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Available evidence suggests that there is no effect of moon phases on suicidal behavior. However, a Finnish study recently reported elevated suicide rates during full-moon, but only among premenopausal women and only in winter. This could not be replicated in an Austrian study and stirred a discussion about whether the Finnish finding was false-positive or if there are unaccounted moderator variables differing between Finland and Austria. The goal of the present study was to provide another replication with data from Sweden, which is geographically more comparable to Finland than Austria. We also investigated the discussed moderator variables latitude and nightly artificial brightness. There were 48,537 suicides available for analysis. The fraction of suicides during the full-moon quarter in winter did not differ significantly from the expected 25% among premenopausal women (23.3%) and in the full sample (24.7%). The incidence risk ratios for full moon quarter in Poisson regression models were 0.96 (95% CI: 0.90-1.02) for premenopausal women and 1.01 (95% CI: 0.99-1.04) for the full sample. According to Bayes-factor analysis, the evidence supports the null-hypothesis (no association) over the alternative hypothesis (some association). We found similar results when we split the data by latitude and artificial nightly brightness, respectively. In line with the Austrian study, there was no increase of suicides in Sweden among premenopausal women in winter during full-moon. The results from the Finnish study are likely false positive, perhaps resulting from problematic but common research and publication practices, which we discuss.

Despite findings from previous studies, there is still little consistent knowledge regarding the co-occurrence patterns of somatic, depressive and anxiety symptoms in childhood and adolescence. Moreover, functional disability due to somatic symptoms at different concomitant levels of depression and anxiety is understudied. The present study examined the co-occurrence patterns of somatic symptoms and symptoms of depression and anxiety, in children and adolescents using two-step cluster analysis. Differences in functional disability due to somatic symptoms were tested with ANCOVA controlling for gender and age. The sample comprised 1127 Italian children and adolescents (48.7% males, n = 549) aged 8–16 years (Mage = 11.7, SD = 2.37). Data were collected using the Children Somatization Inventory-24, the Children Depression Inventory, the Screen for Child Anxiety Related Emotional Disorders, and the Functional Disability Inventory. A four-cluster solution based on the co-occurrence of internalizing symptoms best fit the data. The four clusters were labelled as follows: cluster 1: “High somatic symptoms and average depression/anxiety”; cluster 2: “High somatic symptoms and high depression/anxiety”; cluster 3: “Average somatic symptoms and above average depression/anxiety”; and cluster 4: “Low somatic symptoms and low depression/anxiety”. Significant differences between the four groups according to gender and age were shown. Participants with high levels of somatic, depressive, and anxiety symptoms reported greater functional disability due to somatic symptoms than the other three groups. Our findings indicate that children and adolescents who demonstrate high symptoms of depression and anxiety also reported higher levels of disability in daily life due to somatic symptoms.

The efficacy of antidepressants in the acute treatment of moderate-to-severe depression remains a controversial issue. The minimal important difference (MID) is relevant to judge the clinical significance of treatment effects. In this analysis paper, we discuss estimates of the MID for common depression outcome measures.For the Hamilton Depression Rating Scale 17-item Version (HDRS-17), according to both anchor-based and distribution-based approaches, MID estimates range from 3 to 8 points, and the most accurate values are likely between 3 and 5 points. For the 6-item version (HDRS-6), MID estimates range between 2 and 4 points. For both the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory II (BDI-II), MID estimates range between 3 and 9 points, with estimates of 3–6 points likely being the most accurate. Quality of life appears to be more important to patients than core depression symptoms. We thus also evaluated the Short-Form 36 (SF-36) mental component score, a popular mental-health-related quality of life measure. Its MID estimate is likely about 5 points. By contrast, the average treatment effects of antidepressants on the HDRS-17, HDRS-6, MADRS, BDI-II and SF-36 are 2 points, 1.5 points, 3 points, 2 points and 3–5 points, respectively.In conclusion, the efficacy of antidepressants in the acute treatment of moderate-to-severe depression consistently fails to exceed the lower bound of the MID estimates for common depression outcome measures. The clinical significance of antidepressants thus remains uncertain and we call for more research on quality of life measures, which are the patients’ most valued outcome domains.

Author(s): Hopwood, Christopher J; Krueger, Robert F; Watson, David; Widiger, Thomas A; Althoff, Robert R; Ansell, Emily B; Bach, Bo; Bagby, R Michael; Blais, Mark A; Bornovalova, Marina A; Chmielewski, Michael; Cicero, David C; Conway, Christopher; De Clerq, Barbara; De Fruyt, Filip; Docherty, Anna R; Eaton, Nicholas R; Edens, John F; Forbes, Miriam K; Forbush, Kelsie T; Hengartner, Michael P; Ivanova, Masha Y; Leising, Daniel; Lukowitsky, Mark R; Lynam, Donald R; Markon, Kristian E; Miller, Joshua D; Morey, Leslie C; Mullins-Sweatt, Stephanie N; Ormel, Johan; Patrick, Christopher J; Pincus, Aaron L; Ruggero, Camilo; Samuel, Douglas B; Sellbom, Martin; Tackett, Jennifer L; Thomas, Katherine M; Trull, Timothy J; Vachon, David D; Waldman, Irwin D; Waszczuk, Monika A; Waugh, Mark H; Wright, Aidan GC; Yalch, Mathew M; Zald, David H; Zimmermann, Johannes

Comments on the original article by Pittelkow et al. (see record 2021-72420-014) regarding replication target selection in clinical psychology. The failure to replicate research findings in psychology is a major scientific issue with important practical implications (Pashler & Harris, 2012), especially with respect to psychological interventions in people with serious mental health problems (Hengartner, 2018). The study by Pittelkow et al. (2021) in this issue is thus timely and commendable. They offer a standardized approach based on Bayes factors (BFs) and subsequent qualitative evaluation to determine which intervention studies in clinical psychology have uncertain or questionable evidential support and are thus in need of replication. Overall, for 42.6% of the statistically significant effects studied, the BFs indicated weak or no evidence for the claimed effect. As I detail below, this is likely an underestimate of the weakness of the evidence, since BFs do not take into account systematic research biases that inflate effect estimates. Nevertheless, this alarming finding corresponds reasonably well with the poor replicability of many research findings as demonstrated in previous studies. In the following, I will discuss some of these studies and offer suggestions as to how we could further improve the credibility of research findings.

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch), Previous studies have shown that specific personality dimensions, -e.g., the Big Five-, consistently intercorrelate, such that they form a general factor of personality (GFP). It has been hypothesized that the GFP reflects social effectiveness. Similarly, in the clinical domain, overlap between various psychopathological symptoms has also been reported, leading to a general factor of Psychopathology, or p factor. The aim of this study was to test the overlap between the higher order factors in personality and psychopathology, and how they relate to daily life functioning and communication style. We tested a sample of 165 outpatients of a psychological therapy institute, using a multi-source approach that included self-reports and other ratings. The outpatients’ self-reports of personality, general psychological problems, and interpersonal problems were available. Psychotherapists rated the outpatients’ functioning in daily life with the well-known Global Assessment of Functioning (GAF) scale. A spouse or friend also rated the impact of the patient’s communication/social behavior. Patients with lower GFP scores and higher scores on general psychopathology, displayed more distress and daily functioning deficits (i.e., lower GAF scores) and, in terms of communication styles, were also rated as being less dominant, less in control socially, and more submissive and aggressive. We proposed that part of the overlap between the general factors (GFP, psychopathology factors) may relate to a lower general life functioning and less social effectiveness.

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch) Due to its heterogeneous phenomenology, obsessive-compulsive disorder (OCD) has been subtyped. However, these subtypes are not mutually exclusive. This study presents an alternative subtyping approach by deriving non-overlapping OCD subtypes. A pure compulsive and a mixed obsessive-compulsive subtype (including subjects manifesting obsessions with/without compulsions) were analyzed with respect to a broad pattern of psychosocial risk factors and comorbid syndromes/diagnoses in three representative Swiss community samples: the Zurich Study (n = 591), the ZInEP sample (n = 1500), and the PsyCoLaus sample (n = 3720). A selection of comorbidities was examined in a pooled database. Odds ratios were derived from logistic regressions and, in the analysis of pooled data, multilevel models. The pure compulsive subtype showed a lower age of onset and was characterized by few associations with psychosocial risk factors. The higher social popularity of the pure compulsive subjects and their families was remarkable. Comorbidities within the pure compulsive subtype were mainly restricted to phobias. In contrast, the mixed obsessive-compulsive subtype had a higher prevalence and was associated with various childhood adversities, more familial burden, and numerous comorbid disorders, including disorders characterized by high impulsivity. The current comparison study across three representative community surveys presented two basic, distinct OCD subtypes associated with differing psychosocial impairment. Such highly specific subtypes offer the opportunity to learn about pathophysiological mechanisms specifically involved in OCD.

Background Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. Methods/design A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events. Discussion As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder. Systematic review registration PROSPERO CRD42020220279

Objectives: On 31 January 2020, a new type of coronavirus was first confirmed in Italy and spread rapidly across the country leading to a national lockdown. The aim of this pilot study was to explore the impact of the public health emergency due to COVID‐19 on individual’s mental health among 299 Italian adults after a month of home isolation due to COVID‐19. Design: Cross‐sectional study design. Adults of the general population were invited to a voluntary online health survey. Methods: Hierarchical multiple regressions were used to examine diverse psycho‐social and stressful contextual factors associated with symptoms of psychopathology. Results: Results indicated that females reported higher symptoms of depression, anxiety and circadian rhythm dysregulation, than males. Age and the capacity to adapt to a new environment and to cope with illness were negatively associated with all symptoms of psychopathology. Conversely, engaging in verbally aggressive behaviours and having experienced stressful events related to COVID‐19 were positively related to psychopathological symptoms. Finally, social support was negatively associated with depressive symptoms, and substance use during the past months was related to circadian rhythm dysregulation. Conclusions: The findings of this study raise particular concern about psychological well‐being considering the negative associations between stressful events during the COVID‐19 pandemic, symptoms of psychological distress, and perceived social support. These results have possible significant clinical implications.

The final publication is available at IOS Press through http://dx.doi.org/10.3233/JRS-200033, BACKGROUND: In antidepressant trials for pediatric patients with depression or anxiety disorders, the risk of suicidal events and other severe psychiatric adverse events such as aggression and agitation is increased with antidepressants relative to placebo. OBJECTIVE: To examine whether largely mentally healthy adolescents treated for a non-psychiatric condition are also at increased risk of suicidality and other severe psychiatric disorders. METHODS: This is a re-analysis of a placebo-controlled duloxetine trial for juvenile fibromyalgia based on the main journal article and additional data published in the online supplementary material and on ClinicalTrials.gov. Both serious adverse events related to psychiatric disorders and adverse events leading to treatment discontinuation were defined as severe treatment-emergent psychiatric adverse events. RESULTS: We found that a significant portion of adolescents had treatment-emergent suicidal ideation and behaviour as well as other severe psychiatric adverse events with duloxetine, but no such events were recorded on placebo. The incidence of severe treatment emergent psychiatric adverse events was statistically significantly higher with duloxetine as compared to placebo. CONCLUSIONS: Antidepressants may put adolescents at risk of suicidality and other severe psychiatric disorders even when the treatment indication is not depression or anxiety.

Background Major depressive disorder is a common psychiatric disorder causing great burden on patients and societies. Tricyclic antidepressants are frequently used worldwide to treat patients with major depressive disorder. It has repeatedly been shown that tricyclic antidepressants reduce depressive symptoms with a statistically significant effect, but the effect is small and of questionable clinical importance. Moreover, the beneficial and harmful effects of all types of tricyclic antidepressants have not previously been systematically assessed. Therefore, we aim to investigate the beneficial and harmful effects of tricyclic antidepressants versus ‘active placebo’, placebo or no intervention for adults with major depressive disorder. Methods This is a protocol for a systematic review with meta-analysis that will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, bias will be assessed with the Cochrane Risk of Bias tool—version 2, our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control random errors and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases and trial registers, such as CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov from their inception to 12 May 2021. Clinical study reports will be applied for from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results from the literature searches, extract data and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing tricyclic antidepressants with ‘active placebo’, placebo or no intervention for adults with major depressive disorder. The following interventions will be assessed: amineptine, amitriptyline, amoxapine, butriptyline, cianopramine, clomipramine, desipramine, demexiptiline, dibenzepin, dosulepin, dothiepin, doxepin, imipramine, iprindole, lofepramine, maprotiline, melitracen, metapramine, nortriptyline, noxiptiline, opipramol, protriptyline, tianeptine, trimipramine and quinupramine. Primary outcomes will be depressive symptoms, serious adverse events and quality of life. Secondary outcomes will be suicide or suicide-attempts and non-serious adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses. Discussion Tricyclic antidepressants are recommended by clinical guidelines and frequently used worldwide in the treatment of major depressive disorder. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder. Systematic review registration PROSPERO CRD42021226161.

Background Ecological studies have explored associations between suicide rates and antidepressant prescriptions in the population, but most of them are limited as they analyzed short-term correlations that may be spurious. The aim of this long-term study was to examine whether trends in suicide rates changed in three European countries when the first antidepressants were introduced in 1960 and when prescription rates increased steeply after 1990 with the introduction of the serotonin reuptake inhibitors (SSRIs). Methods Data were extracted from the WHO Mortality Database. Suicide rates were calculated for people aged 10–89 years from 1951–2015 for Italy, 1955–2016 for Austria and 1951–2013 for Switzerland. Trends in suicide rates stratified by gender were analyzed using joinpoint regression models. Results There was a general pattern of long-term trends that was broadly consistent across all three countries. Suicide rates were stable or decreasing during the 1950s and 1960s, they rose during the 1970s, peaked in the early 1980s and thereafter they declined. There were a few notable exceptions to these general trends. In Italian men, suicide rates increased until 1997, then fell sharply until 2006 and increased again from 2006 to 2015. In women from all three countries, there was an extended period during the 2000s when suicide rates were stable. No trend changes occurred around 1960 or 1990. Conclusions The introduction of antidepressants around 1960 and the sharp increase in prescriptions after 1990 with the introduction of the SSRIs did not coincide with trend changes in suicide rates in Italy, Austria or Switzerland.

Background There is ongoing controversy whether antidepressant use alters suicide risk in adults with depression and other treatment indications. Methods Systematic review of observational studies, searching MEDLINE, PsycINFO, Web of Science, PsycARTICLES and SCOPUS for case–control and cohort studies. We included studies on depression and various indications unspecified (including off-label use) reporting risk of suicide and/or suicide attempt for adult patients using selective serotonin reuptake inhibitors (SSRI) and other new-generation antidepressants relative to non-users. Effects were meta-analytically aggregated with random-effects models, reporting relative risk (RR) estimates with 95% CIs. Publication bias was assessed via funnel-plot asymmetry and trim-and-fill method. Financial conflict of interest (fCOI) was defined present when lead authors’ professorship was industry-sponsored, they received industry-payments, or when the study was industry-sponsored. Results We included 27 studies, 19 on depression and 8 on various indications unspecified (n=1.45 million subjects). SSRI were not definitely related to suicide risk (suicide and suicide attempt combined) in depression (RR=1.03, 0.70–1.51) and all indications (RR=1.19, 0.88–1.60). Any new-generation antidepressant was associated with higher suicide risk in depression (RR=1.29, 1.06–1.57) and all indications (RR=1.45, 1.23–1.70). Studies with fCOI reported significantly lower risk estimates than studies without fCOI. Funnel-plots were asymmetrical and imputation of missing studies with trim-and-fill method produced considerably higher risk estimates. Conclusions Exposure to new-generation antidepressants is associated with higher suicide risk in adult routine-care patients with depression and other treatment indications. Publication bias and fCOI likely contribute to systematic underestimation of risk in the published literature. Registration Open Science Framework, https://osf.io/eaqwn/

Background It has been claimed that efficacy estimates based on the Hamilton Depression Rating-Scale (HDRS) underestimate antidepressants true treatment effects due to the instrument’s poor psychometric properties. The aim of this study is to compare efficacy estimates based on the HDRS with the gold standard procedure, the Montgomery-Asberg Depression Rating-Scale (MADRS). Methods and findings We conducted a meta-analysis based on the comprehensive dataset of acute antidepressant trials provided by Cipriani et al. We included all placebo-controlled trials that reported continuous outcomes based on either the HDRS 17-item version or the MADRS. We computed standardised mean difference effect size estimates and raw score drug-placebo differences to evaluate thresholds for clinician-rated minimal improvements (clinical significance). We selected 109 trials (n = 32,399) that assessed the HDRS-17 and 28 trials (n = 11,705) that assessed the MADRS. The summary estimate (effect size) for the HDRS-17 was 0.27 (0.23 to 0.30) compared to 0.30 (0.22 to 0.38) for the MADRS. The effect size difference between HDRS-17 and MADRS was thus only 0.03 and not statistically significant according to both subgroup analysis (p = 0.47) and meta-regression (p = 0.44). Drug-placebo raw score difference was 2.07 (1.76 to 2.37) points on the HDRS-17 (threshold for minimal improvement: 7 points according to clinician-rating and 4 points according to patient-rating) and 2.99 (2.24 to 3.74) points on the MADRS (threshold for minimal improvement: 8 points according to clinician-rating and 5 points according to patient-rating). Conclusions Overall there was no meaningful difference between the HDRS-17 and the MADRS. These findings suggest that previous meta-analyses that were mostly based on the HDRS did not underestimate the drugs’ true treatment effect as assessed with MADRS, the preferred outcome rating scale. Moreover, the drug-placebo differences in raw scores suggest that treatment effects are indeed marginally small and with questionable importance for the average patient.

There is a lack of prospective studies that test pre-specified hypotheses on the role of personality traits in outpatient psychotherapy. A total of 47 patients with a broad range of psychopathological syndromes were enrolled in a prospective 6-month observational study conducted in Zurich, Switzerland. We found evidence for remarkably high differential stability in all Big Five personality traits during the first 6 months of psychotherapy. Mean-level stability was very high in agreeableness and conscientiousness, while modest changes were observed in neuroticism, extraversion and openness. Baseline scores in neuroticism and conscientiousness at the beginning of therapy predicted modest change in self-reported severity of psychopathology over 6 months, but no effect was found in association with therapist-rated functional deficits. We conclude that personality trait levels may change slightly over the course of 6 months of psychotherapy and that both neuroticism and conscientiousness may have weak associations with the self-perceived improvement in psychopathology.

Background: Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking. Methods: We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org , a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms. Results: In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated. Conclusion: PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms.

ObjectivesTo investigate if the treatment effect of antidepressants in patients with depression substantially varies in each patient (patient-by-treatment interaction or treatment heterogeneity), a necessary but largely unexplored prerequisite of personalised antidepressant treatment.DesignMeta-analytic variance comparison of treatment outcome between drug arms and placebo arms of clinical trials, based on the assumption that patient-by-treatment interaction should lead to larger variances in drug arms than placebo arms. To put the results into context, we run simple simulations, assuming different definitions and rates of those who respond especially well to antidepressants.Data sources163 randomised, placebo-controlled trials (51 396 patients) with complete results for pre–post differences, selected from a recently published systematic review.AnalysisVariance ratios (VRs) and coefficients of variance ratios (CVRs) of individual trials were meta-analytically combined. The analysis was repeated for classes of antidepressants and specific antidepressants.ResultsVRs (VR=1.01, CI 0.99 to 1.02) and CVRs (CVR=0.82, CI 0.80 to 0.84) of the antidepressant-treatment arms were comparable or smaller than in placebo arms. Similar results were observed for classes of antidepressants and for specific antidepressants. Our simulation analysis confirmed that equal VRs can only be obtained if they are not more than a few patients who respond slightly above average.ConclusionsThe lack of increased treatment-outcome variance in the antidepressants versus placebo groups in randomised controlled trials indicates that no or only very small subgroups of patients respond particularly well to antidepressants. Thus, the scope for personalised treatment with antidepressants seems to be limited.

Zusammenfassung. In der allgemeinmedizinischen Praxis werden Persönlichkeitseigenschaften der Patienten selten berücksichtigt oder erfasst. In diesem Mini-Review wird zusammengefasst, warum die Bestimmung der Persönlichkeit wichtige Patienteninformationen liefern kann. Es werden Einflüsse von Persönlichkeitseigenschaften auf die allgemeinen Lebensumstände sowie auf die psychische und somatische Gesundheit beschrieben. Zudem werden wissenschaftliche Arbeiten vorgestellt, die einen Zusammenhang zwischen Persönlichkeitseigenschaften, klinischen Krankheitsmarkern und der Gesamtmortalität aufzeigen. Diese Befunde werden im Kontext ausgewählter ätiologischer Modelle diskutiert. Die zusammengetragenen Studien verdeutlichen, dass die Beschreibung der Persönlichkeit die Diagnostik, Prognostik und Behandlungsplanung sinnvoll ergänzen kann.

A representative cohort of six-year old children from the Swiss general population (n ≈ 1200) was assessed in 2006 and re-assessed in 2009 with informant-ratings of personality and externalizing psychopathology. Mean levels of neuroticism (d = 0.80) and to a lesser extent agreeableness (d = 0.37) declined considerably over time on a population-level, but differential stability was high (r range = 0.71–0.95). Age 6 trait-score and trait-change over time in agreeableness related significantly to age 9 externalizing pathology. Path analysis additionally provided evidence for bidirectional covariance between several personality traits and externalizing psychopathology and there were some prospective influences of age 6 psychopathology on subsequent personality change. Differential stability of personality is high, but marked trait-change occurs and is relevant as it prospectively relates to externalizing psychopathology.

Author(s): Hopwood, Christopher J; Kotov, Roman; Krueger, Robert F; Watson, David; Widiger, Thomas A; Althoff, Robert R; Ansell, Emily B; Bach, Bo; Michael Bagby, R; Blais, Mark A; Bornovalova, Marina A; Chmielewski, Michael; Cicero, David C; Conway, Christopher; De Clercq, Barbara; De Fruyt, Filip; Docherty, Anna R; Eaton, Nicholas R; Edens, John F; Forbes, Miriam K; Forbush, Kelsie T; Hengartner, Michael P; Ivanova, Masha Y; Leising, Daniel; John Livesley, W; Lukowitsky, Mark R; Lynam, Donald R; Markon, Kristian E; Miller, Joshua D; Morey, Leslie C; Mullins-Sweatt, Stephanie N; Hans Ormel, J; Patrick, Christopher J; Pincus, Aaron L; Ruggero, Camilo; Samuel, Douglas B; Sellbom, Martin; Slade, Tim; Tackett, Jennifer L; Thomas, Katherine M; Trull, Timothy J; Vachon, David D; Waldman, Irwin D; Waszczuk, Monika A; Waugh, Mark H; Wright, Aidan GC; Yalch, Mathew M; Zald, David H; Zimmermann, Johannes

The aim of this study was to test the validity of the CHR state by focusing on the course of psychosis spectrum symptoms, depression and global functioning in converters and non-converters. A total of 188 CHR-positive subjects (60.2% men) aged between 13 and 35 years (mean = 20.5) at study outset were assessed five times (t0-t4) over a total observation period of 36 months. Conversion to manifest psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). Measures of positive and negative symptoms were assessed with the Structured Interview for Prodromal Syndromes (SIPS), depression with the Calgary Depression Scale (CDS), and global functioning with the Global Assessment of Functioning Scale (GAF). Converters scored higher over time on all SIPS scales apart from grandiosity (Cohen's d: 0.5-0.7; all p < 0.001), higher on the CDS (d = 0.43, p = 0.001) and lower on the GAF (d = 0.69, p < 0.001) than did non-converters. Positive and negative symptoms as well as depression were most severe at study outset (t0) and then declined sharply following a linear function over the three-year observation period (t1-t4) across groups (all linear contrasts p < 0.001). In conclusion, converters showed significantly more psychopathological symptoms and poorer functioning before crossing the diagnostic threshold for manifest psychosis. CHR-subjects who convert to manifest psychosis during follow-up appear to be recovering from illness rather than becoming ill. Major issues involve the poor discrimination of CHR state and psychosis as well as the dichotomous definition of both at-risk and disease states. Further examination in other CHR-samples is warranted.

The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function.

There is increasing interest in the construct validity of higher-order domains of the Big Five personality traits. A total of 831 persons from the Swiss population completed the International Personality Item Pool and an adaptation of the Positive and Negative Affect Scales. Using Goldberg's [1] bass-ackwards method, we found evidence for the general factor of personality (GFP) and the two meta-traits of positive emotionality (blend of low neuroticism and high extraversion) and constraint (blend of high agreeableness and conscientiousness). In association with positive affect, the explanatory power of the GFP (r = 0.43) and positive emotionality (r = 0.37) was largely superior to extraversion (r = 0.24), conscientiousness (r = 0.18), agreeableness (r = 0.09) and openness (r = 0.04), although not neuroticism (r = −0.34). In association with negative affect, neuroticism (r = 0.41), the GFP (r = −0.36) and positive emotionality (r = −0.35) were the most powerful single predictors. We conclude that the higher-order structure of personality is best explained by the meta-traits of positive emotionality and constraint, which correspond closely to the well-established superfactors of internalizing and externalizing. We further demonstrate that these have substantial criterion validity when broad positive and negative affect is the outcome of interest. These findings help to relate Big Five meta-traits to pathological personality. Copyright © 2017 John Wiley & Sons, Ltd.

This paper tests the hypothesis that the association between childhood maltreatment and adult personality dysfunction is at least partially attributable to insecure attachment, that is that attachment style mediates the relationship between childhood maltreatment and adult personality dysfunction. Associations between childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ), anxious and avoidant attachment in romantic relationships, as measured by the Experiences in Close Relationships-Revised (ECR-R), and five personality domains, as measured by the Severity Indices of Personality Problems (SIPP-118), were examined in a sample of 72 psychiatric inpatients. The SIPP-118 domains included relational capacities, identity integration, self-control, responsibility, and social concordance. The direct effect of childhood trauma on all SIPP-118 domains was not significant after controlling for the indirect effect of attachment. In regression modeling, a significant indirect effect of childhood trauma via adult attachment style was found for SIPP-118 relational capacities, identity integration, self-control, and social concordance. Specifically, anxious attachment was a significant mediator of the effect of childhood trauma on self-control, identity integration, and relational domains. These results suggest that childhood trauma impacts a broad range of personality domains and does so in large part through the pathway of anxious romantic attachment style.

Dr Adlington1 recently drew attention to the uncritical promotion of antidepressant drugs by various key opinion leaders and news outlets following the publication of a large meta-analysis by Cipriani and colleagues.2 She also pointed out that the small effect sizes were largely neglected and that most news report did not differentiate mild depression from severe depression. The crucial issues thus are whether the effects of antidepressants are clinically relevant and whether these drugs also work in mild to moderate depression. A leading psychiatric journal recently published a meta-analysis, coauthored by Dr Cipriani, in which the authors purport that their findings demonstrate efficacy of newer generation antidepressants in both mild to moderate and severe depression.3 This article was accompanied by an editorial entitled, ‘The alleged lack of efficacy of antidepressants in non-severe depression: a myth debunked’.4 Obviously, commentators and authors want to disseminate the message that antidepressants are an effective treatment for mild to moderate depression and that practice guidelines should incorporate these findings. However, neither the original paper3 nor the editorial4 does in fact provide evidence that the drugs are clinically effective for any form of depression. Instead, their conclusion appears to rely exclusively on the fact that there is a statistically significant drug-placebo difference in mean symptom change. The same misinterpretation of statistical significance also appears to have fuelled the simplistic and overoptimistic conclusions drawn from the Lancet meta-analysis by Cipriani et al .2 In the following, I will summarise the most recent meta-analytic findings and ponder on the reported average treatment effect. Equating statistical significance with a proof of drug efficacy is a scientific fallacy and I propose that a drug-placebo difference of this magnitude is evidence of a lack of efficacy. The recent meta-analysis by Furukawa et al 3 …

Several international guidelines for the acute treatment of moderate to severe unipolar depression recommend a first-line treatment with antidepressants (AD). This is based on the assumption that AD obviously outperform placebo, at least in the case of severe depression. The efficacy of AD for severe depression can only be definitely clarified with individual patient data, but corresponding studies have only been available recently. In this paper, we point out discrepancies between the content of guidelines and the scientific evidence by taking a closer look at the German S3-guidelines for the treatment of depression. Based on recent studies and a systematic review of studies using individual patient data, it turns out that AD are marginally superior to placebo in both moderate and severe depression. The clinical significance of this small drug-placebo-difference is questionable, even in the most severe forms of depression. In addition, the modest efficacy is likely an overestimation of the true efficacy due to systematic method biases. There is no related discussion in the S3-guidelines, despite substantial empirical evidence confirming these biases. In light of recent data and with their underlying biases, the recommendations in the S3-guidelines are in contradiction with the current evidence. The risk-benefit ratio of AD for severe depression may be similar to the one estimated for mild depression and thus could be unfavorable. Downgrading of the related grade of recommendation would be a logical consequence.

Summary The forthcoming National Institute for Health and Care Excellence depression guideline reviews short-term outcomes for long-term depression. We present effect sizes for long-term outcomes in trials that report these data. Psychological therapies become more effective, whereas antidepressants become less effective over the long term. We review other forms of longitudinal research that support these findings.

Withdrawal reactions when coming off antidepressants have long been neglected or minimised. It took almost two decades after the selective serotonin reuptake inhibitors (SSRIs) entered the market for the first systematic review to be published. More reviews have followed, demonstrating that the dominant and long-held view that withdrawal is mostly mild, affects only a small minority and resolves spontaneously within 1–2 weeks, was at odd with the sparse but growing evidence base. What the scientific literature reveals is in close agreement with the thousands of service user testimonies available online in large forums. It suggests that withdrawal reactions are quite common, that they may last from a few weeks to several months or even longer, and that they are often severe. These findings are now increasingly acknowledged by official professional bodies and societies.

BackgroundThe most effective rehabilitation model for job (re-)entry of people with mental illness is supported employment. A barrier to introducing supported employment into standard care is its temporally unlimited provision, which conflicts with health and social legislation in many European countries.AimsTo test the impact of different ‘placement budgets’, i.e. a predefined maximum time budget for job seeking until take-up of competitive employment.MethodParticipants (116) were randomly assigned to 25 h, 40 h or 55 h placement budgets in an intent-to-treat analysis. We applied the individual placement and support model over 24 months, following participants for 36 months. Primary outcome was employment in the labour market for at least 3 months.ResultsThe proportion of participants obtaining competitive employment was 55.1% in the 25 h group, 37.8% in the 40 h group and 35.8% in the 55 h group. In a Cox regression analysis, time to employment was slightly lower in the 25 h group relative to the 40 h (hazard ratio 1.78, 95% CI 0.88–3.57, P = 0.107) and 55 h groups (hazard ratio 1.74, 95% CI 0.86–3.49, P = 0.122), but this was not statistically significant. The vast majority of all participants who found a job did so within the first 12 months (80.4%).ConclusionA restricted time budget for job finding and placement does not affect the rate of successful employment. In accordance with legislation, a restriction of care provision seems justified and enhances the chances of supported employment being introduced in statutory services.

Regression to the mean and spontaneous improvements are rarely considered in interpretations of treatment trials for acute major depression. Here I suggest that regression to the mean and spontaneous remission may account for most improvements seen in placebo groups and also for a large proportion of variance in the acute treatment outcome of both antidepressant pharmacotherapy and psychotherapy. These findings have important implications for the interpretation of active treatments and placebo response in depression trials.

Background: Some evidence suggests that antidepressants may relate to poor outcomes in depression. The aim of this study was, therefore, to examine, whether antidepressant use may worsen the long-term outcome in real-world psychiatric patients with both primarily affective and non-affective mental disorders. Methods: Based on a total of n = 151 inpatients with a mixed range of diagnoses enrolled at two psychiatric hospitals in Zurich, Switzerland, matched pairs of n = 45 antidepressant users and n = 45 non-users were selected via nearest neighbor propensity score matching. Pairs were matched according to 14 clinically relevant covariates assessing psychosocial impairments, functioning deficits and illness severity. The two outcomes of interest were the number and total duration of all rehospitalisations over a 12-month follow-up after discharge from the hospital based on the official clinical registry. Results: Altogether 35.6% of antidepressant users were rehospitalised at least once, as compared to 22.2% in matched non-users. Two or more rehospitalisations occurred in 22.2% of antidepressant users but only in 2.2% of non-users. In antidepressant users, the mean total duration of rehospitalisations was 22.22 days, as compared to 8.51 in matched non-users. According to Poisson regression analyses, antidepressant use during acute inpatient care prospectively relates to both a higher risk (incidence rate ratio [IRR] = 3.64, 95% confidence interval [95%-CI] = 1.71-7.75, p = 0.001) and a longer duration (IRR = 2.61, 95%-CI = 1.01–6.79, p = 0.049) of subsequent rehospitalisations. These findings were consistently replicated when traditional multivariable regression analysis was applied to the full sample. Findings also replicated when patients with affective and non-affective disorders were analyzed separately. Conclusions: Our findings raise the possibility that, in the long-term, antidepressants may impair recovery and increase the risk of rehospitalisation in patients with both primarily affective and non-affective disorders. More work is required to explore possible aetiopathological pathways leading to psychiatric rehospitalisation.

Background: Individual placement and support (IPS) has proven to be effective for vocational outcomes in people with mental illness. The original concept of IPS requires temporally unlimited provision of support. Using limited placement budgets and investigating factors that predict their effectiveness may inform decisions about resource allocation. Methods: A range of patient characteristics were tested as predictors of employment outcomes in participants who attended six outpatient psychiatric clinics in Switzerland between June 2010 and May 2011. Overall, 116 patients with the full spectrum of psychiatric conditions were randomly assigned and started an IPS intervention, which was provided by three different placement budgets. Support lasted 2 years for those who found a job, and outcomes were repeatedly assessed over 3 years. The intervention ended for those who failed to find competitive employment by the time their placement budget had run out. Results: Of the 15 variables tested, only Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) scores were predictors for obtaining work (for ≥1 day) and for maintaining it over a longer period (>3 months). Higher GAF and lower CGI scores increased the odds of obtaining employment and keeping it for at least 3 months. Functional role impairment, quality of life, self-esteem, or education level did not predict employment. Conclusion: Our data suggest that, if time-restricted budgets are offered to a wide range of patients, such as those included in this study, better functioning and lower symptom severity at baseline are predictive of better employment outcomes (finding and maintaining work) on the first (competitive) labor market in Switzerland. It remains to be investigated whether this holds true under different environmental factors., Frontiers in Psychiatry, 10, ISSN:1664-0640

Background:Involuntary admission (IA) for psychiatric treatment has a history of controversial discussions. We aimed to describe characteristics of a cohort of involuntarily compared to voluntarily admitted patients regarding clinical and socio-demographic characteristics before and after implementation of the new legislation.Methods:In this observational cohort study, routine data of 15’125 patients who were admitted to the University Hospital of Psychiatry Zurich between 2008 and 2016 were analyzed using a series of generalized estimating equations.Results:At least one IA occurred in 4’560 patients (30.1%). Of the 31’508 admissions 8’843 (28.1%) were involuntary. In the final multivariable model, being a tourist (OR = 3.5) or an asylum seeker (OR = 2.3), having a schizophrenic disorder (OR = 2.1), or a bipolar disorder (OR = 1.8) contributed most to our model. Male gender, higher age, prescription of neuroleptics (all OR < 2.0) as well as having a depressive disorder, prescription of psychotherapy, prescription of antidepressants and admission after implementation of the new legislation (all OR > 0.6) were also weakly associated with IA.Conclusions:Besides schizophrenic or bipolar disorders, a small group of patients had an increased risk for IA due to non-clinical parameters (i.e. tourists and asylum seekers). Knowledge about risk factors should be used for the development of multi-level strategies to prevent frequent (involuntary) hospitalizations in patients at risk. On the organizational level, we could show that the new legislation decreased the risk for IA, and therefore may have succeeded in strengthening patient autonomy.

Commenting on “the record number of antidepressants prescribed last year,” Helen Stokes-Lampard, chair of the Royal College of General Practitioners, said that “research has shown [antidepressants] can be very effective when used appropriately.”1 This opinion about whether the number of prescriptions is appropriate is one sided. Firstly, evidence shows that only one in nine people benefit from antidepressants: the remaining eight are unnecessarily put at risk of adverse drug effects.2 Secondly, the effect size for …

In February 2018 the international debate on antidepressant withdrawal was reignited. In response to a letter published in The Times by Davies et al. on the benefits and harms of antidepressants, the Royal College of Psychiatrists publicly stated that ‘[for] the vast majority of patients any unpleasant symptoms experienced on discontinuing antidepressants have resolved within two weeks of stopping treatment’.