Bridging Community Mental Health and Primary Care to Improve Medication Monitoring and Outcomes for Patients With Mental Illness Taking Second-Generation Antipsychotics-Phase 2: Quality Improvement Initiative Over 15 Months.

Objective: To evaluate the effectiveness of a quality improvement (QI) initiative to improve family medicine residents' metabolic monitoring of second-generation antipsychotics (SGAs) for patients comanaged across nonintegrated community mental health and family medicine clinics.Methods: Patients were aged ≥ 18 years seen by family medicine residents and prescribed at least 1 SGA (N = 175). Preparative and scheduled QI interventions were nonblinded and included collaboration across organizations, education, and monthly interprofessional care conferences. The QI outcome included evaluation of pre-post metabolic monitoring laboratory data over the 15-month study period. A subset of patients (n = 26) was reviewed at least once at monthly interprofessional care conferences. Patients were stratified by diagnosis of diabetes (n = 45) and no diabetes (n = 130) at baseline. Analyses of the QI intervention outcomes were framed by the time period of monthly care conferences (January 31, 2019-April 30, 2020) and compared to baseline (the historical time period) (October 31, 2017-January 29, 2019).Results: Improved adherence in glycated hemoglobin (HbA1c) (P = .042) and lipid (P < .001) monitoring per guidelines from baseline to follow-up was seen in the total patient population (N = 175). Patients without diabetes (n = 130) had significant improvement (P = .001) in HbA1c monitoring from baseline to follow-up. The subgroup of patient cases that were discussed at a care conference showed no significant improvement in HbA1c or lipid monitoring.Conclusion: Preparative and scheduled QI interventions provided family medicine residents powerful reminders of the SGA monitoring guidelines that improved the metabolic monitoring behaviors for all patients on SGAs.Prim Care Companion CNS Disord. 2023;25(3)22m03432. Author affiliations are listed at the end of this article.

Detailed assessment and risk factor analysis of corticosteroid-induced psychiatric disorders in pediatric, adolescent, and young adult patients undergoing induction or consolidation therapy for hematologic malignancy.

BACKGROUND: Corticosteroid-induced psychiatric disorders (CIPDs) represent an adverse effect that can cause severe emotional and behavioral problems. The aim of the present study was to assess the incidence and risk factors of CIPDs. METHODS: A retrospective analysis of 92 pediatric and young adult patients with hematologic malignancies was conducted. RESULTS: The incidence of CIPDs in patients receiving a treatment regimen with prednisolone or dexamethasone was 64.9% and 77.5%, respectively, both of which were significantly higher than that in patients not receiving corticosteroids. Independent risk factors and adjusted odds ratios (95% confidence intervals) related to severe CIPD were 2.15 (1.11-4.18) for dexamethasone (using prednisolone as the reference) and 0.81 (0.75-0.87) for age, suggesting that the odds increase with decreasing age. Frequently observed symptoms, respectively in terms of behavioral and emotional problems were defiance, crying, psychomotor excitement, dysphoria, irritability, and depression. To our knowledge, this is the first report to mention the risk factors and characteristics for clinical symptoms of CIPDs during the developmental process. CONCLUSIONS: Healthcare professionals should predict and prepare for psychiatric adverse events prior to chemotherapy in the clinical settings, especially in patients in younger age and receiving a treatment regimen with dexamethasone.

Assessment of psychiatric and behavioral adverse effects of antiepileptic drugs monotherapy: Could they have a neuroendocrine correlation in persons with epilepsy?

OBJECTIVE: The study investigated overall adverse event (AE) burden and specifically psychiatric and behavioral side effects (PBAEs) in persons with epilepsy (PWE) on antiepileptic drugs (AEDs) monotherapy. It also assessed their correlation with neuroendocrine and oxidative stress biomarkers. METHODS: This cross-sectional observational study was conducted at a tertiary care hospital between 2016 and 2018. Persons with epilepsy above 18 years on monotherapy of levetiracetam (LEV) and conventional AEDs {carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA)} for at least 6 months were enrolled. Validated questionnaires, 'Mini-International Neuropsychiatric Interview (MINI 7.02)', 'Depression, Anxiety, and Stress Scale 21 (DASS-21)', 'Buss-Perry Aggression Questionnaire (BPAQ)', 'patient-weighted Quality of life Index in Epilepsy (QOLIE-10)', 'Pittsburgh Sleep Quality Index (PSQI)', and 'Liverpool Adverse Events Profile (LAEP)' were used to assess the PBAEs, quality of life, sleep quality, and AE profile. A subgroup of PWE recruited consecutively were considered for estimation of the following neuroendocrine biomarker levels: brain-derived neurotrophic factor (BDNF), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and total antioxidant capacity (TAC) which were then correlated with scores of above questionnaires. RESULTS: After screening 220 PWE, 163 PWE (58 on LEV and 105 on conventional AEDs) with a mean age of 29 ±â€¯10 years were enrolled. Mini-International Neuropsychiatric Interview revealed that LEV group had higher association with PBAEs and lower quality of sleep compared to conventional AEDs (p = 0.032 and 0.046, respectively). Other scales did not show significant difference between LEV and conventional AEDs. In the subset of PWE (n = 74, 36 on LEV and 38 on conventional AEDs), LEV group had more association with the PBAEs (p = 0.010), higher physical aggression and anger components of BPAQ (p = 0.03 and 0.02, respectively), and more AE (p = 0.049) than conventional AED group. However, there was no significant difference in neuroendocrine biomarker levels. CONCLUSION: Levetiracetam had a higher association with PBAEs and more AE when compared to conventional AEDs. There was no differential correlation of AEDs with the following neuroendocrine markers: BDNF, HVA, 5-HIAA, and TAC. These facts necessitate exploration of other mechanisms for LEV-induced PBAEs.

Increased Risk for New-Onset Psychiatric Adverse Events in Patients With Newly Diagnosed Primary Restless Legs Syndrome Who Initiate Treatment With Dopamine Agonists: A Large-Scale Retrospective Claims Matched-Cohort Analysis.

STUDY OBJECTIVES: Published literature documents increased risk for psychiatric adverse events (P-AEs) following dopamine agonist (DA) initiation for treatment of primary restless legs syndrome (RLS). We examined the association between DA initiation and subsequent new-onset P-AEs among patients with a new diagnosis of RLS who had no history of psychiatric disorder or DA use. METHODS: Selected were adults (age 18 years or older) enrolled through United States employer-sponsored plans and Medicare Advantage from 7/1/2008-12/31/2014, with ≥ 2 years of claims data preceding their first RLS diagnosis ("preindex period"). Excluded were those with psychiatric diagnoses (International Classification of Diseases, Ninth Revision [ICD-9] 290-319) or DA use during the preindex period, and those with possible secondary RLS. Patients who initiated (DA+) versus did not initiate (DA-) DAs were matched 1:1 on age at index RLS diagnosis, sex, geographic region, and employment status, and preindex period comorbid illness burden and number of non-DA drug fills. Using a validated ICD-9-based severity-of-illness psychiatric disorder classification system, we compared likelihoods of new-onset P-AEs between matched pairs during parallel follow-up periods. RESULTS: Identified were 889 matched pairs. Compared with their DA- counterparts, DA+ patients were nearly two times more likely to experience development of any P-AE (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.31-2.24, P < .0001); and similarly more likely to experience the development of a severe (OR 1.68, 95% CI 1.03-2.86, P = .04), moderately severe (OR 1.63, 95% CI 1.17-2.29, P = .004), or mild (OR 1.72, 95% CI 1.12-2.65, P = .01) P-AE. CONCLUSIONS: Compared to DA- matched control patients, patients in whom RLS was newly diagnosed and who initiated de novo DAs demonstrated significantly increased risk for subsequent development of P-AEs of any severity. CITATION: Hankin C, Lee D, Garcia-Borreguero D, Wang Z. Increased risk for new-onset psychiatric adverse events in patients with newly diagnosed primary restless legs syndrome who initiate treatment with dopamine agonists: a large-scale retrospective claims matched-cohort analysis. J Clin Sleep Med. 2019;15(9): 1225-1232.

Varenicline and Nicotine Replacement Use Associated With US Food and Drug Administration Drug Safety Communications.

Importance: Drug safety communications released by the US Food and Drug Administration (FDA) are often based on limited evidence on safety signals after approval. Varenicline may serve as a relevant case study because it was the target of several FDA communications in 2008 and 2009; ultimately, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) dismissed safety concerns on increased suicidal thoughts and aggressive and erratic behavior on December 16, 2016. Objective: To examine the association between FDA drug safety communications and the use of varenicline. Design, Setting, and Participants: Retrospective, longitudinal, cross-sectional study of Veterans Health Administration (VHA) outpatient data from October 1, 2001, through December 31, 2018, and Medicaid drug state use data from July 1, 2006, through September 30, 2018, on varenicline prescribing. Main Outcomes and Measures: Prescribing records for varenicline and nicotine replacement therapy (NRT) in the VHA were extracted, and the number of unique varenicline and NRT users in the VHA per quarter was measured. An interrupted time series analysis was performed to describe the association between FDA safety warnings and the use of varenicline and NRT. To test the generalizability of the findings, similar analyses were conducted using the number of prescriptions reimbursed for varenicline by Medicaid every quarter in 2006-2018. Results: After its addition to the VHA national drug formulary in January 2007, varenicline use presented a steady increase, reaching a peak of 32 581 quarterly unique users in the first quarter of 2008. Within 12 months of the February 1, 2008, public health advisory, quarterly varenicline use in VHA patients decreased by 68.7% (from 32 581 to 10 182 patients; P < .001 for slope change), and NRT use increased by 32.1% (from 55 728 to 73 629 patients; P < .001 for slope change). In Medicaid prescriptions, varenicline use decreased by 38.0% (from 109 308 to 67 761 prescriptions; P < .001 for slope change) within 12 months of the 2008 public health advisory. Twelve months after the publication of the EAGLES trial, which showed no significant increase in psychiatric/behavioral effects with varenicline relative to NRT, use of varenicline increased by 42.7% in VHA patients (from 9251 to 13 199 patients; P = .01 for slope change) and by 26.0% in Medicaid prescriptions (112 063 to 141 122; P = .26 for slope change ). Conclusions and Relevance: With use of varenicline as a case study, early communications from the FDA and VHA followed by a labeling change appeared to be associated with a considerable decrease in drug use, which may have been associated with negative public health consequences.

Effect of reduced use of organic solvents on disability pension in painters.

OBJECTIVE: To investigate whether the decreased use of paints based on organic solvents has caused a decreased risk for neuropsychiatric disorders in painters by studying their incidence in disability pensions. METHODS: The incidence of disability pension in Swedish painters who had participated in health examinations between 1971 and 1993 was studied through linkage with Swedish registers of disability pension over 1971-2010 and compared with the incidence in other construction workers as woodworkers, concrete workers and platers. When phasing out began in the 1970s, about 40% of paints were based on organic solvents and it had decreased to 4% in 1990s. The analysis was adjusted for age, time period, body mass index and smoking. RESULTS: The painters (n=23 065) had an increased risk of disability pension due to neurological diagnosis (n=285, relative risk (RR) 1.92, 95% CI 1.67 to 2.20) and psychiatric diagnosis (n=632, RR=1.61, 95 % CI 1.42 to 1.82). For neurological disorders there was a time trend with a continuously decreasing risk from 1980 onwards, but there was no such trend for psychiatric disorders. CONCLUSIONS: High exposure to organic solvents increased the risk for disability pension in neurological disorders, and the risk decreased when the use of organic solvents decreased. The painters also had an increased risk of disability pension due to psychiatric disorders, but the causes have to be further investigated.

How do smoking cessation medicines compare with respect to their neuropsychiatric safety? A protocol for a systematic review, network meta-analysis and cost-effectiveness analysis.

INTRODUCTION: Cigarette smoking is one of the leading causes of early death in the UK and worldwide. Public health guidance recommends the use of varenicline, bupropion and nicotine replacement therapy (NRT) as smoking cessation aids in the UK. Additionally, the first electronic cigarette has been licensed for use as a smoking cessation medicine. However, there are ongoing concerns about the safety of these medicines. We present a protocol for a systematic review and network meta-analysis (NMA) to determine how these smoking cessation medicines compare to each other with respect to their neuropsychiatric safety in adult smokers. Secondary aims include updating the evidence regarding the effectiveness and cardiovascular safety of these medicines for use in a cost-effectiveness analysis. METHODS AND ANALYSIS: We will include randomised controlled trials and observational studies with control groups comparing monotherapy with varenicline, bupropion, NRT or electronic cigarette and combination therapies to each other, placebo or usual care. The primary composite safety outcome will be serious adverse events, defined as events that resulted in death, were life threatening, required hospitalisation or resulted in significant disability or congenital/birth defect. The preferred effectiveness outcome will be sustained smoking cessation defined as abstinence for a minimum of 6 months as determined by biochemical validation. We will include trials identified by previous reviews and search relevant databases for newly published trials as well as contacting study authors to identify unpublished information. We will conduct fixed-effect and random-effect meta-analyses for each pairwise comparison of treatments and outcome; where these estimates differ, we will consider reasons for heterogeneity, quantified using the between-study variance (τ2). For each outcome, we will construct a NMA in a Bayesian framework which will be compared with the pair-wise results, allowing us to rank treatments. The effectiveness estimates from the NMA will be entered into a probabilistic economic model. ETHICS AND DISSEMINATION: Ethics approval is not required for this evidence synthesis study as it involves analysis of secondary data from randomised controlled trials and observational studies. The review will make an important contribution to the knowledge base around the effectiveness, safety and cost-effectiveness of smoking cessation medicines. Results will be disseminated to the general public, healthcare practitioners and clinicians, academics, industry and policy makers. PROSPERO REGISTRATION NUMBER: CRD42016041302.

Khat use and related addiction, mental health and physical disorders: the need to address a growing risk.

Khat use is a drug problem characteristic of the Eastern Mediterranean Region, which is a widespread culturally accepted practice in some countries and is becoming more prevalent in others. Although limited use may not be accompanied by serious consequences, prolonged exposure could lead to dependence, psychosis and other psychiatric disorders and physical conditions such as hypertension, cardiovascular complications, sexual dysfunction, hepatoxicity and reduced birth weight of infants born to khat-chewing mothers. The widespread use and its burden on health and economy has raised concerns in the Region, although the extent of the problem is not well assessed. Additionally, most countries do not have a clear policy and plan with regard to khat use, and therefore there is hardly any structured prevention and treatment plan in place to respond to the problem. This review presents a picture of the extent of the problem, elaborates on related existing research initiatives and international treaties, policies and health service provisions, and outlines best policy and programme interventions in khat-use countries.

Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

CONTEXT: Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. OBJECTIVE: The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. DESIGN: An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients and Participants, and Intervention: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. RESULTS: The panel identified a 70-100% probability that polybrominated diphenyl ether and organophosphate exposures contribute to IQ loss in the European population. Polybrominated diphenyl ether exposures were associated with 873,000 (sensitivity analysis, 148,000 to 2.02 million) lost IQ points and 3290 (sensitivity analysis, 3290 to 8080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis, €1.58 billion to €22.4 billion). Organophosphate exposures were associated with 13.0 million (sensitivity analysis, 4.24 million to 17.1 million) lost IQ points and 59 300 (sensitivity analysis, 16,500 to 84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis, €46.8 billion to €194 billion). Autism spectrum disorder causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis, 126-631) attributable cases at a cost of €199 million (sensitivity analysis, €79.7 million to €399 million). Attention-deficit hyperactivity disorder causation by multiple EDCs was assigned a 20-69% probability, with 19 300 to 31 200 attributable cases at a cost of €1.21 billion to €2.86 billion. CONCLUSIONS: EDC exposures in Europe contribute substantially to neurobehavioral deficits and disease, with a high probability of >€150 billion costs/year. These results emphasize the advantages of controlling EDC exposure.

Acute and long-term psychiatric side effects of mefloquine: a follow-up on Danish adverse event reports.

BACKGROUND: The aim of the study was to explore the profile of acute and long-term psychiatric side effects associated with mefloquine. METHODS: Subjects (n = 73) reported to a Danish national register during five consecutive years for mefloquine associated side effects were included. Acute psychiatric side effects were retrospectively assessed using the SCL-90-R and questions based on Present State Examination (PSE). Subjects reporting suspected psychotic states were contacted for a personal PSE interview. Electronic records of psychiatric hospitalizations and diagnoses were cross-checked. Long-term effects were evaluated with SF-36. SCL-90-R and SF-36 data were compared to age- and gender matched controls. RESULTS: In the SCL-90-R, clinically significant scores for anxiety, phobic anxiety and depression were found in 55%, 51%, and 44% of the mefloquine group. Substantial acute phase psychotic symptoms were found in 15% and were time-limited. Illusions/hallucinations were more frequently observed among women. Cases of hypomania/mania in the acute phase were 5.5%. Significant long-term mental health effects were demonstrated for the SF-36 subscales mental health (MH), role emotional (RE), and vitality (VT) in the mefloquine group compared to matched controls. CONCLUSION: The most frequent acute psychiatric problems were anxiety, depression, and psychotic symptoms. Data indicated that subjects experiencing acute mefloquine adverse side effects may develop long-term mental health problems with a decreased sense of global quality of life with lack of energy, nervousness, and depression.

Managing the risks of ADHD treatments.

Pharmacotherapy of attention deficit-hyperactivity disorder (ADHD) is a well-established and effective treatment modality. However, ADHD medications are not without side effects. Understanding the prevalence of adverse events and effective management of risks associated with stimulants and other medications used to treat ADHD is central to broad applicability and effective treatment. This review discusses the literature on the prevalence of adverse events and management strategies employed. We searched online MEDLINE/PubMed and Cochrane databases for articles using several keywords relating to adverse events associated with ADHD medication management. We discuss the relevant data on the significance and prevalence of side effects and adverse events, highlight recent updates in the field, and suggest approaches to clinical management.

Compensation for occupational neurological and mental disorders.

Standards for the recognition of occupational diseases (ODs) in Korea were established in 1954 and have been amended several times. In 2013, there was a significant change in these standards. On the basis of scientific evidence and causality, the International Labour Organization list, European Commission schedule, and compensated cases in Korea were reviewed to revise the previous standards for the recognition of ODs in Korea. A disease-based approach using the International Classification of Diseases (10th version) was added on the previous standards, which were agent-specific approaches. The amended compensable occupational neurological disorders and occupational mental disorders (OMDs) in Korea are acute and chronic central nervous system (CNS) disorders, toxic neuropathy, peripheral neuropathy, manganese-related disorders, and post-traumatic stress disorder. Several agents including trichloroethylene (TCE), benzene, vinyl chloride, organotin, methyl bromide, and carbon monoxide (CO) were newly included as acute CNS disorders. TCE, lead, and mercury were newly included as chronic CNS disorders. Mercury, TCE, methyl n-butyl ketone, acrylamide, and arsenic were newly included in peripheral neuropathy. Post-traumatic stress disorders were newly included as the first OMD. This amendment makes the standard more comprehensive and practical. However, this amendment does not perfectly reflect the recent scientific progress and social concerns. Ongoing effort, research, and expert consensus are needed to improve the standard.

Neuropsychiatric adverse events associated with statins: epidemiology, pathophysiology, prevention and management.

Statins, or 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, such as lovastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, rosuvastatin and pitavastatin, are cholesterol-lowering drugs used in clinical practice to prevent coronary heart disease. These drugs are generally well tolerated and have been rarely associated with severe adverse effects (e.g. rhabdomyolysis). Over the years, case series and data from national registries of spontaneous adverse drug reaction reports have demonstrated the occurrence of neuropsychiatric reactions associated with statin treatment. They include behavioural alterations (severe irritability, homicidal impulses, threats to others, road rage, depression and violence, paranoia, alienation, antisocial behaviour); cognitive and memory impairments; sleep disturbance (frequent awakenings, shorter sleep duration, early morning awakenings, nightmares, sleepwalking, night terrors); and sexual dysfunction (impotence and decreased libido). Studies designed to investigate specific neuropsychiatric endpoints have yielded conflicting results. Several mechanisms, mainly related to inhibition of cholesterol biosynthesis, have been proposed to explain the detrimental effects of statins on the central nervous system. Approaches to prevent and manage such adverse effects may include drug discontinuation and introduction of dietary restrictions; maintenance of statin treatment for some weeks with close patient monitoring; switching to a different statin; dose reduction; use of ω-3 fatty acids or coenzyme Q10 supplements; and treatment with psychotropic drugs. The available information suggests that neuropsychiatric effects associated with statins are rare events that likely occur in sensitive patients. Additional data are required, and further clinical studies are needed.

The ACT Mental Health Service for People with Intellectual Disability, 10 years on.

OBJECTIVE: Our aim is to describe the establishment and first 10 years' experience of a specialist team for providing psychiatric services to individuals with intellectual disability. CONCLUSION: This service is unique in Australia in providing a comprehensive mental health assessment and treatment service to this population in a defined catchment area. It can serve as a model for service development in this area of unmet need.

[Assessment on the criminal responsibility of drug-induced mental disorders: a questionnaire survey].

OBJECTIVE: To understand the assessment on the criminal responsibility of drug-induced mental disorders and judicial experts' opinions. METHODS: The judicial experts from institutes of forensic psychiatry in Shanghai were selected. They were asked to finish a self-made questionnaire of assessment on the criminal responsibility of drug-induced mental disorders by letters and visits. RESULTS: Most of experts knew the special regulation, "not suitable for evaluation" towards the criminal responsibility of drug-induced mental disorders of the guideline promulgated by Ministry of Justice. Before and after the guideline was issued, no expert made a no-responsibility opinion in such cases. After the guideline was issued, some experts made a full-responsibility or limited-responsibility opinion in such cases. There was a little disagreement among the experts in the case that the crime was unrelated with mental symptoms or the criminals used drugs even though he knew it could induced insanity. But there were still many obvious disagreements among experts in the case that crime was related to such symptoms and person was no ability to debate. Most experts agreed to settle the disagreements with improved legislative perfection. CONCLUSION: Most experts are not strictly complying with the assessment guidelines during their practice, and there is still an obvious disagreement towards the criminal responsibility of drug-induced mental disorders.

Which drug-induced side effects would be tolerated in the prospect of seizure control?

There is ample evidence that side effects of antiepileptic pharmacotherapy negatively affect quality of life, adherence, and long-term retention. The study was set up to evaluate the anticipated tolerance of common side effects provided that a 50% or 100% reduction of seizure frequency would be achieved. An anonymous inquiry in 79 consecutive patients with epilepsy comprised questions regarding the severity of epilepsy/seizures and the perceived impact of seizures and drug treatment on daily functioning and a 10-tiered rating which assesses 11 common behavioral/psychiatric, cognitive, physiological, or physical side effects according to the degree to which they would be tolerated. Least acceptance was evident for psychiatric side effects followed by cognitive, physiological, and physical side effects. Weight gain and tiredness were the most tolerated side effects. The overall low acceptance of negative side effects was slightly higher in the case of a 100% vs. 50% seizure frequency reduction (28% vs. 21% of the maximum toleration score regarding all side effects). Surely, there is a trade-off between the severity of epilepsy, seizure control, and the acceptance of adverse treatment effects. However, the data disclose that psychiatric and cognitive side effects are least accepted. Thus, consideration of individual tolerance and monitoring of side effects in addition to seizures may increase adherence and therapy success.

Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England.

BACKGROUND: Varenicline (Champix(®)), launched in the UK in December 2006, is indicated for the treatment of smoking cessation in adults (≥18 years of age). In 2008, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK issued a warning suggesting that varenicline was associated with disparate neuropsychiatric symptoms, including depression, suicidal thoughts and behaviour. In response to this regulatory warning, the Drug Safety Research Unit conducted a modified prescription-event monitoring (M-PEM) study to monitor the safety of varenicline. OBJECTIVE: The aim of this study was to estimate the incidence and examine the pattern of neuropsychiatric events reported to general practitioners (GPs) in England during the immediate postmarketing period for varenicline. METHODS: A postmarketing surveillance study was conducted using the observational cohort technique of M-PEM. Patients were identified from dispensed prescriptions issued by primary care physicians between December 2006 and March 2007. Data on exposure, previous history of psychiatric illness and events reported during and after treatment were collected from questionnaires. In order to determine whether hazards for neuropsychiatric events of interest (depression, anxiety, aggression, suicidal ideation, non-fatal self-harm) were non-constant over time (which could indicate a possible association with the drug), the pattern of events was examined by plotting the smoothed hazard function estimate and then fitting a Weibull model. The Weibull model shape parameter (ß) and 95 % confidence interval were used as a test for a non-constant hazard function (where a value of 1 indicates a constant hazard over time). In addition to this analysis, the difference in incidence densities (IDs) between month 1 and months 2-3 were calculated and compared. RESULTS: The cohort comprised of 12,159 patients (median age 47 years [interquartile range 19]; 56.9 % [n = 6924 female]). The number of events reported during treatment, reason for stopping, adverse drug reactions (ADRs), and the p-value for the Weibull shape parameter were as follows: depression (n = 94; 42; 19; p = 0.144); anxiety (n = 94; 49; 9; p = 0.009); aggression (n = 7; 4; 2; p = 0.465); suicidal ideation (n = 8; 4; 1; p = 0.989) and non-fatal self-harm (n = 5; 1; 0; p = 0.771). No differences in the IDs between months 1 and months 2-3 were found for any of the events. CONCLUSION: Whilst between 7 and 17 % of neuropsychiatric events were attributed to the drug by GPs and approximately 20-50 % were given as reasons for stopping, no signal was raised using the ID differences approach, and only anxiety was flagged as a potential signal for an ADR using the Weibull model. The signal for anxiety requires further evaluation to determine whether the drug plays a part in the development of anxiety or whether it is a withdrawal symptom caused by smoking cessation. Analysis methods will lack power when the numbers of events are low even when a large number of participants are included in the study.

Clinician uptake of obesity-related drug information: a qualitative assessment using continuing medical education activities.

BACKGROUND: Medications necessary for disease management can simultaneously contribute to weight gain, especially in children. Patients with preexisting obesity are more susceptible to medication-related weight gain. How equipped are primary care practitioners at identifying and potentially reducing medication-related weight gain? To inform this question germane to public health we sought to identify potential gaps in clinician knowledge related to metabolic adverse drug effects of weight gain. METHODS: The study analyzed practitioner responses to the pre-activity questions of six continuing medical education (CME) activities from May 2009 through August 2010. RESULTS: The 20,705 consecutive, self-selected respondents indicated varied levels of familiarity with adverse metabolic effects and psychiatric indications of atypical antipsychotics. Correct responses were lower than predicted for drug indications pertaining to autism (-17% predicted); drug effects on insulin resistance (-62% predicted); chronic disease risk in mental illness (-34% predicted); and drug safety research (-40% predicted). Pediatrician knowledge scores were similar to other primary care practitioners. CONCLUSIONS: Clinicians' knowledge of medication-related weight gain may lead them to overestimate the benefits of a drug in relation to its metabolic risks. The knowledge base of pediatricians appears comparable to their counterparts in adult medicine, even though metabolic drug effects in children have only become prevalent recently.

Safety and effectiveness of a nurse-led outreach program for assessment and treatment of chronic hepatitis C in the custodial setting.

BACKGROUND: The global burden of disease attributable to chronic hepatitis C virus (HCV) is very large, yet the uptake of curative antiviral therapies remains very low, reflecting the marginalized patient population and the arduous nature of current treatments. METHODS: The safety and effectiveness of a nurse-led model of care of inmates with chronic HCV was evaluated in 3 Australian correctional centers. The model featured protocol-driven assessment, triage, and management of antiviral therapy by specifically trained nurses, with specialist physician support utilizing telemedicine. Outcomes were evaluated qualitatively with key informant interviews, and quantitatively with patient numbers completing key clinical milestones and adverse events. RESULTS: A total of 391 patients with chronic HCV infection were enrolled, of whom 141 (36%) completed the clinical and laboratory evaluations for eligibility for antiviral therapy over 24 months. Treatment was initiated in 108 patients (28%), including 85 (79%) triaged for specialist review conducted by telemedicine only. The demographic and clinical characteristics of the patients who entered the model and completed workup and those who initiated treatment featured a high prevalence of individuals of indigenous background, injection drug users, and those with psychiatric disorder. Serious adverse events occurred in 13 of 108 treated patients (12%) with discontinuation in 8 (7%). The sustained virologic response rate among those with complete follow-up data (n=68) was 69%, and by intention-to treat analysis was 44%. CONCLUSIONS: This nurse-led and specialist-supported assessment and treatment model for inmates with chronic HCV offers potential to substantively increase treatment uptake and reduce the burden of disease.