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BackgroundSeveral single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT® ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD).MethodsMen and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period.ResultsThe GE-XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol-related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side-effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications.ConclusionsOverall, GE-XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE-XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.

An introduction is presented in which the editor discusses articles in the issue on topics including Posttraumatic Stress Disorder (PTSD), Specific Populations, Dual Diagnosis, Treatment needs of women with eating disorders and other related topics.

The author presents clarification about the scope of research papers accepted by the journal.

BACKGROUND: Traditionally, the study of medicine has focused on individual diseases. In reality, however, diseases tend to co-occur in individual patients, a concept known as multimorbidity. Multimorbidity most often is seen in geriatric practice. Empirical data on patients with multiple chronic disorders and clinical care guidelines based on single conditions are insufficient to inform medical care of patients with >1 medical condition. METHODS : This article reviews concepts of multimorbidity in the published o d sliterature in the context of substance use disorders, other psychiatric disorders, and associated social and environmental problems in other populations, including public sector service populations. RESULTS : Besides historically recognized co-occurrence of 3 dimensions of illness, including multiple medical illnesses, psychiatric disorders, and substance use disorders in varying combinations with one another, a fourth dimension of multimorbidity that includes associated social and environmental conditions fits within this construction. CONCLUSIONS : Additional steps are needed to address more effectively the needs of patients with substance use and other psychiatric disorders in the public sector psychiatric systems of care. These efforts will need to address the systems theory approach to multimorbidity that entails the socioeconomic and environmental aspects of their conditions. [ABSTRACT FROM AUTHOR]

Objective: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use.Method: A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale.Results: In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed.Conclusions: Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit. [ABSTRACT FROM AUTHOR]

Background: Citicoline is a dietary supplement that has been used as a neuroprotective agent for neurological disorders such as stroke and dementia. Citicoline influences acetylcholine, dopamine, and glutamate neurotransmitter systems; serves as an intermediate in phospholipid metabolism; and enhances the integrity of neuronal membranes. Interest has grown in citicoline as a treatment for addiction since it may have beneficial effects on craving, withdrawal symptoms, and cognitive functioning, as well as the ability to attenuate the neurotoxic effects of drugs of abuse. Objectives: To review the literature on citicoline's use in addictive disorders. Methods: Using PubMed we conducted a narrative review of the clinical literature on citicoline related to addictive disorders from the years 1900-2013 using the following keywords: citicoline, CDP-choline, addiction, cocaine, alcohol, substance abuse, and substance dependence. Out of approximately 900 first hits, nine clinical studies have been included in this review. Results: Most addiction research investigated citicoline for cocaine use. The findings suggest that it is safe and well tolerated. Furthermore, citicoline appears to decrease craving and is associated with a reduction in cocaine use, at least at high doses in patients with both bipolar disorder and cocaine dependence. Limited data suggest citicoline may also hold promise for alcohol and cannabis dependence and in reducing food consumption. Conclusions: Currently, there is limited research on the efficacy of citicoline for addictive disorders, but the available literature suggests promising results. Future research should employ larger sample sizes, increased dosing, and more complex study designs. [ABSTRACT FROM AUTHOR]

Objectives: Self-report measures require less clinician time to administer than clinician-rated assessments. The Internal State Scale (ISS) is a well-validated self-report measure that assesses symptoms of mania and depression in patients with bipolar disorder (BPD). However, the ISS has never been specifically evaluated in patients with BPD and comorbid substance misuse. Substances can induce mood symptoms complicating diagnosis and mood state assessment. Methods: The ISS was compared with the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS) in 21 patients with BPD and alcohol abuse/dependence at baseline and for up to 16 weeks postbaseline. In addition, ISS-determined mood state was compared to mood state from a structured diagnostic interview. Results: Significant baseline correlations were observed between the ESS depression subscale and HRSD, ISS activation subscale and YMRS, and ISS perceived conflict subscale and BPRS. Significant correlations of baseline to exit change scores were found between the ISS activation and YMRS, but not ISS depression and HRSD, or ISS perceived conflict and BPRS. All participants had a mixed mood state by structured diagnostic interview. The ISS diagnosed the manic/hypomanic portion of this mood state in 76% of participants but found depression in only 38%. Conclusions: As in BPD patients without substance abuse, the ISS generally showed correlations with clinician-rated scales at baseline, with less strong correlations observed on change scores. The ISS diagnosis of mania or hypomania appeared to correspond more highly than depression with the findings from a structured diagnostic interview. [ABSTRACT FROM AUTHOR]

This article presents information about several studies that are published in the previous issues of the "Journal of Dual Diagnosis." In the first study, researchers examined the use of cognitive behavioral therapy (CBT) combined with an antidepressant in outpatients with active injection drug use. This study suggests that patients with active substance use can respond favorably to interventions for depression including CBT. Another study shows that substance use is common in patients with severe psychiatric illness. This trend appears to hold true in Australia as in the United States.

Objective: Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric illness. Therefore, treatments that stabilize mood and decrease drug use or cravings are of great interest. Atypical antipsychotics are in widespread use in patients with bipolar disorder. However, minimal data are available on their use in bipolar patients with comorbid substance abuse. Methods: Open-label, add-on, quetiapine therapy was examined for 12 weeks in 17 outpatients with bipolar disorder and cocaine dependence. Subjects were evaluated with a structured clinical interview; Hamilton Depression Rating (HDRS), Young Mania Rating (YMRS), Brief Psychiatric Rating (BPRS) scales; and Cocaine Craving Questionnaire (CCQ). Urine samples and self-reported drug use were also obtained. Data were analyzed using a last observation carried forward method on all subjects given medication at baseline. Results: Significant improvement from baseline to exit was observed in HDRS, YMRS, BPRS and CCQ scores (p ≤ 0.05). Dollars spent on cocaine and days/week of cocaine use decreased non-significantly, and urine drug screens did not change significantly from baseline to exit. Quetiapine was well tolerated, with no subjects to our knowledge discontinuing because of side-effects. Conclusions: The use of quetiapine was associated with substantial improvement in psychiatric symptoms and cocaine cravings. The findings are promising and suggest larger controlled trials of quetiapine are needed in this population. [ABSTRACT FROM AUTHOR]

The article presents several articles on dual diagnosis published in various journals. It includes "Diagnosis of Comorbid Psychiatric Disorders in Substance Users With the Psychiatric Research Interview for Substance and Mental Disorders for DSM-IV," by D. Hasin, S. Samet, E. Nunes, J. Meydan, K. Matseoane, and R. Waxman. "A Meta-Analysis of Negative Symptoms in Dual Diagnosis Schizophrenia," by S. Potvin, A. A. Sepehry, and E. Stip.

The article presents several studies related to bipolar disorder and substance-related disorders. The studies include "Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders", Trauma exposure and retention in adolescent substance abuse treatment", CO2 hypersensitivity in recent abstinent alcohol dependent individuals: a possible mechanism underlying the high risk for anxiety disorder among alcoholics", and "Animal modeling dual diagnosis schizophrenia: sensitization to cocaine in rats with neonatal ventral hippocampal lesions."

An introduction is presented in which the editor discusses various reports within the issue on topics including treatment of patients with substance use disorders and schizophrenia, development of a psychotic disorder from cannabis use and dual diagnosis patients in the criminal justice system.

An introduction is presented in which the editor discusses several articles in the issue on topics including report on posttraumatic stress symptoms (PTSS), and alcohol misuse in a group of Black college students; and a neuroimaging study of connectivity in patients with schizophrenia.

An introduction to articles in the issue is presented on topics including the use of self-report measures to evaluate severity of psychopathology, smoking cessation in people with bipolar disorder who received Acceptance and Commitment Therapy and a nicotine patch, and the prevalence of dual diagnosis and its impact on service utilization in older people.

Background: Bipolar disorder (BD) frequently co-occurs with substance use disorders (SUDs), and both are associated with cognitive impairment. This study compares cognition between individuals with BD with and without current alcohol use disorder (AUD), cocaine use disorder (CUD), or both, as these disorders may be linked with additive cognitive impairment.Methods: Baseline data were analyzed from five clinical studies of individuals with the aforementioned disorders (N = 373). Participants were grouped as follows: BD-only, BD + AUD, BD + CUD, or BD + AUD + CUD. Cognition was assessed with the Rey Auditory Verbal Learning Test (RAVLT) (verbal learning and memory) and Stroop Color Word Test (executive function). Multiple linear regression models determined if SUD diagnosis, among other demographic and clinical variables, predicted each cognitive test's T-score. Regression equations were used to compute each group's mean T-scores.Results: All groups demonstrated below-average mean T-scores on all tests, with no significant between-group score differences. RAVLT total T-scores were lower than Stroop color-word T-scores within all groups (non-overlapping 95% confidence intervals). Higher daily cocaine use predicted higher Stroop T-scores (p < 0.01) and RAVLT delayed recall T-scores (p < 0.05). No other non-demographic variable, including AUD/CUD group status, predicted cognitive performance.Limitations: A full cognitive battery and some relevant variables (e.g. BD lifetime illness course) were not available. Many participants (42.1%) had additional SUDs.Conclusions: BD with and without AUD/CUD was found to be associated with greater deficits in verbal learning and memory than in executive function. Addressing these impaired domains in dually-diagnosed patients may improve treatment and functional outcomes. [ABSTRACT FROM AUTHOR]

A introduction is presented in which the editor discusses various reports within the issue on topics including cognitive behavioral therapy for schizophrenia patients undergoing treatment for smoking cessations, uncertainty on the effect of smoking on mental illness, and housing for homelessness.

An introduction is presented in which the editor discusses topics within the issue including examination of victimization in people with dual diagnosis; examination of aggression in patients with posttraumatic stress disorder; and suffering in patients with a substance use disorder.

The article discusses the bipolar disorder, a psychiatric disorder marked by alternating episodes of mania and depression. It also brain disorder that causes unusual shifts in a person's mood, energy, and ability to function. The author stressed that the current issue of the Journal examines and analyzes several features of the relationships between bipolar disorder and substance abuse.

Abstract: Mood and substance-use disorders are both associated with cognitive deficits. Patients with mood and substance-use disorders have poorer cognition than patients with only a mood disorder. Pregnenolone may have beneficial effects on mood and cognition. In a proof-of-concept investigation, 70 participants with bipolar disorder or recurrent major depressive disorder and history of substance abuse/dependence (abstinent for ≥14days prior to enrollment) were randomly assigned to receive pregnenolone (titrated to 100mg/day) or placebo for 8weeks. Participants were assessed using the Mini International Neuropsychiatric Interview, Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT-B), and Stroop Test. Mood was assessed bi-weekly, while cognition was evaluated at baseline, and weeks 4 and 8. Groups were compared using a random regression analysis that used all of the available data. The pregnenolone group showed trends toward greater improvement, relative to placebo, on the HRSD and YMRS. A post hoc analysis of completers found a statistically significant reduction in HRSD scores with pregnenolone as compared to placebo. Pregnenolone appeared to be safe and well tolerated. Findings suggest that pregnenolone use may be associated with some improvement in manic and depressive symptoms, but not cognition in depressed patients with a history of substance use. Larger trials examining the impact of pregnenolone on mood in more narrowly defined populations may be warranted. [Copyright &y& Elsevier]