Showing papers in "American Journal of Psychiatry in 2016"
TL;DR: Poststroke depression has been recognized by psychiatrists for more than 100 years, but controlled systematic studies did not begin until the 1970s and recent meta-analyses of randomized controlled trials for the treatment and prevention of PSD have demonstrated the efficacy of antidepressants.
Abstract: Poststroke depression (PSD) has been recognized by psychiatrists for more than 100 years, but controlled systematic studies did not begin until the 1970s. Meta-analyses addressing almost all major clinical issues in the field have emerged because of the relatively small number of patients included in some stroke studies. In order to build large databases, these meta-analyses have merged patients with rigorously assessed mood disorders with major depressive features with patients scoring above arbitrary cutoff points on depression rating scales, thus missing important findings such as cognitive impairment associated with major but not minor depression. Nevertheless, PSD occurs in a significant number of patients and constitutes an important complication of stroke, leading to greater disability as well as increased mortality. The most clinically important advances, however, have been in the treatment and prevention of PSD. Recent meta-analyses of randomized controlled trials for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, randomized controlled trials for prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early antidepressant treatment of PSD appears to enhance both physical and cognitive recovery from stroke and might increase survival up to 10 years following stroke. There has also been progress in understanding the pathophysiology of PSD. Inflammatory processes might be associated with the onset of at least some depressive symptoms. In addition, genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission might be relevant etiological factors. Further elucidation of the mechanism of PSD may ultimately lead to specific targeted treatments.
708 citations
TL;DR: The offspring of depressed parents constitute a high-risk group for psychiatric and medical problems, which begin early and continue through adulthood, and early detection seems warranted.
Abstract: Objective:While the increased risk of psychopathology in the biological offspring of depressed parents has been widely replicated, the long-term outcome through their full age of risk is less known. The authors present a 30-year follow-up of biological offspring (mean age=47 years) of depressed (high-risk) and nondepressed (low-risk) parents.Method:One hundred forty-seven offspring of moderately to severely depressed or nondepressed parents selected from the same community were followed for up to 30 years. Diagnostic assessments were conducted blind to parents’ clinical status. Final diagnoses were made by a blinded M.D. or Ph.D. evaluator.Results:The risk for major depression was approximately three times as high in the high-risk offspring. The period of highest risk for first onset was between ages 15 and 25 in both groups. Prepubertal onsets were uncommon, but high-risk offspring had over 10-fold increased risk. The early onset of major depression seen in the offspring of depressed parents was not offs...
686 citations
TL;DR: It is argued that failure to recognize and consistently emphasize a distinction between circuits underlying two classes of responses elicited by threats has impeded progress in understanding fear and anxiety disorders and hindered attempts to develop more effective pharmaceutical and psychological treatments.
Abstract: Tremendous progress has been made in basic neuroscience in recent decades. One area that has been especially successful is research on how the brain detects and responds to threats. Such studies have demonstrated comparable patterns of brain-behavior relationships underlying threat processing across a range of mammalian species, including humans. This would seem to be an ideal body of information for advancing our understanding of disorders in which altered threat processing is a key factor, namely, fear and anxiety disorders. But research on threat processing has not led to significant improvements in clinical practice. The authors propose that in order to take advantage of this progress for clinical gain, a conceptual reframing is needed. Key to this conceptual change is recognition of a distinction between circuits underlying two classes of responses elicited by threats: 1) behavioral responses and accompanying physiological changes in the brain and body and 2) conscious feeling states reflected in sel...
598 citations
TL;DR: Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes, and effects are more pronounced for those with shorter duration of untreated psychosis.
Abstract: Objective:The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life.Method:Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities.Results:The 223 recipients of NAVIGATE remained in treatment longer, experienced greater ...
549 citations
TL;DR: These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.
Abstract: Objective:Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations.Method:A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, struct...
505 citations
TL;DR: A risk calculator comparable in accuracy to those for cardiovascular disease and cancer is available to predict individualized conversion risks in newly ascertained clinical high-risk cases.
Abstract: Objective:Approximately 20%–35% of individuals 12–35 years old who meet criteria for a prodromal risk syndrome convert to psychosis within 2 years. However, this estimate ignores the fact that clinical high-risk cases vary considerably in risk. The authors sought to create a risk calculator, based on profiles of risk indicators, that can ascertain the probability of conversion to psychosis in individual patients.Method:The study subjects were 596 clinical high-risk participants from the second phase of the North American Prodrome Longitudinal Study who were followed up to the time of conversion to psychosis or last contact (up to 2 years). The predictors examined were limited to those that are supported by previous studies and are readily obtainable in general clinical settings. Time-to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1,000 bootstrap resamples.Results:The 2-year probability of conversion to psychosis was 16%. Higher levels of un...
430 citations
TL;DR: The findings support suicide attempt as an even more lethal risk factor for completed suicide than previously thought and research should focus on identifying risk factors for populations vulnerable to making first attempts and target risk reduction in those groups.
Abstract: Objective:While suicide attempt history is considered to robustly predict completed suicide, previous studies have limited generalizability because of using convenience samples of specific methods/treatment settings, disregarding previous attempts, or overlooking first-attempt deaths. Eliminating these biases should more accurately estimate suicide prevalence in attempters.Method:This observational retrospective-prospective cohort study using the Rochester Epidemiology Project identified 1,490 (males, N=555; females, N=935) Olmsted County residents making index suicide attempts (first lifetime attempts reaching medical attention) between January 1, 1986, and December 31, 2007. The National Death Index identified suicides between enrollment and December 31, 2010 (follow-up 3–25 years). Medical records were queried for sex, age, method, and follow-up care for index attempt survivors. Coroner records yielded data on index attempt deaths.Results:During the study period, 81/1,490 enrollees (5.4%) died by suici...
409 citations
TL;DR: DSM-5 cannabis use disorder is prevalent, associated with comorbidity and disability, and largely untreated, suggesting the need to improve prevention and educate the public, professionals, and policy makers about possible harms associated with cannabis use disorders and available interventions.
Abstract: Objective:Attitudes toward marijuana are changing, the prevalence of DSM-IV cannabis use disorder has increased, and DSM-5 modified the cannabis use disorder criteria. Therefore, updated information is needed on the prevalence, demographic characteristics, psychiatric comorbidity, disability, and treatment for DSM-5 cannabis use disorder.Method:In 2012–2013, 36,309 participants ≥18 years old were interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions–III. Psychiatric and substance use disorders were assessed with the Alcohol Use Disorders and Associated Disabilities Interview Schedule–5.Results:The prevalences of 12-month and lifetime cannabis use disorder were 2.5% and 6.3%. Among those with 12-month and lifetime diagnoses, the mean days of marijuana use per year were 225.3 (SE=5.7) and 274.2 (SE=3.8). The odds of 12-month and lifetime cannabis use disorder were higher for men, Native Americans, unmarried individuals, those with low incomes, and young adults (e.g., among those...
406 citations
TL;DR: In this paper, the efficacy of twice and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression was evaluated in a multicenter, double-blind study, where adults (ages 18-64 years) with treatmentresistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks.
Abstract: Objective:Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.Method:In a multicenter, double-blind study, adults (ages 18–64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Asberg Depression Rating Scale (MADRS).Res...
366 citations
TL;DR: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.
Abstract: Objective:There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted.Method:A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed.Results:Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or et...
303 citations
TL;DR: The progressive brain loss in schizophrenia appears to reflect two different processes: one relatively homogeneous, reflecting accelerated aging of the brain and related to various measures of outcome, and a more variable one, possibly reflecting individual variation and medication use.
Abstract: Objective:Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used support vector regression, a supervised machine learning technique, to address this question.Method:In a longitudinal sample of 341 schizophrenia patients and 386 healthy subjects with one or more structural MRI scans (1,197 in total), machine learning algorithms were used to build models to predict the age of the brain and the presence of schizophrenia (“schizophrenia score”), based on the gray matter density maps. Age at baseline ranged from 16 to 67 years, and follow-up scans were acquired between 1 and 13 years after the baseline scan. Differences between brain age and chronological age (“brain age gap”) and between schizophrenia score and healthy reference score (“schizophrenia gap”) were calculated. Accele...
TL;DR: The APA's most recent practice guideline on antipsychotic treatment in patients with dementia appears to have done just that, with a thorough, balanced, accurate, and current review of available treatments based on medical and scientific literature.
Abstract: Author(s): Reus, Victor I; Fochtmann, Laura J; Eyler, A Evan; Hilty, Donald M; Horvitz-Lennon, Marcela; Jibson, Michael D; Lopez, Oscar L; Mahoney, Jane; Pasic, Jagoda; Tan, Zaldy S; Wills, Cheryl D; Rhoads, Richard; Yager, Joel
TL;DR: The time-limited, short-term use of very low dosages of sublingual buprenorphine was associated with decreased suicidal ideation in severely suicidal patients without substance abuse.
Abstract: Objective:Suicidal ideation and behavior currently have no quick-acting pharmacological treatments that are suitable for independent outpatient use. Suicidality is linked to mental pain, which is modulated by the separation distress system through endogenous opioids. The authors tested the efficacy and safety of very low dosages of sublingual buprenorphine as a time-limited treatment for severe suicidal ideation.Method:This was a multisite randomized double-blind placebo-controlled trial of ultra-low-dose sublingual buprenorphine as an adjunctive treatment. Severely suicidal patients without substance abuse were randomly assigned to receive either buprenorphine or placebo (in a 2:1 ratio), in addition to their ongoing individual treatments. The primary outcome measure was change in suicidal ideation, as assessed by the Beck Suicide Ideation Scale at the end of each of 4 weeks of treatment.Results:Patients who received ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily; mean final dos...
TL;DR: This is the first study to link the effects of pregnant women's distress on the fetus and epigenetic changes in placental genes, which may affect subpopulations of placental cells.
Abstract: Objective:Increased risk of psychopathology is observed in children exposed to maternal prenatal distress, and elevated maternal cortisol and epigenetic regulation of placental glucocorticoid-pathway genes are potential mechanisms. The authors examined maternal distress and salivary cortisol in relation to fetal movement and heart rate (“coupling”) and DNA methylation of three glucocorticoid pathway genes—HSD11B2, NR3C1, and FKBP5—in term placentas.Method:Mood questionnaires and salivary cortisol were collected from 61 women between 24–27 gestational weeks, and fetal assessment was conducted at 34–37 weeks. Placental CpG methylation in the three genes was analyzed using 450K Beadchips and bisulfite sequencing; correlations between maternal and fetal variables and DNA methylation were tested; and maternal distress effects on fetal behavior via DNA methylation were investigated.Results:Perceived stress (Perceived Stress Scale), but not cortisol, was associated with altered CpG methylation in placentas. In t...
TL;DR: This study provides strong converging evidence that a blunted neural response to rewards precedes adolescent-onset depression and symptom emergence and may constitute an important target for screening and prevention.
Abstract: Objective:A blunted neural response to rewards has recently emerged as a potential mechanistic biomarker of adolescent depression. The reward positivity, an event-related potential elicited by feedback indicating monetary gain relative to loss, has been associated with risk for depression. The authors examined whether the reward positivity prospectively predicted the development of depression 18 months later in a large community sample of adolescent girls.Method:The sample included 444 girls 13.5–15.5 years old with no lifetime history of a depressive disorder, along with a biological parent for each girl. At baseline, the adolescents’ reward positivity was measured using a monetary guessing task, their current depressive symptoms were assessed using a self-report questionnaire, and the adolescents’ and parents’ lifetime psychiatric histories were evaluated with diagnostic interviews. The same interview and questionnaire were administered to the adolescents again approximately 18 months later.Results:A bl...
TL;DR: These findings provide novel evidence that common and dissociable deficits within the brain's executive system are present in association with dimensions of psychopathology in youth.
Abstract: Objective:Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction across these disorders is challenging given high comorbidity of conditions. Here the authors investigate executive system deficits in association with dimensions of psychiatric symptoms in youth using a working memory paradigm. The authors hypothesize that common and dissociable patterns of dysfunction would be present.Method:The authors studied 1,129 youths who completed a fractal n-back task during functional magnetic resonance imaging at 3-T as part of the Philadelphia Neurodevelopmental Cohort. Factor scores of clinical psychopathology were calculated using an item-wise confirmatory bifactor model, describing overall psychopathology as well as four orthogonal dimensions of symptoms: anxious-misery (mood and anxiety), behavioral disturbance (attention deficit hyperactivity disorder and conduct disorder), psychosis-spectrum symptoms, and fear (phobias). ...
TL;DR: Data show that most mental disorders are associated with an elevated risk of subsequent psychotic experiences, and further investigation of the underlying factors accounting for these time-order relationships may shed light on the etiology of psychotic experiences.
Abstract: Objective:While it is now recognized that psychotic experiences are associated with an increased risk of later mental disorders, we lack a detailed understanding of the reciprocal time-lagged relationships between first onsets of psychotic experiences and mental disorders. Using data from World Health Organization World Mental Health (WMH) Surveys, the authors assessed the bidirectional temporal associations between psychotic experiences and mental disorders.Method:The WMH Surveys assessed lifetime prevalence and age at onset of psychotic experiences and 21 common DSM-IV mental disorders among 31,261 adult respondents from 18 countries. Discrete-time survival models were used to examine bivariate and multivariate associations between psychotic experiences and mental disorders.Results:Temporally primary psychotic experiences were significantly associated with subsequent first onset of eight of the 21 mental disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, social phobia,...
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TL;DR: This summer, Dr. Roberto Silva joined the team as the Assistant Director and was able to attend the graduation celebration as the authors said farewell to the Class of 2016 and join us for orientation as they welcomed the newest class of medical and physician assistant students to the Rural Track.
Abstract: Another year has flown by and the CU School of Medicine Rural Track is still going strong! We made a lot of progress in 2016 toward our goal of long-term sustainability. This summer, Dr. Roberto Silva joined the team as the Assistant Director. He was able to attend the graduation celebration as we said farewell to the Class of 2016 and join us for orientation as we welcomed the newest class of medical and physician assistant students to the Rural Track.
TL;DR: Right unilateral ultrabrief pulse ECT, combined with venlafaxine, is a rapidly acting and highly effective treatment option for depressed geriatric patients, with excellent safety and tolerability, adding to the evidence base supporting the efficacy of ECT to treat severe depression in elderly patients.
Abstract: Objective:The Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy of right unilateral ultrabrief pulse electroconvulsive therapy (ECT) combined with venlafaxine for the treatment of geriatric depression.Method:PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, combined with open-label venlafaxine at seven academic medical centers. In phase 2 (reported separately), patients who had remitted were randomly assigned to receive pharmacotherapy (venlafaxine plus lithium) or pharmacotherapy plus continuation ECT. In phase 1, depressed patients received high-dose ECT (at six times the seizure threshold) three times per week. Venlafaxine was started during the first week of treatment and continued throughout the study. The primary outcome measure was remission, assessed with the 24-item Hamilton Depression Rating Scale (HAM-D), which was administered three times per week. Secondary outcome measures were post-ECT reorientation and ...
TL;DR: IPT is effective in the acute treatment of depression and may beeffective in the prevention of new depressive disorders and in preventing relapse, and has shown promising effects in some other mental health disorders.
Abstract: Objective:Interpersonal psychotherapy (IPT) has been developed for the treatment of depression but has been examined for several other mental disorders. A comprehensive meta-analysis of all randomized trials examining the effects of IPT for all mental health problems was conducted.Method:Searches in PubMed, PsycInfo, Embase, and Cochrane were conducted to identify all trials examining IPT for any mental health problem.Results:Ninety studies with 11,434 participants were included. IPT for acute-phase depression had moderate-to-large effects compared with control groups (g=0.60; 95% CI=0.45–0.75). No significant difference was found with other therapies (differential g=0.06) and pharmacotherapy (g=–0.13). Combined treatment was more effective than IPT alone (g=0.24). IPT in subthreshold depression significantly prevented the onset of major depression, and maintenance IPT significantly reduced relapse. IPT had significant effects on eating disorders, but the effects are probably slightly smaller than those o...
TL;DR: Analysis of primary outcomes (depressive and negative symptoms) suggests small, beneficial effects of adjunctive antidepressants suggests this augmentation can be accomplished with a low risk of exacerbation of psychosis and adverse effects.
Abstract: Objective:The authors examined the safety and efficacy of antidepressants added to antipsychotic drugs in the treatment of schizophrenia.Method:Multiple databases and previous publications were searched through June 2015 to identify all randomized controlled trials of any add-on antidepressants compared with placebo or no-treatment in schizophrenia. Depressive and negative symptoms (primary outcomes), overall symptoms, positive symptoms, side effects, exacerbation of psychosis, and responder rates were examined. Subgroup, meta-regression, and sensitivity analyses were performed, as well as investigations of publication bias and risk of bias.Results:Eighty-two randomized controlled trials with a total of 3,608 participants were included. Add-on antidepressants appeared more efficacious than controls for depressive symptoms (standardized mean difference: –0.25, 95% CI=–0.38 to –0.12), negative symptoms (standardized mean difference: –0.30, 95% CI=–0.44 to –0.16), overall symptoms (standardized mean differen...
TL;DR: The author examines how well DSM-5 symptomatic criteria for major depression capture the descriptions of clinical depression in the post-Kraepelin Western psychiatric tradition as described in textbooks published between 1900 and 1960.
Abstract: How should DSM criteria relate to the disorders they are designed to assess? To address this question empirically, the author examines how well DSM-5 symptomatic criteria for major depression capture the descriptions of clinical depression in the post-Kraepelin Western psychiatric tradition as described in textbooks published between 1900 and 1960. Eighteen symptoms and signs of depression were described, 10 of which are covered by the DSM criteria for major depression or melancholia. For two symptoms (mood and cognitive content), DSM criteria are considerably narrower than those described in the textbooks. Five symptoms and signs (changes in volition/motivation, slowing of speech, anxiety, other physical symptoms, and depersonalization/derealization) are not present in the DSM criteria. Compared with the DSM criteria, these authors gave greater emphasis to cognitive, physical, and psychomotor changes, and less to neurovegetative symptoms. These results suggest that important features of major depression ...
TL;DR: A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was significantly associated with an increased risk of conversion.
Abstract: Objective:The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder (“at-risk” youths).Method:Offspring 6–18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders.Results:Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms...
TL;DR: Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated, suggesting efficacy for the treatment of bipolar I depression.
Abstract: Objective:The authors evaluated the efficacy, safety, and tolerability of cariprazine, an atypical antipsychotic candidate, in adult patients with acute bipolar I depression.Method:This was an 8-week multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in adult patients with bipolar I disorder experiencing a current major depressive episode. Patients were randomly assigned (1:1:1:1) to receive placebo or cariprazine at 0.75, 1.5, or 3.0 mg/day. The primary and secondary efficacy parameters were change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions severity subscale (CGI-S), respectively, analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population.Results:The intent-to-treat population comprised 571 patients (141 in the placebo group and 140, 145, and 145 in the cariprazine 0.75-, 1.5-, and 3.0-mg/day groups). Cariprazine at 1.5 mg/day showed ...
TL;DR: Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was beneficial in sustaining mood improvement for most patients.
Abstract: Objective:The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1).Method:PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECT treatments over 1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing venlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impres...
TL;DR: This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect, and it presents promising areas of future research.
Abstract: Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity.
TL;DR: The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants.
Abstract: Objective:Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a μ- and κ-opioid partial agonist, buprenorphine, and a μ-opioid antagonist, samidorphan, would exhibit antidepressant activity in patients with major depression.Method:A multicenter, randomized, double-blind, placebo-controlled, two-stage sequential parallel comparison design study was conducted in adults with major depression who had an inadequate response to one or two courses of antidepressant treatment. Participants were randomly assigned to receive adjunctive treatment with 2 mg/2 mg of buprenorphine/samidorphan (the 2/2 dosage group), 8 mg/8 mg of buprenorphine/samidorphan (the 8/8 dosage group), or placebo. Antidepressant effect was measured based on change from baseline to the end of 4 weeks of treatment on the 17-item Hamilton Depression Rating Scale (HAM-D), the Montgom...
TL;DR: The results suggest that it would be unlikely for second-generation antipsychotics to raise the risk of major malformations more than 10-fold beyond that observed in the general population or among control groups using other psychotropic medications.
Abstract: Objective:Second-generation antipsychotics are used to treat a spectrum of psychiatric illnesses in reproductive-age women. The National Pregnancy Registry for Atypical Antipsychotics was established to determine the risk of major malformations among infants exposed to second-generation antipsychotics during pregnancy relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.Method:Women were prospectively followed during pregnancy and the postpartum period; obstetric, labor, delivery, and pediatric medical records were obtained. Eligible enrollees were pregnant women ages 18–45. The Registry is based at the Center for Women’s Mental Health at Massachusetts General Hospital. Women were recruited through provider referral, self-referral, and the Center’s web site.Results:As of December 2014, 487 women were enrolled: 353 who used second-generation antipsychotics and 134 comparison women. Medical records were obtained for 82% of participants. A total of 303 women ...
TL;DR: The findings show that the most consistent dysfunction in youths with disruptive behavior disorder is in the rostro-dorsomedial, fronto-cingulate, and ventral-striatal regions that mediate reward-based decision making, which is typically compromised in the disorder.
Abstract: Objective:Functional magnetic resonance imaging (fMRI) studies in conduct disorder and in oppositional defiant disorder have shown inconsistencies. The aim of this meta-analysis of fMRI studies in disruptive behavior disorders was to establish the most consistent brain dysfunctions and to address task- and subtype-related heterogeneity.Method:Web-based publication databases were searched to conduct a meta-analysis of all whole-brain fMRI studies of youths with disruptive behavior disorder or conduct problems up to August 2015. Sub-meta-analyses were conducted in functional subdomains of emotion processing; in cool and hot executive functions, which refer to goal-directed higher cognitive functions with and without motivational and affective significance; and in a subgroup of youths with additional psychopathic traits. The authors performed a meta-analysis of voxel-based group differences in functional activation using the anisotropic effect-size version of seed-based d mapping.Results:Across 24 studies, 3...
TL;DR: Postpartum psychosis offers an intriguing model to explore etiologic contributions to the neurobiology of affective psychosis and strategies for prevention include lithium prophylaxis immediately postpartum and proactive safety monitoring.
Abstract: Objective:Psychosis or mania after childbirth is a psychiatric emergency with risk for suicide and infanticide.Method:The authors reviewed the epidemiologic and genetic research and physiological postpartum triggers (endocrine, immunological, circadian) of psychosis. They also summarized all systematic reviews and synthesized the sparse clinical studies to provide diagnostic recommendations, treatment options, and strategies for prevention.Results:The incidence of first-lifetime onset postpartum psychosis/mania from population-based register studies of psychiatric admissions varies from 0.25 to 0.6 per 1,000 births. After an incipient episode, 20%−50% of women have isolated postpartum psychosis. The remaining women have episodes outside the perinatal period, usually within the bipolar spectrum. Presumably, the mechanism of onset is related to physiological changes after birth (e.g., hormonal, immunological, circadian), which precipitate disease in genetically vulnerable women. Some women have treatable ca...