Brief Psychiatry Rating Scale Research Articles

Abstract PO4-18-05: Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer

Abstract Introduction- Cannabis is world’s oldest cultivated medicinal plant. It has potential applications in oncology, in reducing chronic pain, stimulating appetite, alleviating nausea/vomiting, improving overall well-being as well as its anti-cancer properties. We conducted a phase-1 dose escalation study to determine safety of pre-operative oral cannabis in breast and oral cavity squamous cell carcinoma (OC-SCC) with an intent to explore its anticancer potential in the “pre-operative” window. The primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Methodology- Primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Non-metastatic breast and OC-SCC patients planned for curative surgery were consented after thorough medical and mini-psychiatric evaluation with Brief Psychiatry Rating Scale (BPRS). The investigational product (IP) comprised of a capsule containing 2.5mg of tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD) in 100 mg monocrotolyn oil extract of dried leaves of C. sativa. The capsules were manufactured in an Ayurvedic GMP facility. The classical 3+3, phase-1 design used modified Fibonacci sequence for dose escalation, starting with 5mg THC+5mg CBD. Patients received IP once a day for 5 days after breakfast with hemodynamic and psychiatric monitoring and underwent the planned surgery on day-6. Pharmacokinetic samples were collected at predefined time-points and plasma levels of THC, 11-OH-THC, 11-COOH-THC and CBD were determined using a validated LC-MS/MS method. Tumour tissue was collected before 1st dose of cannabis and during surgery for biomarker analysis. Results- A total of 12 patients were enrolled (6-breast, 3-buccal mucosa, and 3-tongue cancers). First 3 patients completed the study without DLT at 5+5mg dose. A DLT was observed at dose level-2 (10+10mg) and therefore additional 3 patients were enrolled at the same dose. Two patients out of six at this dose had DLT (anxiety- grade-3 and somnolence- grade-2) necessitating dose de-escalation in the next cohort. At 7.5+7.5mg dose, all 3 patients tolerated the IP(MTD). Ten patients completed the study protocol. Common adverse effects were headache (2/12, grade-1), heavy head (8/12, grade-1), hypotension (2/12, grade-1 and 3), epigastric discomfort (1/12, grade-1), diarrhoea (1/12, grade-1), hyponatremia (1/12, grade-1), hypertension (1/12, grade-2), anxiety (1/12, grade-2). Pharmacokinetics of both CBD and THC was less than dose proportional. At the MTD (7.5+7.5), day-1 and day-5 AUC0-24 [median (range)] for CBD were 21.75 (12.44–41.44) ng/ml−1*h and 24.85 (13.72–35.93) ng/ml−1*h respectively. Similarly, for THC, day 1 and day 5 AUC0-24 were 11.79 (8.06–70.58) ng/ml−1*h and 68.98 (1.78 – 136.17) ng/ml−1*h, respectively. Significant accumulation of both CBD and THC was observed across all doses from day 1 to 5. A high variability in pharmacokinetics was observed for both constituents (CV Cmax = 101.26% and 117.48%; CV AUC0-24 = 102.50% and 112.37% for CBD and THC respectively. The median half-life of CBD and THC was 2.2 (1.6–10.7) and 1.9 (1.6–2.4) h respectively. There was no correlation observed between drug exposure and toxicity. There was no significant change in BPRS score before and after IP. Conclusion- We report the first phase-1 study of cannabis in breast and OC-SCC cancer in pre-operative setting for its anti-cancer potential. Biomarker analysis is awaited. MTD identified will be further explored in phase 2/3 clinical trials in breast, oral cavity, lung and pancreatic cancer with survival endpoints. Citation Format: Rajendra Badwe, Shalaka Joshi, Shiva Thiagarajan, Vikram Gota, Vaibhav Vanmali, Pallavi Daphale, Jayita Deodhar, Rohan Chaubal, Rohini Hawaldar, Jaya Chitra Aadhi, Saurabh Kumar Gupta, Delzaad Deolaliwala, Anil Bhansali, Siddhant Mistry, Satyajeet Singh, Nita Nair, Vani Parmar, Sudeep Gupta. Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-05.

Cognitive recovery in psychiatric disorders: transdiagnostic interdisciplinary intervention in a high intensity partial psychiatric in-patient unit

Aim: The present study aims to analyze the impact on cognitive recovery of an interdisciplinary treatment for acute and severe psychiatric patients. Methods: The present research is a naturalistic observational study of 130 adults (mean age of 47.68 years, 68% women). Clinical severity was assessed using Brief Psychiatry Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), and Hamilton Anxiety Rating Scale (HARS). Functional performance was evaluated using the Functioning Assessment Short Test (FAST), and cognitive impairment by applying the Montreal Cognitive Assessment (MoCA). Patients were clustered into four diagnostic groups (non-affective psychosis, bipolar, depressive, and personality disorders) and had individualized psychopharmacological treatment. They receive a transdiagnostic group program including several interventions that have shown evidence of beneficial effects over the different cognitive domains impaired in mental illness (attention, speed of processing, memory, working memory, reasoning, and problem-solving), as well as social cognition domains (emotion processing and social skills), in combination with psychoeducation and some strategies oriented to achieve healthy lifestyle routines (balanced diet, physical exercise, sleep hygiene, and smoking and alcohol cessation). Results: All clinical scales scores were improved after the end of treatment compared with those achieved at admission (BPRS, MADRS, and HARS scores below the cut-off point for establishing a case diagnosis). MoCA scores improved after the end of treatment concerning admission, both in the total score and in the differentiated cognitive domains, excluding orientation, which remained unchanged in the whole of the sample studied. No statistical significance was found in any comparisons between different diagnostic groups. No correlation between MoCA scores and BPRS, MADRS, or HARS scores at admission or discharge was found. Conclusions: These results show that the interdisciplinary therapeutic intervention can be effective for recovering cognitive impairment associated with mental disorders, irrespective of the diagnosis.

The Effect of Mindfulness-based Cognitive Therapy on Anxiety and Resilience of the School Going Early Adolescents with Anxiety

Background: The increasing mental health problems of Indian adolescents are of great concern but child-health mental service is in a nascent stage. Anxiety is the most common psychological problem found in school-going children. The psychological intervention for this high-risk population at an early stage of adolescence can prevent mental health problems. Aim: The study aimed to assess the applicability and effectiveness of mindfulness-based cognitive therapy (MBCT) on resilience and anxiety of early school-going adolescents with anxiety. Method: This study used pre, post, and follow-up with a randomized control group design. Out of 200 samples screened by Preliminary Identification Performa and Clinical Interview Schedule (PI&CI), General Health Questionnaire-12 (GHQ-12), Spence Children’s Anxiety Scale (SCAS), and Brief Psychiatry Rating Scale (BPRS-C), 72 samples aged between 10 to 14 were included in the final study and grouped into two equal groups through a simple randomized method. Psychological intervention based on mindfulness (PIBM) group with N = 36 received 12 sessions of mindfulness-based intervention (MBCT-C) but only 33 completed up to follow-up. Only N = 32 in Treatment Waiting List (TWL) group completed three assessments who received parental counseling about anxiety. The outcome measures were Child and Adolescent Mindfulness Measure (CAMM), SCAS, Bharathiar University Resilience Scale (BURS). Result: The findings suggested that the PIBM group significantly improved in mindfulness and resilience, and anxiety symptoms were reduced. The effect size observed is strong and the post hoc t-test showed significant change in variables in every assessment duration. The TWL group did not have significant change. Thus MBCT-C is an applicable and effective intervention for a early school-going adolescent with anxiety.

Psychopathology in psychotic disorders: Congruency between self-reported and observer-rated measures highest for affective symptoms and lowest for negative symptoms.

Considering that both observer ratings and patient self-reports on severity of psychopathological symptoms are being used in research and clinical settings, this paper aims to explore the degree of congruence between these two sources. Eighty-two adult outpatients diagnosed with psychotic disorders rated their symptoms using the Brief Symptom Inventory (BSI). Observers assessed patients' functioning using the Brief Psychiatry Rating Scale (BPRS). Self-ratings (overall BSI) were strongly correlated to observers' evaluations (overall BPRS). Anxiety/depression symptoms dimension of the BPRS were significantly associated with all nine symptom dimensions of the BSI, while positive symptoms dimension and unusual and withdrawal behavior in the BPRS showed a significant relationship to seven symptom dimensions as measured with the BSI. Mania/activation in the BPRS was significantly and negatively related only to phobic anxiety in BSI. Eight symptom dimensions of the BSI (interpersonal sensitivity was an exception), as well as unusual and withdrawal behavior and positive symptoms in the BPRS were rated as more severe in unemployed study participants. Self-rated paranoid ideation was higher in less educated participants. No sex or marital status differences were found in the BSI and BPRS dimensions. The obtained pattern of correlations implied that congruence was highest in regards to affective symptomatology, followed by positive symptoms, and lowest for disorganization and withdrawal behavior.

Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia: implications for the role of inflammation.

Previous studies have reported that galectin-3 is involved in inflammatory processes in the central nervous system and that neuroinflammation may play a role in the pathogenesis of schizophrenia. However, the link between schizophrenia and various galectins is unclear. The objective of the present study is to determine whether galectin, a well-known lectin protein that binds to μ-galactoside, is associated with chronic schizophrenia. Thirty-six patients with schizophrenia and 36 healthy controls participated in this study. Schizophrenia symptoms were assessed using the Brief Psychiatry Rating Scale (BPRS). Serum galectin-1 and galectin-3 levels were evaluated using ELISA and compared between the participant groups. Correlation analyses were also performed to examine the relationship between BPRS scores and each galectin level. Serum galectin-3 levels were significantly higher in patients with schizophrenia than they were in controls (p=0.009, d=0.640); however, serum galectin-1 levels were not significantly different between the groups (p=0.513). No significant correlation was identified between serum galectin-3 level and the total BPRS score; however, a significant positive correlation was found between the serum galectin-3 level and the positive symptom score of the BPRS (ρ=0.355; p=0.033). Additionally, a significant negative correlation was identified between serum galectin-3 levels and the negative symptom score of the BPRS (ρ=-0.387; p=0.020). Given the high serum levels of galectin-3 found in patients with schizophrenia compared with that in controls, these findings may support the inflammation hypothesis of schizophrenia.

Comparison of Serum Vitamin D Levels Between Patients with Deficit and Non-deficit Schizophrenia

Aim: Vitamin D deficiency has been proposed to play role in a series of psychiatric disorders including schizophrenia, however there have not been any knowledge regarding relationship between vitamin D deficiency and deficit syndrome schizophrenia (DS). In this study, we aimed to evaluate the relationship between vitamin D deficiency and deficit syndrome by comparing serum vitamin D levels of deficit schizophrenia patients and non-deficit schizophrenia (NDS) patients. Materials and methods: Sixty-six patients who had diagnosis of schizophrenia were included. Twenty-six patients comprised the DS group, while forty patients comprised the NDS group. The severity of illness was assessed with Scale of Assessment of Negative Symptoms (SANS), Scale of Assessment of Positive Symptoms (SAPS), and Brief Psychiatry Rating Scale (BPRS). Vitamin D concentrations of both groups were measured by an electro chemiluminescence method. Results: The groups were similar regarding age and gender ( t= 1.32; p=0.18 and χ2=0.35; p=0.36 , respectively). The mean SANS score and BPRS was higher in DS group compared to NDS group (t= -3.86; p

AYURVEDIC MANAGEMENT OF BIPOLAR AFFECTIVE DISORDER WITH PSYCHOTIC FEATURES: A CASE REPORT

Bipolar Affective Disorder (BPAD) is one of the world’s ten most disabling conditions taking away years of healthy functioning from individuals who have the illness. The prevalence rate is approximately 1 % acros s all populations . The present article deals with a diagnosed case of BPAD with psychotic features came for Ayurvedic treatment . The Ayurvedic diagnosis of Pittaja unmada was made and virechana karma was done. Two assessments were taken before and after vi rechana on BPRS (Brief Psychiatry Rating Scale) and QoL.BD (The Quality of Life in Bipolar Disorder questionnaire) . Patient showed improvement in ‘hostility’ and ‘excitement’ on BPRS and good improvement was observed in items like, ‘Energy levels’, ‘physic al wellness’, ‘refreshing sleep’, ‘satisfactory sleep’, ‘happiness’, ‘concentration’ and ‘memory’ on QoL.BD. Virechana karma plays a key role in the management of pittaja un mada / BPAD. Virechana karma stabilizes mood by reducing manic episode symptoms and improves the quality of life of BPAD patients.

Amisulpride versus Risperidone in the Treatment of Acute Exacerbation of Schizophrenia

Introduction: Amisulpride and risperidone are both atypical antipsychotic having different receptor affinity characteristics. Although there are many studies comparing the efficacy of both drugs with conventional antipsychotics, studies comparing the efficacy of amisulpride with risperidone are less. There are no such studies published till yet from Nepal. This study aims to compare the efficacy and safety of amisulpride with that of risperidone in patients with acute exacerbation of schizophrenia in Nepal. Methods: 100 patients with acute exacerbation of schizophrenia were randomly put on flexible dose of amisulpride (200-1000mg/day) or risperidone (2-10mg/day) for six weeks after three to six day placebo wash-out period. Efficacy was assessed by changes in score of Brief Psychiatry Rating Scale (BPRS). Safety assessment was done by adverse event reporting, physical examination, blood pressure, heart rate monitoring and applying modified Simpson-Angus Scale for extra pyramidal symptoms. Results: Most of the patients in both group responded equally to medication. 84% of amisulpride receiving patients versus 86% in risperidone group responded to treatment. Both drugs were safe and caused comparable extra pyramidal symptoms (amisulpride/risperidone: 14/16). However, risperidone caused more weight gain than amisulpride (64% vs. 12%). Conclusion: Amisulpride and risperidone are equally effective in the treatment of acute exacerbation of schizophrenia. Both drugs were well tolerated. Amisulpride was associated with less weight gain. DOI: http://dx.doi.org/10.3126/jucms.v1i1.8417 Journal of Universal College of Medical Sciences Vol.1(1) 2013: 15-19

Effectiveness and tolerability of long-acting intramuscular risperidone as adjuvant treatment in refractory borderline personality disorder

Dear Editor The lack of effective oral treatments for severely affected patients with borderline personality disorder (BPD) lead us to frequently use depot antipsychotic medication in our personality disorder unit. BPD is characterized by severe instability of interpersonal relationships, of self-image, and of affects resulting in marked impulsivity. The importance of the disorder is reflected in persistent functional impairment and in elevated suicide rates (Cheng et al. 1997; Paris 2005). There is no current consensus on the best treatment for BPD, and different combinations of oral medications are being prescribed by physicians (Paris 2011; Silk 2011). Furthermore low treatment compliance with oral medication is particularly described in these patients due to their characteristic personal instability which might significantly affect the efficiency of the drugs. For that reason, the possibility that lack of efficacy of oral treatments in refractory BPD patients might reflect the lack of compliance needs to be explored. In that sense, we designed a study to explore the benefits of using a depot IM medication, longacting intramuscular risperidone, in the treatment of BPD patients refractory to previous oral medication trials. A total of 49 BPD patients (30 women and 19 men) were included in the study. Inclusion criteria were the following: (1) 18–45 years of age; (2) diagnosis of borderline personality disorder (BPD) according to DSM IV criteria; (3) score equal or greater than 16 in the Zanarini Rating Scale for BPD; (4) “severely or very severely ill” as defined by a score 5 or greater in the CGI severity scale; and (5) refractory to a combination of oral medications commonly used for BPD treatment. Exclusion criteria were (1) current substance use dependence disorder; (2) life history of schizophrenia, schizophreniform disorder, bipolar disorder, or neurological disorders; (3) unstable medical disease or pregnancy; and (4) demonstrated intolerance to oral risperidone. The sample mean age was 27 years (SD±4.5) and the average duration of the disease was 7 years (SD±3.3). Patients were regularly treated in the day-care hospital due to severe behavioral dyscontrol causing markedly functional impairment. The study was approved by the Institutional Ethical Committee, and all patients signed informed consent. Treatment was started with an initial dose of 37.5 mg IM injection of LA risperidone repeated every 2 weeks, which could be raised to 50 mg as to clinical consideration. Patients were evaluated at months 1, 3, and 6 with clinical scales including the Zanarini Rating Scale for BPD, the Hamilton Anxiety Rating Scale, the Brief Psychiatry Rating Scale (BPRS), the Overt Aggression Scale (OAS), the Clinical Global Impression scale (CGI), and the Global Assessment of Functioning (GAF). Gradual significant improvement of severity ratings was observed from the first month and during the first 3 months of treatment (p<0.001), but no significant changes in the CGI scale were observed between the third and sixth J. L. Carrasco (*) :N. Palomares :M. D. Marsa Institute of Psychiatry and Mental Health, Hospital Clinico San Carlos, C/ Martin Lagos s/n, 28040 Madrid, Spain e-mail: jcarrasco.hcsc@salud.madrid.org

Effect of Quetiapine and Norquetiapine on Anxiety and Depression in Major Psychoses Using a Pharmacokinetic Approach

Quetiapine apparently differs from other antipsychotic drugs in terms of its antidepressant activity and efficacy in bipolar depression. The mechanism of this activity is unknown although it may be mediated by its metabolite N-desalkylquetiapine (norquetiapine). The aim of the study was to analyse the relationships between quetiapine and norquetiapine plasma concentrations and clinical improvement in depressive and anxious symptoms. This was a prospective observational study. Recruited patients were evaluated during a clinical post-acute phase. Patients were recruited from patients hospitalized in the Psychiatric Department of Ospedale Maggiore Policlinico of Milan, Italy. After discharge they were followed-up as outpatients. The study involved 41 outpatients (23 males, 18 females; age >18 years) diagnosed as affected by schizophrenia (17 patients), borderline personality disorder (eight patients) or bipolar depression (16 patients) on the basis of the Diagnostic and Statistical Manual of Mental Disorders, fourth text revision (DSM-IV-TR) criteria. Patients were prescribed 50-800 mg of quetiapine (Seroquel®). Patients were evaluated after discharge from the psychiatric department (baseline, T0), after 15 days (T1) and after 3 months (T2) using the Brief Psychiatry Rating Scale (BPRS) with particular reference to the dimensions of depression (items 5, 9 and 13) and anxiety (items 1, 2 and 6). Plasma quetiapine and norquetiapine concentrations were determined by means of high-performance liquid chromatography at T2. There was a significant improvement in the mean BPRS total score, as well as in the dimensions of anxiety and depression. The bipolar patients only showed a significant curvilinear relationship described by a second-order polynomial model between the plasma norquetiapine/quetiapine concentration ratio and the improvement in depression at T2. There was a significant negative linear correlation between the norquetiapine/quetiapine ratio and anxiety in all of the patients. The results of this study confirm the efficacy of quetiapine on both anxious and depressive symptoms. Norquetiapine has a specific effect on anxiety and depressive symptoms, showing a correlation between plasma concentrations and clinical efficacy only in patients with bipolar depression.

A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia

OBJECTIVE To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. METHODS The trial was a double-blind, placebo-controlled, parallel-group design. The eligible patients were randomized into 2 treatment groups: sarsasapogenin group (sarsasapogenin plus risperidone for 8 weeks, n = 41) and placebo group (risperidone only for 8 weeks, n = 39). At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS), Clinical Global Impression (CGI) and Brief Psychiatry Rating Scale (BPRS). The study period for each subject was 8 weeks and duration of overall trial was 2 years. RESULTS Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. CONCLUSION Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.

A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting.

ObjectiveTo evaluate the overall long-term effectiveness of aripiprazole in patients with schizophrenia in a general psychiatric practice setting in Taiwan.MethodsThis was a prospective, open-label, multicenter, post-market surveillance study in Taiwanese patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled. Eligible patients were titrated to aripiprazole (5-30 mg/day) over a 12-week switching phase, during which their previous medication was discontinued. Patients could then enter a 52-week, long-term treatment phase. Aripiprazole was flexibly dosed (5-30 mg/day) at the discretion of the treating physicians. Efficacy was assessed using the Clinical Global Impression scale Improvement (CGI-I) score, the Clinical Global Impression scale Severity (CGI-S) score, The Brief Psychiatry Rating Scale (BPRS), and the Quality of Life (QOL) scale, as well as Preference of Medicine (POM) ratings by patients and caregivers. Safety and tolerability were also assessed.ResultsA total of 245 patients were enrolled and switched from their prior antipsychotic medications, and 153 patients entered the 52-week extension phase. In all, 79 patients (32.2%) completed the study. At week 64, the mean CGI-I score was 3.10 and 64.6% of patients who showed response. Compared to baseline, scores of CGI-S, QOL, and BPRS after 64 weeks of treatment also showed significant improvements. At week 12, 65.4% of subjects and 58.9% of caregivers rated aripiprazole as better than the prestudy medication on the POM. The most frequently reported adverse events (AEs) were headache, auditory hallucinations and insomnia. A total of 13 patients (5.3%) discontinued treatment due to AEs. No statistically significant changes were noted with respect to fasting plasma glucose, lipid profile, body weight, and body mass index after long-term treatment with aripiprazole.ConclusionsAlthough the discontinuation rate was high, aripiprazole was found to be effective, safe and well tolerated in the long-term treatment of Taiwanese patients with schizophrenia who continued to receive treatment for 64 weeks.

Improvement of Negative and Positive Symptoms in Treatment-Refractory Schizophrenia

Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia. In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS). Twenty-one participants completed the study and were used in the analysis. Significant improvement (P < .01) on the total BPRS score, its subscales of positive (effect size [ES] = -1.38) and negative (ES = -3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed. Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients. clinicaltrials.gov Identifier: NCT00757978.

Outcome and length of stay in psychiatric hospitalization, the experience of the University Clinic of Turin

Given the current tendency to shorten psychiatric hospitalization and change its organization, an issue could be raised regarding its outcomes. To analyze features related to length of stay in a short-term inpatient treatment, to study outcomes and to evaluate the diagnosis-specific effects of hospitalization. A sample of 310 consecutive hospitalized patients, with psychotic disorder, depressive disorder and bipolar disorder (DSM IV-TR), was recruited at the University Psychiatric Clinic, Service for Cognitive Disorders, Department of Neuroscience, University of Turin. Severity of illness was rated using the brief psychiatry rating scale (BPRS). We evaluated relations between length of stay and clinical and socio-demographic features (linear regression) and possible differences confronting BPRS scores at admission and discharge in the different diagnostic subgroups (ANOVA for repeated measures). All the sample of patients showed a significant improvement in symptomatology during hospitalization. Worse symptomatology in anxiety-depression domain of BPRS at admission in the whole sample was positively correlated with length of stay. A longer length of stay was also shown in patients with diagnosis of depressive disorder. Finally, a different pattern of improvement of BPRS (total score and domains) was shown between the different diagnostic groups. Brief hospitalization in our service was shown to be highly effective. Different diagnostic groups had different response to hospitalization, showing faster improvement in characteristic symptomatology, but the anxiety-depression domain showed the highest percentage of change for all the diagnostic groups. We therefore suppose that hospitalization has two effects: a specific (due to tailored therapies) and a non-specific one (due to non-specific therapy and to a placebo-like effect).

Effects of the Dopamine D3 Receptor (DRD3) Gene Polymorphisms on Risperidone Response: A Pharmacogenetic Study

Previous observations of the anatomical distribution and pharmacological profile of the dopamine D(3) receptor (DRD3) have indicated its potential role in antipsychotic drug action. Risperidone, an effective first-line atypical antipsychotic agent, exhibits a relatively high affinity for this receptor. Recent studies have reported an association of the Ser9Gly polymorphism in the DRD3 gene with therapeutic response to risperidone, but the results were inconsistent. We therefore postulated that the Ser9Gly polymorphism might be in linkage disequilibrium with an undetected variant that exerts a direct influence on risperidone efficacy. The present study genotyped eight single nucleotide polymorphisms (SNPs) distributed throughout the DRD3 gene and examined five of these for association with treatment outcome, following an 8-week period of risperidone monotherapy in 130 schizophrenic patients from mainland China. Clinical symptoms were assessed before and after the treatment period, using the Brief Psychiatry Rating Scale (BPRS). The confounding effects of non-genetic factors were estimated and the baseline symptom score was included as a covariate for adjustment. Neither was any association observed between the five polymorphisms and improvement in total BPRS scores nor was any combined effect of these variants detected in the haplotype analysis. The current results indicate that genetic variations within the DRD3 gene may not contribute significantly to interindividual differences in the therapeutic efficacy of risperidone.

The “Seroquel” Outcomes Study (SOS): Efficacy and tolerability of quetiapine in a long-term, naturalistic study of patients with schizophrenia

Objective. The “Seroquel” Outcomes Study (SOS) aimed to assess the efficacy and tolerability of quetiapine in patients with schizophrenia in the clinical practice setting. Methods. A 6-month, non-comparative, open-label study in adults with schizophrenia in a standard care setting in Spain. Outpatients received flexibly dosed quetiapine. Efficacy was evaluated using the Brief Psychiatry Rating Scale (BPRS) and the Clinical Global Impression (CGI) scale. BPRS response was defined as≥30% decrease from baseline. Tolerability was assessed using the Simpson–Angus Scale (SAS) and a modified Udvalg for Kliniske Undersogelser (UKU) side-effects scale. Results. A total of 2029 patients enrolled. Significant changes from baseline to Month 6 were recorded for BPRS total and subscale scores (P<0.001). Compared with doses of≥600 mg/day, doses of<400 mg/day were a strong predictor of a lower response rate (OR 0.62; 95% CI: 0.48, 0.82) and higher withdrawal rate (OR 3.3; 95% CI: 2.5, 4.4). Mean change in weight was minimal (+0.4 kg). Somnolence (26.7%), asthenia (12.5%), and constipation (9.8%) were the most common adverse events. Conclusion. Quetiapine was found to improve symptoms of schizophrenia, as indicated by a significant decrease in BPRS scores, and was well tolerated by patients in clinical practice.

Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients

Previous studies have demonstrated that the −141C Ins/Del and TaqI A polymorphisms in the DRD2 gene affect the density of the dopamine D2 receptor. The present study examines the correlation between these two polymorphisms and the therapeutic response to chlorpromazine, a typical antipsychotic drug, in 135 inpatients with schizophrenia. Clinical symptoms were evaluated using the Brief Psychiatry Rating Scale (BPRS) before and after 8 weeks of treatment with 300–600 mg/day of chlorpromazine. Our results show that genotyping −141C Ins/Del may help to predict the efficacy of chlorpromazine treatment ( P = 0.01) due to the fact that patients with no Del allele showed greater improvement than those with Del allele on the overall BPRS ( P = 0.03), and that, therefore, the potential for therapy in patients with schizophrenia is related to the −141C Ins/Del polymorphism in the DRD2 gene. However, no such relationship was found for the TaqI A polymorphism.

Amisulpride vs. Risperidone in Chronic Schizophrenia: Results of a 6-month Double-blind Study

This multicenter, double-blind, randomized study evaluated the efficacy, safety and functional effects of two atypical antipsychotics, amisulpride and risperidone, in patients with chronic schizophrenia (DSM IV) with a recent worsening of symptoms. It was planned as a non-inferiority trial. 309 patients received amisulpride (400–1000 mg/day) or risperidone (4–10 mg/day) for six months. Amisulpride was demonstrated to be not inferior to risperidone with respect to the decrease in Positive and Negative Syndrome Scale (PANSS) total score from baseline (90% 2-sided confidence interval (−5.6; 4.0)). Symptomatic improvement measured with the Brief Psychiatry Rating Scale (BPRS), the PANSS positive subscale, and the Bech Rafaelsen Melancholia Scale was similar in both groups. Amisulpride was significantly (p < .05) superior to risperidone in terms of response (⩾50% improvement in PANSS and BPRS total scores or “very much/much improved” on the Clinical Global Impression Scale) and also demonstrated better functional effects and subjective response. Both treatments were well tolerated and had a similar low incidence of extrapyramidal symptoms; however, amisulpride was associated with less weight gain and endocrine/sexual symptoms.

A pilot study of loading versus titration of valproate in the treatment of acute mania

This double-blind pilot study compares the effectiveness and incidence of adverse effects of oral loading versus titration schedules of valproate in acute mania. Consecutive new admissions for an acute manic episode were prescribed either an oral loading dose (20 mg/kg/day; n = 5; mean age = 33.4) or slower titration dose (10 mg/kg/day, n = 6. mean age = 30.6) of valproate for 7 days without other psychotropic agents. with the exception of benzodiazepines. Daily outcome measures included: serum valproic acid levels, the Young Mania Rating Scale (YMRS), the Brief Psychiatry Rating Scale (BPRS), the Clinical Global Impression Scale (CGI) and the Adverse Effect Rating Scale. The mean serum valproic acid levels were significantly higher in the loading group when compared with the titration group after 1 and 2 days following the initiation of treatment (p < 0.05). After 3 days of treatment there was a trend for the group that received the loading regimen to have slightly more improvement in YMRS scores compared with the titration group. Side-effects were minor for both treatments, however, a higher incidence of side-effects was reported in the titration group, with 50% of patients reporting sedation most likely because of increased use of benzodiazepines. This suggests that a loading dose of valproate is likely safe and may provide an earlier onset of antimanic effects in patients with bipolar disorder. Future studies with larger sample sizes are indicated.

First-episode neuroleptic-free schizophrenics: Concentrations of monoamines and their metabolites in plasma and their correlations with clinical responses to haloperidol treatment

Thirty-two first-episode neuroleptic-free schizophrenics were treated with neuroleptics for 8 weeks. The monoamines and their metabolites, dopamine, norepinephrine, serotonin, homovanillic acid (HVA), 3-methoxy-4-hydroxy-phenylglycol(MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in plasma were measured to examine the association with treatment responses and psychopathology assessed according to the brief psychiatry rating scale (BPRS). No differences were noted in the pretreatment concentrations of monoamines and their metabolites between patients and healthy controls; however, during treatment the concentrations of HVA and MHPG were significantly reduced only in the schizophrenics who responded to treatment. Moreover, the HVA and MHPG reductions correlated significantly with improvements in BPRS scores. Since their plasma levels reflect to some extent central dopaminergic and noradrenergic activities, respectively, the present findings suggest the involvement of these systems in the pathogenesis of schizophrenia as well as the usefulness of such measurements as predictors of responsiveness to neuroleptics.