BACKGROUND: Many patients with borderline personality disorder receive pharmacological treatment, but there is uncertainty about the usefulness of such therapies. AIMS: To evaluate the evidence of effectiveness of pharmacotherapy in treating different facets of the psychopathology of borderline personality disorder. METHOD: A Cochrane Collaboration systematic review and meta-analysis of randomised comparisons of drug v. placebo, drug v. drug, or single drug v. combined drug treatment in adult patients with borderline personality disorder was conducted. Primary outcomes were overall disorder severity as well as specific core symptoms. Secondary outcomes comprised associated psychiatric pathology and drug tolerability. RESULTS: Twenty-seven trials were included in which first- and second-generation antipsychotics, mood stabilisers, antidepressants and omega-3 fatty acids were tested. Most beneficial effects were found for the mood stabilisers topiramate, lamotrigine and valproate semisodium, and the second-generation antipsychotics aripiprazole and olanzapine. However, the robustness of findings is low, since they are based mostly on single, small studies. Selective serotonin reuptake inhibitors so far lack high-level evidence of effectiveness. CONCLUSIONS: The current evidence from randomised controlled trials suggests that drug treatment, especially with mood stabilisers and second-generation antipsychotics, may be effective for treating a number of core symptoms and associated psychopathology, but the evidence does not currently support effectiveness for overall severity of borderline personality disorder. Pharmacotherapy should therefore be targeted at specific symptoms. less...

OBJECTIVE: Weight gain is a possible adverse effect of the use of antipsychotics, and is an important factor for long-term health and treatment compliance. Olanzapine is an atypical antipsychotic known to cause considerable weight gain. A relationship between weight gain and the G protein beta3 subunit gene (GNB3) 825C/T polymorphism has been reported. We therefore examined this possible association in a Korean schizophrenic patient group receiving olanzapine treatment. METHODS: Weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the 825C/T polymorphism was performed using a PCR-based method. RESULTS: We found that long-term treatment with olanzapine resulted in mean gains in weight and body mass index (BMI) of 5.2 kg and 1.93 kg/m(2), respectively. There was a no significant difference in the mean body weight change from baseline to the endpoint after olanzapine treatment between the genotype groups (p=0.796). There were also no significant differences in genotype or allele frequencies between the severe weight-gain (more than 10%) and minimal weight-gain (less than 10%) groups (chi(2)=0.037, p=0.98; chi(2)=0.020, p=0.89). CONCLUSION: The finding from this study thus does not support a relationship between the GNB3 825C/T polymorphism and weight gain in Korean schizophrenic patients receiving olanzapine treatment. less...

CONTEXT: In 2003, the Food and Drug Administration (FDA) required a warning on diabetes risk for second-generation antipsychotic (SGA) drugs. The American Diabetes Association (ADA) and American Psychiatric Association (APA) recommended glucose and lipid testing for all patients starting to receive SGA drugs. OBJECTIVE: To characterize associations between the combined warnings and recommendations and baseline metabolic testing and SGA drug selection. DESIGN: Interrupted time-series analysis. SETTING: California, Missouri, and Oregon. Patients A total of 109 451 individuals receiving Medicaid who began taking SGA medication and a control cohort of 203 527 patients who began taking albuterol but did not receive antipsychotic medication. INTERVENTIONS: Prewarning and postwarning trends in metabolic testing were compared using laboratory claims for the cohort collected January 1, 2002, through December 31, 2005. Changes in SGA prescribing practices were similarly evaluated. MAIN OUTCOME MEASURES: Monthly rates of baseline serum glucose and lipid testing for SGA-treated and propensity-matched albuterol-treated patients and monthly share of new prescriptions for each SGA drug. RESULTS: Initial testing rates for SGA-treated patients were low (glucose, 27%; lipids, 10%). The warning was not associated with an increase in glucose testing among SGA-treated patients and was associated with only a marginal increase in lipid testing rates (1.7%; P = .02). Testing rates and trends in SGA-treated patients were not different from background rates observed in the albuterol control group. New prescriptions of olanzapine (higher metabolic risk) declined during the warning period (annual share decline, 19.9%; P < .001). New prescriptions of aripiprazole (lower metabolic risk) increased during the warning period (share increase, 12.1%; P < .001) but may be attributable to the elimination of prior authorization in California during the same time frame. Quetiapine, risperidone, and ziprasidone use were not associated with the warning. CONCLUSIONS: In a Medicaid-receiving population, baseline glucose and lipid testing for SGA-treated patients was infrequent and showed little change following the diabetes warning and monitoring recommendations. A change in SGA drug selection consistent with intentions to reduce metabolic risk was observed. less...

This article summarizes the current knowledge base on the diagnosis and management of treatment resistant schizophrenia. While the prevalence of treatment resistant schizophrenia is definition dependent, estimates have ranged from 30% to up to 60%. This article first looks into the various diagnostic criteria of treatment resistant schizophrenia. Then the literature is reviewed about the pharmacotherapeutics of its management. Clozapine emerges to be the gold standard. In addition risperidone and high dose olanzapine also emerge as clinically useful options. Other emerging adjunctive treatment options are equally addressed. less...

Background: With the advent of newer antipsychotic drugs, side effects such as sexual dysfunction have been a major contributor toward treatment compliance. There are only a few studies that have compared different atypical antipsychotic agents regarding sexual dysfunction. We have not come across any data in this area on Indian population. Aims: To determine and compare the frequency of sexual dysfunction associated with risperidone, olanzapine, and quetiapine, among patients with clinically stable schizophrenia. Settings and Design: It is a cross-sectional hospital-based study. The subjects were recruited for the study by the purposive sampling technique. Materials and Methods: The total sample size was 102, consisting of 25 each in the quetiapine and risperidone groups, 22 in the olanzapine group, and 30 healthy volunteers. A Brief Psychiatric Rating Scale and Sexual Functioning Questionnaire (SFQ) were administered. The Kruskal Wallis test was used to compare the variables in the demographic data and the mean chlorpromazine equivalent doses of the study groups. To analyze the sexual dysfunction, the mean scores on all the domains of sexual functioning in SFQ were compared across the study groups using the Chi square test, for proportions. Results and Conclusion: Twenty-three percent of the healthy volunteers had some impairment in one or more domains of sexual functioning. For the medication groups this was 96, 88, and 90%, respectively for risperidone, quetiapine, and olanzapine. However, there was statistically no significant difference across the study groups although it was relatively less with quetiapine. less...

Objective: Atypical antipsychotics are increasingly drugs of first choice in schizophrenia. Amisulpride, a new atypical antipsychotic, is reported to be effective for both positive and negative symptoms of schizophrenia in Western countries but Indian experience is limited. The aim of the present study was therefore to conduct a trial of amisulpride versus olanzapine in Indian schizophrenia patients. Methods: Eighty adult patients of either sex were randomized to receive standard doses of the two drugs orally, in a single blind manner, for 12 weeks, with follow up at 4 and 8 weeks. Effectiveness was assessed by changes in scores on the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms (SAPS), Scale for Assessment of Negative Symptoms (SANS), and physician-administered Clinical Global Impression (CGI) scale. Tolerability was assessed by treatment-emergent adverse drug reactions (ADRs). Results: Evaluable were 39 patients on amisulpride and 38 on olanzapine. The groups were comparable at baseline with respect to demographics, illness duration and rating scores. Final BPRS score was lower for olanzapine (33.2 +/- 9.44) than for amisulpride (37.7 +/- 9.67). SAPS and SANS scores and CGI rating improved individually in both arms but remained comparable between groups throughout the study period, but olanzapine reduced SAPS score to a greater extent. ADRs were encountered in 67.5% and 47.5% of patients (p = 0.113) on amisulpride and olanzapine, respectively. Tremor and insomnia were more frequent with amisulpride, while olanzapine caused more weight gain and sedation. No serious ADRs occurred. Conclusions: Amisulpride, although comparable to olanzapine on some measures, did not match the improvement seen with the latter drug in BPRS and SAPS scores. Despite differences in ADR profiles, overall tolerability was satisfactory for both drugs. In Indian patients, amisulpride should therefore be an alternative to olanzapine to a limited extent, such as when weight gain and sedation are undesirable. less...

BACKGROUND: Measles virus is a highly prevalent neurotropic virus capable of causing persistent infections within the central nervous system. METHODS: We measured IgG class antibodies to measles in 820 individuals including 138 with recent onset psychosis, 378 with persistent schizophrenia, and 304 non-psychiatric controls. Levels of antibodies among the groups were compared by bivariate and by multivariate analyses and correlated with clinical and demographic variables. RESULTS: The level of measles antibodies in individuals with a recent onset of psychosis was greater than the level of antibodies in individuals with persistent schizophrenia or individuals without a history of a psychiatric disorder (p<.00001). The level of measles antibodies in the individuals with persistent schizophrenia was greater than the level of measles antibodies in the controls (p<.001). Recent onset of psychosis was associated with having elevated levels of measles antibodies, defined as the 90th percentile of the levels of the controls, with an odds ratio of 8.0 (95% CI 4.6, 14.0); persistent schizophrenia was associated with having this level with an odds ratio of 2.3 (95% CI 1.4, 3.7). Within the psychiatric groups, measles antibody levels were associated with age, race, and current treatment with the antipsychotic medication, olanzapine. CONCLUSIONS: The reasons for elevated levels of measles antibodies in the psychiatric groups are not known with certainty and should be studied in prospective investigations. less...

In this paper we investigate mortality in short-term placebo-controlled trials conducted to demonstrate efficacy and safety of atypical antipsychotic drugs for the treatment of schizophrenic patients in the acute phase of illness. Arguments are provided, why short-term placebo-controlled studies are required. This is an integrated analysis of results from randomized placebo-controlled trials conducted pre-licensing for risperidone, olanzapine, quetiapine IR, ziprasidone, risperidone consta, aripiprazole, paliperidone, and quetiapine XR. Information was retrieved from study publications, EPAR, and from the FDA SBA, all in the public domain. 7553 patients were randomized in the remaining 23 short-term acute phase clinical trials. 2/5738 patients died after having been randomized to an active treatment. 5/1815 died in the placebo group. The crude odds-ratio for an increased death risk with placebo treatment is 7.92 (95% confidence interval (1.45 to 40.87), two sided P=0.0134). Death narratives show: (i) both deaths in active treatment groups occurred during randomized treatment period, (ii) two deaths in the placebo group of a trial in the elderly were observed in patients with severe co-morbidities not usually included in a randomized trial, and (iii) two further deaths in the placebo groups occurred 9 and 23days after the end of the randomized treatment period. Under these circumstances the crude odds-ratio for an increased risk of death for patient with placebo as compared to active treatment is 1.58 (95% confidence interval (0.14-17.45), two sided P=0.71). Confidence intervals are generally wide indicating a still limited knowledge about a potential increase in mortality with placebo treatment. Unless, however, society is willing to take the risk that ineffective drugs are licensed and cause undetected harm thereafter, or is willing to restrict licensing to drugs that are superior to current treatments, short-term placebo-controlled trials in the acute phase of schizophrenia are necessary. Measures are proposed to minimize risks. less...

A 31-year-old male, diagnosed with schizophrenia and receiving maintenance treatment with olanzapine, was prescribed methylphenidate for comorbid attention deficit hyperactivity disorder (adhd). The adhd symptoms diminished and there were hardly any side-effects. No increase in psychotic symptoms occurred. The patient used far fewer amphetamines and benzodiazepines. In theory, stimulants and antipsychotics produce opposite effects. Relevant literature on the subject is discussed. less...

BACKGROUND: There is currently mixed opinion regarding the value of using atypical antipsychotics to treat anorexia nervosa (AN). AIMS: To evaluate the literature on the use of atypical antipsychotics in AN. METHOD: A review of all studies and clinical guidelines published before September 2009 involving use of an atypical antipsychotic in patients with AN. Analysis is by narrative synthesis. RESULTS: Forty-three publications or study protocols were found, including four randomized-controlled trials, five open-label trials and 26 case reports. The most studied drugs were olanzapine, quetiapine and risperidone. Atypical antipsychotics appear safe and there is some evidence of positive effects on depression, anxiety and core eating disordered psychopathology in patients with anorexia nervosa. Currently there is insufficient evidence to confirm atypical antipsychotics enhance weight gain in this setting. CONCLUSIONS: Further high quality evidence is needed in this area in order to provide practical guidance to clinicians. However, the main challenge is to persuade adequate numbers of AN patients to participate in research trials. Copyright (c) 2010 John Wiley & Sons, Ltd and Eating Disorders Association. less...