Rhabdomyolysis reported for children and adolescents treated with antipsychotic medicines: a case series analysis

published_or_final_versio

Rhabdomyolysis reported for children and adolescents treated with antipsychotic medicines: a case series analysis

published_or_final_versio

Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone

Data on baseline (antipsychotic-naïve) age, weight, and height and change in these over three subsequent follow up time points up to 313.6 days (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 subsamples, results are reported from the white Arabs (N=144). Age and gender-normed BMI-standardised 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 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 weight, adjusting for height, age, gender and diagnosis (A/G, P=0.035, β=-3.62, compared to G/G). rs1137101 (G/G, P=0.018, OR=4.13 compared to A/A) and rs1805094 C-allele carriers (P=0.019, OR=0.51) showed nominally significant associations with change in BMI z categories. Our data support and replicate previous relevant associations for these variants including with weight gain on risperidone, whilst being the first to report such associations in those of Arab ethnicity

Review on the current use of antipsychotic drugs in children and adolescents

Antipsychotic (neuroleptic) drugs are used in the treatment of various psychiatric disorders in children and adolescents. There is a lack of information about the efficacy and safety of antipsychotics in young people. Much of the information available is extrapolated from adult studies; in particular, little is known about the long-term effects of these drugs on the development of the central nervous system. Over the last two decades, typical antipsychotics have largely been replaced by atypical antipsychotics. With this increase in use of atypical antipsychotic drugs, there has been growing concern about the appropriate use of these drugs and the fact that they appear to be associated with metabolic abnormalities such as weight gain, diabetes and related cardiovascular effects. This paper provides a review of current practice and evidence based use of antipsychotic drugs in children.link_to_OA_fulltex

Pharmacogenetics of weight gain in young people treated with Risperidone

Oral Presentation - Paediatrics – Mental and General HealthConference Theme: Applying pharmacoepidemiology to improve health care in AsiaAim/Objective: To investigate the association between weight gain and specifi c genotypes in young people treated with risperidone. • To genotype three specifi c genes (HTR2c receptors, LEP and LEPR) which are thought to be likely candidates for association between risperidone and weight gain. • To assess the association between the genotypes of each gene and weight gain. Methods: A retrospective multicentre study was conducted in outpatient mental health clinics/hospitals in the UK and the Kingdom of Saudi Arabia. Analysis was undertaken using TaqMan technology for genotyping and for statistical analysis, SPSS 21 for Windows was used. Results: 200 patients were genotyped, and 197 genotypes were successfully “Called”. All genotyping passed Hardy-Weinberg checking. For all genes, we found no signifi cant association with risperidone –induced weight gain after controlling for baseline weight, age, diagnosis and ethnicity. Signifi cant association was found between baseline BMI-Z, patients with a lower baseline BMI gaining more weight; age at onset of risperidone treatment (p<0.005), younger patients tending to gain more weight (p<0.005) for all 5 SNPs tested, and a signifi cant association between weight gain and ethnicity, individuals of Arab origin being more likely to gain weight than Caucasians (p=0.011- p=0,014) for all SNPs. No association with gender was found for any genotypes. Conclusion: In this sample there does not appear to have been a signifi cant association with risperidone-induced weight gain and any of the genotypes tested. Further studies exploring ethnic variations and age at onset of treatment are warranted, and a larger sample may have yielded more signifi cant results