Valproic acid for agitation in the intensive care unit: an observational study of psychiatric consults.

BACKGROUND: Agitation is a common clinical problem encountered in the intensive care unit (ICU). Treatment options are based on clinical experience and sparse quality literature. AIM: The aim of this study was to describe the effect of valproic acid (VPA) as adjuvant treatment for agitation in the ICU, identify predictors of response to VPA and evaluate the independent effect of VPA on agitation compared to standard of care (SOC). METHOD: This retrospective single center observational study evaluated adult patients admitted to the ICU for whom a psychiatric consultation was requested for agitation management, with agitation defined as a Richmond Agitation Sedation Score of 2 or greater. A descriptive analysis of the proportion of agitation-free patients per day of follow-up, the incidence of agitation-related-events, as well as the evolution of co-medications use over time are presented. A logistic regression model was used to assess predictors of VPA response, defined as being agitation-free on Day 7 and generalized estimating equations were used to evaluate the independent effect of VPA as adjuvant therapy for agitation in the critically ill. RESULTS: One hundred seventy-five patients were included in the study with 78 receiving VPA. The percentage of agitation-free patients on VPA was 6.5% (5/77) on Day 1, 14.1% (11/78) on Day 3 and 39.5% (30/76) on Day 7. Multivariate regression model for clinical and demographic variables identified female gender as predictor of response on Day 7 (OR 6.10 [1.18-31.64], p = 0.03). The independent effect of VPA was non-significant when compared to SOC. CONCLUSION: Although VPA used as adjuvant treatment was associated with a decrease in agitation, its effect when compared to SOC did not yield significant results.

Mindful Melody: feasibility of implementing music listening on an inpatient psychiatric unit and its relation to the use of as needed medications for acute agitation.

BACKGROUND: In this quality improvement project, we set out to study the effectiveness and feasibility of using music as an adjunct or replacement for pharmacologic agitation management on an inpatient psychiatric unit. We hypothesized music intervention would not only assist in de-escalation/calming of agitated patients, but also reduce overall administration of PRN medications on the unit. METHOD: The project included 172 volunteer participants over 6 months: Three months without music available and 3 months with a music de-escalation option. During the latter period, patients were given the option of selecting a preferred music genre and provided with wireless headphones for up to 30 min. The number of as needed (PRN) medications administered for agitation and anxiety (including oral, sublingual, and intramuscular routes) was compiled from raw data using pharmacy records. Patients and nurses were provided with self-report surveys regarding the music intervention. RESULTS: The average weekly PRN medication administrations decreased significantly during the 3 months with music for both haloperidol (8.46 [+/- 1.79, p < 0.05] to 5.00 [+/- 1.44, p < 0.05] administrations/week) and olanzapine (9.69 [+/- 2.32, p < 0.05] to 4.62 [+/- 1.51, p < 0.05] administrations/week), compared to the 3 months prior to music implementation. There was a non-significant increase in administration of lorazepam (3.23 [+/- 1.09, p < 0.05] to 6.38 [+/- 2.46, p < 0.05] average administrations/week). The patient survey responses were 96% positive (non-neutral; either agree or strongly agree with calming effect). Nurses agreed that the project was easy to implement; 56% agreed that music helped to calm patients down. Other exploratory outcomes included observed reductions in average length of hospital stay and number of seclusion events. CONCLUSION: Music may play a significant role in reducing the utilization of PRN agitation medications on acute inpatient psychiatric units. More studies are needed to expand on these findings and explore the effect of PRN music on other therapeutic outcomes. TRIAL REGISTRATION: Protocol registration NCT04514432 , retrospectively registered on 08/13/2020.

Agitation in schizophrenia: origins and evidence-based treatment.

PURPOSE OF REVIEW: Agitation associated with schizophrenia remains an important clinical concern and if not managed effectively, can escalate into aggressive behavior. This is a review of the recent biomedical literature on agitation in individuals with schizophrenia. RECENT FINDINGS: Themes in the recent literature include consideration of comorbidities such as cigarette smoking and cannabis use. Surveys reveal that pharmacological approaches to manage agitation have changed little, with haloperidol remaining in common use and intramuscular administration of antipsychotics and/or benzodiazepines being frequently administered to more severely agitated/aggressive individuals. Of note, ketamine has been recently adopted for use in severe agitation in medical emergency departments, but the risk of this medication for people with schizophrenia is unclear. At present, inhaled loxapine remains the only rapidly acting noninjectable FDA-approved treatment for agitation associated with schizophrenia. In development is an intranasal formulation for olanzapine (a well characterized atypical antipsychotic already approved to treat agitation) and a sublingual film for dexmedetomidine (an α2-adrenergic agonist used as an anesthetic and now being repurposed). SUMMARY: Comorbidities can contribute to agitation and can make an accurate differential diagnosis challenging. The ongoing development of rapidly acting novel formulations of antiagitation medications, if successful, may facilitate clinical treatment by providing additional options.

New insights and rethinking of cinnabar for chemical and its pharmacological dynamics.

Cinnabar is an attractive mineral with many different uses. It is reported that cinnabar is one of the traditional Chinese's medicines extensively use. The main objective of this critical review is to identify the current overview, concept and chemistry of cinnabar, which includes the process developments, challenges, and diverse options for pharmacology research. It is used as a medicine through probable toxicity, especially when taking overdoes. This review is the first to describe the toxicological effects of cinnabar and its associated compounds. Nuclear magnetic resonance (NMR) dependent metabolomics could be useful for examination of the pharmaceutical consequence. The analysis indicated that the accurate preparation methods, appropriate doses, disease status, ages with drug combinations are significant factors for impacting the cinnabar toxicity. Toxicologically, synthetic mercury sulfide or cinnabar should be notable for mercuric chloride, mercury vapor and methyl mercury for future protection and need several prominent advancements in cinnabar research.

A randomised controlled trial of Lavender (Lavandula Angustifolia) and Lemon Balm (Melissa Officinalis) essential oils for the treatment of agitated behaviour in older people with and without dementia.

OBJECTIVE: Lavender and Lemon Balm essential oils are popular in the management of older person agitation due to their ease of application, minimal side effects and low interaction with concurrent medications. This study addressed limitations in the literature to evaluate and compare effectiveness of Lavender and Lemon Balm essential oils on the agitated behaviour of older people with and without dementia living in residential aged care facilities [RACFs]. METHODS: Forty-nine nursing home residents with dementia (n=39) and without dementia (n=10) exhibiting agitation participated in this study. Participants were randomised to a counterbalanced, repeated measures design experiment that tests the treatments Lavender, Lemon Balm, and Placebo (Sunflower oil). Treatments were administered once daily for two-weeks followed by a two-week washout period before commencing the subsequent treatment. All participants trialed all three treatments over a 10-week period. Data were collected on the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory (CMAI). RESULTS: A significant difference was shown when essential oils effect were compared between the cognitive groups. Post hoc analysis reports Lemon Balm more effective in reducing NPI agitation (p = .04) and CMAI physical non-aggressive behaviour (PNAB) (p = .02) in residents without dementia. Lemon Balm less effective in reducing NPI irritability (p = 0.01) and Lavender more effective in reducing CMAI PNAB (p = 0.04) in dementia. CONCLUSION: The findings support an opposing effect of Lemon Balm and Lavender in reducing agitated behaviour between the participant cognitive groups. There was no reduction in agitation with treatments when compared to placebo independent of cognitive groups.

Multiprofessional care for delirium patients in intensive care: integrative review. / Cuidados multiprofissionais para pacientes em delirium em terapia intensiva: revisão integrativa.

OBJECTIVE: To describe the multiprofessional care for the management of critical patients in delirium in the ICU from the evidences found in the literature. METHODS: This integrative review was carried out in the period from February 1 to June 30, 2016 through searches on PubMed, Scopus, Web of Science, and CINAHL, with the following descriptors: delirium, critical care e intensive care units, which brought up 17 original papers. RESULTS: A bundle and a guideline, two systematic reviews, evidence 1a and four clinical trials, evidence 1b and 2b, cohort and observational studies were found. The multiprofessional care was presented to better understand the diagnosis of delirium, sedation pause, early mobilization, pain, agitation and delirium guidelines, psychomotor agitation, cognitive orientation, sleep promotion, environment and family participation. CONCLUSION: The care for delirium is wide and not specific, which determines its multifactorial aspect.

Cuidados multiprofissionais para pacientes em delirium em terapia intensiva: revisão integrativa / Cuidados multiprofesionales para pacientes en delirium en la terapia intensiva: revisión integrativa / Multiprofessional care for delirium patients in intensive care: integrative review

Resumo OBJETIVO Descrever os cuidados multiprofissionais para manejo de pacientes críticos em delirium na UTI a partir das evidências encontradas na literatura. MÉTODOS Trata-se de uma revisão integrativa realizada no período de 1º de fevereiro a 30 de junho de 2016 através de busca nas bases de dados PubMed, Scopus, Web of Science e CINAHL com os descritores delirium, critical care e intensive care units que finalizou com 17 estudos originais. RESULTADOS Foram encontrados um bundle e uma diretriz, duas revisões sistemáticas, evidência 1a e quatro ensaios clínicos, evidência 1b e 2b, os demais estudos de coorte e observacionais. Os cuidados multiprofissionais foram apresentados para melhor entendimento em diagnóstico de delirium, pausa de sedação, mobilização precoce, diretrizes para dor, agitação e delirium, agitação psicomotora, orientação cognitiva, promoção do sono, ambiente e participação da família. CONCLUSÃO Os cuidados para delirium são abrangentes e pouco específicos, determinando seu aspecto multifatorial.

Resumen OBJETIVO Se objetivó describir los cuidados multiprofesionales para manejo de pacientes críticos en delirium en la UTI a partir de las evidencias encontradas en la literatura. MÉTODOS Se trata de una revisión integradora realizada en el período del 1 de febrero al 30 de junio de 2016 a través de búsqueda en PubMed, Scopus, Web of Science, and CINAHL con descriptores delirium, critical care e intensive care units que finalizó 17 estudios originales. RESULTADOS Fueron encontrados un bundle, una directriz, dos revisiones sistemáticos, evidencia 1a, cuatro ensayos clínicos, evidencia 1b y 2b, los demás estudios de cohorte y observacionales. Los cuidados multiprofesionales fueron presentados para mejor entenderse el diagnóstico de delirium, pausa de sedación, movilización temprana, directrices para dolor, agitación, y delirium, agitación psicomotora, orientación cognitiva, promoción de sueño, ambiente y participación de la familia. CONCLUSIÓN Los cuidados para delirium son más amplio y poco específicos, determinando su aspecto multifactorial.

Abstract OBJECTIVE To describe the multiprofessional care for the management of critical patients in delirium in the ICU from the evidences found in the literature. METHODS This integrative review was carried out in the period from February 1 to June 30, 2016 through searches on PubMed, Scopus, Web of Science, and CINAHL, with the following descriptors: delirium, critical care e intensive care units, which brought up 17 original papers. RESULTS A bundle and a guideline, two systematic reviews, evidence 1a and four clinical trials, evidence 1b and 2b, cohort and observational studies were found. The multiprofessional care was presented to better understand the diagnosis of delirium, sedation pause, early mobilization, pain, agitation and delirium guidelines, psychomotor agitation, cognitive orientation, sleep promotion, environment and family participation. CONCLUSION The care for delirium is wide and not specific, which determines its multifactorial aspect.

[Improvement of Stress Resistance and Quality of Life of Adults with Nervous Restlessness after Treatment with a Passion Flower Dry Extract].

BACKGROUND: The passion flower dried ethanolic extract investigated in this non-interventional study has well-documented calmative effects and good tolerability. We investigated the effects of this extract on the stress resistance (resilience) and quality of life (QoL) of patients suffering from nervous restlessness. The addiction potential of the drug and the course of symptoms were also evaluated. METHODS: Adult patients aged ≤ 95 years with the diagnosis 'nervous restlessness' were treated for 12 weeks with a dried ethanolic extract of passion flower (Passiflora incarnata L.). Standardized questionnaires were used to evaluate the resilience (RS-13), QoL (EQ-5D including EQ-VAS), and the addiction potential (BDEPQ). RESULTS: After 12 weeks of treatment, significant (p < 0.001) improvements were measured in the patients' resilience (RS-13: from 52.1 to 67.7 points) and QoL (EQ-VAS: from 47.9 to 75.0 points). Also, the mean BDEPQ score was significantly (p < 0.001) reduced (from 23.0 to 19.3 points). The mean values of all accompanying symptoms (inner restlessness, sleep disturbance, exhaustion, fear, lack of concentration, transpiration, nausea, trembling, and palpitation) improved significantly (p < 0.001). Tolerability of treatment was rated as 'very good' or 'good' by the majority of the patients. Three cases of mild adverse events (tiredness) were reported. CONCLUSION: The passion flower extract investigated in the present study appears to be effective in improving resilience and QoL in patients suffering from nervous restlessness and is well tolerated.

Agitation in Alzheimer Disease as a Qualifying Condition for Medical Marijuana in the United States.

OBJECTIVE: To determine the extent to which states and localities include dementia as a qualifying condition for medical marijuana and how common this indication is. METHODS: The authors reviewed authorizing legislation and medical marijuana program websites and annual reports for the states and localities where medical marijuana is legal. RESULTS: Of the 24 states and localities where medical marijuana is legal, dementia is a qualifying condition in 10 (41.7%), primarily for agitation of Alzheimer disease. In the five states where information was available regarding qualifying conditions for certification, dementia was the indication for <0.5% of medical marijuana certifications. CONCLUSION: Dementia is somewhat commonly listed as a potential qualifying condition for medical marijuana. Currently, few applicants for medical marijuana list dementia as the reason for seeking certification. However, given increasingly open attitudes toward recreational and medical marijuana use, providers should be aware that dementia is a potential indication for licensing, despite lack of evidence for its efficacy.

Effectiveness of Inhaled Loxapine in Dual-Diagnosis Patients: A Case Series.

OBJECTIVES: Episodes of psychotic agitation are frequent in patients with dual diagnosis, that is, in patients with concomitant psychiatric and substance use disorders. Rapid intervention is needed to treat the agitation at a mild stage to prevent the escalation to aggressive behavior. Inhaled loxapine has been demonstrated to rapidly improve symptoms of mild-to-moderate agitation in adults with psychiatric disorders (schizophrenia and bipolar disorder), but data on patients with dual diagnosis are scarce. METHODS: This study is a retrospective review of data from a case series of patients with dual diagnosis, which were attended for symptoms of agitation while at the emergency room (n = 9), in the outpatient clinic (n = 4), or during hospitalization (n = 1) at 1 center in Spain. All patients received inhaled loxapine for treating the agitation episodes. RESULTS: Data from 14 patients with dual diagnosis were reviewed. All patients had 1 or more psychiatric disorders (schizophrenia, bipolar I disorder, drug-induced psychotic disorder, posttraumatic stress, borderline or antisocial personality disorder, depression, or anxiety) along with a variety of substance use disorders (alcohol, cocaine, cannabis, amphetamines, hypnotics and antianxiety drugs, caffeine, or street drugs). Overall, only 1 dose of inhaled loxapine (9.1 mg) was needed to calm each patient during an acute episode of agitation. CONCLUSIONS: Inhaled loxapine was rapid, effective, and well accepted in all dual-pathology patients presenting with acute agitation in the emergency setting. Inhaled loxapine facilitated both patient cooperation and an adequate management of his or her disease.

Effects of Dexmedetomidine Infusion on the Recovery Profiles of Patients Undergoing Transurethral Resection.

Transurethral resection has been the gold standard in the operative management of benign prostatic hyperplasia and bladder tumor; however, it is associated with several complications that may cause patient discomfort. We evaluated the usefulness of continuous infusion of dexmedetomidine on emergence agitation, hemodynamic status, and recovery profiles in patients undergoing elective surgery by a randomized clinical trial. Sixty patients aged 30 to 80 yr who were scheduled for elective transurethral resection under general anesthesia were included in this study. Participants were randomly assigned to two groups (control group, group C; dexmedetomidine group, group D). A total of 60 male patients were enrolled in this study and randomly assigned to group C (n=30) or group D (n=30). The quality of emergence in group D was marked by a significantly lower incidence of emergence agitation than in group C (P=0.015). Patients in group D therefore felt less discomfort induced by the indwelling Foley catheter than those in group C (P=0.022). No statistically significant differences were found between the two groups with respect to side effects including bradycardia (P=0.085), hypotension (P=0.640), and postoperative nausea and vomiting (P=0.389). Our study showed that intraoperative dexmedetomidine infusion effectively reduced the incidence and intensity of emergence agitation and catheter-induced bladder discomfort without delaying recovery time and discharge time, thus providing smooth emergence during the recovery period in patients undergoing transurethral resection (Clinical Trial Registry No. KT0001683).

Effects of Dexmedetomidine Infusion on the Recovery Profiles of Patients Undergoing Transurethral Resection

Transurethral resection has been the gold standard in the operative management of benign prostatic hyperplasia and bladder tumor; however, it is associated with several complications that may cause patient discomfort. We evaluated the usefulness of continuous infusion of dexmedetomidine on emergence agitation, hemodynamic status, and recovery profiles in patients undergoing elective surgery by a randomized clinical trial. Sixty patients aged 30 to 80 yr who were scheduled for elective transurethral resection under general anesthesia were included in this study. Participants were randomly assigned to two groups (control group, group C; dexmedetomidine group, group D). A total of 60 male patients were enrolled in this study and randomly assigned to group C (n=30) or group D (n=30). The quality of emergence in group D was marked by a significantly lower incidence of emergence agitation than in group C (P=0.015). Patients in group D therefore felt less discomfort induced by the indwelling Foley catheter than those in group C (P=0.022). No statistically significant differences were found between the two groups with respect to side effects including bradycardia (P=0.085), hypotension (P=0.640), and postoperative nausea and vomiting (P=0.389). Our study showed that intraoperative dexmedetomidine infusion effectively reduced the incidence and intensity of emergence agitation and catheter-induced bladder discomfort without delaying recovery time and discharge time, thus providing smooth emergence during the recovery period in patients undergoing transurethral resection (Clinical Trial Registry No. KT0001683).

Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep--A randomized, placebo-controlled trial.

The anxiolytic effect of Silexan, a patented active substance with an essential oil produced from Lavandula angustifolia flowers, was investigated in patients with anxiety-related restlessness and disturbed sleep. 170 out-patients with a diagnosis of restlessness (ICD-10 R45.1), a Hamilton Anxiety Scale (HAMA) total score ≥18 points and ≥2 points for HAMA items 'Tension' and 'Insomnia' participated in this randomized, double-blind trial and received 80mg Silexan or placebo once daily for 10 weeks. Patients with clinically important other psychiatric or neurological disorders potentially interfering with the assessment of treatment efficacy were excluded. Outcome variables were the HAMA as well as the Pittsburgh Sleep Quality Index (PSQI), the Zung Self-rating Anxiety Scale, a State Check inventory and the Clinical Global Impressions questionnaire. In the Silexan group the HAMA total score decreased from an average of 25.5±6.0 points at baseline to 13.7±7.0 points at treatment end, compared to a decrease from 26.5±6.1 to 16.9±9.8 for placebo, corresponding to decreases of 12.0 and 9.3 points (marginal means), respectively (group difference: p=0.03, ANCOVA with factor treatment and baseline value as covariate). In all outcome measures the treatment effect of Silexan was more pronounced than with placebo. According to the HAMA, 48.8% and 33.3% of the patients were responders (Silexan, placebo; reduction ≥50%; p=0.04) and 31.4% and 22.6% achieved remission (HAMA<10; p=0.20). 33.7% (Silexan) and 35.7% (placebo) of the participants reported adverse events. The study confirms the calming and anxiolytic efficacy of Silexan.

Mother/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders.

Neurodevelopmental impairment in the serotonergic system may be involved in autism spectrum disorder. Yokukansan is a traditional herbal remedy for restlessness and agitation in children, and mother-infant co-administration (MICA) to both the child and the nursing mother is one of the recommended treatment approaches. Recent studies have revealed the neuropharmacological properties of Yokukansan (YKS), including its 5-HT1A (serotonin) receptor agonistic effects. We investigated the influence of YKS treatment on behavior in a novel environment and on brain monoamine metabolism during the nursing period in an animal model of neurodevelopmental disorders, prenatally BrdU (5-bromo-2'-deoxyuridine)-treated rats (BrdU-rats). YKS treatment did not influence locomotor activity in BrdU-rats but reduced grooming in open-field tests. YKS treatment without MICA disrupted the correlation between locomotor behaviors and rearing and altered levels of serotonin and its metabolite in the cerebellum. These effects were not observed in the group receiving YKS treatment with MICA. These data indicate a direct pharmacological effect of YKS on the development of grooming behavior and profound effects on cerebellar serotonin metabolism, which is thought to be influenced by nursing conditions.

Sensory and nurturing nonpharmacological interventions for behavioral and psychological symptoms of dementia.

This article is part three of a four-part series addressing the use of nonpharmacological interventions in place of or in conjunction with psychotropic medications in older adults with cognitive impairment. Acquiring a better understanding of the mechanics for how each intervention works makes selection of an intervention easier at the time it is needed. Selection of the appropriate nonpharmacological intervention is based on person-centered care and how to adapt and implement it for each individual. Selection also depends on target behavior, behavior triggers, and the physical and cognitive functioning of the individual with the behavioral and psychological symptoms of dementia. Nonpharmacological interventions can be implemented by all staff members, not just recreational and activity personnel. The Centers for Medicare & Medicaid Services initiative would like to see all staff involved with these interventions, which can be implemented on the spot, as they are needed, to prevent, reduce, or stop a particular behavior. The current article will describe sensory and nurturing interventions, present the evidence supporting their use, and provide information on effective implementation.

Hyperactivity, concentration difficulties and impulsiveness improve during seven weeks' treatment with valerian root and lemon balm extracts in primary school children.

BACKGROUND: Valerian root and lemon balm extracts have previously shown efficacy and excellent tolerability in children<12 years suffering from restlessness and insomnia. We now examined whether treatment with a fixed combination of both may also improve concentration, hyperactivity and impulsiveness. METHODS: 169 primary school children suffering from hyperactivity and concentration difficulties but not meeting ADHS criteria were treated in an observational study by 27 office based pediatricians with a recommended daily dose of 640 mg valerian root extract WS(®) 1014 and 320 mg lemon balm extract WS(®) 1303 (Sandrin(®)), and evaluated by pediatricians and parents using standardized questionnaires at baseline, weeks 2 and 7. RESULTS: The fraction of children having strong/very strong symptoms of poor ability to focus decreased from 75% to 14%, hyperactivity from 61% to 13%, and impulsiveness from 59% to 22%. Parent rated social behavior, sleep and symptom burden showed highly significant improvements. Only in two children mild transient adverse drug reactions were observed. CONCLUSION: In primary school children with restlessness, concentration difficulties and impulsiveness treatment with WS(®) 1014 and WS(®) 1303 (Sandrin(®)) provides a viable option in addition to counseling and education.

A case series on the use of lavendula oil capsules in patients suffering from major depressive disorder and symptoms of psychomotor agitation, insomnia and anxiety.

OBJECTIVE: Symptoms of agitation, anxiety and insomnia are frequent among patients with major depressive disorder (MDD) during the first weeks of psychiatric care. But a substantial number of patients declines taking pharmaceutical medication to avoid side effects. Therefore, an alternative herbal medication is needed. Clinical studies demonstrated that lavender oil capsules, termed Lasea®, have an anxiolytic effect comparable to Lorazepam and significantly reduce insomnia and agitation in non-depressed patients. Therefore, the aim of this retrospective case series was to analyze the effectiveness of Lasea® for patients with MDD and symptoms of anxiety, insomnia and psychomotor agitation. DESIGN: Eight cases were analyzed retrospectively regarding the dosage, length of treatment, possible side effects and effectiveness of Lasea®. SETTING: All cases were treated at the Department of Psychiatry at Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin in a naturalistic setting. MAIN OUTCOME MEASURE: Effectiveness was measured by a change in the Hamilton Rating Scale for Depression (HAMD-17) total score and subscores. RESULTS: In 6 cases, the combination of Lasea® and an antidepressant resulted in a reduction of MDD. Lasea® also reduced agitation in 6 cases. Psychological anxiety was reduced in 5, somatic anxiety in 4 cases whereas sleep-onset and sleep-maintenance insomnia improved in 3 cases each. CONCLUSIONS: The results demonstrate that Lasea® reduces some of the anxiety related symptoms and sleep disturbances in MDD patients. Furthermore Lasea® significantly reduces psychomotor agitation. Additionally, the results indicate a significant global improvement stemming from the combinational therapy of Lasea® and antidepressant medication.

A novel analog of olanzapine linked to sarcosinyl moiety (PGW5) demonstrates high efficacy and good safety profile in mouse models of schizophrenia.

UNLABELLED: Schizophrenia is a chronic mental disorder related to hypo-functioning of glutamatergic neurotransmission. N-methyl-D-aspartate-receptor (NMDA-R) positive modulators were reported to reduce schizophrenia symptoms. However, their efficacy is low and inconsistent. We developed a novel antipsychotic possessing an olanzapine moiety linked to the positive modulator of glutamate NMDA-R sarcosine (PGW5) and characterized the pharmacodynamic properties of the novel molecule in-vivo using MK-801 and in-vitro using receptor binding analysis. We investigated the pharmacological activity of PGW5 (olanzapine linked to sarcosinyl moiety) in male mice (BALB/c or C57BL). In an open field test, up to 50mg/kg PGW5 did not affect motility while higher doses were sedative. PGW5 (25-50mg/kg po) antagonized MK-801 (0.15 mg/kg ip) and amphetamine-induced (5mg/kg ip) hyperactivity. PGW5 (25mg/kg po/d) treatment for 15 or 22 days exhibited antidepressant and anxiolytic activity in mice. Moreover, PGW5, but not olanzapine, attenuated phencyclidine (PCP)-induced deficits of social preference in mice and promoted the expression of brain derived neurotrophic factor (BDNF) in the hippocampus and the frontal cortex and glutamic acid decarboxylase (GAD67) in the hippocampus. Mice treated with PGW5 (25 and 50mg/kg/d) for 28 days did not show toxic effects in terms of weight gain and blood-chemistry analysis. CONCLUSIONS: PGW5 is a novel and safe antipsychotic, efficacious against schizophrenia-like positive and negative symptoms at nonsedative doses. The drug shows anxiolytic and antidepressant activity, and improves impaired social performance in phencyclidine (PCP) treated mice. The mechanism underlying its activity seems to involve potentiation of NMDA receptor as well as stimulation of brain BDNF and GAD67 expression.

Neuroprotective and cognitive enhancing effects of a multi-targeted food intervention in an animal model of neurodegeneration and depression.

Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits.