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.

Studies with electroconvulsive therapy (ECT) in elderly focus mainly on the assessment of possible side effects on the cognitive functioning; there are few studies that evaluate the effectiveness.

Evaluate the effectiveness of this treatment in the population over 65 years.

Perform a preliminary study to evaluate the response to ECT of ≥ 65 years patients with depression.

We carry out a descriptive study based on patients treated in the last 10 years in the ECT Unit of Centro Hospitalar Psiquiátrico de Lisboa.

Our initial sample consisted of 457 patients. We select patients aged ≥ 65 years with depression, and with complete data, including electroconvulsive parameters, and initial and final Hamilton Rating Scale for Depression (HRSD) scores (n = 59). Of this, 81.36% (n = 48) had unipolar depression, and 18.64% (n = 11) had bipolar depression. In the first group, the mean variation between the initial and final scores in HRSD was 13.88 points, and 27.10% (n = 13) of the patients ended the treatment in the normal range of HRSD score. In the second group, the mean variation was 12.82, and 63.60% (n = 7) ended the treatment in the normal range of HRSD. Considering the initial and final HRSD scores, it appears that unipolar depression group presents higher values (severe depression) (P < 0.05). When we compare the mean variation between the initial and final HRSD scores, we didn’t observe a statistically significant difference between the two groups. There was a clinical improvement in both.

The acute treatment with ECT appears to improve depressive symptoms in bipolar and unipolar depression, when considering an elderly population.

The authors have not supplied their declaration of competing interest.

Repetitive transcranial magnetic stimulation (rTMS) is a new treatment, used for different psychotic disorders mainly depression.

Assessing knowledge and attitude toward rTMS among psychiatrists in Saudi Arabia, and determining factors affecting that.

To ensure that psychiatrists have sufficient knowledge regarding rTMS. A good knowledge will most likely have a positive impact on their attitude.

Cross-sectional study was conducted through an online survey. The study population is all psychiatrists in Saudi Arabia. A new valid and reliable questionnaire was developed.

Sample of 96 psychiatrists enrolled in the study, 81% were males. Participant's mean age was 37 years. Half of participants were consultants. The sample mainly consists of general psychiatrists (65%). The study showed that 80% of psychiatrists have an efficient knowledge about rTMS. Consultants have higher knowledge than residents do. Abroad training has no association with the level of knowledge or attitude. Seventy-nine percent of psychiatrists have a positive attitude toward rTMS. Only 53% of psychiatrists agreed to receive (rTMS) in case they were in a psychotic depressive condition. Minority (7%) of psychiatrists would not refer their patients for rTMS.

Most of psychiatrists have a good knowledge and a positive attitude toward rTMS. Those who have high level of training and experience show higher level of knowledge. Articles are found to be a better source for updating knowledge. Having an rTMS treated person in the family or relatives will positively affect the psychiatrist's attitude.

The authors have not supplied their declaration of competing interest.

Electroconvulsive therapy (ECT) is one of the most polarizing treatments in medicine. Although the treatment effect is well documented in clinical studies, there is a lack of data regarding patients treated in an ordinary clinical setting. In 2013, we established a regional register of neurostimulation treatment in Western Norway.

To describe the use of ECT at the Haukeland university hospital in Bergen.

Patients treated with ECT between June 2013 and June 2015 were included in the register.

One hundred and forty-seven patients received ECT during the 2 years period. The mean age was 58.4 years (22–91 years), 67% were female. Half of the patients (49.7%) had been treated with ECT previously. Indication for treatment was depression in 137 patients (93.2%), of which 29 (19.7%) were moderately, and 69 patients (46.9%) severely depressed, and additional 37 patients (25.2%) presented with severe depression with psychotic features. All but two patients were treated with right unilateral electrode placement, with a mean of 9.7 (3–22) treatments.

The mean MADRS before treatment was 34.2 (4–56) and after treatment 11.9 (0–39). One hundred and ten patients (74.8%) responded to treatment; of which 89 (60.5%) remitted (response defined as a 50% or greater decrease from MADRS baseline score, remission defined as MADRS ≤ 12). Twenty patients (13%) continued with continuation or maintenance ECT after the index series.

The authors have not supplied their declaration of competing interest.

Depression is the most common co-occurring syndrome in schizophrenia, which affects up to 60% of patients. Depression aggravates negative symptoms and cognitive deficit and can deteriorate social functioning, quality of life and outcome of the disease. Insufficient clinical response to adequate pharmacotherapy determines rising interest to brain stimulation techniques such as rTMS.

The primary goal was to evaluate safety and efficacy of rTMS in treatment-resistant schizophrenia patients with dominant depressive and negative symptoms in open non-controlled trial.

Thirty-one schizophrenia (ICD-10) patients with evident depression (CDSS ≥ 6) and negative symptoms and with stable low rate positive symptoms on combined adequate pharmacotherapy (antipsychotic + antidepressant), which have not been changed for at least 6 weeks, were included to the study.

All patients received 15-Hz rTMS on the left dorsolateral prefrontal cortex (100% intensity, 1800 pulses per session, 5 sessions per week, 15 sessions per course) with 8-shaped coil of Neuro-MS/D stimulator (Neurosoft). The primary efficacy measure was 50% CDSS score reduction after the 3rd week of treatment. The secondary measures were weekly reduction rates for CDSS and for PANSS negative syndrome scale.

Twenty (64,5%) patients respond to rTMS. Final mean CDSS score reduction was 55,2% (P = 0,000004), and mean PANSS negative scale score reduction was 21,3% (P = 0,000012). Two patients (6,5%) were excluded due to persistent headaches, no serious adverse events were observed.

rTMS is safe and effective strategy for the management of treatment-resistant depression in schizophrenia and can alleviate negative symptoms. Further sham-controlled studies are needed.

The authors have not supplied their declaration of competing interest.

We previously reported that deep brain stimulation (DBS) in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) is effective in reducing symptoms in severe treatment-resistant obsessive-compulsive disorder patients.

To examine the long-term evolution of obsessive compulsive disorder (OCD) symptoms in 24 patients treated with chronic electrical stimulation in IC/BST.

We aimed to examine the evolution of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and to determine if a number of predictors assessed before surgery are significantly related to this evolution.

We used a linear mixed model to investigate the evolution of the Y-BOCS in 24 patients. Data was collected in a naturalistic manner. Seven hundred measurements, taken during a total of 1836 follow-up months, are included in this analysis.

Our analysis showed a long-term, sustained effect of electrical stimulation in the IC/BST. After a fast initial decline of OCD symptoms, these symptoms stay relatively stable. In addition, results show a strong ON/OFF effect of stimulation (e.g., due to battery depletion). Beside the ON/OFF effect of stimulation, the surgery itself has no additional effect on OCD symptoms. The Beck Depression Inventory (BDI) at baseline was the only predictor significantly related to the evolution of the Y-BOCS. A higher BDI at baseline seemed to be related to a smaller decrease of the Y-BOCS over time.

Electrical stimulation in the IC/BST has a fast and sustained effect on OCD symptoms.

The authors have not supplied their declaration of competing interest.

The alpha rhythm (EEG) in prefrontal regions has been related with the emotional equilibrium, predisposition for a positive mood (Urry et al., 2004) and the activation of the approximation system (Davidson and Irwin, 1999). Superficial neurostimulation application (SNSA) provokes an increase of such rhythm in prefrontal and temporal areas (Bardasano et al., 2010).

To demonstrate that the increase of alpha synchronization is a common factor in the satisfactory evolution of patients with different pathologies.

Thirty patients with different symptoms (hostility, anxiety, bruxism and obsessive symptoms) received 20 weekly sessions of 45 minutes long using the SNSA.

–SNSA topology system: it is a machine for superficial stimulation that uses electricity through superficial electrodes which are placed on feet and hands and an electrode over the 7th cervical vertebra;

–digital encephalogram;

–Faraday cage.

The alpha rhythm was incremented in 85% of the cases in anterior regions of the brain, related with the improvement of scale's punctuation.

The alpha rhythm has been showed to be presented in all individuals that improved their symptoms after the application of SNSA (Fig. 1).

The authors have not supplied their declaration of competing interest.

The four-step integrative model of psychotherapy is concerned with individual's needs, wants, rights and decisions in that order. It may carry a promise for deep and changing vision for patients with borderline personality disorder (BPD).

The study of the illuminating and changing effect of dealing with BPD patients in view of their needs, wants, rights and decisions.

To evaluate the effect of group work through the hierarchy of the four-step integrative model with BPD patients and to help them explore false and true elements of their femininity.

Forty-three female patients (age range: 19-37) diagnosed according to DSM-IV diagnostic criteria for BPD were enrolled in a dynamic psychotherapy group. Their progress was evaluated using Borderline evaluation of severity over time (BEST) and they wrote down detailed comments about their experience quarterly.

Results of regular attendants for 2 years were included (35 = 81.4%). The results of BEST showed a significant reduction of BPD severity at the end of 1 and 2 years. During psychotherapy sessions and within their quarterly comments, patients expressed their change in terms of moving from a state of cunning, manipulation, aggression, arrogance, envy and rejection (as stemming from their false femininity) into wisdom, confrontation, patience, pride, healthy competition and containment respectively (as stemming from their true femininity).

Patients with BPD may gain a better insight and genuine change as they realize what is false and what is true about their femininity in the context of attending four-step integrative model group psychotherapy.

The authors have not supplied their declaration of competing interest.