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.
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.
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 ...
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...
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.
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.
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.
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.
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.
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 ...
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...
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.
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.
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.
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