Search

Background Chronic anticholinergic medication (ACM) prescribing with antipsychotics when no longer clinically indicated can lead to serious side effects and adversely impact patient quality of life. Objectives Through modifications of previously described deprescribing strategies undertaken in an academic, schizophrenia clinic, this quality improvement (QI) project aimed to bolster ACM deprescription where clinically appropriate among patients with schizophrenia and other psychiatric disorders at a community mental health center. Methods A multidisciplinary team involving clinical pharmacists and psychiatrists created web streaming video medical education accredited modules, supplemented by small groups sessions and case consultations, and provided these to psychiatrists and nurse practitioners at a community mental health center over a one-year period. Electronic medical record reports were also generated, highlighting patients who were receiving one of two ACM used in the clinic: benztropine and/or trihexyphenidyl; these were periodically distributed to support appropriate deprescription. Patient education infographic material focused on ACM were also created and deployed. Results One hundred and twenty-six patients were identified as receiving benztropine or trihexyphenidyl in March 2019. One hundred and six (84%) were on one or both of these medications for at least six months. The mean (±SD) age of the study sample was 53.4 (±12.6) years; a third of the sample was over 60 years. Thirty-seven patients, or 29.4%, had their ACM discontinued or the dosage reduced. Deprescription was not associated with age, sex, race, or diagnosis. Deprescription was not associated with antipsychotic polypharmacy, first versus second generation, or oral versus long acting preparation. Conclusions These results suggest that deprescription of ACM in a community mental health center can occur with prescriber education and support. However, results from previous stages of this QI project, where much higher rates of deprescription were demonstrated, indicate the important benefit of more direct clinical pharmacist support and involvement in the process.

Behavioral health home models are increasingly being utilized to provide physical-behavioral health integration for individuals with mental illness. The Behavioral Health Home Plus model (BHHP) is a phased approach designed to instill a culture of wellness, provide wellness coaching, and offer care coordination for individuals with serious mental illness. The present study utilized a 12-month Learning Collaborative to implement scaling of BHHP in two cohorts totaling 24 community mental health provider organizations in Pennsylvania to include population-wide screening and intervention for tobacco use and hypertension. Providers reported increases in screening rates and wellness goals related to tobacco use and hypertension, as well as reductions in tobacco use and blood pressure readings among participating individuals. Evidence presented indicates that a Learning Collaborative of community mental health providers is a feasible quality improvement approach to scale integration of physical and behavioral health care for individuals with serious mental illness.

Introduction:Autism is included as a certifiable disability in the Indian Rights of Persons with Disability Act, 2016. The Indian Scale for Assessment of Autism (ISAA), developed by the Government of India and mandated for certifying disability, is a detailed instrument that needs trained mental health experts and takes time to administer. The current project was planned to develop a simple, easy to use screening tool based on the ISAA to identify possible cases in the community.Methods:The project is planned in three phases. During the first phase, data collected during the development of the ISAA ( N = 433/436 children with autism) will be used to identify questions answered as frequently, mostly, and always. During the second phase, the psychometric properties of the screening tool based on these items will be evaluated among research participants recruited from hospitals and special schools ( n = 100). In the third phase, the screening questionnaire will be administered in the community ( n = 500).Results:The most frequently answered questions will be selected for inclusion in the proposed screening tool. The number of items in the screening tool will be kept as few as possible, with yes or no responsesDiscussion:Indian Autism Screening Questionnaire (IASQ) will be tested as a screening version of ISAA, which can be used by community health workers, teachers, or school counselors. The IASQ will not provide a diagnosis of autism. A positive screening result should be followed by a thorough assessment by a trained specialist. Analyzing the psychometric properties of the test can help ensure cost-effective screening of the community to identify autism.

The present project utilized a Learning Collaborative (LC) to disseminate the Behavioral Health Home Plus (BHHP) physical-behavioral health integration model to providers serving two behavioral health populations at risk for adverse health conditions: youth psychiatric residential treatment facilities (five sites) and adult opioid treatment providers (seven sites). Following the positive results of a randomized controlled trial utilizing an LC to implement two behavioral health home models in community mental health provider organizations serving adults with serious mental illness, Community Care Behavioral Health Organization facilitated integration of the models to scale health and wellness supports to additional behavioral health care delivery settings. This paper presents provider results focused on BHHP implementation training, LC implementation, physical health and wellness promotion within sites, and BHHP model sustainment plans. Provider self-reported data indicate that the LC approach is a successful tool for integrating and sustaining BHHP model components in routine care.

The Indian Autism Screening Questionnaire (IASQ), derived from the Indian Scale for Assessment of Autism ISAA (the mandated tool for autism in India), is an autism screening instrument for use in the general population by minimally trained workers. While ISAA has 40 items with four anchor points, the IASQ is a 10-item questionnaire with yes/no answers. It was initially validated using the ISAA. During its development the ISAA was itself compared to the Childhood Autism Rating Scale version 1 (ISAA Manual). In the present study, we evaluated both the ISAA and the IASQ in relation to the Childhood Autism Rating Scale version 2 (CARS-2). Methods: Participants were recruited from three settings: a referral clinic for neurodevelopmental conditions run by the Department of Paediatrics of a tertiary care teaching hospital (NDC OPD), the outpatient department of an institute for disability and rehabilitation (NIEPID), and from the community (CGOC). Persons between ages 3–18 were recruited following consent or assent (parent and child/adolescent). The IASQ was administered by a minimally trained administrator. It was followed by ISAA and the CARS-2 (in alternating order, by different evaluators blind to each other) (CARS2 SV (Standard Version) and CARS2 HF (High Functioning) as applicable). Sensitivity, specificity and area under the Receiver Operator Characteristics (ROC) curve were calculated for IASQ and CARS2, as well as for ISAA and CARS2. Concordance between CARS2 and ISAA was calculated using kappa coefficient. Results: A total of 285 participants (NIEPD n = 124; NDC OPD, n = 4; CGOC n = 157) (a total of 70 with autism and 215 controls) participated. IASQ and CARS2 were administered on 285 participants, while IASQ and ISAA were administered on 264 participants. When IASQ was compared to CARS2, sensitivity was 97%, specificity 81%, PPV 63%, NPV 99% at cut off 1 while these values were 97%, 92%, 79% and 99% respectively at cut off 2. There was high concordance between CARS2 and ISAA (Kappa 0.907, pConclusions: IASQ has satisfactory sensitivity, specificity and concordance when compared with CARS2; it can be used for screening children with autism in community. The ISAA also showed a high concordance with CARS2, as it had with the older version of CARS.

The calcium-binding protein S100b is secreted by glial cells in the brain and is also expressed by melanocytes. In nanomolar concentrations, S100b is considered to be a neurotrophic factor, but in micromolar concentrations, it is thought to reflect CNS injury and inflammation. Seen as a potential biomarker in traumatic brain injury, meta-analytic data from several studies report that S100b levels are significantly higher in persons with long standing schizophrenia, but also among first-episode patients compared to healthy control subjects. However, ethnic or racial differences are typically not mentioned when reporting levels of S100b. We assessed serum S100b levels in persons with schizophrenia (n = 136) who were participants in two independent research studies using the same enzyme-linked immunoassay (ELISA). African-American subjects had significantly higher levels of S100b (41.9 pg/ml ± 62.2) than Caucasian subjects (24.9 pg/ml ± 45.4) in the combined dataset (Mann-Whitney U = 1307, p

Background Long-term prescribing of anticholinergic medications (ACM) for antipsychotic-associated extrapyramidal symptoms (EPS) is not recommended, yet is widely prevalent. Adverse effects of ACM include memory impairment, dry mouth, constipation, blurred vision, urinary retention, and tachycardia, which can seriously impact quality of life. This quality improvement deprescription project sought to reduce chronic ACM use in patients with serious mental illness (SMI). Methods Education directed at psychiatrists combined with clinical pharmacy support for deprescription was used to target clinically stable patients diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder with no EPS and ACM prescriptions of ≥6 months. Scales were used to assess anticholinergic adverse effects, memory impairment, and quality of life. ACMs were tapered and discontinued over 1 to 6 months. Results More than 75% of targeted patients successfully tapered or discontinued ACM, which coincided with significant improvements in anticholinergic adverse effects, memory impairment, and quality of life. Approximately 10% of patients were restarted on ACM for re-emergent EPS. Conclusions For most clinically stable patients with SMI without EPS, our findings suggest that gradual deprescription of chronic ACM is clinically appropriate, well tolerated, and improves quality of life. A randomized trial could provide more definitive answers.

Background: Suboptimal management of depression in type 2 diabetes mellitus (T2DM) often translates into poor glycemic control, medical complications, and impaired quality of life. Feasibility and effectiveness of collaborative care models of depression in diabetes in low- and middle-income countries (LMICs) remain unexplored. DIAbetes Mellitus ANd Depression (DIAMAND) study, a multicentric single-blind randomized controlled trial (SBRCT) comparing effectiveness of fluoxetine and mindfulness in primary care settings, addresses this gap in scientific literature. Methods: This trial conducted in diverse geographic settings of New Delhi, Bengaluru, and Bhubaneswar will comprise module-based training of primary care providers (PCPs) for screening, diagnosing, and managing depression in diabetes in phase I. Phase II will involve four-arm parallel group RCT on 350 participants with T2DM with comorbid depressive episode randomly allocated to receive fluoxetine, mindfulness therapy, fluoxetine plus mindfulness therapy, or treatment as usual at primary care settings. Interventions would include fluoxetine (up to 60 mg/day) and/or sessions of mindfulness for 16 weeks. Primary outcomes on standardized rating scales include depression scores (Hamilton Depression Rating Scale), treatment adherence (Adherence to Refill and Medication Scale), self-care (Diabetes Self-Management Questionnaire), diabetes-related distress (Diabetes Distress Scale), and glycemic control. Secondary outcomes include quality of life (World Health Organization Quality of Life Brief version [WHO-QOL BREF]) and mindfulness (Five Facets Mindfulness Questionnaire). Discussion: This RCT will investigate the effectiveness of module-based training of PCPs and feasibility of collaborative care model for managing depression in T2DM in primary care settings in LMICs and effectiveness of fluoxetine and/or mindfulness in improving diverse outcomes of T2DM with major depression.

Behavioral health home models are increasingly being utilized to provide physical-behavioral health integration for individuals with mental illness. The Behavioral Health Home Plus model (BHHP) is a phased approach designed to instill a culture of wellness, provide wellness coaching, and offer care coordination for individuals with serious mental illness. The present study utilized a 12-month Learning Collaborative to implement scaling of BHHP in two cohorts totaling 24 community mental health provider organizations in Pennsylvania to include population-wide screening and intervention for tobacco use and hypertension. Providers reported increases in screening rates and wellness goals related to tobacco use and hypertension, as well as reductions in tobacco use and blood pressure readings among participating individuals. Evidence presented indicates that a Learning Collaborative of community mental health providers is a feasible quality improvement approach to scale integration of physical and behavioral health care for individuals with serious mental illness.

The original version of this article unfortunately contained an error in the figure The article is published with incorrect version of Fig. 3 and it does not match with the text. Hence, the correct Fig. 3 is presented here. The original article has been corrected.

IntroductionCurrently available screening questionnaires for Autism spectrum disorders were tested in developed countries, but many require additional training and many are unsuitable for older individuals, thus reducing their utility in lower/ middle- income countries. We aimed to derive a simplified questionnaire that could be used to screen persons in India.MethodsWe have previously validated Indian Scale for Assessment of Autism (ISAA), that is now mandated for disability assessment by the Government of India. This detailed tool requires intensive training and it is time consuming. It was used to derive a new screening questionnaire: 1) items most frequently scored as positive by participants with autism in original ISAA validation study were modified for binary scoring following expert review. 2) In a new sample, clinically diagnosed individuals with/without autism were administered the screening tool and ISAA following written informed consent. Its psychometric properties were determined.ResultsA 10-item scale named Indian Autism Screening Questionnaire (IASQ) was prepared in Hindi and English. Thereafter 145 parents/caregivers of participants (autism, n = 90, other psychiatric disorders, n = 55) (ages 3–18), were administered IASQ and ISAA (parents/caregivers plus observation) by separate interviewers, blind to each other and to diagnosis. At a cutoff of 1, sensitivity was 99%, specificity 62%, Positive Predictive Value 81%, and Negative Predictive Value 95%. Test-retest reliability was r = 0.767 (CI = 0.62–0.86) and interrater reliability- Krippendorff”s-alpha was 0.872. The area under Receiver Operating Characteristic Curve (ROC) was 95%. There was a significant difference on IASQ-scores between participants with and without a clinical diagnosis of Autism (t = 14.57, pDiscussionThe IASQ is a simple, easy to use screening tool with satisfactory reliability and validity, that can be administered to caregivers in 15 minutes and provides information about DSM 5 criteria for autism. It may be applicable outside India, following additional adaptation, for community-based studies.

Objective To determine if adjunctive treatment with a standardized extract of Withania somnifera (WSE), with known anti-inflammatory and immunomodulating properties, improves psychopathology and stress in patients with schizophrenia or schizoaffective disorder (DSM-IV-TR). Methods Patients experiencing an exacerbation of symptoms were assigned to WSE (1,000 mg/d) or placebo for 12 weeks, added to their antipsychotic medication, in a random-assignment, double-blind, placebo-controlled study conducted from April 2013 to July 2016. Primary outcomes were change from baseline to end of treatment on the Positive and Negative Syndrome Scale (PANSS total, positive, negative, and general symptoms) between treatment groups. Secondary outcomes evaluated stress and inflammatory indices using the Perceived Stress Scale (PSS), S100 calcium-binding protein B (S100B), and C-reactive protein (CRP). Results Sixty-six randomized patients (n = 33 per group) provided efficacy data. Beginning at 4 weeks and continuing to the end of treatment, WSE produced significantly greater reductions in PANSS negative, general, and total symptoms (Cohen d: 0.83, 0.76, 0.83), but not positive symptoms, when compared to placebo. PSS scores improved significantly with WSE treatment compared to placebo (Cohen d: 0.58). CRP and S100B declined more in the WSE group but were not significantly different from placebo. Adverse events were mild to moderate and transient; somnolence, epigastric discomfort, and loose stools were more common with WSE. No significant between-treatment differences were noted in body weight, vital signs, or laboratory measures, which remained stable. Conclusions This early study suggests that adjunctive treatment with a standardized extract of Withania somnifera provides significant benefits, with minimal side effects, for negative, general, and total symptoms and stress in patients with recent exacerbation of schizophrenia. Trial registration ClinicalTrials.gov identifier: NCT01793935.

Background There is a critical gap between needs and available resources for mental health treatment across the world, particularly in low- and middle-income countries (LMICs). In countries committed to increasing resources to address these needs it is important to conduct research, not only to assess the depth of mental health needs and the current provision of public and private mental health services, but also to examine implementation methods and evaluate mental health approaches to determine which methods are most effective in local contexts. However, research resources in many LMICs are inadequate, largely because conventional research training is time-consuming and expensive. Adapting a hackathon model may be a feasible method of increasing capacity for mental health services research in resource-poor countries. Methods To explore the feasibility of this approach, we developed a ‘grantathon’, i.e. a research training workshop, to build capacity among new investigators on implementation research of Indian government-funded mental health programmes, which was based on a need expressed by government agencies. The workshop was conducted in Delhi, India, and brought together junior faculty members working in mental health services settings throughout the country, experienced international behavioural health researchers and representatives of the Indian Council for Medical Research (ICMR), the prime Indian medical research funding agency. Pre- and post-assessments were used to capture changes in participants’ perceived abilities to develop proposals, design research studies, evaluate outcomes and develop collaborations with ICMR and other researchers. Process measures were used to track the number of single-or multi-site proposals that were generated and funded. Results Participants (n = 24) generated 12 single- or multi-site research grant applications that will be funded by ICMR. Conclusion The grantathon model described herein can be modified to build mental health services research capacity in other contexts. Given that this workshop not only was conceptualised and delivered but also returned results in less than 1 year, this model has the potential to quickly build research capacity and ultimately reduce the mental health treatment gap in resource-limited settings.

Preclinical research shows that compounds acting at α7 nicotinic receptors (nAChRs) can reduce nicotine self-administration, suggesting that a positive allosteric modulator (PAM) of α7 receptors, JNJ-39393406, may aid smoking cessation. Moreover, individuals with schizophrenia, who have very high rates of smoking, have reduced expression of α7 nAChRs and may particularly benefit from this compound. In two parallel studies using a within-subject cross-over design, 36 healthy smokers (Study 1) and 62 smokers with schizophrenia (Study 2), both groups high in quit interest, attempted to initiate quitting temporarily during each of two 3-week phases. Treatments were the α7 nicotinic receptor PAM JNJ-39393406 (100 mg b.i.d.) or placebo (double-blind, counter-balanced). In each phase, all smoked ad lib with no drug on week 1 or during dose run-up on week 2, and then tried to quit every day during week 3. Abstinence (confirmed by CO

Oxidative stress and neuroinflammation may contribute to decreased neuronal activity in schizophrenia by affecting the high metabolic demand parvalbumin-containing fast-spiking cortical interneurons. We measured the effects of the antioxidant and anti-inflammatory Ashwagandha (Withania Somnifera; WSE) on event-related potentials (ERPs). Eleven patients with long-term schizophrenia participated in a pilot double-blind adjunctive medication study: 6 took WSE, 5 placebo. Participants heard pitch (10%) and duration deviants (10%) among standard tones (80%) in a mismatch negativity (MMN) task while watching a silent movie. They also performed 2 auditory oddball tasks, either counting rare pitch deviants (15%) or ignoring sounds. For the oddball tasks, a 500-ms duration 40-Hz click train was presented between tones. ERPs were measured before administration of WSE or placebo (T1) and 3 months later (T2). Preliminary analyses indicated improvements in duration MMN with WSE ( = 1.28) but not with placebo ( = 0.27). In the oddball task, the WSE group showed a larger P3 from T1 to T2 (attend = 0.47; ignore = 0.69) compared to placebo (attend = 0.24; ignore = 0.29). Gamma-band steady-state potentials in the WSE group displayed greater attention-related amplitude increase at T2 ( = 0.59) than the placebo group ( = 0.07). WSE intake appears to recover some of the impaired early sensory/cognitive potentials in schizophrenia, possibly by reversing oxidative stress and neuroinflammation. These pilot data indicate further investigation into such adjunctive target pharmacotherapy is warranted.

OBJECTIVE Virtually no clinical trials for smoking cessation have been undertaken in bipolar disorder. Varenicline has shown efficacy for smoking cessation, but warnings about neuropsychiatric adverse events have been issued. We assessed the efficacy and safety of varenicline in euthymic bipolar subjects motivated to quit smoking. METHOD Clinically stable adult patients with DSM-IV bipolar disorder (n = 60) who smoked ≥ 10 cigarettes per day were randomized to a 3-month, double-blind, placebo-controlled varenicline trial and a 3-month follow-up. Study enrollment was completed from February 2010 through March 2013. Varenicline was dosed using standard titration, and smoking cessation counseling was provided to all patients. The primary outcome was defined as a 7-day point prevalence of self-reported no smoking verified by expired carbon monoxide level < 10 ppm at 12 weeks. Psychopathology and side-effects were assessed at each visit. RESULTS At 3 months (end of treatment), significantly more subjects quit smoking with varenicline (n/n = 15/31, 48.4%) than with placebo (n/n = 3/29, 10.3%) (OR = 8.1; 95% CI, 2.03-32.5; P < .002). At 6 months, 6 of 31 varenicline-treated subjects (19.4%) remained abstinent compared to 2 of 29 (6.90%) assigned to placebo (OR = 3.2; 95% CI, 0.60-17.6; P = .17). Psychopathology scores remained stable. Ten serious adverse events occurred (n = 6, varenicline; n = 4, placebo). Abnormal dreams occurred significantly more often in varenicline-treated subjects (n/n = 18/31, 61.3%) than in those receiving placebo (n/n = 9/29, 31%; Fisher exact test, P = .04). Eight varenicline-treated and 5 placebo-assigned subjects expressed fleeting suicidal ideation, a nonsignificant difference. CONCLUSIONS Varenicline shows efficacy for initiating smoking cessation in bipolar patients, but medication trials of longer duration are warranted for maintaining abstinence. Vigilance for neuropsychiatric adverse events is prudent when initiating varenicline for smoking cessation in this patient population. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01010204.

Objective: Cognitive impairments contribute significantly to inadequate functional recovery following illness episodes in bipolar disorder, yet data on treatment interventions are sparse. We assessed the cognitive effects of a standardized extract of the medicinal herb Withania somnifera (WSE) in bipolar disorder. Method: Sixty euthymic subjects with DSM-IV bipolar disorder were enrolled in an 8-week, double-blind, placebo-controlled, randomized study of WSE (500 mg/d) as a procognitive agent added adjunctively to the medications being used as maintenance treatment for bipolar disorder. Study enrollment and data analyses were completed between December 2008 and September 2012. Cognitive testing at baseline and 8 weeks assessed primary efficacy outcomes. Psychopathology and adverse events were monitored at scheduled visits. Results: Fifty-three patients completed the study (WSE, n = 24; placebo, n = 29), and the 2 groups were matched in terms of demographic, illness, and treatment characteristics. Compared to placebo, WSE provided significant benefits for 3 cognitive tasks: digit span backward (P = .035), Flanker neutral response time (P = .033), and the social cognition response rating of the Penn Emotional Acuity Test (P = .045). The size of the WSE treatment effect for digit span backward was in the medium range (Cohen d = 0.51; 95% CI, 0.25–0.77). None of the other cognitive tasks showed significant betweengroup differences. Mood and anxiety scale scores remained stable, and adverse events were minor. Conclusions: Although results are preliminary, WSE appears to improve auditory-verbal working memory (digit span backward), a measure of reaction time, and a measure of social cognition in bipolar disorder. Given the paucity of data for improving cognitive capacity in bipolar disorder, WSE offers promise, appears to have a benign side-effects profile, and merits further study. Trial Registration: ClinicalTrials.gov identifier: NCT00761761

Objectives1. A quality performance improvement (QI) project to implement an electronic screening and monitoring tool to record components of the metabolic syndrome (e-MSD) during clinic visits by persons with serious mental illness (SMI). 2. To encourage psychiatrists to use this tool in their documentation.MethodsWorking with the information technology staff; five psychiatrists developed, tested, revised and embedded the e-MSD tool into the medication management document within the electronic health record. A continuing medical education program on metabolic syndrome was developed, and released to psychiatrists and mental health clinicians. Psychiatrist offices at one clinic were equipped with weighing scales, sphygmomanometers, waist circumference tapes and a QI project was initiated.ResultsAt one month, 9 to 12% of the anthropometric measures (height, weight, body mass index, waist circumference, and blood pressure) were recorded in 974 unique patient encounters, and 1 year later the numbers moved upwards - 15 to 41%. Towards the end of Year 1, a patient care associate was hired to measure the anthropometric measures, and one year later, the documented rates increased to 75-80%. Laboratory recordings (glucose and lipids) remained ≤ 8% throughout the first year, but moved upwards to 25% in Year 2.DiscussionNotwithstanding significant administrative and technical support for this QI project, changing clinician practice to screen, monitor and document metabolic indices in persons with SMI in the ambulatory setting changed significantly after the hiring of a patient care associate. Efforts to obtain laboratory measures in real-time remain a challenge. Next steps include interventions to promote weight loss and smoking cessation in SMI patients, and effective communication with their primary care doctors.

Epidemiology can help us understand who is at risk for developing a disorder, what may happen to them, and perhaps even why people get the disorder to begin with. In this chapter, we will review the incidence and prevalence of schizophrenia and related psychotic disorders, as well as factors affecting such rates. Risk factors for psychosis include socio-demographics (e.g., gender, age, migrant status, class), predisposing factors (e.g., season of birth, perinatal trauma), and precipitating factors (e.g., substance use, psychosocial stress). We will highlight controversial issues such as traumatic life events, prenatal infection, and cannabis use, considering how epidemiological factors can shed light on the pathogenesis of schizophrenia and related illnesses.

Background Targeting glutamatergic dysfunction provides an exciting opportunity to improve cognitive impairment in schizophrenia. One treatment approach has targeted inadequate antioxidant defenses at glutamatergic synapses. Animal and human data suggest NMDA antagonists worsen executive cognitive controls — e.g. increase perseverative responses and impair set-shifting. We conducted a preliminary study to test the hypothesis that l -carnosine, an antioxidant and anti-glycation agent which is co-localized and released with glutamate would improve executive dysfunction, a cognitive domain associated with glutamate. Methods Seventy-five symptomatically stable adults with chronic schizophrenia were randomly assigned to l -carnosine as adjunctive treatment (2 g/day) or a matched placebo in a double-blind manner for 3 months. Cognitive domains (executive dysfunction, memory, attention and motor speed) were assessed using a computerized battery at baseline, 4 and 12 weeks, along with psychopathology ratings and safety parameters. Results The l -carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo but reversal reaction times and errors were not significantly different between treatments. On the strategic target detection test, the l -carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo. Other cognitive tests showed no significant differences between treatments. Psychopathology scores remained stable. The carnosine group reported more adverse events (30%) compared with the placebo group (14%). Laboratory indices remained within acceptable ranges. Conclusions These preliminary findings suggest that l -carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia.

Accessible summary • The use of the pedometer to monitor walking as an adjunctive intervention to antipsychotic medications for individuals with schizophrenia may be feasible. • Automatic devices or technological tools such as pedometers can provide the most reliable and consistent data on physical activity in this population. • Exercise fitness and body appearance were the primary motives for subject in this study. Abstract The purpose of this prospective and observational design study was to assess the feasibility of using a pedometer and step log to explore level of physical activity (PA) and to assess motivation to be physically active in adults with schizophrenia. Descriptive statistics were used to analyse data of 7 male and 5 female subjects. Pedometer data indicated that subjects walked an average of 4731.03 (±3318.19) steps and 5002.58 (±3041.03) during the first week and second week of the study, respectively. A minimum 30-min walk was recorded on an average of 3.67 (±1.82) days (week one) and 4.5 (±1.88) days (week two). Step logs, inconsistently maintained by subjects, were not able to be analysed. Examination of the Motives for Physical Activity Measure-Revised (MPAM-R) at baseline indicates that exercise fitness and body appearance were subjects' primary motives for PA participation. Study findings indicate that it is feasible to use a pedometer to monitor the level of PA. However, maintenance of a concurrent step log requires further consideration to determine realistic outcomes. Extrinsically focused motivations for PA in this study sample may predict low PA adherence.

This study evaluated changes in the metabolic syndrome (MetS) parameters among patients with schizoaffective disorder-bipolar type who had previously participated in a randomized, placebo-controlled study of topiramate (Chengappa et al., 2007). Topiramate (or placebo) was added to pre-existing mood-stabilizer and/or antipsychotic treatment. Nearly 41% of the 46 participants with fully available data met criteria for MetS at the pre-study baseline, and six (13%) additional subjects met criteria for MetS during the 16-week study. Several subjects (mostly topiramate treated) showed the hypothesized and expected loss in body weight and this correlated with improved glycosylated hemoglobin or systolic and diastolic blood pressure measurements or improvements in lipid levels, whereas a few patients had inconsistent results. Limitations of the study include the lack of targeted treatments for specific components of the metabolic syndrome, and no controls for exercise, diet or concomitant medications. Nevertheless, screening, monitoring and targeted treatment for the metabolic syndrome in psychiatric patients is increasingly becoming the standard of practice. Moreover and especially pertinent to the readership of this journal is that as the prevalence of overweight and MetS have increased worldwide, the World Health Organization has proposed lower cut-off thresholds for obesity in Asia. Furthermore, lower thresholds for waist circumference have also been recommended for Asians.

It is known that people with schizophrenia make poor dietary choices and smoke at alarmingly high rates. There is also anecdotal evidence that they may ingest large amounts of caffeine. However, while smoking habits in this population have been examined, no recent study has quantified caffeine consumption taking into account various dietary caffeine sources unrelated to coffee including convenience foods such as candy bars, chocolate or soft drinks, and compared results to US population data.We employed 24-h diet recalls to assess dietary habits in a sample of outpatients suffering from schizophrenia or schizoaffective disorder. Caloric intake and caffeine consumption were quantified and the relationship to various sociodemographic variables including body mass index (BMI) and dietary quality was examined.146 patients were recruited. Mean BMI in the sample was 32.7+/-7.9. Patients ingested 3,057+/-1,132 cal on average. Patients smoked at higher rates (59.6% vs. 23.4%, por =0.001), higher numbers of cigarettes/day (24+/-14.4 vs. 13.5+/-11.3, t=8.549, p0.001) and ingested more caffeine (471.6+/-584.6 mg vs. 254.2+/-384.9 mg, t=6.664, p0.001) than US population comparisons. Caffeine consumption was correlated to the number of cigarettes smoked daily (r=0.299, por =0.001), but not to BMI (r=0.134, p=0.107) or dietary parameters such as caloric intake (r=0.105, p=0.207).Community-dwelling schizophrenia patients consume significantly more caffeine and nicotine than US population comparisons. Clinicians should be aware that while a significant proportion of patients are overweight and have poor dietary quality - which merits lifestyle counseling on its own - there is a lack of correlation between those factors and smoking and caffeine intake. Thus, lifestyle modification counseling in all patients should address smoking and caffeine intake concurrently.

Introduction Brain phospholipids are uniquely rich in polyunsaturated fatty acids (PUFAs). Most PUFAs such as α-linolenic acid 18:3(n-3), eicosapentaenoic acid 20:5(n-3), and docosahexaenoic acid 22:6(n-3) are essential and must be provided through the diet. PUFAs are also very sensitive to oxidative stress. Decreased essential fatty acid content has been observed in cell membranes of various tissue types of schizophrenia patients, including neural cell membranes. A number of mechanisms may account for these deficits, such as inadequate dietary supply or increased oxidation. It is known that patients with schizophrenia make poor dietary choices. However, whether their dietary fatty acid or antioxidant intake is insufficient and contributes to the observed deficiencies has not been assessed. Methods After obtaining informed consent, a 24-h diet recall was administered to elicit nutritional information in 146 outpatients with schizophrenia. Intake of fatty acids and antioxidants including vitamins A, C, and E was compared to U.S. population standards according to the National Health and Nutrition Examination Survey Cycle III (NHANES III) results. Results Saturated and polyunsaturated fatty acid (PUFA) intake was significantly higher in schizophrenia patients than in controls ( p ≤ 0.05; p ≤ 0.005, respectively). No differences were found with regard to dietary intake of γ-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3). Similarly, antioxidant intake was not different between schizophrenia patients and controls. Conclusion The observed cell membrane deficits in PUFA and essential fatty acid content do not appear to derive from decreased dietary supply. Rather, intrinsic membrane phospholipid metabolism abnormalities may be causative. Overall increased fat intake in schizophrenia patients may contribute to the development of serious medical comorbidities, and further advance the risk for cumbersome metabolic side effects of antipsychotic treatment such as new-onset diabetes mellitus.

Introduction Many patients with schizophrenia are exposed to serious health risks associated with their excess body weight. Evidence exists that even a moderate amount of weight loss may have significant health benefits. Thus, weight control in schizophrenia patients has become an important treatment goal. Although studies in the general population show that satisfaction with body weight is an important predictor for engagement in various weight loss measures, the perspective of schizophrenia patients has not been assessed. Method Information on self-reported weight perception, desire to lose weight as well as weight loss attempts was obtained according to methods employed in the National Health and Nutrition Examination Survey, Cycle III (NHANES III). Body weight and height were measured and body mass index (BMI) was calculated. Results Perception of body weight and desire to lose weight were correlated to BMI. Both obese female and male subjects (BMI⩾30) were aware of their weight status. However, whereas overweight females (BMI>25≤29.9) accurately perceived themselves so, males in this category had difficulties perceiving themselves overweight, and consequently neither wanted to lose weight, nor tried to lose weight. As means of weight loss, caloric restriction (diet) was most frequently employed (by more than 80% of study subjects); yet only a third of study subjects (34.4%) engaged in the recommended combination of diet and exercise to lose weight. Questionable weight loss practices were also frequently employed, especially among women. Conclusions Obese patients (BMI≥30) were generally aware of their excess body weight and wanted to lose weight. Only non-obese, yet overweight males (BMI>25≤29.9) did not perceive themselves as overweight and consequently did not try to lose weight. Weight loss practices did not always follow established recommendations. Especially women were likely to approach weight loss with questionably appropriate and unsafe methods.

ResumenLa combinación de clozapina y otros medicamentos potencialmente leucocitopénicos puede plantear un riesgo mayor de neutrocitopenia. Sin embargo, la neutrocitopenia puede no deberse siempre a la clozapina. Al añadir medicamentos potencialmente leucocitopénicos, los profesionales clínicos deben buscar posibles alternativas, en especial porque la clozapina es un fármaco que se utiliza a menudo como último recurso en el tratamiento de la esquizofrenia resistente.

Background: Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. Method: This 14-week, multicenter, openlabel, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. Results: Seventy-two patients were enrolled. The mean± SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (‐2.0± 3.79 and ‐1.1± 3.11 kg, respectively). More patients in the BT group than in the UC group had lost ≥ 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost ≥ 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (completer population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). Conclusion: BT may be an effective method for weight reduction in patients with chronic psychotic illness. (J Clin Psychiatry 2005;66:205‐212)

Objectives: To evaluate the point prevalence of the metabolic syndrome in patients with schizoaffective disorder – bipolar type. Methods: Consenting patients who were participants in an ongoing clinical trial of adjunctive topiramate treatment for schizoaffective disorder, bipolar type were evaluated at baseline for the point prevalence of the metabolic syndrome. The criteria for the metabolic syndrome included: (a) waist circumference > 102 cm (40 inches) in males, or > 88 cm (35 inches) in females; (b) fasting serum triglyceride levels ≥ 150 mg/dL; (c) fasting high density lipoproteins (HDL) cholesterol

The prevalence of obesity in the United States population is increasing, and similar trends can be observed among schizophrenia patients. No thorough examination of the actual nutritional composition of the diet of schizophrenia patients in the United States has been carried out. We therefore employed a 24-hour diet recall in 146 schizophrenia outpatients to gather information on different nutritional variables, such as total caloric intake and total fat, protein, carbohydrate, cholesterol, and fiber content. Data were subsequently compared to data for the general population collected in the Third National Health and Nutrition Examination Survey (NHANES III). Schizophrenia patients as a group ate more food when compared to NHANES III subjects, but the relative percentages of calories derived from fat, protein, and carbohydrates were not found to be different. Therefore, it is unlikely that schizophrenia patients make dietary choices different from those of people in the general population. Instead, schizophrenia patients seem to eat more of the same food.

Concomitant medications are frequently used in the treatment of resistant psychiatric conditions to augment the primary psychotropic agent or to ameliorate side effects. The present study evaluated the prescription of concomitant psychiatric medications for psychiatric inpatients that were prescribed either olanzapine at its first commercial availability or another first-line antipsychotic agent. Sixty-nine newly admitted patients (mainly with schizophrenia) who were prescribed either olanzapine (n = 35) or another first-line antipsychotic agent (n = 34) were assessed (for the prescription of other concomitant psychotropic drugs) before (2-4 weeks prior to study) and following 8 weeks of treatment (unless discharged sooner). The results indicate that significantly fewer olanzapine-treated subjects were prescribed anticholinergic agents as compared to those prescribed other first-line antipsychotic agents, and a similar trend was noted in the prescription of mood stabilizers as well. Olanzapine-treated subjects used less as needed (PRN) antipsychotic medication compared to pre-olanzapine treatment period. Olanzapine-treated subjects used more anxiolytic agents compared to the control group in the early stages of treatment, probably due to the greater baseline severity of illness. These data suggest that olanzapine use is associated with less use of anticholinergic and mood-stabilizing agents as compared to older antipsychotic agents. These results also suggest that there is less need for PRN antipsychotic medication following olanzapine treatment. More severely ill subjects may require more anxiolytics during olanzapine initiation. The need for less anticholinergic and mood-stabilizing agent use with olanzapine could lead to greater adherence to long-term treatment and perhaps decreased cost (i.e. use of blood and organ system monitoring with mood stabilizers). At the end of treatment, olanzapine-treated subjects had statistically significantly lesser concomitant medicine usage compared to control subjects.

BACKGROUND: Obesity is prevalent in individuals with serious mental illness (SMI). OBJECTIVE: The purpose of this study is to examine the feasibility of a telephone-delivered physical activity (PA) intervention for outpatients with serious mental illness to maintain PA and to explore the preliminary efficacy of the intervention on health status. DESIGN: This study used a randomized experimental design. The treatment group received pedometers and eight weekly phone calls; the control group received written information regarding PA. Descriptive statistics were used to analyze data collected at baseline and 8 weeks. RESULTS: Twenty-two subjects with SMI (mean age = 44.09 ± 7.6 years; 54.5% were male) were recruited and 16 subjects completed the study in 8 weeks. PA ( z = −2.37, p = .02) increased in the treatment group ( n = 8) whereas the control group ( n = 8) maintained baseline PA level ( z = −1.61, p = .11). Health outcomes were not changed ( ps > .05). CONCLUSION: Telephone-delivered intervention is feasible and has the potential to improve PA in individuals with SMI.

Chengappa KNR, Turkin SR, Schlicht PJ, Murphy SL, Brar JS, Fagiolini A, Houck PR, Garbutt RG, Fredrick N. A Pilot, 15-month, randomised effectiveness trial of Risperidone long acting injection (RLAI) versus oral atypical antipsychotic agents (AAP) in persons with bipolar disorder.Objective:Long-acting injectible antipsychotic agents are rarely considered in the treatment of bipolar patients [bipolar disorder (BPD)]. We posited that BPD patients receiving risperidone long-acting injections [Risperidone long-acting injections (RLAIs)] would experience fewer negative clinical events than those receiving oral atypical antipsychotic agents (AAP).Methods:Adult BPD patients in a hypomanic, manic or mixed episode were randomised to either oral risperdone followed by RLAI (n= 23) or an AAP (n= 25) for 15 months. Any mood stabilizers were continued. An independent clinician board declared any clinical events that occurred but the treatment assignment was concealed.Results:Nine of the 48 patients who participated in this study did not improve, leaving 39 patients in 1-year extension. RLAI patients received the following bi-weekly dosages: 25 mg (n= 9), 37.5 mg (n= 8), and 50 mg (n= 6). The AAP group included aripiprazole (n= 11, 15–30 mg/day), quetiapine (n= 8, 300–700 mg/day), olanzapine (n= 5, 15–25 mg/day), and ziprasidone, (n= 1, 160 mg/day). In total, 47 clinical events were declared. The RLAI-treated group experienced significantly fewer clinical events (mean: 0.86 ± 0.73) compared with the AAP group (1.61 ± 1.29),t= 2.29, d.f. = 37,p= 0.028 (95% CI = 0.087–1.421). Of all, 50% of the AAP subjects gained ≥ 7% of their baseline body weight as did 38% of the RLAI-treated patients.Conclusions:RLAI-treated patients experienced significantly fewer negative clinical events. Further exploration should focus on which subtypes of BPD patients might benefit from RLAI treatment. Weight gain in BPD subjects requires clinical attention. Limitations include an open design, small sample size and the inability to conclude on whether this strategy is useful for depressive episodes.

Objectives: Depressive symptoms are prevalent in older adults, and physical activity (PA) may have beneficial effects on depression. The purpose of this study was to explore the association between physical activity and depressive symptoms, taking into account demographic factors, and the associations between selected demographic factors and physical activity levels in community-dwelling older adults (age≥60 years). Methods: Data were drawn from the National Health and Nutrition Examination Survey 2005-2006. Descriptive statistics and logistic models were used in data analysis. Results: Four percent of participants reported moderate depressive symptoms, and 24% of subjects exhibited sedentary PA. Factors associated with increased risk of moderate depression included age, sedentary PA, and chronic medical conditions (ps

Obesity and associated medical conditions may have an impact on morbidity and even mortality in patients with psychiatric disorders. The authors present the results of a survey of the prevalence of obesity and selected medical conditions among 420 consecutively admitted psychiatric inpatients at a long-stay facility and compare these data with those reported in the literature. Female psychiatric subjects had considerably higher rates of being either overweight or obese (69%) as compared to women in the general U.S. population (51%). Male psychiatric subjects did not differ significantly from their counterparts in the general population in being overweight or obese (nearly 55%). The majority of psychiatric subjects with essential hypertension, diabetes mellitus, dyslipidemias, cardiovascular disease, or sleep apnea were either overweight or obese (72%–87%). In this cross-sectional study, no associations could be deduced between psychotropic drug classes and specific medical conditions. No specific psychiatric diagnostic category was associated with a significantly greater prevalence of any specific medical condition, except that subjects with schizoaffective disorder appeared to have a higher prevalence of type II diabetes mellitus (11.6%). Subjects with predominant substance or alcohol abuse or dependence disorders had a lower prevalence of obesity and associated medical conditions. Obesity—either independently or additively along with a sedentary lifestyle, unhealthy dietary habits, and nicotine dependence—may have a serious impact on coexisting medical comorbidity in psychiatric patients. Judicious monitoring for obesity and rapid pharmacological and nonpharmacological intervention, where appropriate, by concerned clinicians may improve several coexisting medical conditions in psychiatric patients and thereby improve patients' overall quality of life.

Weight gain frequently accompanies treatment with antipsychotics. In order to determine whether newer antipsychotic agents differ from each other with respect to weight gain, we compared two cohorts of patients with DSM-IV schizophrenia who had newly started treatment with either risperidone or olanzapine. After obtaining informed consent, data regarding body weight and height were culled from existing medical records of 100 patients (50 patients in each treatment group). Baseline body weight, close to the time of starting the new medication, and body mass index [BMI = weight (kg)/height (m) squared] were compared to the body weight and BMI following 4 months of treatment. There was no significant change in mean body weight or BMI in the group treated with risperidone (baseline weight = 83.1 kg +/- 20.5, follow-up = 82.8 kg +/- 19.9; matched pair t = 0.66, P = n.s.; baseline BMI = 29.6 +/- 9.4, follow-up = 29.5 +/- 9.1; matched pair t = 0.79, P = n.s.). However, in the group treated with olanzapine, there was a significant increase in both mean body weight and BMI (baseline weight = 84.9 kg +/- 25.0, follow-up = 87.1 kg +/- 25.1; matched pair t = 4.62, P0.001; baseline BMI = 29.5 +/- 7.4, follow-up = 30.3 +/- 7.5; matched pair t = 4.43, P0.001). In this naturalistic study, treatment with olanzapine was associated with a mean weight gain of about 2 kg from baseline, in patients with schizophrenia, while treatment with risperidone was associated with no mean weight change.

INTRODUCTION: The present study explores the relationships among psychotropic medications, illness-related parameters, patient demography, suicidality, and levels of functioning in a voluntary bipolar case registry. METHODS: Four hundred and fifty-seven subjects with bipolar I disorder were selected from a voluntary registry for subjects with bipolar illness. Demographic characteristics, psychotropic medications, age at onset of illness, duration of illness, number of hospitalizations, the ability to live independently, employment and driving status as well as the history of suicidal attempts were obtained through a structured phone interview. RESULTS: Subjects treated with antidepressants had a shorter duration of illness, while patients treated with antipsychotic drugs had an earlier onset of illness. The number of hospitalizations for mania was fewer among patients taking a combination of lithium and carbamazepine as compared to patients not receiving them, while subjects taking neuroleptics had more hospitalizations as compared to subjects not receiving them. The number of psychotropic agents prescribed correlated positively with the number of hospitalizations for depressive episodes. Curiously, no correlations were found between the types of psychotropic agents prescribed and the levels of functioning or a history of suicidal attempts. Interestingly, our results suggest that more than half of the subjects were unable to live independently or to work due to their illness. Also, more than 50% of the subjects had at least one suicidal attempt, the majority occurred during depressive episodes. CONCLUSIONS: Our results suggest that subjects with bipolar I disorder have high rate of suicidal attempts and may have serious functional impairments. Language: en

Objective: To evaluate the impact of risperidone on seclusion and restraint in patients at a state psychiatric facility, shortly after risperidone's release. Methods Patients who were in the hospital for at least 3 months prior to receiving risperidone and subsequently received risperidone for at least 3 months formed the cohort. A mirror-image design was used with duration to a maximum of 1 year before and 1 year after initiation of risperidone. The hospital population that did not receive either risperidone or clozapine during the same time period was used for comparison of trends of seclusion and restraint. Results Seventy-four patients (most with schizophrenia) met the inclusion criteria of the risperidone group. There were statistically significant decreases in the number of seclusion hours (2.2 [SD 5.5] to 0.26 [SD 0.06]) and of events (0.23 [SD 0.59] to 0.05 [SD 0.14]) per person per month during risperidone treatment, compared with the prerisperidone treatment period (P = 0.01). The comparison group also evidenced decreases on these measures during the same time period, but the risperidone-treated cohort achieved a proportionally greater reduction. There were similar trends toward reduction in the restraint measures during risperidone treatment compared with prerisperidone, but these did not achieve statistical significance. The comparison group also showed slightly decreased use of restraints over the study period. Conclusions Risperidone appears to have had a positive impact on seclusion in this state-hospital psychiatric population. These data support the positive impact of risperidone on violence found in other studies. Violence and aggression are major factors that affect morale among psychiatric patients and staff. So, any benefit in this regard as a result of antipsychotic drug treatment is salutary for patients, families, and health care providers.

Introduction: Combination treatment, rather than monotherapy, is prevalent in the treatment of subjects with bipolar disorder, probably due to the complex and phasic nature of the illness. In general, prescription patterns may be influenced by the demographic characteristics of patients as well. We evaluated prescription patterns and the influence of demographic variables on these patterns in a voluntary registry of subjects with bipolar disorder. Methods: A subset of data from a larger voluntary registry was extracted for demographic variables and psychotropic medication use that had been reported in the month prior to registration by ambulatory, non-hospitalized subjects with bipolar I disorder in 1995/96 (n=457). Results: Among the thymoleptic agents, lithium was prescribed in over 50% of subjects, valproate in approximately 40%, and carbamazepine in 11% of subjects. Eighteen percent of subjects had no prescription for thymoleptic agents. Nearly one-third of all subjects were receiving antipsychotic agents, of whom two-thirds were receiving the traditional neuroleptic agents. More than half of all subjects were receiving concomitant antidepressants, of whom nearly 50% received the SSRI antidepressants and nearly 25% received buproprion. Approximately 40% of subjects received benzodiazepines. Only 18% of subjects received monotherapy, and nearly 50% received three or more psychotropic agents. In general, no associations were noted between demographic parameters including age, gender, marital or educational status, and psychotropic prescriptions. Conclusion: Consistent with the anecdotal reports, these data confirm that combination treatment is far more common than monotherapy. Demography appears to have a minimal impact on cross-sectional prescription patterns in subjects with bipolar disorder. Given that combination treatments are the rule rather than the exception, we should strive to achieve rational, yet pragmatic, treatment guidelines and algorithms to minimize the risks while maximizing the benefits of these combination treatments for patients with bipolar disorder.

This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p < 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.

Objective: Anticonvulsant agents such as carbamazepine and valproate are alternatives to lithium in treating subjects with bipolar disorder. Topiramate (Topamax®), a new antiepileptic agent, is a candidate drug for bipolar disorder. We evaluated topiramate as adjunctive treatment for bipolar patients. Methods: Eighteen patients with DSM-IV bipolar I disorder [mania (n=12), hypomania (n=1), mixed episode (n=5), and rapid cycling (n=6)], and two subjects with schizoaffective disorder – bipolar type, resistant to current mood-stabilizer treatment were initiated on topiramate, 25 mg/day, increasing by 25–50 mg every 3–7 days to a target dose between 100 and 300 mg/day, as other medications were held constant for 5 weeks. The Young Mania Rating Scale (Y-MRS), Hamilton Depression Rating Scale (Ham-D), and Clinical Global Impression-Bipolar Version Scale (CGI-BP) were used to rate subjects weekly. Results: By 5 weeks, 12 (60%) subjects were responders, i.e., 50% reduction in the Y-MRS scores and a CGI of ‘much’ or ‘very much improved’. Three subjects were ‘minimally improved’, four showed no change, and one was ‘minimally worse’. Six subjects had parasthesia, three experienced fatigue, and two had ‘word-finding’ difficulties; in all cases, side effects were transient. All patients lost weight with a mean of 9.4 lb in 5 weeks, and a significant reduction in body mass index (BMI) occurred too. Conclusions: Topiramate appears to have efficacy for the manic and mixed phases of bipolar illness. Other preliminary data suggest antidepressant efficacy too. Among obese bipolar subjects, the weight loss potential of topiramate may be beneficial. If controlled trials confirm these initial results, topiramate may be a significant addition to the available treatments for bipolar disorder.

Background: In spite of some inherent limitations, naturalistic data can provide information on populations that have greater heterogeneity than can controlled clinical trials and on functional outcomes that may be especially important in clinical practice. In the present retrospective naturalistic study, we evaluated key clinical outcomes among the first wave of risperidone-treated patients at a state psychiatric hospital. Method: Outcome data were extracted from the charts of 142 patients 2 years after initiation of treatment with risperidone. Their diagnoses included DSM-III-R schizophrenia (57%), schizoaffective disorder (22%), dementia and other organic conditions (7%), bipolar disorder (5%), and other psychiatric disorders (9%). Results: During the 2-year period, 92 of 142 patients were discharged from the hospital: 61 (43%) were discharged on risperidone treatment and 31 (22%) were discharged on treatment with other drugs. At the time of the study, 50 of 142 patients were still in the hospital: of these, 18 (13%) were still receiving risperidone. The modal maximum daily dose of risperidone was 4.1 mg in patients discharged on risperidone treatment and 7.5 mg in patients still in the hospital. All groups were granted more ward privileges after starting risperidone, the most being granted to patients discharged from the hospital on risperidone treatment (p

A series of cases are reported in which patients on aripiprazole have developed akathisia, although the literature states that the rate is negligible.

Changes in regional cerebral blood flow (rCBF), associated with performance of an auditory verbal supraspan memory task, were studied in eight remitted DSM-III-R schizophrenic patients and eight pair-wise matched normal controls. Four positron emission tomography (PET) scans, using the [15O]-H2O technique, were acquired: two while subjects fixated a cross hair and two while performing a verbal free-recall supraspan memory task. Task performance showed typical patterns of recency and primacy effects in both groups; however, patients performed more poorly than controls on the primary (working) memory aspect of the task. Regions showing rCBF changes overlapped in both groups and were similar to those seen in previous studies of normals; however, patients had smaller increases in rCBF than controls in frontal and superior temporal cortical regions bilaterally. Our results suggest that remitted patients with schizophrenia demonstrate impairments of capacity-limited information processing, which may be related to metabolic dysfunction within a distributed network of brain structures, including the prefrontal and temporal cortical regions; however, dysfunction limited to the frontal cortex cannot be ruled out by the results of this experiment.

Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (D3RG) locus was investigated. Initial analysis of pooled results from published studies revealed a significant excess of individuals homozygous for either allele among the patients. The association was next tested in two cohorts ascertained independently at Pittsburgh, Pennsylvania and at Houston, Texas. The Pittsburgh sample was comprised of patients with schizophrenia (DSM-III-R) (n = 130). The controls belonged to two groups: adults screened for the absence of substance abuse or major psychiatric illness (n = 128), and neonates (n = 160). Multivariate analysis suggested an association with allele 1 of the biallelic D3RG polymorphism in comparison with the adult, but not the neonatal, controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.69, confidence intervals 1.80, 104.30). Survival analysis suggested an earlier age of onset among male patients homozygous for allele 2. The Houston cohort included Caucasian patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria, n = 50), and normal controls matched for gender (n = 51). In this group, no significant associations were noted among all the patients or among subgroups of patients based on family history or age of onset. Possible reasons for the discordant results are discussed. © 1996 Wiley-Liss, Inc.

In view of a reported association between schizophrenia and the 5-HT2 receptor gene locus, as well as an association with treatment refractoriness at this locus, a case-control association study was conducted using a biallelic polymorphism. The distribution of the polymorphism was investigated among patients with schizophrenia (DSM-III-R, n = 174) and unaffected controls (n = 239). No significant differences in genotype distributions or allele frequencies were noted between the two groups. In support of the earlier report, a significant excess of individuals homozygous for allele C2 was noted among patients who responded unsatisfactorily to antipsychotic medication in comparison with the controls (odds ratio 1.78; 95% confidence intervals 1.06, 2.97). However, this difference was not significant following multivariate analysis. This study does not support an association between the 5-HT2 receptor gene locus and schizophrenia or subgroups based on treatment response.

Serum interleukin-6 (IL-6) was measured in picograms/ml (pg/ml) using an immunoassay (ELISA) in healthy individuals (n = 148), of whom 128 were classified as dextral and 20 as non-dextral, as per a laterality questionnaire. Only 3 (15%) non-dextral individuals had serum IL-6 levels above the lower limit of the assay sensitivity as compared to 59 (46%) of dextral individuals (P < 0.013). There were no significant correlations between previously determined mitogen stimulated interleukin-2 production and autoantibodies in a subset of the same individuals. While this data does not provide casual information, it adds to the evidence of the asymmetric regulation of immune functions by the cerebral hemispheres.

Using an enzyme immunoassay (ELISA), we measured serum interleukin-6 (IL-6) concentration in 128 schizophrenic patients (24 of whom were never medicated) and in 110 normal control subjects. Mean serum IL-6 concentration was significantly higher in the schizophrenic patients as compared with the control subjects (p = 0.009). Comparisons within the patient group revealed that serum IL-6 was significantly correlated with duration of illness (r = 0.32, p = 0.0004). After covariation for duration of illness, there was no relationship between IL-6 levels and the production of autoantibodies, clinical state, or medication status. Thus, elevated serum IL-6 levels in schizophrenia develop during the course of illness and may be related to treatment or to disease progression.