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Objective: Increasing evidence suggests that immunological and inflammatory dysfunctions may play an important role in predisposition, onset, and progression of schizophrenia and related psychosis. The activation of cells of the mononuclear phagocyte system, especially microglia and monocytes, has been reported in schizophrenia. We carried out this systematic review and meta-analysis to investigate if there are significant differences in monocyte count comparing healthy controls with people suffering from schizophrenia and related disorders. Methods: We searched main electronic databases; nine records met all our criteria and were included in the meta-analysis. Meta-analyses based on random effects models have been carried out generating pooled standardised mean differences (SMDs) of monocyte count in peripheral blood between schizophrenia and related psychosis and healthy controls. Heterogeneity was estimated. Relevant sensitivity and subgroup analyses were conducted. Results: Patients showed higher monocyte count as compared with healthy control (SMD = 0.393; p = 0.001). Heterogeneity across studies was from moderate to high (I2 = 65.952%); sensitivity analysis leaving out two studies responsible for most of the heterogeneity showed a slightly higher SMD. Subgroup analyses confirmed this result, showing no significant differences in the effect size across different study characteristics. Conclusions: Monocyte count can be considered an indirect marker of microglia activation in the central nervous system. Thus, the observed higher monocyte count in patients could be considered as a possible peripheral marker of microgliaʼs activation in schizophrenia disorder. [ABSTRACT FROM AUTHOR]

Objectives: Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR, MLR and PLR in non-affective psychosis. Methods: Eight studies have been identified from the main electronic databases. Meta-analyses based on random-effects models have been carried out generating pooled standardised mean differences (SMDs) between non-affective psychotic patients and healthy controls (HCs). Results: Subjects with non-affective psychosis had a significant higher NLR and MLR as compared with HC (respectively SMD = 0.715; P < 0.001; I2=57.565% and SMD = 0.417; P = 0.001; I2=65.754%), confirmed by heterogeneity-based sensitivity analysis. Subgroup analyses showed no differences in effect size across different study characteristics, including drug treatment status, diagnosis, and setting. Meta-regression showed that age influenced the relationship between non-affective psychosis and MLR. A trend of significance, not confirmed by heterogeneity-based sensitivity analysis, was observed in PLR with patients showing higher PLR than HC. Conclusions: Our meta-analysis supports the hypothesis that an inflammatory activation occurs in non-affective psychosis and inflammatory ratios, especially NLR and MLR, may be useful to detect this activation. [ABSTRACT FROM AUTHOR]

Background: Subjects with intellectual disability (ID) are vulnerable to experience psychiatric disorders. The present authors performed a systematic review and meta‐analysis to estimate the prevalence of co‐occurring psychiatric disorders, excluding co‐occurring autism spectrum disorders, in subjects with intellectual disability. Method: The present authors performed a random‐effects meta‐analysis of the prevalence of psychiatric disorders in adults and adolescents with intellectual disability. Results: Twenty‐two studies were included. The pooled prevalence of any co‐occurring psychiatric disorders in intellectual disability was 33.6% (95% CI: 25.2%–43.1%) with high heterogeneity but no publication bias. Prevalence was lower in population‐based studies, in studies that used ICD criteria for the psychopathology and in studies with low risk of bias. The prevalence was higher in mild, moderate and severe intellectual disability than in profound intellectual disability. Conclusions: Psychiatric disorders are common in subjects with intellectual disability, and the present authors found that clinical and methodological moderators affect the pooled prevalence. [ABSTRACT FROM AUTHOR]

Background: Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania.Methods: We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy.Results: Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98).Conclusions: Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the epidemiological impact of suicidal ideation after stroke is required to identify subjects needing personalised interventions.Objective: The aim of this meta-analysis was to estimate rates and correlates of suicidal ideation among stroke survivors.Methods: We searched via Ovid, Medline, Embase and PsycInfo from database inception until August 2016. Predefined outcomes were (1) rates of suicidal ideation based on random-effects pooled proportion and (2) relevant sociodemographic and clinical correlates, using random-effects odds ratio (OR) or standardised mean difference (SMD) for categorical and continuous variables, respectively.Results: Fifteen studies and 13 independent samples, accounting for 10 400 subjects, were included in meta-analyses. The pooled proportion of suicidal ideation among stroke survivors was 11.8% (7.4% to 16.2%), with high heterogeneity across studies (I2=97.3%). Current (OR=11.50; p<0.001) and past (OR=6.96; p<0.001) depression, recurrent stroke (OR=1.77; p<0.001), disability (SMD=0.58; p=0.01) and cognitive impairment (SMD=-0.22; p=0.03) were all associated with suicidal ideation. Moreover, suicidal ideation was less likely in stroke survivors who were married (OR=0.63; p<0.001), employed (OR=0.57; p=0.02) and had higher education levels (OR=0.55; p=0.002).Conclusion: Despite some limitations, this meta-analysis shows that about one out of eight stroke survivors has suicidal ideation. Thus, there is enough evidence to support the use of routine screening and early interventions to prevent and treat suicidal ideation after stroke, especially among subjects carrying specific correlates. [ABSTRACT FROM AUTHOR]

Objective: Depression and neuropathy are frequent complications of type 2 diabetes. The current meta-analysis aimed to estimate the association between depression and neuropathy in subjects with type 2 diabetes.Methods: We systematically searched electronic databases for articles published up to February 2015, providing data on the association between depression and neuropathy in individuals with type 2 diabetes. No language restrictions were applied. The meta-analysis generated random-effect odds ratios with 95% confidence intervals (95% CI). Risk of publication bias and heterogeneity were estimated using the Egger test and I(2) index, respectively. Leave-one-out analysis was performed. Data were analysed using stata.Results: Thirteen studies were included in the meta-analysis. Data on the association between depression and neuropathy were available for 3898 individuals with type 2 diabetes. Pooled analysis showed an association between depression and neuropathy, with an odds ratio of 2.01 (95% CI: 1.60-2.54; p < 0.001). There was no risk of publication bias (p = 0.064), and heterogeneity was moderate (I(2)  = 44.5%). Leave-one-out analysis confirmed consistency of the findings. The association appeared partly influenced by age, because studies selecting older people (sample mean age > 65 years) showed a slightly higher estimate for the association.Conclusions: We found an association between depression and neuropathy among people with type 2 diabetes. Because of the cross-sectional nature of included studies, the relationship between these two conditions might be bidirectional. Further research exploring factors that might moderate or mediate this association is needed. Targeted interventions for comorbid depression and neuropathy should be implemented in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Previous reports showed a high prevalence of obesity, diabetes, hypertension, and dyslipidemia among people suffering from posttraumatic stress disorder (PTSD). However, there is a lack of reviews that systematically analyze the relationship between PTSD and metabolic syndrome. We conducted a systematic review and meta-analysis aimed at estimating the association between PTSD and metabolic syndrome. Methods: We systematically searched PubMed, Embase, and Web of Science. We included observational studies assessing the prevalence of metabolic syndrome in a sample with PTSD and in a comparison group without PTSD. Data were analyzed using Review manager 5.1. Odds ratios (OR) with 95% confidence intervals were used as an association measure for pooled analysis, based on a random-effects model. Results: Six articles were eligible according to the inclusion criteria, for an overall number of 528 individuals suffering from PTSD and 846 controls without PTSD. The pooled OR for metabolic syndrome for people with PTSD was 1.37 (1.03-1.82). Statistical heterogeneity between the included studies was low ( I2=22%). Conclusions: Despite some limitations, the findings of this systematic review and meta-analysis confirmed our hypothesis that individuals suffering from PTSD have a greater risk of metabolic syndrome. The potential role of unknown factors or mediators that might clarify the nature of this association needs further research. [ABSTRACT FROM AUTHOR]

Background. Depression after stroke may have great burden on the likelihood of functional recovery and long-term outcomes. Objective. To estimate the association between depression after stroke and subsequent mortality. Methods. A systematic search of articles using PubMed and Web of Science databases was performed. Odds ratios (ORs) and hazard ratios (HRs) were used as association measures for pooled analyses, based on random-effects models. Results. Thirteen studies, involving 59,598 subjects suffering from stroke (6,052 with and 53,546 without depression), had data suitable for meta-analysis. The pooled OR for mortality at followup in people suffering from depression after stroke was 1.22 (1.02-1.47). Subgroups analyses highlighted that only studies with medium-term followup (2-5 years) showed a statistically significant association between depression and risk of death. Four studies had data suitable for further analysis of pooled HR. The meta-analysis revealed a HR for mortality of 1.52 (1.02-2.26) among people with depression after stroke. Conclusions. Despite some limitations, this paper confirms the potential role of depression on post stroke mortality. The relationship between depression and mortality after stroke seems to be related to the followup duration. Further research is needed to clarify the nature of the association between depression after stroke and mortality. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "International Society for Bipolar Disorders Task Force on Suicide: Meta-Analyses and Meta-Regression of Correlates of Suicide Attempts and Suicide Deaths in Bipolar Disorder" by A. Schaffer and colleagues in a 2014 issue.

A letter to the editor is presented in response to the article "Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators," by D. Vancampfort and colleagues in March 2013 issue.

People with schizophrenia treated with second-generation antipsychotics (SGAs) have lower plasma adiponectin levels, as compared with general population, that may lead to metabolic abnormalities. However, the contribution of different SGAs on adiponectin dysregulation is still unclear. The objective of this systematic review and meta-analysis was to estimate differences in adiponectin levels among people with schizophrenia treated with different SGAs. We systematically searched for observational studies published up to March 2015 in main electronic databases. Different SGAs were included if data on adiponectin were available from at least three different samples involving as a minimum five participants per treatment arm. Standardized mean differences with relevant 95% confidence intervals were generated. I 2 was used to test heterogeneity among studies. Eight studies were included with data suitable for carrying out four different comparisons: Clozapine vs. Olanzapine (including n =877 individuals with schizophrenia); Clozapine vs. Risperidone ( n =660); Olanzapine vs. Risperidone ( n =738); Quetiapine vs. Risperidone ( n =186). There were no differences on adiponectin levels between people taking Clozapine and those taking Olanzapine ( p =0.86), but high heterogeneity was detected ( I 2 =82%). Both individuals taking Clozapine ( p <0.001; I 2 =0%) and those taking Olanzapine ( p =0.02; I 2 =9%), but not subjects treated with Quetiapine ( p =0.47; I 2 =0%), had adiponectin levels significantly lower than people taking Risperidone. Our findings are consistent with previous evidence showing greater metabolic abnormalities attributable to Clozapine and Olanzapine, as compared with other SGAs. Although mechanisms whereby both these SGAs influence adiponectin remain unexplained, its reduction might mediate relevant abnormalities. Prospective evaluations of long-term effects of different SGAs on adiponectin are needed. [ABSTRACT FROM AUTHOR]

Abstract A fair amount of subjects with schizophrenia do not respond to clozapine and are defined 'ultra-resistant'. In this systematic review and meta-analysis, we tested the efficacy of adjunctive second-generation antipsychotics (SGAs) for main symptom domains (positive, negative, and depressive symptoms) in individuals with clozapine-resistant schizophrenia. We searched main electronic databases till December 2017. We included twelve double-blind, randomized, placebo-controlled trials (RCTs), evaluating the efficacy of SGAs for clozapine non/partial responders. We did not find any difference between SGAs and placebo (standardized mean difference, SMD = −0.21; p = 0.170; I2 = 68.0%) in improving positive symptoms. The effect size varied according to RCT duration (p = 0.025) and assessment methods (p = 0.016). Low-moderate effects of SGAs on both negative (SMD = −0.38; p = 0.005; I2 = 62.7%) and depressive symptoms (SMD = −0.35; p = 0.003; I2 = 4.9%), were estimated. In sum, our meta-analysis highlights the lack of efficacy of SGAs as add-on treatment for positive symptoms in clozapine-resistant schizophrenia. A small benefit of SGAs was estimated for both negative and depressive symptoms. Further RCTs are needed to establish efficacy and tolerability of SGAs or other augmentation strategies for different symptoms of clozapine-resistant schizophrenia. Highlights • Twelve RCTs are included in this meta-analysis on clozapine-resistant schizophrenia. • Clozapine augmentation with a SGA shows no improvement in positive symptoms. • Small effect is estimated for negative and depressive symptoms. • Adjunctive SGAs in clozapine-resistant schizophrenia have only partial benefit. [ABSTRACT FROM AUTHOR]

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p < 0.001; I 2  = 82.4% and SMD = 0.425; p = 0.048; I 2  = 86.53%). Heterogeneity-based sensitivity analyses confirmed these findings. Subgroup analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. [ABSTRACT FROM AUTHOR]

Evidence suggests an association between low lipid levels and suicidality in subjects with severe mental disorders. This is the first systematic review and meta-analysis aimed at exploring differences in lipid profile between suicide attempters and non-attempters with bipolar disorder. We included observational studies providing comparative cross-sectional data on total cholesterol, LDL-cholesterol and triglycerides levels. We searched main Electronic Databases, identifying 11 studies that met our inclusion criteria, including also unpublished data. Meta-analyses based on random-effects models were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity among studies was estimated using the I 2 index. The meta-analyses included data on lipid profile from 11 studies based on 288 subjects with and 754 without suicide attempt, respectively. No differences in total cholesterol (SMD: − 0.10; 95%CI: − 0.30 to 0.10; p = 0.34), LDL-cholesterol (SMD: − 0.26; 95%CI: − 0.65 to 0.13; p = 0.19), and triglycerides (SMD: − 0.06; 95%CI: − 0.31 to 0.19; p = 0.63) were detected. Heterogeneity across studies was low-moderate and no risk of publication bias was found. Subgroup analyses showed no differences on effect size across different study characteristics, including different time-frames of suicide attempt, except for small sample size. Therefore, the evidence for an association between serum lipid profile and suicidality in bipolar disorder cannot be claimed. More research is needed to better understand the mechanisms underlying suicidal behaviours in bipolar patients, exploring further peripheral biomarkers as this may help clinicians screen and prevent suicidality. [ABSTRACT FROM AUTHOR]

Schizophrenia is likely to be associated with immunological abnormalities. However, antipsychotics may induce immunomodulatory effects, by influencing plasma cytokines. In order to distinguish these influences, we carried out a systematic review and meta-analysis exploring the acute effect of antipsychotics on candidate cytokines plasma levels (IL-1β, IL-2, IL-6, IL-17, IFN-γ, TNF-α) among drug-naïve subjects with first episode psychosis. We searched main Electronic Databases, identifying eight studies meeting our inclusion criteria. Plasma cytokines values were used to estimate standardized mean differences. Heterogeneity across studies was evaluated using the I 2 index and controlled in relevant sensitivity analyses. IL-2 (p = 0.023) and IL-6 (p = 0.012) levels showed a significant decrease after four weeks of antipsychotic treatment. Relevant sensitivity analysis confirmed these findings. IL-1β had high between-study heterogeneity. However, leaving out one study, a significant decrease after treatment was found. IL-6 and IL-2, and possibly IL-1β, could be considered state markers, decreasing after antipsychotic treatment, whilst TNF-α, IL-17, and IFN-γ might be considered trait markers. Options for novel treatments in FEP, involving cytokine-modulating agents, should be further studied. [ABSTRACT FROM AUTHOR]

The current systematic review and meta-analysis aimed at exploring acute effects of intravenous (IV) ketamine, an antagonist of N-methyl-D-aspartate (NMDA), in subjects with current suicidal ideation. We included clinical trials testing a single IV dose of ketamine and assessing changes in suicidal ideation within 4 h after treatment. Meta-analyses based on random-effects models, were carried out generating pooled standardized mean differences (SMDs) between endpoint and baseline scores. Heterogeneity among studies was estimated using the I 2 index. We searched main Electronic Databases, identifying five studies that met our inclusion criteria. The trials included 99 subjects treated with IV ketamine bolus or infusion. Data showed a large (SMD = −0.92; 95%CI: −1.40 to −0.44; p < 0.001) and consistent ( I 2 = 21.6%) decrease of suicidal ideation, with effects comparable between IV bolus and infusion ketamine. Additional analyses confirmed the efficacy of ketamine across different time points. However, relevant, emerging evidence should be considered as ‘very low’ so far. Randomized, controlled and adequately powered trials are needed. [ABSTRACT FROM AUTHOR]

The aim of this systematic review and meta-analysis was testing whether low versus high doses of second-generation antipsychotics (SGAs) are associated with different clinical benefits and harms for the acute treatment of bipolar depression. We included clinical trials comparing different doses of the same SGA monotherapy for bipolar depression. SGAs defined daily doses were used to define high and low doses. Clinical benefit outcomes included improvement, response and remission rates on Montgomery-Asberg Depression Rating Scale. Clinical harm outcomes included all-cause and adverse effect-related discontinuation rates. Data from seven clinical trials testing high and low doses of quetiapine (4 trials), cariprazine, lurasidone, and ziprasidone (1 trial each), showed no differences between lower and higher doses of selected SGAs on improvement, response and remission rates, without significant heterogeneity across studies (I 2 = 0%). Subgroup analyses based on single SGAs confirmed the clinical benefit comparability between low and high doses. However, clinical harm favorable differences for low doses on all-cause (p = 0.01) and adverse effects-related discontinuation (p = 0.001) were found. In sum, this meta-analysis showed that, although no benefits were found in terms of symptoms improvement, response and remission rates, there were clear disadvantages in prescribing higher rather than lower doses of selected SGAs. The uniform methodological strength of studies increases confidence in our findings. These data need to be integrated with individual patient characteristics (e.g., clinical urgency and adverse effect sensitivity) to optimize management of acute bipolar depression. [ABSTRACT FROM AUTHOR]

Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I 2 index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I 2 = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I 2 = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I 2 = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research. [ABSTRACT FROM AUTHOR]

People with alcohol and substance use disorders (AUDs/SUDs) show worse facial emotion recognition (FER) than controls, though magnitude and potential moderators remain unknown. The aim of this meta-analysis was to estimate the association between AUDs, SUDs and FER impairment. Electronic databases were searched through April 2015. Pooled analyses were based on standardized mean differences between index and control groups with 95% confidence intervals, weighting each study with random effects inverse variance models. Risk of publication bias and role of potential moderators, including task type, were explored. Nineteen of 70 studies assessed for eligibility met the inclusion criteria, comprising 1352 individuals, of whom 714 (53%) had AUDs or SUDs. The association between substance related disorders and FER performance showed an effect size of −0.67 (−0.95, −0.39), and −0.65 (−0.93, −0.37) for AUDs and SUDs, respectively. There was no publication bias and subgroup and sensitivity analyses based on potential moderators confirmed core results. Future longitudinal research should confirm these findings, clarifying the role of specific clinical issues of AUDs and SUDs. [ABSTRACT FROM AUTHOR]

Background People with schizophrenia are more likely than general population to suffer from metabolic abnormalities, with second-generation antipsychotics (SGAs) increasing the risk. Low plasma adiponectin levels may lead to metabolic dysregulations but evidence in people with schizophrenia, especially for the role of SGAs, is still inconclusive. Objective To compare plasma adiponectin levels between people with schizophrenia and healthy controls, and to estimate the relative effect of schizophrenia and SGAs on adiponectin. Methods We performed a systematic review and meta-analysis of observational studies published up to 13 June 2014 in main electronic databases. Pooled standardized mean differences (SMDs) between index and control groups were generated. Appropriate subanalyses and additional subgroup analyses were carried out. Results Data from 2735 individuals, 1013 with and 1722 without schizophrenia, respectively, were analysed. Schizophrenia was not associated with lower adiponectin levels (SMD of −0.28, 95%CI: −0.59, 0.04; p = 0.09). However, individuals with schizophrenia taking SGAs had plasma levels significantly lower than controls ( p = 0.002), which was not the case of drug free/drug naïve subjects ( p = 0.52). As regards single antipsychotic drugs clozapine ( p < 0.001) and olanzapine ( p = 0.04) – but not risperidone ( p = 0.88) – were associated with adiponectin levels lower than controls. Conclusions People with schizophrenia per se may not have levels of adiponectin lower than controls, though treatment with SGAs is associated with this metabolic abnormality. This bears clinical significance because of hypoadiponectinemia involvement in cardiovascular diseases, even if mechanisms whereby SGAs affect adiponectin remain unexplained. Longitudinal studies evaluating long-term effects of SGAs on adiponectin are needed. [ABSTRACT FROM AUTHOR]

Background Both individuals with bipolar (BD) and those with alcohol (AUD) and other substance (SUD) use disorders are likely to attempt suicide. Comorbidity of BD and AUD/SUD may increase the likelihood of suicide attempts. We conducted a meta-analysis to estimate the association of comorbid AUD/SUD and suicide attempts in subjects with BD in the literature to date. Methods Electronic databases through January 2013 were searched. Studies reporting rates of suicide attempts in people with co-occurring BD and AUD/SUD were retrieved. Comorbid AUD and SUD and suicide attempts rates as well as demographic, clinical, and methodological variables were extracted from each publication or obtained directly from its authors. Results Twenty-nine of 222 studies assessed for eligibility met the inclusion criteria, comprising a total of 31,294 individuals with BD, of whom 6308 (20.1%) had documented suicide attempts. There were consistent findings across the studies included. As compared to controls, subjects with BD and comorbid AUD/SUD were more likely to attempt suicide. The cross-sectional association estimates showed random-effects pooled crude ORs of 1.96 (95% CI=1.56–2.47; p <0.01), 1.72 (95% CI=1.52–1.95; p <0.01), and 1.77 (95% CI=1.49–2.10; p <0.01), for combined AUD/SUD, AUD, and SUD. There was no publication bias and sensitivity analyses based on the highest quality studies confirmed core results. Limitations The effects of the number and the type of suicide attempts could not be investigated due to insufficient information. Conclusions Comorbid AUD and SUD in individuals with BD are significantly associated with suicide attempts. Individuals with this comorbidity should be targeted for intensive suicide prevention efforts. [ABSTRACT FROM AUTHOR]

Abstract: Background: Assessing factors associated with non-fatal overdose is important as these could be useful to identify individuals with substance use disorders at high risk of adverse outcomes and consequences. Depression may play an important role in terms of overdose risk. We aimed to test if drug users suffering from a depressive disorder might have significantly higher risk of non-fatal overdose as compared with drug users without depression. Methods: We conducted a systematic review and meta-analysis. PubMed, Embase and Web of Knowledge were searched. The pooled analyses were based on prevalence rates, risk difference (RD) and odds ratio (OR), reporting 95% confidence intervals (CIs). The combined estimates were obtained weighting each study according to random effects model for meta-analysis. Results: Seven articles, involving 12,019 individuals, and run in the US, Canada, Sweden, Norway, and Australia, were included. Pooled analyses comparing depressed with not depressed individuals highlighted a RD (95% CIs) for non-fatal overdose of 7.3% (4.8–9.7%) and an OR (95% CIs) of 1.45 (1.17–1.79). The subgroups analyses based on specific characteristics of included studies confirmed the association between depression and overdose. Conclusions: Depressive disorders seem to be important factors associated to the risk of non-fatal overdose. Longitudinal studies might appropriately clarify causal inference issues. Future research should address the role of depressive disorders as predictors of subsequent non-fatal overdoses. [Copyright &y& Elsevier]