Objective Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk. Methods We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors. Results The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors. Conclusions Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk.
Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD) between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI). Six RCTs and one open-label placebo-controlled studies (including post-hoc reports) representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-)manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS) (SMD −0.74, 95% CI −1.20 to −0.28, n SGA = 907, control = 652). Meta-analysis demonstrated that participants in receipt of SGA (n = 979) experienced a large improvement in the Montgomery–Åsberg Depression Rating Scale (MADRS) scores (SMD −1.08, 95% CI −1.35 to −0.81, p < 0.001) vs. placebo (n = 678). Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable and clinically definitive conclusions.
BackgroundPreliminary placebo-controlled evidence paved the ground to the US Food and Drug Administration approval extension of lisdexamfetamine for the treatment of moderate-to-severe binge eating disorder (BED) in adults.ObjectivesTo provide a preliminary qualitative and quantitative synthesis of the placebo-controlled, randomized clinical trials (RCTs) considering the efficacy and tolerability of lisdexamfetamine in the acute and/or maintenance treatment of moderate-to-severe BED in adults.MethodsA preliminary, yet comprehensive, systematic review was performed by accessing a broad range of resources providing publicly available data about lisdexamfetamine at the time of inquiry (March 2016). Study eligibility criteria, participants, and interventions were considered focusing on major clinical and functional outcomes of either efficacy or tolerability of lisdexamfetamine in the treatment of moderate-to-severe BED in adults.ResultsMeta-analysis of data pooled from three acute RCTs significantly favored lisdexamfetamine over placebo in the reduction of binge eating days/week, Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating total score, weight, response, and remission rates (all, P≤0.01). In contrast, discontinuation rates due to treatment-emergent adverse events were significantly higher among patients in receipt of lisdexamfetamine (relative risk 2.19, P=0.04) versus placebo.LimitationsPublication, selection, performance, attrition, reporting, sponsorship, and “diagnostic shift” biases. Lack of inclusion of adverse event effects other than those requiring discontinuation of the trial(s), as well as lack of information about clinically relevant psychiatric or other medical comorbidities, limits the overall generalizability of pooled results.ConclusionAcross the included acute phase RCTs, lisdexamfetamine (at 30, 50, or 70 mg/day) led to significant reduction in a number of clinically relevant outcomes compared to placebo. Moreover, safety concerns related to adverse events, high discontinuation rates, and the need for additional long-term maintenance of RCTs solicit careful monitoring of the drug in terms of overall safety and tolerability by further RCTs.
Low omega-3 polyunsaturated fatty acid (PUFA) levels are seen in major depression. We examined effects of six weeks of fish oil supplementation on clinical characteristics in 16 patients with symptomatic major depressive disorder, and tested plasma phospholipid levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as correlates of clinical response. Depression symptoms improved after supplementation (p=0.007). The reduction in depression severity was not predicted by baseline PUFA levels but did exhibit a relationship with endpoint PUFAs, correlating negatively with DHA as a percentage of plasma phospholipids (DHA%; R2=0.60, p=0.004), adjusting for endpoint EPA%; and correlating positively with endpoint EPA% (R2=0.58, p=0.007), adjusting for endpoint DHA%. Thus, the higher the proportion of DHA to EPA, the greater the reduction in depression severity (r=−0.43, p=0.097). Five patients showed a decrease of > 50% on the 17-item Hamilton Depression Rating Scale and a final score < 7 and were thus not only responders but met standard criteria for remission, and were distinguished from non-responders by higher levels of DHA% (p=0.03). This pilot study suggests that post-supplementation DHA% levels may be a necessary target for antidepressant response to fish oil, and that this may depend to some extent on the efficacy of EPA conversion to DHA.
Communication skills are paramount in all areas of medicine but particularly in psychiatry due to the challenges posed by mental health patients and the essential role of communication from diagnosis to treatment. Despite the prevalence of psychiatric disorders in different medical specialties, particularly in primary care settings, communication skills in psychiatry and their training are not well studied and are often not included in the undergraduate medical curriculum. Our paper explores the relevance of teaching communication competencies in psychiatry for undergraduate medical students. Our work focused on reviewing the methods for teaching communication skills to undergraduate students in Psychiatry. Eleven studies were selected to be included in this review. We found considerable heterogeneity among methods for teaching communication skills but also some common elements such as the use of simulated patients and providing feedback. This review has identified two models: the Calgary–Cambridge interview model and the Kolb cycle-based model. However, most studies still lack a theoretical background model. We believe that the inclusion of communication skills training in medical curricula is fundamental to teaching medical students general communication skills but also specific training on establishing adequate communication with psychiatric patients. However, more research is needed to determine the best method for training but also regarding its translation to patient care and cost-effectiveness.
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