Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

Educating Health Professionals about Drug and Device Promotion: Advocates' Recommendations

Mansfield and colleagues outline the recommendations from four advocacy groups for improving the education of health professionals on promotion of drugs and devices

Season of birth and handedness in Serbian high school students

<p>Abstract</p> <p>Background</p> <p>Although behavioural dominance of the right hand in humans is likely to be under genetic control, departures from this population norm, i.e. left- or non-right-handedness, are believed to be influenced by environmental factors. Among many such environmental factors including, for example, low birth weight, testosterone level, and maternal age at birth, season of birth has occasionally been investigated. The overall empirical evidence for the season of birth effect is mixed.</p> <p>Methods</p> <p>We have investigated the effect of season of birth in an epidemiologically robust sample of randomly selected young people (n = 977), all born in the same year. A Kolmogorov-Smirnov type statistical test was used to determine season of birth.</p> <p>Results</p> <p>Neither the right-handed nor the non-right-handed groups demonstrated birth asymmetry relative to the normal population birth distribution. There was no between-group difference in the seasonal distribution of birth when comparing the right-handed to the non-right-handed groups.</p> <p>Conclusion</p> <p>The present study failed to provide support for a season of birth effect on atypical lateralisation of handedness in humans.</p

A card game for the treatment of delusional ideas: A naturalistic pilot trial

BACKGROUND: "Michael's game" is a card game which aims at familiarizing healthcare professionals and patients with cognitive behavioral therapy of psychotic symptoms. This naturalistic study tests the feasibility and the impact of the intervention in various naturalistic settings. METHOD: Fifty five patients were recruited in seven centers. They were assessed in pre and post-test with the Peters Delusion Inventory – 21 items (PDI-21). RESULTS: Forty five patients completed the intervention significantly reducing their conviction and preoccupation scores on the PDI-21. CONCLUSION: This pilot study supports the feasibility and effectiveness of "Michael's game" in naturalistic setting. Additional studies could validate the game in a controlled fashion

Voice-selective prediction alterations in nonclinical voice hearers

Auditory verbal hallucinations (AVH) are a cardinal symptom of psychosis but also occur in 6-13% of the general population. Voice perception is thought to engage an internal forward model that generates predictions, preparing the auditory cortex for upcoming sensory feedback. Impaired processing of sensory feedback in vocalization seems to underlie the experience of AVH in psychosis, but whether this is the case in nonclinical voice hearers remains unclear. The current study used electroencephalography (EEG) to investigate whether and how hallucination predisposition (HP) modulates the internal forward model in response to self-initiated tones and self-voices. Participants varying in HP (based on the Launay-Slade Hallucination Scale) listened to self-generated and externally generated tones or self-voices. HP did not affect responses to self vs. externally generated tones. However, HP altered the processing of the self-generated voice: increased HP was associated with increased pre-stimulus alpha power and increased N1 response to the self-generated voice. HP did not affect the P2 response to voices. These findings confirm that both prediction and comparison of predicted and perceived feedback to a self-generated voice are altered in individuals with AVH predisposition. Specific alterations in the processing of self-generated vocalizations may establish a core feature of the psychosis continuum.The Authors gratefully acknowledge all the participants who collaborated in the study, and particularly Dr. Franziska Knolle for feedback on stimulus generation, Carla Barros for help with scripts for EEG time-frequency analysis, and Dr. Celia Moreira for her advice on mixed linear models. This work was supported by the Portuguese Science National Foundation (FCT; grant numbers PTDC/PSI-PCL/116626/2010, IF/00334/2012, PTDC/MHCPCN/0101/2014) awarded to APP

How do General Practitioners experience providing care for their psychotic patients?

BACKGROUND: In primary care, GPs usually provide care for patients with chronic diseases according to professional guidelines. However, such guidelines are not available in the Netherlands for patients with recurring psychoses. It seems that the specific difficulties that GPs experience in providing care for these patients hinder the development and implementation of such guidelines. This study aims to explore the chances and problems GPs meet when providing care for patients susceptible for recurring psychoses, including schizophrenia and related disorders, bipolar disorder, and psychotic depression. METHODS: A qualitative study of focus group discussions with practising GPs in both town and rural areas. Transcripts from three focus groups with 19 GPs were analysed with the computer program 'Kwalitan'. Theoretical saturation was achieved after these three groups. RESULTS: Analysis showed that eight categories of factors influenced the GPs' care for psychotic patients: patient presentation (acute vs. chronic phase), emotional impact, expertise, professional attitude, patient related factors, patient's family, practice organization, and collaboration with psychiatric specialists. CONCLUSION: Current primary care for psychotic patients depends very much on personal characteristics of the GP and the quality of local collaboration with the Mental Health Service. A quantitative study among GPs using a questionnaire based on the eight categories mentioned above would determine the extent of the problems and limitations experienced with this type of care. From the results of this quantitative study, new realistic guidelines could be developed to improve the quality of care for psychotic patients

Cannabis-induced psychosis like experiences are associated with high schizotypy

Objective: Recent studies have suggested that cannabis use is a risk factor for developing schizophrenia. We tested the hypothesis that cannabis use increases the likelihood of psychosis-like experiences in non-clinical participants who scored highly on a measure of schizotypy. Method: The psychological effects of cannabis were assessed in 137 healthy individuals (76% female, mean age 22 years) using a newly developed questionnaire concerned with subjective experiences of the drug: the Cannabis Experiences Questionnaire. The questionnaire has three subscales: Pleasurable Experiences, Psychosis-Like Experiences and After-Effects. Respondents also completed the brief Schizotypal Personality Questionnaire. Results: Cannabis use was reported by 72% of the sample. Use per se was not significantly related to schizotypy. However, high scoring schizotypes were more likely to report both psychosis-like experiences and unpleasant after-effects associated with cannabis use. The pleasurable effects of cannabis use were not related to schizotypy score. Conclusion: High scoring schizotypes who use cannabis are more likely to experience psychosis-like phenomena at the time of use, and unpleasant after-effects. Our results are consistent with the hypothesis that cannabis use is a risk factor for full psychosis in this group. Copyright (c) 2006 S. Karger AG, Basel

Editorial Board

Source at http://dx.doi.org/10.1186/s12888-017-1345-8 Background: The duration of untreated psychosis is determined by both patient and service related factors. Few studies have considered the geographical accessibility of services in relation to treatment delay in early psychosis. To address this, we investigated whether treatment delay is co-determined by straight-line distance to hospital based specialist services in a mainly rural mental health context. Methods: A naturalistic cross-sectional study was conducted among a sample of recent onset psychosis patients in northern Norway (n = 62). Data on patient and service related determinants were analysed. Results: Half of the cohort had a treatment delay longer than 4.5 months. In a binary logistic regression model, straight-line distance was found to make an independent contribution to delay in which we controlled for other known risk factors. Conclusions: The determinants of treatment delay are complex. This study adds to previous studies on treatment delay by showing that the spatial location of services also makes an independent contribution. In addition, it may be that insidious onset is a more important factor in treatment delay in remote areas, as the logistical implications of specialist referral are much greater than for urban dwellers. The threshold for making a diagnosis in a remote location may therefore be higher. Strategies to reduce the duration of untreated psychosis in rural areas would benefit from improving appropriate referral by crisis services, and the detection of insidious onset of psychosis in community based specialist services

The association between delusional-like experiences, and tobacco, alcohol or cannabis use: a nationwide population-based survey

<p>Abstract</p> <p>Background</p> <p>Previous population-based studies have found that delusional-like experiences (DLE) are prevalent in the community, and are associated with a wide range of mental health disorders including substance use. The aim of the study was to explore the association between DLE and three commonly used substances - tobacco, alcohol and cannabis.</p> <p>Methods</p> <p>Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. The Composite International Diagnostic Interview was used to identify DLE, common psychiatric disorders, and substance use. We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors.</p> <p>Results</p> <p>Of 8 773 participants, 8.4% (n = 776) subjects endorsed one or more DLE. With respect to tobacco use, compared to nonusers, DLE were more common in those who (a) had daily use, (b) commenced usage aged 15 years or less, and (c) those who smoked heavily (23 or more cigarettes per day). Participants with cannabis use disorders were more likely to endorse DLE; this association was most prominent in those with an onset of 16 years or younger. In contrast, the pattern of association between DLE versus alcohol use or dependence was less consistent, however those with early onset alcohol use disorders were more likely to endorse DLE probe items.</p> <p>Conclusions</p> <p>While cannabis use disorders have been previously linked with DLE, our findings linking alcohol and tobacco use and DLE suggest that the influence of these substances on psychosis-related outcomes warrants closer scrutiny in longitudinal prospective studies.</p

The psychometric characteristics of the revised depression attitude questionnaire (R-DAQ) in Pakistani medical practitioners: a cross-sectional study of doctors in Lahore

BACKGROUND: Depression is common mental health problem and leading contributor to the global burden of disease. The attitudes and beliefs of the public and of health professionals influence social acceptance and affect the esteem and help-seeking of people experiencing mental health problems. The attitudes of clinicians are particularly relevant to their role in accurately recognising and providing appropriate support and management of depression. This study examines the characteristics of the revised depression attitude questionnaire (R-DAQ) with doctors working in healthcare settings in Lahore, Pakistan. METHODS: A cross-sectional survey was conducted in 2015 using the revised depression attitude questionnaire (R-DAQ). A convenience sample of 700 medical practitioners based in six hospitals in Lahore was approached to participate in the survey. The R-DAQ structure was examined using Parallel Analysis from polychoric correlations. Unweighted least squares analysis (ULSA) was used for factor extraction. Model fit was estimated using goodness-of-fit indices and the root mean square of standardized residuals (RMSR), and internal consistency reliability for the overall scale and subscales was assessed using reliability estimates based on Mislevy and Bock (BILOG 3 Item analysis and test scoring with binary logistic models. Mooresville: Scientific Software, 55) and the McDonald's Omega statistic. Findings using this approach were compared with principal axis factor analysis based on Pearson correlation matrix. RESULTS: 601 (86%) of the doctors approached consented to participate in the study. Exploratory factor analysis of R-DAQ scale responses demonstrated the same 3-factor structure as in the UK development study, though analyses indicated removal of 7 of the 22 items because of weak loading or poor model fit. The 3 factor solution accounted for 49.8% of the common variance. Scale reliability and internal consistency were adequate: total scale standardised alpha was 0.694; subscale reliability for professional confidence was 0.732, therapeutic optimism/pessimism was 0.638, and generalist perspective was 0.769. CONCLUSIONS: The R-DAQ was developed with a predominantly UK-based sample of health professionals. This study indicates that this scale functions adequately and provides a valid measure of depression attitudes for medical practitioners in Pakistan, with the same factor structure as in the scale development sample. However, optimal scale function necessitated removal of several items, with a 15-item scale enabling the most parsimonious factor solution for this population