Treatment of Clozapine-Associated Sialorrhea: The Role of Benzamide Derivatives.

PURPOSE: Hypersalivation is one of the most prevalent and distressing adverse effects associated with clozapine treatment. Currently, there is no standard therapeutic approach toward how to overcome it. Clinicians use various medications for managing this adverse effect. However, some of the agents are not effective enough, whereas others can induce other adverse effects. Recently, several reviews have been published on the treatment of clozapine-associated hypersalivation, in which the focus was on drugs from various pharmacological groups, and little attention was paid to drugs from the group of substituted benzamides. The intention of this brief narrative review is to draw the attention of clinicians to the use of the benzamide group for the treatment of this unpleasant adverse effect. METHODS: A MEDLINE search was conducted to identify published treatment studies and case reports in the literature from 2000 to September 2021, concerning a treatment of clozapine-associated hypersalivation, mainly substituted benzamides. RESULTS: Accumulating evidence during the last 2 decades indicates that agents derived from the benzamide group may be effective and safe agents for treatment of clozapine-associated hypersalivation. Whether with a psychotropic effect or without, medications from this group may produce a beneficial response. CONCLUSIONS: Substitute benzamide derivatives have emerged as effective and well-tolerated agents for treatment clozapine-associated hypersalivation.

Biological Sex and IgE Sensitization Influence Severity of Depression and Cortisol Levels in Atopic Dermatitis.

BACKGROUND: Depression is a common comorbid condition with atopic dermatitis (AD), particularly during the active disease cycle. Controversial results regarding the contribution of biological sex, immunoglobulin E (IgE) sensitization, and cortisol on AD severity and comorbid depression justify further investigation. OBJECTIVE AND METHODS: To explore the influence of sex and IgE sensitization on biochemical and psychological parameters, and severity of AD, a case-control study of 105 volunteers (56 AD, 49 healthy controls (HC); 50 males, 55 females) was conducted over 10 weeks, starting at dermatological symptom onset. Disease severity, serum IgE, cortisol and testosterone levels, and depression scores were assessed at study baseline and after 10 weeks of conventional treatment. RESULTS: Dermatological severity differed among AD males by IgE sensitization and was elevated in males with extrinsic atopic dermatitis (EAD). Hamilton Depression Rating Scale (HAMD) scores were elevated in all patients at study baseline and improved with symptom reduction to HC levels, except female EAD. Severity of depression and dermatitis were correlated in EAD males at baseline and at week 10. Serum cortisol was elevated in male EAD at baseline, in contrast to males with intrinsic atopic dermatitis (IAD) at week 10. In addition, cortisol levels were found negatively correlated with SCORAD and HAMD scores in EAD males at week 10. CONCLUSION: Pathophysiological features of AD and depression are likely related to different inflammation-based effects and appear to be biological sex-dependent. Cortisol levels depend on biological sex and IgE sensitization in AD and increase in males with EAD at exacerbation and IAD males at resolution. Biological sex-related disease triggers, IgE sensitization, and cortisol levels are important for the understanding of the mechanisms underlying AD and comorbid depression.

Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.

Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC.

Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial.

AIMS: Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA. METHODS: Sixty out- and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, double-blind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side-effects. RESULTS: Analysis was by linear mixed model. Fifty-two participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated. CONCLUSIONS: Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.

Association between tobacco smoking and bipolar affective disorder: clinical, epidemiological, cross-sectional, retrospective study in outpatients.

PURPOSE: Although high rates of smoking have been reported among psychiatric patients, only a few studies examined the prevalence of smoking in bipolar disorder, and findings are inconsistent. We investigated smoking among bipolar patients. METHODS: We examined the prevalence of smoking in of 102 patients that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for bipolar I disorder in Israel and evaluated the relationship between smoking and demographic and clinical data. RESULTS: Fifty-five of the bipolar patients (53.9%) smoked, with a rate that is 2.36 times higher than among the general population in Israel (22.8%). Significant relationships were revealed between smoking and lifetime history of alcohol dependence/abuse (P = .02), between smoking and history of drug use (P ≤ .01), and between smoking and age of illness onset (P = .04). LIMITATIONS: The cross-sectional nature of the study and the relatively small sample size preclude generalization of the findings. Nicotine levels were not measured; thus, the information regarding smoking was subjective. CONCLUSIONS: Bipolar patients smoke more than the general population. Bipolar patients that are moderate or heavy smokers are more likely than nonsmokers to consume alcohol and abuse psychoactive substances. Contrary to findings of previous studies, no association was found between clinical variables of bipolar patients and smoking.

An accurate wearable hydration sensor: Real-world evaluation of practical use.

A wearable body hydration sensor employing photoplethysmographic and galvanic biosensors was field evaluated using 240 human participants with equal numbers of men and women volunteers. Monitoring of water mass loss due to perspiration was performed by medical balance measurements following one of two different treadmill physical exercise regimens over 90 minutes in 15-minute intervals with intervening 10-minute rest periods. Participants wore two different models of the dehydration body monitor device mated to commercially-available smartwatches (Samsung Gear S2 and Samsung Gear Fit2). Device output was recorded by Bluetooth wireless link to a standard smartphone in 20-second blocks. Comparison of the devices with the standard measurement method (change in body mass measured by medical balance) indicated very close agreement between changes in body water mass and device output (percent normalized mean root square error averaged approximately 2% for all participants). Bland-Altman analyses of method agreement indicated that <5% of participant values fell outside of the 95% confidence interval limits of agreement and all measured value differences were normally distributed around the line of equality. The results of this first-ever field trial of a practical, wearable hydration monitor suggests that this device will be a reliable tool to aid in geriatric hydration monitoring and physical training scenarios.

Link between temperament traits, brain neurochemistry and response to SSRI: insights from animal model of social behavior.

BACKGROUND: Dominant-submissive relationships depend upon functionality of the neural circuits involving monoaminergic neurotransmission. Behavioral profiles of selectively bred dominant (Dom) and submissive (Sub) mice have been proposed to mimic hyperthymic- or depressive-like temperaments observed in patients with affective disorders. These mice differentially respond to psychotropic agents and stressful stimuli, however, the mechanisms underlying these differences remain unclear. To address these mechanisms, we analyzed the brain monoamine content and responses to paroxetine (PXT) in Dom and Sub mice. METHODS: The behavioral effects of PXT (3 mg/kg, single injection) were assessed with the Elevated Plus Maze (EPM) and Forced Swim Test (FST). Monoamine tissue content was analyzed by HPLC-ECD. RESULTS: Compared to Dom, Sub mice had decreased levels of serotonin (5-HT) in the brainstem (BS), reduced levels of norepinephrine (NE) in the prefrontal cortex (PFC), hippocampus (HPC), and striatum (STR) and elevated levels of dopamine (DA) in PFC, HPC, STR and BS. In EPM, PXT administration increased locomotion and exploration in Dom mice, with no effect in Sub mice. In FST, PXT disrupted immobility in Dom mice only. The PXT-produced differences in regional monoamine content were strain-dependent and consistent with the behavioral alterations. LIMITATIONS: Chronic PXT treatment, in vivo monoamine assays and sex-dependent analysis were out of the scope of this study and will be performed in the future in order to provide an in-depth evaluation of the neurochemical mechanisms underlying temperament-dependent responses to SSRIs. CONCLUSIONS: Our findings suggest neurochemical mechanisms that underlie temperament-based response to antidepressant treatment.

Fire Disaster Readiness: Preparation for the Evacuation of Medical Facilities During Fires in Haifa, Israel, 2016.

When a fire occurs, there is little time to escape. In less than 30 seconds, a fire can rage out of control, filling the area with heat and toxic thick smoke (Purdue University Fire Department, 2017; http://www.purdue.edu/ehps/fire/fire-101.html.) In 2010, following the successful evacuation of Maale Ha'Carmel Mental Health Center during a raging forest fire in the area, a comprehensive investigation was performed to evaluate the management of the evacuation process and to systematically elicit lessons learned from the incident. In 2016, a forest fire erupted in the same geographic area that required the evacuation of Fliman Geriatric Rehabilitation Hospital, and methodical debriefing identified the strengths and weaknesses of the evacuation process in that hospital. The lessons learned from the evacuation of these two health care facilities, which were at the focus of major fires in Israel in 2010 and in 2016, are presented. (Disaster Med Public Health Preparedness. 2019;13:375-379).

Comparative accuracy of optical sensor-based wearable system for non-invasive measurement of blood glucose concentration.

Non-invasive biosensors for indirect evaluation of routinely-measured blood components by sweat analysis have broad potential clinical applications. This trial tested a wrist-borne non-invasive glucose monitor (NIGM) to measure blood glucose (BG) levels using photoplethysmographic (PPG) optical sensors. Our aim was to determine the accuracy of the device in comparison with a standard, invasive clinical method for blood glucose monitoring. Adult participants (n = 200) of both sexes from 18 to 75 were recruited for the study. Exclusion criteria: hemophilia and other serious coagulation disorders, impaired venous access, other serious medical conditions. A biosensor was placed on the right wrist of each participant for a non-invasive indirect BG measurement. In parallel, blood from the antecubital vein was collected and glucose levels were assessed with YSI 2300 Bioanalyzer. The measurements were performed twice: before and after food intake, with a 1-h interval between measurements. There were no limitations to food type and quantity. In both anteprandial (ρ = 0.8994, p < 0.0001) and postprandial (ρ =0.9382, p < 0.0001) glucose measurements, NIGM correlated with values obtained by the YSI 2300 reference device - there was no significant difference between the two methods. Plotted on a Parkes Error Grid for Type II diabetes, NIGM readings did not deviate from those of the YSI 2300 in any clinically-significant way, with the majority of correlated readings falling within Parkes zone A. Very few readings fell within Parkes zone B. In anteprandial measurements, the mean bias between methods for all patient volunteers was 3.705 ±â€¯7.838. In postprandial measurements gave a mean bias of 1.362 ±â€¯10.15 for all patient glucose data. The mean absolute relative difference of currently available glucometer models ranges from 5.6% to 20.8%. The NIGM falls in the lower end of this error range at 7.40-7.54%, indicating that PPG-chemochrome sensors are capable of producing results comparable with those of direct measure glucometers. Data presented here demonstrates the reliability and accuracy of the NIGM system as an adjunctive, and perhaps substitutive, non-invasive tool for blood glucose monitoring.

Curcumin as Add-On to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Introduction of old and new generations of antipsychotics leads to significant improvements in the positive symptoms of schizophrenia. However, negative symptoms remain refractory to conventional trials of antipsychotic therapy. Recently, there were several open clinical human trials with curcumin. Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including antioxidative and neuroprotective effects. The studies showed that curcumin improved the negative symptoms of schizophrenia. The purpose of our study was to examine the efficacy of curcumin as an add-on agent to regular antipsychotic medications in patients with chronic schizophrenia. METHODS: Thirty-eight patients with chronic schizophrenia were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 3000 mg/d curcumin or placebo combined with antipsychotics from January 2015 to February 2017. The outcome measures were the Positive and Negative Symptoms Scale (PANSS) and the Calgary Depression Scale for Schizophrenia. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. There was a significant response to curcumin within 6 months in total PANSS (P = 0.02) and in the negative symptoms subscale (P = 0.04). There were no differences in the positive and general PANSS subscales, and the Calgary Depression Scale for Schizophrenia scores between the treatment and placebo groups. No patient complained of any adverse effect. CONCLUSIONS: The promising results of curcumin as an add-on to antipsychotics in the treatment of negative symptoms may open a new and safe therapeutic option for the management of schizophrenia. However, these results should be replicated in further studies.ClinicalTrials.gov Identifier: NCT02298985.

Adjunctive Pregnenolone Ameliorates the Cognitive Deficits in Recent-Onset Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: This study aimed to examine the effect of add-on treatment with the neurosteroid pregnenolone (PREG) on neurocognitive dysfunctions of patients with recent-onset schizophrenia (SZ) and schizoaffective disorder (SA). METHOD: Sixty out- and inpatients that met DSM-IV criteria for SZ/SA were randomized to an 8-week, double-blind, randomized, placebo-controlled, 2-center trial. Participants received either pregnenolone (50 mg/d) or placebo added on to antipsychotic medications. Computerized Cambridge Automated Neuropsychological Test Battery measures were administered at baseline and after 4 and 8 weeks of treatment. ANOVA and paired t- or z-tests were applied to examine between- and within-group differences over time. RESULTS: Compared to placebo, adjunctive PREG significantly reduced the deficits in visual attention measured with the Matching to Sample Visual Search task (p=0.002), with moderate effect sizes (d=0.42). In addition, a significant improvement was observed from baseline to end-of-study with respect to the visual (p=0.008) and sustained attention (Rapid Visual Information Processing, p=0.038) deficits, and executive functions (Stockings of Cambridge, p=0.049; Spatial Working Memory, p<0.001) among patients receiving PREG but not among those receiving placebo (all p's>0.05). This beneficial effect of PREG was independent of the type of antipsychotic agents, gender, age, education, and illness duration. CONCLUSIONS: Pregnenolone augmentation demonstrated significant amelioration of the visual attention deficit in recent-onset SZ/SA. Long-term, large-scale studies are required to obtain greater statistical significance and more confident clinical generalization.

Successful Use of Escitalopram for the Treatment of Visual Hallucinations in Patients With Parkinson Disease.

INTRODUCTION: Patients with Parkinson disease (PD) frequently experience visual hallucinations (VH). Visual hallucinations are most often viewed as an adverse effect of antiparkinsonian treatment. Possible treatments for this disturbance include a reduction of antiparkinsonian medications, adding atypical antipsychotics, or cholinesterase inhibitors. Some studies demonstrated that selective serotonin reuptake inhibitors may be an optional treatment for patients experiencing psychosis or agitation in dementia. Currently, there is no standard recommended treatment for VH in patients with PD. We present here our clinical experience with escitalopram (selective serotonin reuptake inhibitor) for treating this disturbance. METHODS: Thirteen patients with PD (8 men and 5 women; age range 67-83 years) experiencing VH were openly treated with escitalopram 10 or 15 mg/d as add-on. Efficacy was assessed at baseline, then after 4 and 8 weeks of treatment using Clinical Global Impression-Severity and Clinical Global Impression-Improvement. RESULTS: At the end of the 4th week of treatment, of 13 patients, 11 subjects demonstrated improvement, and in only 2 patients were there no changes in their condition. After an additional 4 weeks, 2 of the responders showed very significant improvement, 6 demonstrated much improvement, and 3 patients demonstrated minimal improvement. Only 1 patient showed no change in his condition. One additional patient stopped taking escitalopram after 5 weeks because of an absence of improvement in his state. CONCLUSIONS: Escitalopram was well tolerated as treatment of VH in PD patients. This medication could be a promising optional therapy for this disturbance; however, further randomized controlled and bigger studies are necessary.

Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study.

The beneficial effect of sulpiride augmentation of clozapine therapy for treatment-resistant schizophrenia patients is enhanced by its antisalivatory effect on clozapine-induced hypersalivation (CIH). Amisulpride, similar to sulpiride, is a substitute benzamide derivative with higher selective binding to the D2/D3 dopamine receptor. We hypothesized that add-on amisulpride would also be beneficial in controlling CIH. In a randomized, double-blind, placebo-controlled cross-over study, 20 clozapine-treated schizophrenia (DSM-IV criteria) inpatients with CIH were randomly initially assigned to add-on amisulpride (nine patients; 400 mg/day up-titrated from 100 mg/day over 1 week) or placebo (11 patients). Primary outcome was change in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Other measures included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale (CGI) and Simpson-Angus Scale (SAS). Mean NHRS indices were considerably lower with amisulpride (1.79 +/- 1.25) than with placebo (2.63 +/- 1.33) [F(1,38) = 5.36, P < 0.05]. With amisulpride treatment, there was a significant improvement on the negative symptoms subscale of the PANSS [F(3,57) = 3.76, P < 0.05], but not on the SAS, CGI or other subscales of the PANSS (all F < 1). Short-term amisulpride augmentation has a strong ameliorating effect on CIH. A long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time.

Sulpiride addition for the treatment of clozapine-induced hypersalivation: preliminary study.

BACKGROUND: Hypersalivation is a common, troublesome side effect of clozapine treatment. It occurs in 31-54% of clozapine treated patients. Management of this stigmatizing side effect may reduce noncompliance. Reports in the literature have shown beneficial clinical effects of combined clozapine-sulpiride therapy as measured by the Brief Psychiatric Rating Scale, and we found that this treatment combination also has very strong antisalivatory activity for clozapine-induced hypersalivation. METHODS: 18 patients (12 female, 6 male) with clozapine-induced hypersalivation received sulpiride (150-300 mg/day) in addition to ongoing clozapine treatment (from 100 mg/d to 800 mg/d). Baseline, 7 day and 21 day follow-up values were recorded for the 5-point Nocturnal Hypersalivation Rating Scale. RESULTS: At the end of the trial only 3 patients complained of minimal sialorrhea, and the mean Nocturnal Hypersalivation Rating Scale scale values showed a significant reduction in sialorrhea (delta baseline-endpoint -.2.78 +/- 0.87). CONCLUSIONS: Our findings support reports of the beneficial effect of clozapine-sulpiride combination therapy and suggest that sulpiride addition may contribute to the amelioration of clozapine-induced hypersalivation.

Clinico-Epidemiological Comparison of Delusion-Prominent and Hallucination-Prominent Clinical Subgroups of Paranoid Schizophrenia.

BACKGROUND: Though hallucinations and delusions are prominent basic impairments in schizophrenia, reports of the relationship between hallucinatory and delusional symptoms among schizophrenia patients are scant. AIMS: To examine the epidemiological and clinical differences between mainly hallucinatory and mainly delusional subgroups of paranoid schizophrenia patients. METHODS: One hundred schizophrenia patients, paranoid type, were recruited. In a cross-sectional study, participants were divided into Mainly Hallucinatory (H) and Mainly Delusional (D) subgroups. Demographic variables were compared and clinical characteristics were evaluated using the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression Scale. The Quality-of-Life Enjoyment and Satisfaction Questionnaire-18 was used to assess quality of life. RESULTS: Clinically, the H group was more heterogeneous as expressed by the broader range of scores that described the clinical picture of patients in that subgroup (in 43 of 78 variables, 55.13%) and similar ranges of scores (31 of 78 variables, 39.74%) for patients in the D group. Duration of hospitalization was significantly longer in group H than in group D (p=0.047). There was no statistically significant difference between the H and D subgroups in demographic characteristics. CONCLUSIONS: There are distinct epidemiological and clinical differences between the H and D subgroups, with more severe positive and negative symptoms and greater functional impairment in the H group. Paranoid schizophrenia patients with prominent hallucinations have poorer prognosis and need intensive therapeutic rehabilitation beginning with onset-of-illness. Further genetic studies and comparisons of fMRI and/or PET findings are warranted to investigate additional distinctive characteristics of these subgroups.

Amisulpride as add-on treatment for resistant obsessive-compulsive disorder: retrospective case series.

UNLABELLED: Obsessive-compulsive disorder (OCD) is one of the most common and disabling psychiatric disorders. Treatment with selective serotonin reuptake inhibitors (SSRIs) shows significant improvement; however, residual symptoms remain in most patients despite continued treatment. For partial or nonresponding patients to multiple SSRIs, augmentation strategies are usually recommended. Here we present a consecutive sample of patients with resistant OCD treated with amisulpride augmentation to SSRIs. METHODS: We present 10 patients (5 males, 5 females) experiencing resistant OCD. Subjects were treated openly for 6 weeks with amisulpride 200 mg/d as add-on, excluding 1 patient who was treated with only 100 mg/d due to acute extrapyramidal adverse effect on a larger dose. Efficacy was assessed at baseline and after 6 weeks of treatment using the Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impression-Severity, and Clinical Global Impression-Improvement. RESULTS: The treatment was generally well tolerated without serious events. In all patients, average Yale-Brown Obsessive-Compulsive Scale scores diminished from 25.3 ± 5.96 points at baseline to 12.2 ± 5.98 at the sixth week (P < 0.0005). Of 10 patients, 7 had significant and partial improvement, and 3 patients did not demonstrate any improvement. CONCLUSIONS: Treatment-resistant OCD patients positively responded and well tolerated amisulpride add-on to their ongoing regular pharmacotherapy. This case series demonstrates that amisulpride could be a promising optional therapy for patients who have resistant OCD. Further randomized controlled studies are necessary.

Blood BDNF level is gender specific in severe depression.

Though the role of brain derived neurotrophic factor (BDNF) as a marker for major depressive disorder (MDD) and antidepressant efficacy has been widely studied, the role of BDNF in distinct groups of patients remains unclear. We evaluated the diagnostic value of BDNF as a marker of disease severity measured by HAM-D scores and antidepressants efficacy among MDD patients. Fifty-one patients who met DSM-IV criteria for MDD and were prescribed antidepressants and 38 controls participated in this study. BDNF in serum was measured at baseline, 1st, 2nd and 8th treatment weeks. Depression severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D). BDNF polymorphism rs6265 (val66met) was genotyped. We found a positive correlation between blood BDNF levels and severity of depression only among untreated women with severe MDD (HAM-D>24). Serum BDNF levels were lower in untreated MDD patients compared to control group. Antidepressants increased serum BDNF levels and reduced between-group differences after two weeks of treatment. No correlations were observed between BDNF polymorphism, depression severity, duration of illness, age and BDNF serum levels. Further supporting the role of BDNF in the pathology and treatment of MDD, we suggest that it should not be used as a universal biomarker for diagnosis of MDD in the general population. However, it has diagnostic value for the assessment of disease progression and treatment efficacy in individual patients.

Evacuation of a mental health center during a forest fire in Israel.

Tirat Carmel Mental Health Center was successfully evacuated in December 2010 during a ravaging forest fire in the nearby Carmel Mountains. A total of 228 patients were successfully evacuated from the center within 45 minutes. No fatalities or injuries associated with the evacuation occurred. We believe that the efficient functioning of the administrative and medical staff provides a replicable model that can contribute to the level of awareness and readiness of hospital staff members for natural and manmade disasters.

"Hearing voices" in schizophrenia: who's voices are they?

Paranoid schizophrenia is a subtype within the group of schizophrenia disorders. In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), delusions and hallucinations are the first and second symptoms required for the diagnosis of schizophrenia. Empirical data and clinical observations allow us to present the hypothesis that paranoid schizophrenia can be divided into two subgroups: (1) Hallucinatory subgroup, patients with prominent hallucinations and delusions influenced by auditory hallucinations, (2) Delusional subgroup, patients with prominently impaired thought content, in which hallucinations are not significant clinical factors. Furthermore, we believe that auditory hallucinations are not disturbances of perception but rather of thought - or "pseudo-perceptions". According to our hypothesis there are epidemiological and clinical differences between the hallucinatory and delusional subgroups of patients diagnosed with schizophrenia, paranoid type. Patients in the Hallucinatory subgroup have more severe positive and negative symptoms and greater functional impairment than the patients in the Delusional subgroup. A patient deep in thought might not realize that he is thinking (malfunction of thought) but is rather "hearing voices" without external stimulus. Thus, hearing voices is not a disturbance of perception but rather of thought - or "pseudo-perception". The prognosis seems to be poorer for paranoid schizophrenia patients with prominent hallucinations, thus therapeutic rehabilitation programs for hallucinatory patients need to be developed accordingly. Further research is warranted to investigate additional aspects of these two groups.

Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study.

OBJECTIVES: Depression is a widespread mental disorder in which nearly half of the affected people have recurrent symptoms. Drug combinations may produce cumulative adverse effects, especially in elderly and physically ill patients. It was demonstrated that curcumin possesses antidepressive activity in various animal models of depression, and a combination of curcumin with some antidepressants potentiates the antidepressive effect of these agents. We sought to evaluate the efficacy of curcumin as an antidepressive agent in a combination with other antidepressants in patients with major depression. METHODS: Forty patients with a first episode of depression participated in a 5-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 500-mg/d curcumin or placebo together with antidepressants (escitalopram or venlafaxine) during August 2010 until June 2011. The outcome measures were Clinical Global Impression-Severity Scale, Hamilton Depression Rating Scale, and Montgomery-Asberg Depression Rating Scale. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. These changes became significant from the first visit after 7 days of treatment. There was no difference between curcumin and placebo, which means negative results. However, the patients in the curcumin group demonstrated a trend to a more rapid relief of depressive symptoms in comparison to those in the placebo group. None of the patients complained of any adverse effect during the study. CONCLUSIONS: Although there is no definitive proof that curcumin can induce an earlier beneficial effect of antidepressive agents, it seems like an extended study is needed to prove it, using higher therapeutic doses of curcumin.