerance, and mood states showed favorable changes from pre- to post-MBSR in the current study. Baseline distress tolerance significantly moderated reductions on perceived stress, supporting the primary hypothesis that individuals with lower baseline distress tolerance evidenced a greater decline in perceived stress following MBSR. For a one-unit increase on the self-reported baseline Distress Tolerance Scale, reported perceived stress scores decreased by 2.5 units (p < .0001). Conclusions: The finding that individuals with lower baseline distress tolerance evidenced a greater decline in perceived stress may offer hints about who is most likely to benefit from MBSR and other mindfulness-based treatments. Identifying moderators of treatment outcomes may yield important benefits in matching individuals to treatments that are most likely to work for them.
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.
Despite widespread use, how clinicians use the DSM in psychiatric practice is not well understood. Recognizing public and professional attitudes toward the DSM are integral to future DSM development, to assess a commonly held assumption such as that the DSM is used primarily for coding, and to assess its clinical utility. A convenience sample of Psychiatric Times readers was surveyed to assess the DSM's use in clinical practice. A total of 394 behavioral health care practitioners fully completed the online survey. Results suggest that the DSM, beyond administrative and billing use, is used for communication with health care providers, for teaching diagnoses to trainees, and, importantly, as an educational tool to inform patients and caregivers alike.
Purpose/Background To add to limited evidence on the Abnormal Involuntary Movement Scale (AIMS) as a measure of tardive dyskinesia (TD) in clinical practice settings, the characteristics and correlates of AIMS scores were assessed. Methods/Procedures Veterans with schizophrenia/schizoaffective, bipolar, or major depressive disorders receiving antipsychotics and at least 1 AIMS score during October 1, 2014, to September 30, 2015, were identified. Tardive dyskinesia was determined by the International Classification of Diseases, Ninth Revision, Clinical Modification, codes. Correlates of AIMS scores were examined using χ2 or t tests. Odds ratios and β parameters with 95% confidence intervals for categorical and continuous variables associated with AIMS scores were derived from a multivariate logistic and linear regression, respectively. Findings/Results Among 7985 veterans receiving antipsychotics, only 4706 (58.9%) had at least 1 AIMS examination. Of these, 229 (4.9%) were diagnosed with possible TD. The mean total AIMS scores and AIMS awareness/incapacitation scores were significantly higher for patients with TD (both P < 0.0001). Comparing diagnostic threshold criteria of AIMS ratings, only 17.5% to 37.1% of veterans with TD were successfully identified. Among TD patients, 21.4% had a total score of moderate-severe and 15.3% had ratings of at least mild movements in 2 or more body regions. In the regression analyses, being older, African-American, having schizophrenia/schizoaffective disorder, and receiving antipsychotics or benztropine significantly increased the severity of AIMS scores. Higher AIMS scores were not predictive of outcomes other than marital status in socioeconomic or healthcare domains. Implications/Conclusions Although the AIMS is essential for TD research, its value in clinical practice without training and oversight remains unclear. Efforts to adapt screening procedures to clinical needs may be worthwhile.
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