The MOODS-SR is a self-report instrument consisting of 161 dichotomous items. It is designed to assess lifetime presence of mood spectrum psychopathology. Recently, it has been proposed that a subset of 33 items can be used to distinguishing bipolar disorder.

To evaluate psychometric properties of a 33-item subset and to propose a clinically relevant cut-off for screening for bipolar disorder.

Patients with mood disorders were recruited from outpatient services at Sahlgrenska University Hospital. Patients and a convenience sample of healthy controls were offered to fill in the MOODS-SR. A post-hoc analysis was conducted for the 33-items subset of the MOODS-SR.

The subset showed high internal consistency (Cronbach α = 0.95). The mean scores of patients with bipolar disorder (22.7 ± 6.4) were significantly higher than those of the unipolar (11.3 ± 4.9) and control group (7.0 ± 7.0, P < 0.005). A significant correlation was found between YMRS (r = 0.50, P < 0.005) and the 33-item subset, but not with MADRS (r = –0.22, P = 0.223).

The 33-item subset of MOODS-SR showed promising psychometric properties, including good known-group validity. It discriminated bipolar patients from unipolar patients and healthy subjects. The clinical usefulness of these finding needs further investigation.

The authors have not supplied their declaration of competing interest.

To examine the impact of appearance comparison behaviours, trait body dissatisfaction and eating pathology on women's state body dissatisfaction and engagement in disordered eating behaviours in daily life.

Using ecological sampling method (ESM), 116 women residing in Australia, completed a baseline questionnaire containing the trait-based measures, before being signalled by an iPhone app six times daily, for seven days, to self-report on their recent appearance comparison behaviours, current state body dissatisfaction and recent disordered eating behaviours.

Multi-level modelling revealed that upward comparisons (comparisons against more attractive individuals) elicited increases in state body dissatisfaction (β = 0.89, P < .001) and disordered eating behaviours (β = 0.29, P = .002). Contrastingly, downward comparisons (comparisons against less attractive individuals) elicited decreases in state body dissatisfaction (β = –0.31, P = .048) and, unexpectedly, increases in disordered eating behaviours (β = 0.46, P < .01). The frequency of appearance comparison engagement, regardless of whether it was upward or downward comparisons, was also predictive of increased disordered eating behaviours (β = 0.12, P < .001). In addition, eating pathology and trait body dissatisfaction were directly associated with higher state body dissatisfaction, and increased in disordered eating behaviours (all P < .001).

These findings highlight the general negative impact that appearance comparisons have on fluctuating states of body dissatisfaction and eating pathology, as well as illustrating how trait characteristics partially account for this volatility. These findings provide further information that may be used to inform eating disorder prevention and intervention efforts.

The authors have not supplied their declaration of competing interest.

Disgust propensity (DP) and disgust sensitivity (DS) contribute to individual differences in the experience of disgust. Studies have shown that DP and DS are predictive of some anxiety (e.g., spider phobia and blood-injection-injury phobia) and obsessive-compulsive and related disorders.

The aim of this study was to develop and validate a Portuguese version of the Disgust Propensity and Sensitivity Scale-Revised (DPSS-R; van Overveld= et al., 2006) for use in Portuguese-speaking populations.

Two hundred and six participants (162 females), with ages between 18 and 47 (M = 25.92; SD = 8.75), filled in the DPSS-R, which was first translated and adapted into Portuguese language by individuals highly proficient in English and then back-translated by a bilingual with no prior knowledge of the scale. Finally, the DPSS-R was subjected to a think-aloud procedure.

The results showed good internal consistency (Cronbach's alfa = .833) for a DPSS-R. The two subscales displayed an adequate internal consistency (DPCronbach's alfa = .776; DSCronbach's alfa = .790). Test-retest analysis documented good intraclass correlation coefficient for the two subscales (ICCPropensity = .889; ICC Sensitivity = .900). We also confirmed the bifactorial structure using a confirmatory factor analysis, since we obtained appropriate values in all goodness of fit indices (χ2df = 1,906; CFI = .94; PCFI = .736; GFI = .93; PGFI = .607; RMSEA = .067).

DPSS-R obtained good psychometric properties and may therefore be proposed as a valid instrument to assess DS and DP in the Portuguese population. This instrument may provide an important contribute to study the development and maintenance of psychopathology associated with disgust.

The authors have not supplied their declaration of competing interest.

Mood instability is an important problem but has received relatively little research attention. Natural language processing (NLP) is a novel method, which can used to automatically extract clinical data from electronic health records (EHRs).

To extract mood instability data from EHRs and investigate its impact on people with mental health disorders.

Data on mood instability were extracted using NLP from 27,704 adults receiving care from the South London and Maudsley NHS Foundation Trust (SLaM) for affective, personality or psychotic disorders. These data were used to investigate the association of mood instability with different mental disorders and with hospitalisation and treatment outcomes.

Mood instability was documented in 12.1% of people included in the study. It was most frequently documented in people with bipolar disorder (22.6%), but was also common in personality disorder (17.8%) and schizophrenia (15.5%). It was associated with a greater number of days spent in hospital (B coefficient 18.5, 95% CI 12.1–24.8), greater frequency of hospitalisation (incidence rate ratio 1.95, 1.75–2.17), and an increased likelihood of prescription of antipsychotics (2.03, 1.75–2.35).

Using NLP, it was possible to identify mood instability in a large number of people, which would otherwise not have been possible by manually reading clinical records. Mood instability occurs in a wide range of mental disorders. It is generally associated with poor clinical outcomes. These findings suggest that clinicians should screen for mood instability across all common mental health disorders. The data also highlight the utility of NLP for clinical research.

The authors have not supplied their declaration of competing interest.

Stimuli that are relevant to our survival, especially those that signal the presence of a threat in the environment (e.g., threatening faces), automatically attract our attention.

The same may be true for faces displaying subtle disease cues as they may signal danger of potential contamination and, hence, disease-avoidance behaviour, which was the focus of the present research.

The present study investigated, for the first time to our knowledge, whether faces with disease cues (DF), compared to control stimuli (faces without such cues) (CF), interfered with the participants’ performance in a letter discrimination task.

Eighty-six (44 women) university students volunteered to participate in a letter discrimination task where 240 DF and 240 CF were presented.

The results confirmed our hypothesis by showing that for DF, compared to CF, participants took longer to discriminate the target letters. Moreover, the results from a further rating task showed that DF, compared to CF, were rated as significantly more disgusting and associated with disease, thus confirming our experimental manipulation and suggesting that disgust may be driving automatic attention to DF.

Our findings provide important insights on the possible influence of exogenous attention to disease cues in social avoidance behaviour, which may have relevant implications in clinical disorders with disgust at its core.

The authors have not supplied their declaration of competing interest.

Longer duration of untreated illness, longer duration of current episode, and severity of medication side effects may negatively influence the psychosocial functioning in major affective and anxiety disorders. Studies also suggested the involvement of sensory perception in emotional and psychopathological processes.

The objective of this study is to investigate the nature of the association between duration of untreated illness, duration of current episode, and severity of medication side effects.

The study is aimed to examine the relationship between sensory processing disorders (SPD), duration of untreated illness, duration of current illness episode, and the severity of side effects related to psychoactive medications.

The sample included 178 participants with an age ranging from 17 to 85 years (mean = 53.84 ± 15.55); psychiatric diagnoses were as follow: unipolar major depressive disorder (MDD) (50%), bipolar disorder (BD) (33.7%), and anxiety disorders (16.3%). subjects completed a socio-demographic questionnaire, the Udvalg for Kliniske Undersøgelser (UKU), and Adolescent/Adult Sensory Profile (AASP) questionnaire.

Longer duration of current episode correlated with greater registration of sensory input and lower avoidance from sensory input among unipolar patients, lower registration of sensory input, and higher tendency for sensory sensitivity/sensation avoidance among bipolar participants. In addition? longer duration of current episode correlated with lower sensory sensitivity/avoidance among anxiety participants, respectively. Mean UKU total scores were associated with lower sensory sensitivity among bipolar individuals as well.

SPD expressed in either hypo-/hypersensitivity may be used to clinically characterize subjects with major affective and anxiety disorders.

The authors have not supplied their declaration of competing interest.

It is assumed that dysfunctional meta-cognitive beliefs about one's thoughts increase problematic appraisals and coping behaviors, which further contribute to the development of mental disorders (Wells and Matthews, 1994; Wells, 2000). Although this research interest originated around generalized anxiety disorder (GAD), recent studies have begun to examine similar meta-cognitive processes in other disorders. The majority of studies using Meta-cognitions Questionnaire (MCQ; Cartwright-Hatton & Wells, 1997) and its variants to assess meta-cognitive beliefs.

We conducted a meta-analysis to integrate empirical findings on group differences in meta-cognitive beliefs between healthy individuals and patients with various psychiatric disorders.

We followed the PRISMA guideline (Liberati et al., 2009). A systematic literature search was conducted. We included studies that involved a diagnosed psychiatric group and healthy controls (aged 18 or above), reported group comparisons of metacognition, and were published during the period of 1990–27 August 2015. Effect sizes were computed.

A final set of 43 studies was included. Large combined effect sizes were found on each subdomain of the MCQ, indicating increased levels of dysfunctional meta-cognitive beliefs in patients. Subgroup analyses were carried out based on psychiatric diagnosis (i.e. psychosis, n = 10; GAD, n = 7; obsessive-compulsive disorder, OCD, n = 15; anorexia nervosa, n = 5). All patient groups were more dysfunctional on each subtype of meta-cognitive beliefs than controls. Effect size of U/D was particularly large for GAD, and that of CSC was particularly large for OCD.

Dysfunctional meta-cognitive beliefs are evident across several psychiatric disorders, with specific types of beliefs being more marked in certain diagnoses.

The authors have not supplied their declaration of competing interest.

Olanzapine is an atypical antipsychotic medication, previously expected to be safe in terms of hematological side effects and an alternative choice to clozapine in patients who develop hematotoxicities. However, since olanzapine was introduced to the market, a lot of cases reports have been published revealing it could cause hematoxicity. Some of them indicate that olanzapine induces agranulocytosis. Because of that, it raises the concerns about hematological safety of olanzapine.

To date, no review discusses this topic specifically, so we conducted a systemic review to explore and address this issue.

We searched Pubmed, Google Scholar, Ovid and Medline databases for articles between 1998 and 2015 that include keywords olanzapine, leukopenia, neutropenia, and agranulocytosis.

A total of 38 publications were identified. The case reports included patients aged 16 to 83 years. Doses ranged from 2.5 to 30 mg. After starting treatment, onset of hematotoxicity varied from the first day to 2–3 years, but most commonly within the first month. Also, olanzapine could induce leukopenia in patients who have never developed drug-related leukopenia.

Among antipsychotic medications, olanzapine is the third leading cause of neutropenia and the second leading cause of atypical antipsychotic medication. Because of the small body of literature regarding the hematotoxic side effects of olanzapine, we encourage further research to understand the mechanism by which olanzapine causes granulocytopenia. The identification of risk factors could facilitate the development of new surveillance guidelines in patients taking olanzapine. We recommend that the guidelines of using and monitoring olanzapine need to be reconsidered.

The authors have not supplied their declaration of competing interest.

Psychotropic drugs are among the most utilized medications in Europe.

To perform an international comparison of the utilization trends of antidepressants, anxiolytics, hypnotics and sedatives (AHS).

We used data from the Organization for Economic Cooperation and Development (OECD). We used the World Health Organization's Defined Daily Dosage (DDD) per 1000 inhabitants per day (DHD) methodology. We performed a general comparison between 14 European countries and a more detailed comparative analysis between Portugal, Italy, Spain and Germany. These countries were selected according to the following criteria: similar 12-month prevalence of mental health disorders, similar results for negative mental health (SF-36 questionnaire) and similar standardized death rates for suicide.

Portugal had the highest overall utilization of antidepressants and AHS in 2011, amounting to 110.7 DHD, and the highest increase in utilization of AHS (1.8%) from 2003 and 2011. Concerning antidepressants, Portugal had the third highest utilization of these drugs in 2011 (78.3 DHD). Regarding the more detailed comparative analysis, utilization of AHS was still significantly higher in Portugal. Considering antidepressants, Portugal experienced an increasing utilization, which grew by approximately 11.4% from 2003 and 2008. From 2009 onward the utilization increased but at a slower pace.

The very high utilization of these drugs, especially of AHS, is a worrying fact since this might indicate an inadequate treatment choice for anxiety and depressive disorders. Further research is needed to better understand the relationship of these findings with regulations concerning utilization of psychotropic drugs and compliance with best medical practices between distinct European countries.

The authors have not supplied their declaration of competing interest.

Evidences for antipsychotics augmentation for schizophrenic patients with suboptimal efficacy have been lacking although it has been widespread therapeutic strategy in clinical practice.

The purpose of this study was to investigate the efficacy and tolerability of blonanserin augmentation with an atypical antipsychotics (AAPs) in schizophrenic patients.

A total of 100 patients with schizophrenia partially or completely unresponsive to treatment with an AAP recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to existing AAPs which were maintained during the study period. Efficacy was primarily evaluated using Positive and Negative Syndrome Scale (PANSS) at baseline, week 2, 4, 8, and 12. Predictors for PANSS response (≥ 20% reduction) was investigated.

The PANSS total score was significantly decreased at 12 weeks after blonanserin augmentation (–21.0 ± 18.1, F = 105.849, P < 0.001). Response rate on PANSS at week 12 was 51.0%. Premature discontinuation was occurred in 17 patients (17.0%) and 4 patients among them discontinued the study due to adverse events. Nine patients experienced significant weight gain during the study. Response to blonanserin augmentation was associated with severe (PANSS > 85) baseline symptom (OR = 10.298, P = 0.007) and higher dose (> 600 mg/day of chlorpromazine equivalent dose) of existing AAPs (OR = 4.594, P = 0.014).

Blonanserin augmentation improved psychiatric symptoms of schizophrenic patients in cases of partial or non-responsive to an AAP treatment with favorable tolerability. Patients with severe symptom despite treatment with higher dose of AAP were benefited from this augmentation. These results suggested that blonanserin augmentation could be an effective strategy for specific patients with schizophrenia.

The authors have not supplied their declaration of competing interest.

Emerging preclinical and clinical evidence suggests a potential role of nicotinic acetylcholine receptors in the pathophysiology of depression. Several clinical trials have investigated the efficacy of nicotinic acetylcholine receptor antagonists in treatment-resistant depression. We performed this meta-analysis to investigate whether nicotinic acetylcholine receptor antagonists significantly improve symptoms in patients with major depressive disorder who have an inadequate response to standard antidepressant therapy.

A comprehensive literature search identified 6 randomized controlled trials. These 6 trials, which included 2067 participants, were pooled for this meta-analysis using a random-effects model.

Nicotinic acetylcholine receptor antagonists failed to show superior efficacy compared to placebo in terms of the mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) score [mean difference = –0.12 (95% CI = –0.96 to 0.71); response rate (risk ratio [RR] = 0.92 (95% CI = 0.83 to 1.02)); and remission rate [RR] = 1.01 (95% CI= 0.83 to 1.23)].

This meta-analysis failed to confirm preliminary positive evidence for the efficacy of nicotinic acetylcholine receptor antagonists in treatment-resistant depression. Further studies investigating the efficacy of various alternative treatment strategies for treatment-resistant depression will help clinicians to better understand and choose better treatment options for these populations.

The authors have not supplied their declaration of competing interest.

The primary aim of this non-inferiority study was to investigate the clinical effectiveness and safety of generic escitalopram (Lexacure) versus branded escitalopram (Lexapro) for patients with major depressive disorder (MDD).

The present study included 158 patients who were randomized (1:1) to receive a flexible dose of generic escitalopram (n = 78) or branded escitalopram (n = 80) over a 6-week single-blind treatment period. The clinical benefits in the two groups were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS), the 17-item Hamilton Depression Rating Scale (HDRS), the Clinical Global Impressions-Severity Scale (CGI-S), and the Clinical Global Impressions-Improvement Scale (CGI-I) at baseline, week 1, week 2, week 4, and week 6. The frequency of adverse events (AEs) was also assessed to determine safety at each follow-up visit.

At week 6, 28 patients (57.1%) in the generic escitalopram group and 35 patients (67.3%) in the branded escitalopram group had responded to treatment (P = 0.126), and the remission rates (MADRS score: ≤ 10) were 42.9% (n = 21) in generic escitalopram group and 53.8% (n = 28) in the branded escitalopram group (P = 0.135). The most frequently reported AEs were nausea (17.9%) in the generic escitalopram group and nausea (20.0%) in the branded escitalopram group.

The present non-inferiority study demonstrated that generic escitalopram is a safe and effective initial treatment for patients with MDD and may also be considered as an additional therapeutic option for this population.

The authors have not supplied their declaration of competing interest.

To document patient characteristics and treatment patterns in a real-world population diagnosed with attention-deficit/hyperactivity disorder (ADHD).

This was a retrospective chart review of children/adolescents (6–17 years) diagnosed with ADHD in the UK, Germany and Netherlands who initiated stimulant monotherapy (SM), non-stimulant (atomoxetine) monotherapy (NSM) or polypharmacy (SM/NSM ± SM/NSM or other psychotropics) on/after 1-1-2012. To facilitate descriptive comparisons, cohort quotas were imposed: ∼50% SM; ∼25% NSM; ∼25% polypharmacy. Index date was first SM, NSM or polypharmacy treatment on/after 1-1-2012. Patients were required to have ≥ 6 months’ pre-index (baseline) history and ≥ 12 months’ post-index follow-up. Analyses were descriptive.

In total, 497 patients were included (mean [SD] age: 10.8 [2.9] years; 77% male); 65% (SM), 63% (NSM) and 83% (polypharmacy) had at least marked baseline ADHD severity based on Clinical Global Impressions scale (P < 0.05 SM/NSM vs polypharmacy). Ninety percent (SM), 75% (NSM) and 73% (polypharmacy) were pharmacotherapy naïve at index (all P < 0.10); 61% (SM), 65% (NSM) and 72% (polypharmacy) received previous behavioural therapy. In SM patients, methylphenidate was predominant (most frequent brands: Concerta® [29%], Medikinet® [28%]); in polypharmacy patients, methylphenidate plus atomoxetine (22%) or other psychotropic (19%) was most common. Index therapy switch was common, particularly in polypharmacy patients (25%) (P < 0.05 vs SM [14%] and NSM [13%]). Switches were precipitated by poor response in 75% of cases overall.

Polypharmacy patients generally presented a more complicated history (including higher ADHD severity) and treatment pathway versus monotherapy patients. Index therapy switches were commonplace and more frequent in polypharmacy patients, often due to poor response.

The authors have not supplied their declaration of competing interest.

Sexual function is important for patients’ well-being but it is acommon side effect of SSRI and SNRI, included desvenlafaxine.

Evaluate incidence and characteristics of sexual dysfunction caused bydesvenlafaxine in the clinical practice.

One hundred and thirty-three patients with recently introduced desvenlafaxinetreatment are recruited from Barakldo and Uribe-Kosta Mental Health Centresin Biscay, Spain. UKU scale is administered to measure sexual side effects.Statistical analysis is performed using SPSS v.22.

Sexual dysfunction is observed in 5 patients (3.7%) at 50 and 100 mg/d (2 and3 patients, respectively) desvenlafaxine doses. Two patients (1.5%) haveexperimented more than one sexual side effect. Regarding gender differences,the most frequent sexual dysfunctions are diminished sexual desire (5.5%)and erectile dysfunction (5.5%) in men and orgasmic dysfunction (1.2%) inwomen (P-values are 0.034; 0.034 and 0.408, respectively).Discontinuation is decided in 60% of patients.

Desvenlafaxine has a well-tolerated sexual side effect profile in generalpopulation. There are some gender-related differences both in presentationand perception, as it has been described with other drugs, and this shouldbe taken into account by prescriptors.

The authors have not supplied their declaration of competing interest.

Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD.

Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants.

The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/depressive episode) and MDD.

A systematic search was conducted on PubMed/Medline/Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords.

Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics.

Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs.

The authors have not supplied their declaration of competing interest.

The aim of this work is to study the efficacy of loxapine inhalation powder on agitated patients in a psychiatric inpatient unit.

Nineteen patients sample, with an average age of 39.4 years old, diagnosed with schizophrenia, bipolar disorder or schizoaffective disorder. Patients inhaled loxapine 10 mg, using the staccato system, when they suffered a psychomotor agitation. The clinical efficacy was measured as a change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and in the Young Mania Rating Scale (YMRS) one hour after the administration of loxapine.

A mean of 9.8 points reduction (22.6 at baseline and 12.7 one hour after the administration) was found on the PANSS-EC (t-test, P < .001) and 68.4% of the patients were considered responders as they obtained a reduction of at least 40% of the basal score. On 10 of the total of the agitated patients showed an improvement of the psychomotor excitement, and this allowed the clinicians to remove the physical restraint; on 6 of the agitated patients the physical restraint could be avoided during the whole treatment; and 3 of the patients experienced a reduction of the excitement. The reduction on PANNS-EC on the latest group was not statistically significant (t-test, P = .121).

Inhaled loxapine was a non-invasive, rapid and effective alternative treatment for acute agitation in a psychiatric inpatient unit. It resulted more effective on mild and moderate cases; not been significantly effective on the severe cases of agitation.

The authors have not supplied their declaration of competing interest.

The symptoms of bipolar disorder are sometimes misrecognised for unipolar depression and inappropriately treated with antidepressants. This may be associated with increased risk of developing mania. However, the extent to which this depends on what type of antidepressant is prescribed remains unclear.

To investigate the association between different classes of antidepressants and subsequent onset of mania/bipolar disorder in a real-world clinical setting.

Data on prior antidepressant therapy were extracted from 21,012 adults with unipolar depression receiving care from the South London and Maudsley NHS Foundation Trust (SLaM). multivariable Cox regression analysis (with age and gender as covariates) was used to investigate the association of antidepressant therapy with risk of developing mania/bipolar disorder.

In total, 91,110 person-years of follow-up data were analysed (mean follow-up: 4.3 years). The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). The most frequently prescribed antidepressants were SSRIs (35.5%), mirtazapine (9.4%), venlafaxine (5.6%) and TCAs (4.7%). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with SSRIs (hazard ratio 1.34, 95% CI 1.18–1.52) and venlafaxine (1.35, 1.07–1.70).

In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression.

The authors have not supplied their declaration of competing interest.

The hepatic safety of agomelatine was assessed in 49 phase II and III studies. The aim was to analyze the characteristics of patients who developed an increase in transaminases whilst taking agomelatine.

A retrospective pooled analysis of changes in serum transaminase in 7605 patients treated with agomelatine (25 mg or 50 mg/day) from 49 completed studies was undertaken. A significant increase in serum transaminase was defined as > 3-fold the upper limit of normal (> 3 ULN). Final causality was determined in a case-by-case review by five academic experts.

Transaminase increased to > 3 ULN in 1.3% and 2.5% of patients treated with 25 mg and 50 mg of agomelatine respectively, compared to 0.5% for placebo. The onset of increased transaminases occurred at < 12 weeks in 64% of patients. The median time to recovery (to ≤ 2ULN) was 14 days following treatment withdrawal. Liver function tests recovered in 36.1% patients despite the continuation of agomelatine, suggesting the presence of a liver adaptive mechanism. Patients with elevated transaminases at baseline, secondary to obesity and fatty liver disease (NAFLD), had an equally increased risk of developing further elevations of transaminases with agomelatine and placebo. This reflects the widespread fluctuations of serum transaminases in patients with NAFLD.

The overall incidence of abnormal transaminases was low and dose dependent. No specific population was identified regarding potential risk factors. Withdrawal of agomelatine led to rapid recovery, and some patients exhibited an adaptive phenomenon. The liver profile of agomelatine seems safe when serum transaminases are monitored.

The authors have not supplied their declaration of competing interest.

The total costs of schizophrenia increased to 2576 million Euros in 2013 in Spain, or 2.7% of the annual cost of health services. The hospitalizations, along with other intermediate resources, such as Day Hospital, etc., significantly contribute to the increase of economic burden. In Spain, the average hospital stay of schizophrenic patients is 18.24 days, totalling to an average cost of 6,753 Euros/patient (370.23 Euros/patient/day).

The sample selected included patients from both sexes, aged between 18 and 65 years old, with diagnostic criteria of schizophrenia (according to DSM-IV and ICD-10), admitted in the Mental Health Hospital Unit (MHHU), Úbeda between 2012 and 2013, with registered visits of at least 2 outpatient visits or 1 hospitalization related to the schizophrenia diagnosis (n = 48).

After the start of treatment with the injectable antipsychotic drug of prolonged duration, the number of patients that required hospitalization for any psychiatric motive went from 24 patients (49.7%) to 11 patients (22.4%; P < 0.001). The patients who started treatment with PAP during hospitalization had an average stay of 15.7 days, as compared to 18.24 days of average hospital stay due to schizophrenia in Spain. The direct costs of hospitalization stays due to psychiatric reasons decreased from 162,071.88 Euros to 74,282.95 Euros (P < 0.001).

This observational study shows us that the treatment with PAP reduced the average length of the hospital stay, and resulted in a decreased percentage of re-admissions as compared to oral treatments for schizophrenia. These data led to savings of more than 50% of the direct costs of hospitalization.

The authors have not supplied their declaration of competing interest.

Antipsychotic-induced hyperpolactinemia (AIH) is associated with disturbing clinical symptoms, such as sexual dysfunctions, menstrual disorders and galactorrhea. Long-term studies of dopamine agonists in AIH are scarce.

To assess efficacy and safety of cabergoline use in psychiatric patients with AIH, including impact on sexual function and quality of life(QoL).

It was an open-labeled non-randomized naturalistic prospective comparison of cabergoline vs nо treatment in 84 chronic psychiatric patients (F/M = 77/7) with AIH. Cabergoline treatment was started in 44 patients, the сontrol group included 40 patients who rejected the treatment with cabergoline. For assessment of QoL, sexual dysfunction and other hyperprolactinemia symptoms, UKU side effects rating scale (UKU) and SF-36 were used.

The main and control groups were comparable on all main clinical and psychiatric characteristics. The effective cabergoline dose was 0,25-3 (median-0,5) mg weekly; total cabergoline exposure–534 patient-weeks. Normal prolactin levels were achieved after 4-44 (median-14) weeks in 95% of patients. At 3 months after cabergoline discontinuation, prolactin remained normal in 71%, and AIH recurred in 29% of patients. Prolactin normalization was associated with significant reduction of menstrual disorders, galactorrhea, improvement of UKU scores on sexual desire, orgastic dysfunction, total UKU score and SF-36 scores on subscales of social functioning (P = 0,006), role-emotional (P = 0,042), and mental health (P = 0,049). The rate of psychosis exacerbation in control group was higher than in the treatment group (37,5% vs 0%; P < 0,001).

Cabergoline is effective and safe in majority of AIH patients. Long-term cabergoline treatment is not associated with psychosis exacerbation. Beyond reversal of typical AIH symptoms, treatment with cabergolin improves sexual function and QoL.

The authors have not supplied their declaration of competing interest.