Anatoly Kreinin

Curcumin as an Add-On to Antidepressive Treatment: A Randomized, Double-Blind, Placebo-Controlled, Pilot Clinical Study

ObjectivesDepression 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. MethodsForty 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. ResultsAnalysis 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. ConclusionsAlthough 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.

Selective breeding for dominant and submissive behavior in Sabra mice

BACKGROUND The Dominant-Submissive Relationship (DSR) model used here was developed for mood stabilizing and antidepressant drug testing. Treatment of submissive animals with known antidepressants significantly reduced submissive behavior in a dose-dependent manner. We hypothesized that if submissive behavior in DSR is a valid model of depression, it should be possible to show a genetic predisposition for this trait, since clinical studies support a genetic component for depression. METHODS To test this hypothesis, we applied selective breeding on outbred Sabra mice based on DSR paradigm. RESULTS Here we have demonstrated that the frequency of DSR formation gradually increased across four generations of outbred Sabra mice, when animals inbred for the dominant trait were paired with those inbred for the submissive trait. Chronic imipramine administration (10mg/kg) significantly reduced submissive behavior in the F2 generation consistent with the effect seen in unselected C57BL/6J mice. CONCLUSIONS We conclude that increased frequency of DSR formation suggest a genetic component of these two phenotypes, and strengthens the predictive and face validity of the DSR test. Selective breeding may aid in a better understanding of the genetic basis of dominant and submissive behavior, important elements in the etiology of affective disorders.

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.

The role of the PACAP signaling system in depression.

Major Depressive Disorder (MDD) is a psychiatric condition that represents an important public health concern in modern society. Current pharmacological antidepressant treatments improve depressive symptoms through complex mechanisms that are incompletely understood. There is a consensus that in the clinic they act through the modulation of monoaminergic neurotransmission, primarily involving the serotonin and norepinephrine systems. Recent studies have suggested that action of antidepressants on synaptic plasticity is mediated by their regulatory influence not only upon small-molecule neurotransmitters, but also via neuropeptides which may act both as neurotransmitters and as neuromodulators. Prominent among these neuropeptides is PACAP, whose signaling system is intensively studied for its pleiotropic involvement in various physiological and pathological conditions. This review outlines the current knowledge concerning the PACAP signaling systems involvement in depressive disorders.

Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation

Abstract Objectives. Previous publications demonstrated substitute benzamides as effective agents in treatment of clozapine-induced sialorrhea (CIS). The aim of this study was to compare efficacy of amisulpride and moclobemide (both from the substitute benzamide group) in controlling, or at least minimizing, CIS. Methods. The study was designed as a 6-week, two-center, fixed-dose, comparison study of 400 mg/day of amisulpride versus 300 mg/day of moclobemide as an adjunctive treatment in 53 schizophrenia and schizoaffective disorder patients (diagnosed according to DSM-IV) suffering from CIS. The patients were treated with each medication during 2 weeks, followed by a washout period of 2 weeks. Primary outcome measures included the reduction in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Secondary outcomes included the Positive and Negative Syndrome Scale (PANSS), Manic State Assessment Scale, and Extrapyramidal Symptom Rating Scale (ESRS). Results. Both amisulpride and moclobemide were very effective in reducing CIS. Almost 74% of patients treated with amisulpride and 83% of patients treated with moclobemide showed some level of improvement on NHRS. Only in one patient treated with amisulpride, CIS worsened. Conclusions. Both medications were safe and effective as treatment of CIS. Although moclobemide exceeded amisulpride in antisalivation activity, treatment of CIS with amisulpride leads to improvement in psychotic symptoms.

Moclobemide treatment of clozapine-induced hypersalivation: pilot open study.

Objectives:Clozapine-induced hypersalivation (CIHS) affects a mean of approximately 30% patients and is a troublesome adverse effect that leads to massive compliance problems in patients with schizophrenia. For the management of this distressing adverse effect, different pharmacological agents have been recommended, yet none of them have been proven to be effective. The aim of our study was to investigate moclobemide, a reversible monoamine oxidase inhibitor-A, as an additional possibility for controlling or at least minimizing CIHS. Methods:We enrolled 14 patients with schizophrenia who experienced CIHS. Moclobemide (150-300 mg/d) was added to their conventional regular treatment during 14 days. Hypersalivation was assessed at the start of the treatment and at its end point by the 5-point Nocturnal Hypersalivation Rating Scale. Results:Two thirds of the subjects who experienced CIHS have demonstrated a beneficial effect after the addition of moclobemide, whereas one third of them have been nonresponders. None of the patients had any adverse effects. Conclusions:We assume that moclobemide can be another additional and safe medication for the treatment of CIHS; however, more data, based on controlled studies, are needed.

Amisulpride as Add-on Treatment for Resistant Obsessive-Compulsive Disorder: Retrospective Case Series

&NA;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. MethodsWe 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. ResultsThe 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. ConclusionsTreatment-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.

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

Abstract 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.

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.