A growing body of literature has linked atypical antipsychotics (AAPs) to an increased propensity for weight gain and metabolic disturbances, including type 2 diabetes. While weight gain is a leading risk factor for diabetes, evidence suggests that AAPs may influence glucose homeostasis independently of changes in adiposity. These ‘direct’ drug effects have been consistently supported by animal models, where following even a single dose of certain AAPs immediate effects are observed with noted perturbations on insulin sensitivity, and insulin secretion. However, the mechanisms underlying these effects remain poorly understood. Also, the translational value of the acute dosing rodent model has not been established in humans. As such, we set out to first elucidate mechanisms of these ‘direct’ effects by deconstructing antipsychotic receptor binding profiles using selective antagonists and gold standard clamping techniques to examine effects on glucose metabolism. We also investigated antipsychotic administration directly into the brain in rodents to tease out central vs. peripheral effects on glucose metabolism. Finally, we examined whether the effects of a single dose of olanzapine on glucose metabolism could be replicated in healthy humans, independently of adiposity or the confounding effects of the illness of schizophrenia. Our findings suggest that cholinergic, serotonergic, and dopaminergic pathways may be involved in antipsychotic-induced glucose dysregulation. We also suggest that such effects may be mediated in part through the central nervous system. Our results in humans suggest that acute drug effects may be less pronounced than in rodents, failing to note an effect on insulin sensitivity or secretion, but observing other early perturbations in lipid and glucose metabolism. Taken together, the work here begins to elucidate mechanisms underlying the diabetogenic risk associated with AAPs, findings which have important implications given the widespread use of these drugs, as well as the increased mortality attributable to cardiovascular disease that defines those with schizophrenia.

A growing body of literature has linked atypical antipsychotics (AAPs) to an increased propensity for weight gain and metabolic disturbances, including type 2 diabetes. While weight gain is a leading risk factor for diabetes, evidence suggests that AAPs may influence glucose homeostasis independently of changes in adiposity. These ‘direct’ drug effects have been consistently supported by animal models, where following even a single dose of certain AAPs immediate effects are observed with noted perturbations on insulin sensitivity, and insulin secretion. However, the mechanisms underlying these effects remain poorly understood. Also, the translational value of the acute dosing rodent model has not been established in humans. As such, we set out to first elucidate mechanisms of these ‘direct’ effects by deconstructing antipsychotic receptor binding profiles using selective antagonists and gold standard clamping techniques to examine effects on glucose metabolism. We also investigated antipsychotic administration directly into the brain in rodents to tease out central vs. peripheral effects on glucose metabolism. Finally, we examined whether the effects of a single dose of olanzapine on glucose metabolism could be replicated in healthy humans, independently of adiposity or the confounding effects of the illness of schizophrenia. Our findings suggest that cholinergic, serotonergic, and dopaminergic pathways may be involved in antipsychotic-induced glucose dysregulation. We also suggest that such effects may be mediated in part through the central nervous system. Our results in humans suggest that acute drug effects may be less pronounced than in rodents, failing to note an effect on insulin sensitivity or secretion, but observing other early perturbations in lipid and glucose metabolism. Taken together, the work here begins to elucidate mechanisms underlying the diabetogenic risk associated with AAPs, findings which have important implications given the widespread use of these drugs, as well as the increased mortality attributable to cardiovascular disease that defines those with schizophrenia.

Second-generation antipsychotics (SGAs) are prescribed for treatment of psychosis. A major side effect of SGAs is an increased risk of metabolic syndrome (MetS) with symptoms of hypertension, hyperlipidemia, hyperglycemia, and truncal obesity. A clinic in the northeastern United States was not screening patients for MetS when being treated with SGAs. The purpose of this project was to educate staff on MetS risk factors, signs, symptoms, and patient management with a goal to improve their knowledge of MetS. Lewin's change theory provided a conceptual framework for the project. The project question explored the development and evaluation of an educational module on MetS increased staff knowledge. Educational content was guided by current literature and the American Psychiatric Association and American Diabetic Association practice guidelines. Five expert panel members, consisting of 3 psychiatrists, an advance practice nurse, and a registered nurse reviewed the education program and evaluated content using a Likert-type questionnaire. Expert panel evaluations indicated that the module content contained useful clinical information on MetS screening for patients on SGAs. After panel review, the program was presented to 7 clinic staff. Pretest and posttest questionnaires asked 10 multiple choice questions and results were compared. Questions on SGA side effects, MetS complications, prevalence, baseline assessment measures, lab work, and needed collaboration were answered correctly by 6 of the participants pretest and all questions after receiving the education program. The project has the potential to promote positive social change through staff education on MetS screening for patients, thus improving patient outcomes.

Background. Little is known about longitudinal prescribing practices for psychoactive medications for individuals with intellectual disabilities and developmental disabilities (IDDD) who are living in community settings. Methods. Computerized pharmacy records were accessed for 2344 community-based individuals with IDDD for whom a total of 3421 prescriptions were written during a 17-month period of study. Forty-two psychoactive medications were rank ordered in terms of prescription frequency. Results. Fifty-two per cent (52%) of all prescriptions written during the study period were for psychoactive medications. Anticonvulsant, antipsychotic and antidepressant medications were the most commonly filled prescriptions among psychoactive medications. Sixty per cent (62%) of the study population was given prescriptions for more than one psychoactive medication and 36% received three or more psychoactive medications. During the study period there was a statistically significant increase in prescriptions filled for olanzapine, risperidone, valproic acid, and clonazepam whereas prescriptions filled for thioridazine, haloperidol, and benzotropine showed a significant decline (P < 0.05-0.001). Distribution of psychoactive drug class by age showed that the majority of prescriptions were filled for individuals between 20 and 50 years with the exception of prescriptions for psychostimulants which peaked for individuals prior to 20 years. Conclusions. (1) Analysis of pharmacy billing records provides a method for assessing prescribing patterns of psychoactive medications in community-based individuals with IDDD. (2) Polypharmacy for psychoactive medications is prevalent in this setting. (3) The second-generation antipsychotic medications are prominently represented by an increasing number of filled prescriptions during the study period.