Do antipsychotics increase diabetes risk in children and adolescents?

INTRODUCTION: Glucose dysregulation and type 2 diabetes mellitus (T2DM) are feared antipsychotic drug adverse effects. Despite increasing utilization, data about antipsychotic risk of T2DM in youth are scarce. AREAS COVERED: We conducted a systematic PubMed/MEDLINE search until 15 May 2014 focusing on studies with \u3e/= 20 youths age

Antipsychotics and schizophrenia, and their relationship to diabetes

TOOLS SHAREThe relationship between diabetes and schizophrenia is complex and multifactorial. Disease‐specific effects, environment and antipsychotic medications are all thought to interact and play a role. Citing a case vignette as illustration, Dr Clare Whicher, Dr Sarah Brewster and Professor Richard Holt here analyse the evidence base and provide practical management advice

Safety and tolerability of antipsychotic-mood stabilizer co-treatment in the management of acute bipolar disorder: results from a systematic review and exploratory meta-analysis

Introduction: Mood stabilizer (MS) plus antipsychotic (AP) co-treatment is common in patients with acute bipolar disorder (BD), but adverse effects (AEs) of this strategy have not been systematically reviewed. Areas covered: We conducted a systematic review searching PubMed/MEDLINE and PsycINFO on April 1, 2015 for randomized trials in \u3e= 20 adults with acute manic/mixed or depressed BD comparing MS or AP monotherapy with their combination that reported quantitative AE data. Pooled together, MS+AP versus MS monotherapy (studies = 18, n = 4419) was associated with significantly higher burden regarding 21/53 (39.6%) individual AEs, particularly weight gain-related (5/5 = 100%), extrapyramidal (5/12 = 41.7%) and glucose/lipid-related AEs (3/8 = 37.5%). AP+MS versus AP monotherapy (studies = 3, n = 397) was associated with significantly higher burden regarding 4/21 (19.0%) individual AEs (\u3e= 1 AE, tremor, sedation/somnolence, vomiting). Expert opinion: Efficacy advantages of AP+MS co-treatment versus monotherapy should be balanced with its greater AE burden. AE risk is higher for adding AP to MS (17 additional AEs) than adding MS to an AP, including the particularly concerning cardiometabolic AEs. More data are needed, as only one or two studies provided data for 21/21 (100%) AEs of MS augmentation of AP, and 13/53 (24.5%) AEs of AP augmentation of MS, and as sparse data suggest clinically relevant AE differences across individual AP+MS combinations

Intratumoral dispersion, retention, systemic biodistribution, and clearance of a small-size tumor necrosis factor-α-expressing MIDGE vector after nonviral in vivo jet-injection gene transfer

For nonviral applications of therapeutic DNA, highly efficient and safe vector systems are of crucial importance. In the majority of nonviral approaches plasmid vectors are in use. A novel minimalistic gene expression vector (MIDGE) has been developed to overcome the limitations of plasmid vectors. This small-size double-stranded linear DNA vector has shown improved transgene expression. However, only limited knowledge on uptake, biodistribution, and clearance of this vector exists. In this study we investigated the intratumoral and systemic biodistribution, clearance, and expression kinetics of the tumor necrosis factor (TNF)-{alpha}-carrying MIDGE-CMVhTNF vector in NMRI-nu/nu mice with subcutaneously xenotransplanted human A375 melanoma. Biodistribution was analyzed by quantitative real-time PCR in tumors, blood, and organs 0 to 60 min and 3 to 48 hr after intratumoral jet-injection of 50 {mu}g of MIDGE-CMVhTNF. We examined TNF mRNA expression in tumor tissue and organs, using real-time RT-PCR and TNF-specific ELISA. High levels of MIDGE DNA in the tumor tissue demonstrated efficient gene transfer of the small-size vector, resulting in inhomogeneous DNA dispersion and efficient transgene expression. Intratumoral jet-injection of the vector DNA was accompanied by leakage into the blood circuit and appearance in peripheral organs within 5 min to 6 hr. However, this did not lead to TNF-α expression and was followed by rapid vector clearance resulting in the disappearance of MIDGE DNA 24 hr after gene transfer. These data provide important new information for the kinetics of intratumoral and systemic biodistribution and rapid clearance of the jet-injected small-size MIDGE vector