Depressive and Anxiety Symptoms Predict Obsessive and Compulsive Cravings among Depressed Alcoholics.

Objectives: Alcohol craving is often associated with mood symptoms and predicts alcohol use in individuals with alcohol dependence. However, little is known about the impact of mood symptoms on alcohol craving in comorbid mood disorders and alcohol dependence. This study examines the predictive value of depressive and anxiety symptoms for obsessive and compulsive aspects of alcohol craving in adults with comorbid Major Depressive Disorder (MDD) and Alcohol Dependence. Methods: Fifty-five adults (47% female; mean age of 39.35 (SD=8.80)) with DSM-IV diagnoses of comorbid MDD and alcohol dependence were prospectively assessed over a six-month period. They completed the Hamilton Rating Scales for Depression and Anxiety, the Alcohol Timeline Followback, the Obsessive Compulsive Drinking Scale (OCDS), the Alcohol Dependence Scale (ADS), and the Addiction Severity Index (ASI). The linear mixed model analyses for repeated measures was used to test weather depressive and anxiety symptoms predict OCDS subscale scores. Results: Depressive and anxiety symptoms were strongly associated with obsessive and compulsive subscales of the OCDS. Baseline ASI-alcohol scores were associated with both the obsessive and compulsive and with the obsessive subscale scores in the predictive model including depressive symptoms, and that including anxiety symptoms respectively. Conclusions: Results suggest that depressive and anxiety symptoms predict obsessive and compulsive aspects of alcohol craving in adults with comorbid MDD and alcohol dependence. Assessing the severity of depressive and anxiety symptoms and alcohol use in this population may identify those more likely to experience intense alcohol craving states and at increased risk of relapse.

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.

BACKGROUND: Several 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). METHODS: Men 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. RESULTS: The 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. CONCLUSIONS: Overall, 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.

Medical Comorbidities in Bipolar Disorder.

PURPOSE OF REVIEW: Bipolar disorder (BD) medical comorbidity presents significant clinical and public health concerns with serious impact on health. The aim of this article is to present an updated narrative review of original research articles (case control, longitudinal cohort, and cross-sectional studies) and meta-analyses published in English language journals from January 2013 to May 2017 focusing on general medical comorbidity in BD, including the added risks of iatrogenic factors relevant to the treatment of BD. RECENT FINDINGS: We found numerous patterns of association between BD and various medical disorders involving multiple organ systems. One pattern indicated reciprocal increase in the rate of each comorbid condition, such as an increased rate of BD in asthma or migraine, and likewise an increase in the rate of asthma or migraine in patients with BD. A second pattern was a predominantly unidirectional increase in the rate of BD in patients with certain medical disorders, such as multiple sclerosis or cerebellar diseases. A third pattern was a predominantly unidirectional increased rate of medical disorders in patients with BD. One study suggested the potential involvement of genetic mechanisms for the association between BD and migraine. Most of the studies had cross-sectional or retrospective designs, and many relied on analysis of large administrative databases inviting multiple potential biases. Our review highlights the association between BD and a variety of medical disorders. Further research is needed to elucidate the potential underlying etiopathological mechanisms that contribute to observed comorbidities. The results of this review also emphasize the need for comprehensive screening for medical disorders in BD and for adoption of an integrated model of care to address these complex comorbidities.

Management of comorbid bipolar disorder and substance use disorders.

BACKGROUND: The comorbidity of substance use disorders (SUDs) in bipolar disorder is among the highest in psychiatric disorders. Evidence-based controlled psychosocial or pharmacological interventions trials, which may guide treatment decisions, have not been systematically reviewed. OBJECTIVE: To present a narrative review of the public health and clinical significance of this condition, including diagnostic and treatment implications, and to evaluate controlled trials conducted to date. METHODS: Controlled trials reports in the English language were identified from multiple electronic databases and hand-searching bibliographies. We searched for treatment studies of bipolar disorder and comorbid SUDs (alcohol, cocaine, stimulants, opioid, tobacco, cannabis). Search period included all reports through September of 2016. We selected only randomized psychosocial studies or double-blind, placebo-controlled pharmacotherapy trials. We also reviewed reports of the public health and clinical significance and principle of managements of this condition. RESULTS: We identified 16 treatment studies: 3 psychotherapy, and 13 pharmacotherapy trials. The following medications were evaluated: lithium carbonate, valproate, lamotrigine, topiramate, naltrexone, acamprosate, disulfiram, quetiapine, and citicoline. SUDs have substantial impact on the recognition and management of bipolar disorder. Integrated psychosocial interventions are helpful in decreasing substance abuse. Valproate and naltrexone may decrease alcohol use and citicoline may decrease cocaine use and enhance cognition. CONCLUSIONS: There is a very limited number of pharmacotherapy and an even smaller number of psychosocial interventions. Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.

Differential Impact of Depressive and Manic Mood States on Alcohol Craving in Comorbid Bipolar Alcoholism: Preliminary Findings.

OBJECTIVES: To examine the differential impact of depressive and manic mood states on alcohol craving in patients with bipolar disorder and comorbid alcoholism. METHODS: Forty-four men and women, ages 18-65, with DSM-IV-TR comorbid diagnoses of bipolar I disorder and alcohol dependence were assessed over a three-month period to examine the extent to which their depressive and manic symptoms were associated with alcohol cravings (i.e., desire to use and not to use alcohol) at each assessment point, controlling for age, ethnicity, socio-economic status, baseline alcohol use, and number of assessments. RESULTS: Both manic and depressive symptoms were associated with greater desire to use alcohol. Only depressive symptomatology was associated with reduced desire not to use alcohol, and desire not to use alcohol declined over the course of the three-month treatment period. CONCLUSION: Whereas enhanced desire to drink alcohol may be a conditioned reaction to both manic and depressed mood states, desire not to drink alcohol may be more of an indicator of treatment motivation, which is negatively affected by depressed mood. Depressive symptoms may warrant prioritization and aggressive targeting early in treatment given that desire to refrain from alcohol use was only influenced by depressive symptoms and declined over the course of treatment.

Co-Occurring Disorders: A Challenge for Mexican Community-Based Residential Care Facilities for Substance Use.

OBJECTIVE: In Mexico, specialized treatment services for people with co-occurring disorders are limited within public health services, while private options are deemed too costly. More than 2,000 community-based residential care facilities have risen as an alternative and are the main source of treatment for individuals with substance use disorders; however, suboptimal practices within such facilities are common. Information on the clinical characteristics of patients receiving care in these facilities is scarce and capacity to provide high-quality care for co-occurring disorders is unknown. The aims of this study were to examine the prevalence of co-occurring disorders in patients receiving treatment for substance use in these community-based residential centers and to assess whether the presence of co-occurring disorders is associated with higher severity of substance use, psychiatric symptomatology, and other health risks. METHODS: This study was conducted with 601 patients receiving treatment for substance use disorders at 30 facilities located in five Mexican states, recruited in 2013 and 2014. Patients were assessed with self-report measures on substance use, service utilization, suicidality, HIV risk behaviors, psychiatric symptomatology, and psychiatric disorder diagnostic criteria. RESULTS: The prevalence of any co-occurring disorder in this sample was 62.6%. Antisocial personality disorder was the most prevalent (43.8%), followed by major depressive disorder (30.9%). The presence of a co-occurring disorder was associated with higher severity of psychiatric symptoms (aB = .496, SE = .050, p < .05); more days of substance use (aB = .219, SE = .019, p < .05); current suicidal ideation (aOR = 5.07, 95% CI [2.58, 11.17]; p < .05), plans (aOR = 5.17 95% CI [2.44, 12.73]; p < .05), and attempts (aOR = 6.43 95% CI [1.83, 40.78]; p < .05); more sexual risk behaviors; and more contact with professional services (aOR = 1.77, 95% CI [1.26, 2.49], p < .05). CONCLUSIONS: Co-occurring disorders are highly prevalent in community-based residential centers in Mexico and are associated with significantly increased probability of other health risks. This highlights the need to develop care standards for this population and the importance of clinical research in these settings.

Polysomnographic sleep disturbances in nicotine, caffeine, alcohol, cocaine, opioid, and cannabis use: A focused review.

BACKGROUND AND OBJECTIVES: In the United States, approximately 60 million Americans suffer from sleep disorders and about 22 million Americans report substance dependence or use disorders annually. Sleep disturbances are common consequences of substance use disorders and are likely found in primary care as well as in specialty practices. The aim of this review was to evaluate the effects of the most frequently used substances-nicotine, alcohol, opioids, cocaine, caffeine, and cannabis-have on sleep parameters measured by polysomnography (PSG) and related clinical manifestations. METHODS: We used electronic databases such as PubMED and PsycINFO to search for relevant articles. We only included studies that assessed sleep disturbances using polysomnography and reviewed the effects of these substances on six clinically relevant sleep parameters: Total sleep time, sleep onset latency, rapid-eye movement, REM latency, wake after sleep onset, and slow wave sleep. RESULTS: Our review indicates that these substances have significant impact on sleep and that their effects differ during intoxication, withdrawal, and chronic use. Many of the substance-induced sleep disturbances overlap with those encountered in sleep disorders, medical, and psychiatric conditions. Sleep difficulties also increase the likelihood of substance use disorder relapse, further emphasizing the need for optimizing treatment interventions in these patients. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Our review highlights the importance of systematically screening for substance use in patients with sleep disturbances and highlights the need for further research to understand mechanisms underlying substances-induced sleep disturbances and on effective interventions addressing these conditions.

Paradoxical Decrease in Striatal Activation on an fMRI Reward Task Following Treatment in Youth with Co-morbid Cannabis Dependence/Major Depression.

Reward behavior, including reward behavior involving drugs, has been shown to be mediated by the ventral striatum and related structures of the reward system. The aim of this study was to assess reward-related activity as shown by fMRI before and after treatment among youth with comorbid cannabis dependence and major depression. We hypothesized that the reward task (Delgado et al., 2003) would elicit activation in the reward system, and that the level of activation in response to reward would increase from the beginning to the end of the 12-week treatment study as levels of depressive symptoms and cannabis use decreased. Six subjects were recruited from a larger treatment study in which all received Cognitive Behavioral Therapy/Motivational Enhancement Therapy (CBT/MET), and also were randomized to receive either fluoxetine or placebo. Each of the six subjects completed an fMRI card- guessing/reward task both before and after the 12-week treatment study. As hypothesized, the expected activation was noted for the reward task in the insula, prefrontal, and striatal areas, both before and after treatment. However, the participants showed lower reward-related activation after treatment relative to pre-treatment, which is opposite of what would be expected in depressed subjects who did not demonstrate a comorbid substance use disorder. These paradoxical findings suggest that the expected increase in activity for reward associated with treatment for depression was overshadowed by a decrease in reward-related activation associated with treatment of pathological cannabis use in these comorbid youth. These findings emphasize the importance of comorbid disorders in fMRI studies.

The dynamic origins of positive health and wellbeing.

The causes of wellbeing and illbeing interact with feedback dynamics resulting in the same set of traits giving rise to a variety of health outcomes (multi-finality) and different traits giving rise to the same health outcome (equi-finality). As a result, a full understanding of health and its disorders must be in terms of a complex adaptive system of causes, rather than in terms of categorical diagnoses or sets of symptoms. The three domains of person-centered integrative diagnosis (PID) are considered here as interacting components of a complex adaptive system comprised of health status (functioning/wellness versus disability/disorder), experience of health (self-awareness/fulfillment versus misunderstanding/suffering) and contributors to health (protective versus risk factors). The PID domains thereby allow healthcare and health promotion to be understood in terms of measurable components of a complex adaptive system. Three major concepts of health are examined in detail to identify their dynamic origins: Psychological Maturity, Flourishing and Resilience. In humanistic psychology, psychological maturity (i.e. healthy personality, mental wellbeing) involves the development of high self-directedness, high co-operativeness and high self-transcendence, but self-transcendence is nevertheless devalued in individualistic and materialistic cultures except when people must face adversity and ultimate situations like suffering or the threat of death. Psychological Maturity develops through two complementary processes often labeled as Flourishing and Resilience. Flourishing is the development of one's potential to live optimally, especially as the result of favorable circumstances, whereas Resilience is positive adaptation to life despite adverse circumstances. As a result of the complex feedback dynamics between the processes of flourishing and resilience, each person is a unique individual who has a variety of paths for achieving positive health and wellbeing open to him or her. Person-centered health promotion and care can thereby be approached as a creative life project that can be conducted with the assistance of healthcare workers who are both therapeutic allies and well-informed experts.

TREATMENT TRIAL AND LONG-TERM FOLLOW-UP EVALUATION AMONG COMORBID YOUTH WITH MAJOR DEPRESSION AND A CANNABIS USE DISORDER.

OBJECTIVE: This study compared the acute phase (12-week) and the long-term (1 year) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the cannabis use of youth with comorbid major depressive disorder (MDD) and an cannabis use disorder (CUD)(cannabis dependence or cannabis abuse). We hypothesized that fluoxetine would demonstrate efficacy in the acute phase trial and at the 1-year follow-up evaluation. Data is also provided regarding the prevalence of risky sexual behaviors in our study sample. METHODS: We recently completed the first double-blind placebo-controlled study of fluoxetine in adolescents and young adults with comorbid MDD/CUD. A total of 70 persons participated in the acute phase trial, and 68 of those persons (97%) also participated in the 1-year follow-up evaluation. Results of the acute phase study have already been presented (Cornelius, Bukstein, et al., 2010), but the results of the 1 year follow-up assessment have not been published previously. All participants in both treatment groups also received manual-based cognitive behavioral therapy (CBT) and motivation enhancement therapy (MET) during the 12-week course of the study. The 1-year follow-up evaluation was conducted to assess whether the clinical improvements noted during the acute phase trial persisted long term. RESULTS: During the acute phase trial, subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in depressive symptoms and in cannabis-related symptoms. However, no significant difference was noted between the floxetine group and the placebo group on any treatment outcome variable during the acute phase trial. End of study levels of depressive symptoms were low in both the fluoxetine group and the placebo group. Most of the clinical improvements in depressive symptoms and for cannabis-related symptoms persisted at the 1-year follow-up evaluation. CONCLUSIONS: Fluoxetine did not demonstrate greater efficacy than placebo for treating either the depressive symptoms or the cannabis-related symptoms of our study sample during the acute phase study or at the 1-year follow-up assessment. The lack of a significant treatment effect for fluoxetine may at least in part reflect efficacy of the CBT/MET psychotherapy. A persistence of the efficacy of the acute phase treatment was noted at the 1-year follow-up evaluation, suggesting long-term effectiveness for the CBT/MET psychotherapy.

Suicidal Ideation Associated with PCL Checklist-Ascertained PTSD among Veterans Treated for Substance Abuse.

This manuscript begins by reviewing the literature concerning the use of the SCID versus the PCL for diagnosing PTSD, and by reviewing the literature regarding the presence of suicidal ideation as a clinical correlate of PTSD. This manuscript then describes our recent study involving PTSD among Veterans, which assessed the presence of suicidal ideation as a clinical correlate of PTSD, as diagnosed by the SCID versus as diagnosed by the PCL. We hypothesized that the presence of suicidal ideation would be associated with a diagnosis of PTSD. Subjects were 101 Veterans recruited from VA behavioral health and substance use treatment clinics in the VA Pittsburgh Healthcare System. The study compared correlations of suicidal ideation with PTSD as determined with the PTSD Checklist versus the Structured Clinical Interview for DSM-IV, and utilized question 9 of the Beck Depression Inventory for assessing presence of SI. PTSD was diagnosed in 15 subjects using the SCID, and in 15 subjects using the PTSD Checklist. SI were reported by 16 subjects. The presence of SI was significantly associated with the diagnosis of PTSD on the PCL (chi-square=5.73, df=1, p=0.017) but not on the SCID (chi-square=0.08, df=1, p=0.773). These findings suggest that SI associated with the diagnosis of PTSD among Veterans are better ascertained by the PCL as compared to the more elaborate diagnostic algorithm used in the SCID. The current study finding raises the possibility that a less complicated diagnostic assessment instrument such as the PCL may be superior to the SCID, a more complicated instrument for diagnosing PTSD, at least in some populations.

Evaluation of cognitive behavioral therapy/motivational enhancement therapy (CBT/MET) in a treatment trial of comorbid MDD/AUD adolescents.

OBJECTIVE: Behavioral therapies developed specifically for co-occurring disorders remain sparse, and such therapies for comorbid adolescents are particularly rare. This was an evaluation of the long-term (2-year) efficacy of an acute phase trial of manualized cognitive behavioral therapy/motivation enhancement therapy (CBT/MET) vs. naturalistic treatment among adolescents who had signed consent for a treatment study involving the SSRI antidepressant medication fluoxetine and CBT/MET therapy for comorbid major depressive disorder (MDD) and an alcohol use disorder (AUD). We hypothesized that improvements in depressive symptoms and alcohol-related symptoms noted among the subjects who had received CBT/MET would exceed that of those in the naturalistic comparison group that had not received CBT/MET therapy. METHODS: We evaluated levels of depressive symptoms and alcohol-related symptoms at a two-year follow-up evaluation among comorbid MDD/AUD adolescents who had received an acute phase trial of manual-based CBT/MET (in addition to the SSRI medication fluoxetine or placebo) compared to those who had received naturalistic care. RESULTS: In repeated measures ANOVA, a significant time by enrollment status difference was noted for both depressive symptoms and alcohol-related symptoms across the two-year time period of this study, with those receiving CBT/MET demonstrating superior outcomes compared to those who had not received protocol CBT/MET therapy. No significant difference was noted between those receiving fluoxetine vs. those receiving placebo on any outcome at any time point. CONCLUSIONS: These findings suggest long-term efficacy for an acute phase trial of manualized CBT/MET for treating comorbid MDD/AUD adolescents. Large multi-site studies are warranted to further clarify the efficacy of CBT/MET therapy among various adolescent and young adult comorbid populations.

Outlining the bases of person-centred integrative diagnosis.

UNLABELLED: RATIONAL AND AIMS: As diagnosis is a critical first step for clinical care, it was early recognized that an appropriate diagnostic model was necessary as informational basis for person-centred clinical care. METHODS: The design of a person-centred integrative diagnosis model was based on literature reviews and work meetings in London, Paris, Geneva, Preston, UK and Uppsala, Sweden over the past 2 years. RESULTS AND CONCLUSION: The current person-centred integrative diagnosis model argues for a broader concept of diagnosis and covers both ill health and positive health through the following three levels: Health Status (from illness to recovery/wellness and from disabilities to adaptive functioning), Experience of Health (cultural factors and values concerning ill health and positive health) and Contributory Factors (including internal and external risk and protective factors). Each of these domains will be evaluated with standardized categories and dimensions as well as narratives. Specific attention is paid to evaluators (clinicians, patient, family and other carers) and the interactive evaluation process.

Person-centred integrative diagnosis: conceptual bases and structural model.

OBJECTIVES: To review the conceptual bases of Person-centred Integrative Diagnosis (PID) as a component and contributor to person-centred psychiatry and medicine and to outline its design and development. METHOD: An analysis was conducted of the historical roots of person-centred psychiatry and medicine, tracing them back to ancient Eastern and Western civilizations, to the vicissitudes of modern medicine, to recent clinical and conceptual developments, and to emerging efforts to reprioritize medicine from disease to patient to person in collaboration with the World Medical Association, the World Health Organization, the World Organization of Family Doctors, the World Federation for Mental Health, and numerous other global health entities, and with the coordinating support of the International Network for Person-centered Medicine. RESULTS: One of the prominent endeavours within the broad paradigmatic health development outlined above is the design of PID. This diagnostic model articulates science and humanism to obtain a diagnosis of the person (of the totality of the person's health, both ill and positive aspects), by the person (with clinicians extending themselves as full human beings), for the person (assisting the fulfillment of the person's health aspirations and life project), and with the person (in respectful and empowering relationship with the person who consults). This broader and deeper notion of diagnosis goes beyond the more restricted concepts of nosological and differential diagnoses. The proposed PID model is defined by 3 keys: broad informational domains, covering both ill health and positive health along 3 levels: health status, experience of health, and contributors to health; pluralistic descriptive procedures (categories, dimensions and narratives); and evaluative partnerships among clinicians, patients, and families. An unfolding research program is focused on the construction of a practical guide and its evaluation, followed by efforts to facilitate clinical implementation and training. CONCLUSIONS: PID is aimed at appraising overall health through pluralistic descriptions and evaluative partnerships, and leading through a research program to more effective, integrative, and person-centred health care.

Mood stabilizers in the treatment of substance use disorders.

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids. The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.