Frank Besag - Academia.edu (original) (raw)

Papers by Frank Besag

Drug Safety, Dec 20, 2022

Pediatric Drugs, May 27, 2019

Pharmacoepidemiology and Drug Safety, Jun 30, 2017

Complex Psychiatry, 2018

Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequ... more Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5–323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17–17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in the subsamples, results are reported for the white Arab population (n = 144). Age- and gender-normed body mass index (BMI)-standardized z scores (BMI z) were calculated (LMSgrowth program). Linear regression was performed for baseline weight and BMI z, while change in BMI z was assessed using random effects ordered logistic regression. The following single nucleotide polymorphisms (SNPs) were analyzed: rs7799039 in the LEP promoter, rs1805094 (previously rs8179183), rs1137100 and rs1137101 in the LEPR, and rs1414334 in HTR2C. We found a nominally significant association between rs7799309 and baseline wei...

Journal of Autism and Developmental Disorders, 2021

There are many case reports of seizures apparently associated with the prescription of antipsycho... more There are many case reports of seizures apparently associated with the prescription of antipsychotics. This study aimed to examine whether there is an association between the prescription of antipsychotics and incident seizures in individuals with autism spectrum disorder using retrospective data based on patients’ chart review. A cohort study was conducted to compare the rate of incident seizure between 3923 users of antipsychotics with 10,086 users of other psychotropics. This was followed by a self-controlled case series (SCCS) analysis of 149 patients to eliminate the effect of time-invariant confounders. The results showed no evidence of increased risk of seizure after exposure to antipsychotic agents (Hazard Ratio 1.28, 95% CI 0.74–2.19) compared to other psychotropics.

CNS Drugs, 2020

Background: Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associ... more Background: Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available. Objectives: To ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS. Methods: We did a population-based study using data from the Hong Kong Hospital Authority's Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91 to 120 days before the index date. To adjust for potential time-trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications, and acute medical conditions. Results: 297 647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time-trend, and case-crossover adjusted for time-trend and potential confounders analysis were 8.00 (95% confidence interval 3.42-18.69), 5.88 (2.46-14.04), and 4.77 (1.95-11.66). Version Date: 20200812 Conclusions: Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded. Key points • In the cohort analysis of 297 647 antipsychotic users, the incidence risk of NMS was 0.11%. • Recent antipsychotic use was consistently associated with an increased risk of NMS in case-crossover and analyses adjusted for changes in prevalence of antipsychotic exposures over time. The increased risk was observed for a period of about 20 to 40 days before the diagnosis of NMS.

The Lancet Child & Adolescent Health, 2020

Journal of Autism and Developmental Disorders, 2019

Autism spectrum disorder (ASD) is a lifelong disorder. In the UK, risperidone is the only psychot... more Autism spectrum disorder (ASD) is a lifelong disorder. In the UK, risperidone is the only psychotropic medication approved for the management of the behavioural symptoms that may accompany autism. This is a population-based study aimed to provide an evaluation of the changing trend in the incidence and prevalence of ASD and to analyse the pattern of psychotropic medication prescribing in the UK. 20,194 patients with ASD were identified. The prevalence increased 3.3-fold from 0.109 per 100 persons in 2009 to 0.355 per 100 persons in 2016. Approximately one-third of the identified cohort was prescribed at least one psychotropic medication. Although the medications approved to manage the symptoms of ASD are limited, the prescribing of such medications is increasing.

Electroencephalography and Clinical Neurophysiology, 1995

The Journal of Pediatrics, 1995

In this multicenter study, the efficacy and tolerabiUty of lamotrigine were assessed in 285 child... more In this multicenter study, the efficacy and tolerabiUty of lamotrigine were assessed in 285 children less than 13 years of age, recruited from 37 centers in 11 countries. Methods: Pooled data from five open add-on studies have been analyzed. All the cNIdren had treatment-resistant epilepsy and most had two or more seizure types. Seizure frequency and global evaluation were assessed at the end of four successive 12-week periods of therapy. Results: Seizure frequency was reduced by 50% or more in one third of the patients. Lamotrigine was effective in all seizure types examined, particularly for typical and atypical absence seizures. Atonic seizures also responded well. Improvement was well maintained during the treatment period. The maintenance dose had to be adjusted according to concomitant medication; dose ranges were I to 5 mg/kg per day for children taking valproate and 5 to 15mg/kg per day for those not taking valproate. The commonest reported adverse experiences were somnolence, rash, vomiting, and seizure exacerbations. Adverse experiences led to withdrawal of treatment from 36 patients (12.6%). Conclusions: These results indicate that lamotrigine is well tolerated and is effective for a broad range of seizure types, especially absence seizures and atonic seizures.

Epileptic disorders : international epilepsy journal with videotape, 2006

Epileptic disorders : international epilepsy journal with videotape, 2005

In April 2004, a group of physicians with an interest in nonconvulsive status epilepticus represe... more In April 2004, a group of physicians with an interest in nonconvulsive status epilepticus representing a spectrum of opinion met in Oxford, sponsored by the Epilepsy Research Foundation (a charitable organization), to discuss and debate the definition, diagnosis and treatment of nonconvulsive status epilepticus. We felt that such a meeting would be useful, as nonconvulsive status epilepticus is a subject that provokes strong reactions, perhaps largely due to the relative lack of evidence and the surfeit of opinion. The meeting was arranged such that there were formal talks followed by a discussion led by one of the attendees. We present here the extended abstracts of the main talks with the points raised by the discussants. Despite disagreements on certain issues there was much in the way of consensus. First, it was agreed that nonconvulsive status epilepticus is a term that covers a range of disparate conditions with varying prognoses and treatments. The agreed definition was thus ...

Mental Health and Illness Worldwide

Therapeutic Advances in Psychopharmacology

Background: Bipolar disorder (BD) is a cyclic mood disorder characterised by alternating episodes... more Background: Bipolar disorder (BD) is a cyclic mood disorder characterised by alternating episodes of mania/hypomania and depression interspersed with euthymic periods. Lamotrigine (LTG) demonstrated some mood improvement in patients treated for epilepsy, leading to clinical studies in patients with BD and its eventual introduction as maintenance therapy for the prevention of depressive relapse in euthymic patients. Most current clinical guidelines include LTG as a recommended treatment option for the maintenance phase in adult BD, consistent with its global licencing status. Aims: To review the evidence for the efficacy and safety of LTG in the treatment of all phases of BD. Methods: PubMed was searched for double-blind, randomised, placebo-controlled trials using the keywords: LTG, Lamictal, ‘bipolar disorder’, ‘bipolar affective disorder’, ‘bipolar I’, ‘bipolar II’, cyclothymia, mania, manic, depression, depressive, ‘randomised controlled trial’, ‘randomised trial’, RCT and ‘place...

Philosophical Magazine

ABSTRACT

CNS Drugs

Melatonin is widely available either on prescription for the treatment of sleep disorders or as a... more Melatonin is widely available either on prescription for the treatment of sleep disorders or as an over-the-counter dietary supplement. Melatonin has also recently been licensed in the UK for the short-term treatment of jetlag. Little is known about the potential for adverse events (AEs), in particular AEs resulting from long-term use. Concern has been raised over the possible risks of exposure in certain populations including pre-adolescent children and patients with epilepsy or asthma. The aim of this systematic review was to assess the evidence for AEs associated with short-term and longer-term melatonin treatment for sleep disorders. A literature search of the PubMed/Medline database and Google Scholar was conducted to identify randomised, placebo-controlled trials (RCTs) of exogenous melatonin administered for primary or secondary sleep disorders. Studies were included if they reported on both the types and frequencies of AEs. Studies of pre-term infants, studies of < 1 week in duration or involving single doses of melatonin and studies in languages other than English were excluded. Findings from open-label studies that raised concerns relating to AE reports in patients were also examined. Studies were assessed for quality of reporting against the Consolidated Standards of Reporting Trials (CONSORT) checklist and for risk of bias against the Cochrane Collaboration risk-of-bias criteria. 37 RCTs met criteria for inclusion. Daily melatonin doses ranged from 0.15 mg to 12 mg. Subjects were monitored for up to 29 weeks, but most studies were of much shorter duration (4 weeks or less). The most frequently reported AEs were daytime sleepiness (1.66%), headache (0.74%), other sleep-related AEs (0.74%), dizziness (0.74%) and hypothermia (0.62%). Very few AEs considered to be serious or of clinical significance were reported. These included agitation, fatigue, mood swings, nightmares, skin irritation and palpitations. Most AEs either resolved spontaneously within a few days with no adjustment in melatonin, or immediately upon withdrawal of treatment. Melatonin was generally regarded as safe and well tolerated. Many studies predated publication of the CONSORT checklist and consequently did not conform closely to the guidelines. Similarly, only eight studies were judged ‘good’ overall with respect to the Cochrane risk-of-bias criteria. Of the remaining papers, 16 were considered ‘fair’ and 13 ‘poor’ but publication of almost half of the papers preceded that of the earliest version of the guidelines. Few, generally mild to moderate, AEs were associated with exogenous melatonin. No AEs that were life threatening or of major clinical significance were identified. The scarcity of evidence from long-term RCTs, however, limits the conclusions regarding the safety of continuous melatonin therapy over extended periods. There are insufficient robust data to allow a meaningful appraisal of concerns that melatonin may result in more clinically significant adverse effects in potentially at-risk populations. Future studies should be designed to comply with appropriate quality standards for RCTs, which most past studies have not.

Expert Opinion on Pharmacotherapy

ABSTRACT Introduction: Lennox-Gastaut syndrome (LGS) is a chronic, epileptic encephalopathy, char... more ABSTRACT Introduction: Lennox-Gastaut syndrome (LGS) is a chronic, epileptic encephalopathy, characterized by multiple seizure types, distinctive slow spike-wave patterns in the electroencephalogram (EEG), and severe cognitive and behavioral comorbidities. Seizures are typically refractory and long-term prognosis is poor. No antiseizure drug (ASD) is fully effective as a monotherapy. Clobazam (CLB) was licensed in the United States in 2011 as an adjunctive therapy for seizures in LGS. In 2018, a new formulation, CLB oral soluble film (COSF) (AQST-120), was approved by the Federal Drug Administration (FDA) for the same indication. Areas covered: The authors summarize current pharmacological options and guidelines for the management of seizures in LGS and efficacy and safety findings from phase II and III randomized controlled trials of adjunctive CLB in patients with LGS. An open-label extension trial is also considered. A pharmacokinetic comparison of COSF and CLB tablets is also undertaken. Expert opinion: CLB is partly effective as an add-on therapy in treating seizures in LGS. Adverse effects, pharmacokinetic interactions and the potential for tolerance with long-term treatment should be weighed against the clinical benefit when considering the introduction of CLB in this population. COSF has a similar pharmacokinetic profile to CLB tablets and may help to improve adherence to treatment.

Neuropsychiatric Disease and Treatment

Autism is more common in people with epilepsy, approximately 20%, and epilepsy is more common in ... more Autism is more common in people with epilepsy, approximately 20%, and epilepsy is more common in people with autism with reported rates of approximately 20%. However, these figures are likely to be affected by the current broader criteria for autism spectrum disorder (ASD), which have contributed to an increased prevalence of autism, with the result that the rate for ASD in epilepsy is likely to be higher and the figure for epilepsy in ASD is likely to be lower. Some evidence suggests that there are two peaks of epilepsy onset in autism, in infancy and adolescence. The rate of autism in epilepsy is much higher in those with intellectual disability. In conditions such as the Landau-Kleffner syndrome and nonconvulsive status epilepticus, the epilepsy itself may present with autistic features. There is no plausible mechanism for autism causing epilepsy, however. The co-occurrence of autism and epilepsy is almost certainly the result of underlying factors predisposing to both conditions, including both genetic and environmental factors. Conditions such as attention deficit hyperactivity disorder, anxiety and sleep disorders are common in both epilepsy and autism. Epilepsy is generally not a contraindication to treating these conditions with suitable medication, but it is important to take account of relevant drug interactions. One of the greatest challenges in autism is to determine why early childhood regression occurs in perhaps 25%. Further research should focus on finding the cause for such regression. Whether epilepsy plays a role in the regression of a subgroup of children with autism who lose skills remains to be determined.

Neurology, Jan 16, 2018

Should patients with epilepsy be monitored during sleep to prevent sudden unexpected death in epi... more Should patients with epilepsy be monitored during sleep to prevent sudden unexpected death in epilepsy (SUDEP)? The study by van der Lende et al.1 provides additional evidence that the answer is probably yes in certain populations. These investigators compared the incidence of SUDEP at 2 residential centers for adults with severe epilepsy (>90% had convulsive seizures, and ∼50% were on ≥3 antiepileptic drugs). The center with less intensive nocturnal monitoring had a nearly 3-fold higher SUDEP incidence that was not explained by other factors (e.g., seizure severity). Sadly, despite monitoring, supervision, and expert care at both centers, the SUDEP rate remained 2- to 5-fold greater than population-based studies of patients with epilepsy. Unlike some other case-control studies, the incidence of SUDEP was higher among individuals with higher IQ and less benzodiazepine use.