Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis.

BACKGROUND: Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature. METHODS: We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables. FINDINGS: From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial. INTERPRETATION: Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm. FUNDING: None.

Impact of different surgical and non-surgical interventions on health-related quality of life after thoracolumbar burst fractures without neurological deficit: protocol for a comprehensive systematic review with network meta-analysis.

INTRODUCTION: There is no international consensus on how to treat thoracolumbar burst fractures (TLBFs) without neurological deficits. The planned systematic review with network meta-analyses (NMA) aims to compare the effects on treatment outcomes, focusing on midterm health-related quality of life (HRQoL). METHODS AND ANALYSIS: We will conduct a comprehensive and systematic literature search, identifying studies comparing two or more treatment modalities. We will search MEDLINE, EMBASE, Google Scholar, Scopus and Web of Science from January 2000 until July 2023 for publications. We will include (randomised and non-randomised) controlled clinical trials assessing surgical and non-surgical treatment methods for adults with TLBF. Screening of references, data extraction and risk of bias (RoB) assessment will be done independently by two reviewers. We will extract relevant studies, participants and intervention characteristics. The RoB will be assessed using the revised Cochrane RoB V.2.0 tool for randomised trials and the Newcastle-Ottawa Scale for controlled trials. The OR for dichotomous data and standardised mean differences for continuous data will be presented with their respective 95% CIs. We will conduct a random-effects NMA to assess the treatments and determine the superiority of the therapeutic approaches. Our primary outcomes will be midterm (6 months to 2 years after injury) overall HRQoL and pain. Secondary outcomes will include radiological or clinical findings. We will present network graphs, forest plots and relative rankings on plotted rankograms corresponding to the treatment rank probabilities. The ranking results will be represented by the area under the cumulative ranking curve. Analyses will be performed in Stata V.16.1 and R. The quality of the evidence will be evaluated according to the Grading of Recommendations, Assessment, Development and Evaluations framework. ETHICS AND DISSEMINATION: Ethical approval is not required. The research will be published in a peer-reviewed journal.

Presentations to the Emergency Department for Problems Related to Mental Health: Sex Differences in Adolescents.

BACKGROUND: Adolescents aged sixteen to eighteen years are mostly treated in adult emergency departments. In a study at our tertiary adult emergency department (ED) at the University Hospital in Bern (Inselspital), Switzerland, we found that adolescents significantly more often present with psychiatric problems than adults. The study at hand aimed to characterise those adolescents presenting to the ED triaged with a chief complaint regarding mental health. Furthermore, the goal was to assess sex differences in terms of diagnosis, suicidal ideation, substance use, as well as social impact. METHODS: We conducted a single-centre, retrospective review of presentations to our adult ED related to the mental health of adolescents aged 16 to 18 years, covering the period from January 2013 to July 2017. Anonymised data were extracted from medical reports referring to the ED visits that were triaged as mental-health-related, and we assessed these for diagnosis, acute and previous suicidal ideation, history of self-harm, external aggression, substance use and social problems. We focused on patient characterisation and defining sex differences. RESULTS: Data were analysed for a total of 612 consultations by adolescents who presented to our ED with problems related to mental health. Women accounted for 61.1% of cases. The most frequent diagnoses were reactions to severe stress and adjustment disorders (19.1%), followed by alcohol use disorders (17.6%), intentional self-harm (17.3%), and affective disorders (13.7%). Males had lower odds for intentional self-harm (OR 0.10, 95% 0.05-0.21, p < 0.001) as well as disorders of personality and behaviour (OR 0.09, 95% 0.21-0.37, p < 0.001), whereas they had higher odds of being admitted due to use of alcohol (OR 2.51, 95% 1.65-3.83, p < 0.001). Of all cases, 31.7% reported acute suicidal ideation, with a significantly lower odds ratio in males (OR 0.58, 95% 0.41-0.84, p = 0.004). The most common source for referral to the ED was family members (25.2%). Males had twice the odds of reporting alcohol consumption as well as use of cannabis (in both cases p < 0.001). In 27.9% of all cases, familial problems were reported, with males having significantly lower odds of being exposed to these (OR 0.64, 95% 0.44-0.94, p = 0.021), whereas they had higher odds of reporting educational problems (OR 1.68, 95% 1.04-2.72, p = 0.035). CONCLUSIONS: Adolescents aged sixteen to eighteen years presenting to the ED with problems related to mental health are an important subgroup of ED presentations and should be thoroughly assessed for suicidal ideation, substance use, as well as familial and educational problems. Assessment and establishment of post-ED care are of particular importance in this vulnerable patient group.

Hyperthyroidism and clinical depression: a systematic review and meta-analysis.

Hyperthyroidism and clinical depression are common, and there is preliminary evidence of substantial comorbidity. The extent of the association in the general population, however, has not yet been estimated meta-analytically. Therefore we conducted this systematic review and meta-analysis (registered in PROSPERO: CRD42020164791). Until May 2020, Medline (via PubMed), PsycINFO, and Embase databases were systematically searched for studies on the association of hyperthyroidism and clinical depression, without language or date restrictions. Two reviewers independently selected epidemiological studies providing laboratory or ICD-based diagnoses of hyperthyroidism and diagnoses of depression according to operationalized criteria (e.g. DSM) or to cut-offs in established rating scales. All data, including study quality based on the Newcastle-Ottawa Scale, were independently extracted by two authors. Odds ratios for the association of clinical depression and hyperthyroidism were calculated in a DerSimonian-Laird random-effects meta-analysis. Out of 3372 papers screened we selected 15 studies on 239 608 subjects, with 61% women and a mean age of 50. Relative to euthyroid individuals, patients with hyperthyroidism had a higher chance of being diagnosed with clinical depression: OR 1.67 ([95% CI: 1.49; 1.87], I2: 6%; prediction interval: 1.40 to 1.99), a result supported in a number of sensitivity and subgroup analyses. The OR was slightly less pronounced for subclinical as opposed to overt hyperthyroidism (1.36 [1.06; 1.74] vs. 1.70 [1.49; 1.93]). This comorbidity calls for clinical awareness and its reasons need investigation and may include neurobiological mechanisms, common genetic vulnerability and a generally heightened risk for clinical depression in patients with chronic somatic disorders.

Dose effects of tricyclic antidepressants in the treatment of acute depression - A systematic review and meta-analysis of randomized trials.

BACKGROUND: Tricyclic antidepressants (TCA) continue to be an important group of drugs, but it is unclear whether a dose-response relationship is supported by high-level evidence. METHODS: Systematic review in the Cochrane Collaboration's Central Register of Controlled Trials (CENTRAL) of studies randomizing patients to at least two doses of one TCA, complemented by searches in Medline, Embase, and PsycInfo. In multilevel regression, we calculated the standardized mean difference (SMD) in antidepressant efficacy per mg TCA dose increase, and we analyzed drop-outs due to adverse events. Finally, we computed random effects meta-analyses of all dose comparisons investigated in a minimum of two studies. RESULTS: Out of 5365 studies screened, we included 15 randomized trials on 24 comparisons of 14 different dose contrasts. We found a statistically non-significant positive effect of increasing the dose: 0.34 SMD with 100 mg/d dose increase ([-0.03; 0.70] p = 0.073). While several comparisons showed no clear signal of a dose gradient, 300 mg of imipramine/desipramine is statistically significantly superior to 150 mg (SMD: 0.80 [0.28; 1.33], p = 0.003, I2: 0%). Drop-outs increased with higher doses, albeit not statistically significantly: Odds ratio (OR) of 1.44 with 100 mg dose increase [0.54; 3.86]. Overall, risk of bias was high. LIMITATIONS: Limited number of studies with mainly high risk of bias. CONCLUSIONS: So far, data on a dose-response relationship in TCAs from direct dose comparisons are inconclusive. Clinically, escalation to high doses may be justified if side effects are bearable.

Structured Interventions to Optimize Polypharmacy in Psychiatric Treatment and Nursing Homes: A Systematic Review.

BACKGROUND: Polypharmacy is a common clinical issue. It increases in prevalence with older age and comorbidities of patients and has been recognized as a major cause for treatment complications. In psychiatry, polypharmacy is also commonly seen in younger patients and can lead to reduced treatment satisfaction and incompliance. A variety of structured polypharmacy interventions have been investigated. This systematic review provides a comprehensive overview of the field and identifies research gaps. METHODS: We conducted a systematic review on structured interventions aimed at optimizing polypharmacy of psychotropic and somatic medication in psychiatric inpatient and outpatient settings as well as nursing homes. A search protocol was registered with PROSPERO (CRD42020187304). Data were synthesized narratively. RESULTS: Fifty-eight studies with a total of 30,554 participants met the inclusion criteria. Interventions were most commonly guided by self-developed or national guidelines, drug assessment scores, and lists of potentially inappropriate medications. Tools to identify underprescribing were less commonly used. Most frequently reported outcomes were quantitative drug-related measures; clinical outcomes such as falls, hospital admission, cognitive status, and neuropsychiatric symptom severity were reported less commonly. Reduction of polypharmacy and improvement of medication appropriateness were shown by most studies. CONCLUSIONS: Improvement of drug-related outcomes can be achieved by interventions such as individualized medication review and educational approaches in psychiatric settings and nursing homes. Changes in clinical outcomes, however, are often nonsubstantial and generally underreported. Patient selection and intervention procedures are highly heterogeneous. Future investigations should establish standards in intervention procedures, identify and assess patient-relevant outcome measures, and consider long-term follow-up assessments.

Combining Antidepressants vs Antidepressant Monotherapy for Treatment of Patients With Acute Depression: A Systematic Review and Meta-analysis.

IMPORTANCE: Combining antidepressants is frequently done in the treatment of acute depression, but studies have yielded conflicting results. OBJECTIVE: To conduct a systematic review and meta-analysis assessing efficacy and tolerability of combination therapy. Combinations using presynaptic α2-autoreceptor antagonists or bupropion were investigated separately. DATA SOURCES: MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were systematically searched from each database inception through January 2020. STUDY SELECTION: Randomized clinical trials (RCTs) comparing combinations of antidepressants with antidepressant monotherapy in adult patients with acute depression were included. DATA EXTRACTION AND SYNTHESIS: Following guidelines from Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and recommendations from the Cochrane Handbook, 2 reviewers independently performed a literature search, study selection, data extraction, and evaluation of risk of bias. Data were pooled in random-effects analyses. MAIN OUTCOMES AND MEASURES: Primary outcome was efficacy measured as standardized mean difference (SMD); secondary outcomes were response, remission, change from baseline in rating scale scores, number of dropouts, and number of dropouts due to adverse events. RESULTS: Thirty-nine RCTs including 6751 patients were eligible. Combination treatment was statistically significantly associated with superior treatment outcomes relative to monotherapy (SMD = 0.31; 95% CI, 0.19-0.44). Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors was superior to other combinations (SMD = 0.37; 95% CI, 0.19-0.55). Bupropion combinations were not superior to monotherapy (SMD = 0.10; 95% CI, -0.07 to 0.27). Numbers of dropouts and dropouts due to adverse events did not differ between treatments. Studies were heterogeneous, and there was indication of publication bias (Egger test result was positive; P = .007, df = 36), but results remained robust across prespecified secondary outcomes and sensitivity and subgroup analyses, including analyses restricted to studies with low risk of bias. CONCLUSIONS AND RELEVANCE: In this meta-analysis of RCTs comparing combinations of antidepressants with antidepressant monotherapy, combining antidepressants was associated with superior treatment outcomes but not with more patients dropping out of treatment. Combinations using an antagonist of presynaptic α2-autoreceptors may be preferable and may be applied as a first-line treatment in severe cases of depression and for patients considered nonresponders.

Offspring's risk for suicidal behaviour in relation to parental death by suicide: systematic review and meta-analysis and a model for familial transmission of suicide.

BACKGROUND: Exposure to parental suicide has been associated with increased risk for suicide and suicide attempts, although the strength of this association is unclear as evidence remains inconsistent. AIMS: To quantify this risk using meta-analysis and identify potential effect modifiers. METHOD: A systematic search in PubMed, PsycInfo and Embase databases to 2020 netted 3614 articles. Inclusion criteria were: observation of history of parental death by suicide, comparison with non-exposed populations and definition of suicide and suicide attempt according to standardised criteria. We focused on population-based studies. The primary outcome was the pooled relative risk (RR) for incidence of suicide attempt and suicide in offspring of a parent who died by suicide compared with offspring of two living parents. Additionally, we compared the RR for attempted and completed suicide after parental suicide with the RR for attempted and completed suicide after parental death by other causes. RESULTS: Twenty studies met our inclusion criteria. Offspring exposed to parental suicide were more likely to die by suicide (RR = 2.97, 95% CI 2.50-3.53) and attempt suicide (RR = 1.76, 95% CI 1.58-1.96) than offspring of two living parents. Furthermore, their risk of dying by or attempting suicide was significantly higher compared with offspring bereaved by other causes of death. CONCLUSIONS: The experience of losing a parent to suicide is a strong and independent risk factor for suicidal behaviour in offspring. Our findings highlight the need for prevention strategies, outreach programmes and support interventions that target suicide-related outcomes in the exposed population.

Association of Hypothyroidism and Clinical Depression: A Systematic Review and Meta-analysis.

Importance: Hypothyroidism is considered a cause of or a strong risk factor for depression, but recent studies provide conflicting evidence regarding the existence and the extent of the association. It is also unclear whether the link is largely due to subsyndromal depression or holds true for clinical depression. Objective: To estimate the association of hypothyroidism and clinical depression in the general population. Data Sources: PubMed, PsycINFO, and Embase databases were searched from inception until May 2020 for studies on the association of hypothyroidism and clinical depression. Study Selection: Two reviewers independently selected epidemiologic and population-based studies that provided laboratory or International Statistical Classification of Diseases and Related Health Problems diagnoses of hypothyroidism and diagnoses of depression according to operationalized criteria (eg, Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases and Related Health Problems) or cutoffs in established rating scales. Data Extraction and Synthesis: Two reviewers independently extracted data and evaluated studies based on the Newcastle-Ottawa Scale. Summary odds ratios (OR) were calculated in random-effects meta-analyses. Main Outcomes and Measures: Prespecified coprimary outcomes were the association of clinical depression with either hypothyroidism or autoimmunity. Results: Of 4350 articles screened, 25 studies were selected for meta-analysis, including 348 014 participants. Hypothyroidism and clinical depression were associated (OR, 1.30 [95% CI, 1.08-1.57]), while the OR for autoimmunity was inconclusive (1.24 [95% CI, 0.89-1.74]). Subgroup analyses revealed a stronger association with overt than with subclinical hypothyroidism, with ORs of 1.77 (95% CI, 1.13-2.77) and 1.13 (95% CI, 1.01-1.28), respectively. Sensitivity analyses resulted in more conservative estimates. In a post hoc analysis, the association was confirmed in female individuals (OR, 1.48 [95% CI, 1.18-1.85]) but not in male individuals (OR, 0.71 [95% CI, 0.40-1.25]). Conclusions and Relevance: In this systematic review and meta-analysis, the effect size for the association between hypothyroidism and clinical depression was considerably lower than previously assumed, and the modest association was possibly restricted to overt hypothyroidism and female individuals. Autoimmunity alone may not be the driving factor in this comorbidity.

[Lithium Withdrawal Symptoms - A Systematic Review]. / Entzugssyndrom nach dem Absetzen von Lithium ­ Eine systematische Literaturübersicht.

BACKGROUND: Withdrawal symptoms of lithium have not been systematically assessed to date. AIM: Systematic review of withdrawal symptoms after discontinuation of pharmacological treatment with lithium. METHODS: Systematic literature search in PubMed and reference lists of relevant articles. We included clinical trials and case reports. RESULTS: Out of 249 articles, six met our inclusion criteria, entailing six trials and a case series. Four trials and three case reports point to the existence of a withdrawal syndrome after discontinuation of lithium. Occurrence of symptoms was not dependent on the primary disorder for which lithium was initiated. Frequently reported symptoms were irritability, restlessness and somatic symptoms like vertigo, dizziness or lightheadedness. Symptoms occurred within the first week and were generally mild and self-limiting within weeks. CONCLUSION: Current evidence indicates that withdrawal symptoms after discontinuation of lithium can occur. There is a need for controlled studies of high methodological quality in order to assess predictors of and prevention strategies for discontinuation syndromes.

Mental health effects of infection containment strategies: quarantine and isolation-a systematic review and meta-analysis.

Due to the ongoing COVID-19 pandemic, an unprecedented number of people worldwide is currently affected by quarantine or isolation. These measures have been suggested to negatively impact on mental health. We conducted the first systematic literature review and meta-analysis assessing the psychological effects in both quarantined and isolated persons compared to non-quarantined and non-isolated persons. PubMed, PsycINFO, and Embase databases were searched for studies until April 22, 2020 (Prospero Registration-No.: CRD42020180043). We followed PRISMA and MOOSE guidelines for data extraction and synthesis and the Newcastle-Ottawa Scale for assessing risk of bias of included studies. A random-effects model was implemented to pool effect sizes of included studies. The primary outcomes were depression, anxiety, and stress-related disorders. All other psychological parameters, such as anger, were reported as secondary outcomes. Out of 6807 screened articles, 25 studies were included in our analyses. Compared to controls, individuals experiencing isolation or quarantine were at increased risk for adverse mental health outcomes, particularly after containment duration of 1 week or longer. Effect sizes were summarized for depressive disorders (odds ratio 2.795; 95% CI 1.467-5.324), anxiety disorders (odds ratio 2.0; 95% CI 0.883-4.527), and stress-related disorders (odds ratio 2.742; 95% CI 1.496-5.027). Among secondary outcomes, elevated levels of anger were reported most consistently. There is compelling evidence for adverse mental health effects of isolation and quarantine, in particular depression, anxiety, stress-related disorders, and anger. Reported determinants can help identify populations at risk and our findings may serve as an evidence-base for prevention and management strategies.

Controlled drinking-non-abstinent versus abstinent treatment goals in alcohol use disorder: a systematic review, meta-analysis and meta-regression.

BACKGROUND AND AIMS: The proportion of untreated patients with alcohol use disorder (AUD) exceeds that of any other mental health disorder, and treatment alternatives are needed. A widely discussed strategy is to depart from the abstinence paradigm as part of controlled drinking approaches. This first systematic review with meta-analysis aims to assess the efficacy of non-abstinent treatment strategies compared with abstinence-based strategies. METHODS: CENTRAL, PubMed, PsycINFO and Embase databases were searched until February 2019 for controlled (randomized and non-randomized) clinical trials (RCTs and non-RCTs) among adult AUD populations, including an intervention group aiming at controlled drinking and a control group aiming for abstinence. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Collaboration guidelines, literature search, data collection and risk of bias assessment were carried out independently by two reviewers [International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD42019128716]. The primary outcome was the proportion of participants consuming alcohol at or below the recommended threshold. Secondary outcomes were social functioning, drinking reductions, abstinence rates and dropouts. Using random-effects models, RCTs and non-RCTs were analyzed separately. Sensitivity and subgroup analyses accounted for methodological rigor, inclusion of goal-specific treatment, length of follow-up and AUD severity. RESULTS: Twenty-two studies (including five RCTs) with 4204 patients were selected. There was no statistically significant difference between both treatment paradigms in RCTs [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 0.51-3.39]. Non-randomized studies of free goal choice favored abstinence-orientation (OR = 0.60, 95% CI = 0.40-0.90), unless goal-specific treatment was provided (OR = 0.79, 95% CI = 0.40-1.56), or in studies of low risk of bias (OR = 0.73, 95% CI = 0.49-1.09) or with long follow-up (OR = 1.49, 95% CI = 0.78-2.85). Effect sizes were not clearly dependent upon AUD severity. Abstinence- and controlled drinking interventions did not clearly differ in their effect on social functioning and drinking reductions. CONCLUSIONS: Available evidence does not support abstinence as the only approach in the treatment of alcohol use disorder. Controlled drinking, particularly if supported by specific psychotherapy, appears to be a viable option where an abstinence-oriented approach is not applicable.

Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis.

OBJECTIVE: Avoiding withdrawal symptoms following antipsychotic discontinuation is an important factor when planning a safe therapy. We performed a systematic review and meta-analysis concerning occurrence of withdrawal symptoms after discontinuation of antipsychotics. DATA SOURCES: We searched the databases CENTRAL, Pubmed, and EMBASE with no restriction to the beginning of the searched time period and until October 1, 2019 (PROSPERO registration no. CRD42019119148). STUDY SELECTION: Of the 18,043 screened studies, controlled and cohort trials that assessed withdrawal symptoms after discontinuation of oral antipsychotics were included in the random-effects model. Studies that did not implement placebo substitution were excluded from analyses. The primary outcome was the proportion of individuals with withdrawal symptoms after antipsychotic discontinuation. We compared a control group with continued antipsychotic treatment in the assessment of odds ratio and number needed to harm (NNH). DATA EXTRACTION: We followed guidelines by the Cochrane Collaboration, PRISMA, and MOOSE. RESULTS: Five studies with a total of 261 individuals were included. The primary outcome, proportion of individuals with withdrawal symptoms after antipsychotic discontinuation, was 0.53 (95% CI, 0.37-0.70; I2 = 82.98%, P < 0.01). An odds ratio of 7.97 (95% CI, 2.39-26.58; I2 = 82.7%, P = 0.003) and NNH of 3 was calculated for the occurrence of withdrawal symptoms after antipsychotic discontinuation. CONCLUSION: Withdrawal symptoms appear to occur frequently after abrupt discontinuation of an oral antipsychotic. The lack of randomized controlled trials with low risk of bias on antipsychotic withdrawal symptoms highlights the need for further research.

Correction to: Migration and schizophrenia: meta-analysis and explanatory framework.

In the original article, the reference number #36 is listed with the wrong list of authors. The first author was unfortunately omitted. The correct reference #36 should read: Lasalvia A, Bonetto C, Tosato S, Cristofalo D, Salazzari D et al (2014) First-contact incidence of psychosis in north-eastern Italy: influence of age, gender, immigration and socioeconomic deprivation. Br J Psychiatry 205:127-134. https://doi.org/10.1192/bjp.bp.113.134445 .Additionally, this reference is cited in Table 1 and Fig. 2 as "Bonetto (2015)" and the correct citation is "Lasalvia (2014)".

Migration and schizophrenia: meta-analysis and explanatory framework.

Systematic reviews and meta-analyses suggest that there are increased rates of schizophrenia and related psychoses in first- and second-generation migrants and refugees. Here, we present a meta-analysis on the incidence of non-affective psychotic disorders among first- and second-generation migrants. We found substantial evidence for an increased relative risk of incidence among first- and second-generation migrants compared to the native population. As heterogeneity of included studies was high, effect estimates should be interpreted with caution and as guiding values rather than exact risk estimates. We interpret our findings in the context of social exclusion and isolation stress, and provide an explanatory framework that links cultural differences in verbal communication and experienced discrimination with the emergence of psychotic experiences and their neurobiological correlates. In this context, we discuss studies observing stress-dependent alterations of dopamine neurotransmission in studies among migrants versus non-migrants as well as in subjects with psychotic disorders. We suggest that social stress effects can impair contextualization of the meaning of verbal messages, which can be accounted for in Bayesian terms by a reduced precision of prior beliefs relative to sensory data, causing increased prediction errors and resulting in a shift towards the literal or "concrete" meaning of words. Compensatory alterations in higher-level beliefs, e.g., in the form of generalized interpretations of ambiguous interactions as hostile behavior, may contribute to psychotic experiences in migrants. We thus suggest that experienced discrimination and social exclusion is at the core of increased rates of psychotic experiences in subjects with a migration background.

Resource consumption of multi-substance users in the emergency room: A neglected patient group.

BACKGROUND: Multi-substance use is accompanied by increased morbidity and mortality and responsible for a large number of emergency department (ED) consultations. To improve the treatment for this vulnerable group of patients, it is important to quantify and break down in detail the ED resources used during the ED treatment of multi-substance users. METHODS: This retrospective single centre case-control study included all ED consultations of multi-substance users over a three-year study period at a university hospital in Switzerland. Resource consumption of these patients was compared to an age-matched control group of non-multi-substance users. RESULTS: The analysis includes 867 ED consultations of multi-substance users compared to 4,335 age-matched controls (5:1). Multi-substance users needed more total resources (median tax points [medical currency] (IQR): 762 (459-1226) vs. 462 (196-833), p<0.001), especially physician, radiology, and laboratory resources. This difference persisted in multivariable analysis (geometric mean ratio (GMR) 1.2, 95% CI: 1.1-1.3, p = 0.001) adjusted for sociodemographic parameters, consultation characteristics, and patient comorbidity; the GMR was highest in ED laboratory and radiology resource consumption. Among multi-substance user, indirect and non-drug-related consultations had higher ED resource consumption compared to drug-related consultations. Furthermore, leading discipline as well as urgency were predictors of ED resource consumption. Moreover, multi-substance users had more revisits (55.2% vs. 24.9%, p<0.001) as well as longer ED and in-hospital stays (both: GMR 1.2, 95% CI: 1.1-1.3, p<0.001). CONCLUSION: ED consultations of multi-substance users are expensive and resource intensive. Multi-substance users visited the ED more often and stayed longer at the ED and in-hospital. The findings of our study underline the importance of this patient group. Additional efforts should be made to improve their ED care. Special interventions should target this patient group in order to decrease the high frequency and costs of emergency consultations caused by multi-substance users.

Risk of Psychosis Among Refugees: A Systematic Review and Meta-analysis.

Importance: This systematic review and meta-analysis is, to date, the first and most comprehensive to focus on the incidence of nonaffective psychoses among refugees. Objective: To assess the relative risk (RR) of incidence of nonaffective psychosis in refugees compared with the RR in the native population and nonrefugee migrants. Data Sources: PubMed, PsycINFO, and Embase databases were searched for studies from January 1, 1977, to March 8, 2018, with no language restrictions (PROSPERO registration No. CRD42018106740). Study Selection: Studies conducted in Denmark, Sweden, Norway, and Canada were selected by multiple independent reviewers. Inclusion criteria were (1) observation of refugee history in participants, (2) assessment of effect size and spread, (3) adjustment for sex, (4) definition of nonaffective psychosis according to standardized operationalized criteria, and (5) comparators were either nonrefugee migrants or the native population. Studies observing ethnic background only, with no explicit definition of refugee status, were excluded. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for extracting data and assessing data quality and validity as well as risk of bias of included studies. A random-effects model was created to pool the effect sizes of included studies. Main Outcomes and Measures: The primary outcome, formulated before data collection, was the pooled RR in refugees compared with the nonrefugee population. Results: Of the 4358 screened articles, 9 studies (0.2%) involving 540 000 refugees in Denmark, Sweden, Norway, and Canada were included in the analyses. The RR for nonaffective psychoses in refugees was 1.43 (95% CI, 1.00-2.05; I2 = 96.3%) compared with nonrefugee migrants. Analyses that were restricted to studies with low risk of bias had an RR of 1.39 (95% CI, 1.23-1.58; I2 = 0.0%) for refugees compared with nonrefugee migrants, 2.41 (95% CI, 1.51-3.85; I2 = 96.3%) for refugees compared with the native population, and 1.92 (95% CI, 1.02-3.62; I2 = 97.0%) for nonrefugee migrants compared with the native group. Exclusion of studies that defined refugee status not individually but only by country of origin resulted in an RR of 2.24 (95% CI, 1.12-4.49; I2 = 96.8%) for refugees compared with nonrefugee migrants and an RR of 3.26 (95% CI, 1.87-5.70; I2 = 97.6%) for refugees compared with the native group. In general, the RR of nonaffective psychosis was increased in refugees and nonrefugee migrants compared with the native population. Conclusions and Relevance: Refugee experience appeared to be an independent risk factor in developing nonaffective psychosis among refugees in Denmark, Sweden, Norway, and Canada. These findings suggest that applying the conclusions to non-Scandinavian countries should include a consideration of the characteristics of the native society and its specific interaction with the refugee population.