Metabolic Monitoring of Child and Adolescent Patients on Atypical Antipsychotics by Psychiatrists and Primary Care Providers.

BACKGROUND: Antipsychotic drug use in children has doubled from 2001 to 2007 with concomitant increase in obesity. Second-generation antipsychotic (SGA) medication use is associated with weight gain, metabolic derangements, and blood sugar and lipid abnormalities in children. The American Psychiatric Association and the American Diabetes Association have recommended metabolic monitoring guidelines for patients using SGA. STUDY QUESTION: The study objective was to investigate and compare metabolic monitoring for SGA medications in psychiatry (PSY), and pediatrics and family medicine [primary care providers (PCP)] outpatient clinics of a university medical center. STUDY DESIGN: This is a retrospective study of 149 charts of patients newly prescribed with SGA, ages 5-18 years, from their initial visit in the outpatient clinics. MEASURES AND OUTCOMES: Compliance with recommended metabolic monitoring was evaluated for initial and subsequent clinic visits. Parameters included body mass index, waist circumference, blood pressure, fasting plasma glucose, and fasting lipid profile. RESULTS: Of the 149 charts, 110 patients were in PSY and 39 in PCP. The parameter most regularly monitored was body mass index (baseline: PSY 88.3%, PCP 97.4%; 12 weeks: PSY 86.4%, PCP 85.0%; and 24 weeks: PSY 91.8%, PCP 100%). Fasting plasma glucose (baseline: PSY 18.9%, PCP 25.6% and 12 weeks: PSY 8.6%, PCP 10.0%) and fasting lipid profile (baseline: PSY 12.7%, PCP 25.6% and 12 weeks: PSY 7.0%, PCP 10.0%) had low completions rates. No difference was seen in metabolic monitoring by sex or ethnic group. CONCLUSIONS: Metabolic monitoring rate of child and adolescent patients on SGAs was low overall. No statistically significant differences were seen between psychiatry and PCP except a significantly higher rate of fasting plasma glucose level monitoring at baseline among PCP. Limitations to the study include the small sample size obtained for the period investigated and insufficient documentation in some electronic charts. Extending the period studied may increase the statistical significance of the data.

Off-Label Use of Clozapine in Children and Adolescents-A Literature Review.

BACKGROUND: Clozapine is a second-generation antipsychotic typically used for refractory schizophrenia or otherwise psychotic pathology. There are no FDA or manufacturer guidelines for use of clozapine in pediatric population. We investigated the current state of research concerning the use of clozapine in pediatric patients. AREAS OF UNCERTAINTY: We describe consistent calls for more research into the long-term and short-term effects of clozapine use in a young patient population. Despite the strongly supported efficacy, questions concerning clear indications for use and risk-benefit analysis persist. We acknowledge that a more comprehensive meta-analysis would greatly benefit the field. However, this is the first article of its kind for clozapine in recent history, and therefore, serves as a focus and reference point for future, more in-depth analyses. DATA SOURCES: We conducted a search of PubMed, ClinicalKey, PsycINFO, and MEDLINE databases. Keywords used included, in varying combinations: clozapine, off-label, indications, children and adolescent, pediatric, behavioral, suicidality, psychosis, early and very-early onset schizophrenia, side-effect profile, and long-term use. Further criteria and selection are described in Methods below. RESULTS: We describe the documented efficacy of clozapine for the management of refractory psychotic and nonpsychotic symptoms in the pediatric population. The authors highlight the risk of unmanaged early-onset schizophrenia, aggressive or suicidal behavior, and severe nonpsychotic pathology. Unfortunately, these studies are generally small. There is little consistency in when clozapine is prescribed, how long it is administered, and how long patients are followed. Despite the lack of FDA and manufacturer guidelines, clozapine continues to be used for the benefit of young patients. CONCLUSIONS: Indications for prescription of clozapine should be revisited, given the data presented in this manuscript of a low risk-benefit ratio for properly chosen patients. Larger studies should be conducted to provide more statistical power and determine clear guidelines for use, risk of side effects, and long-term adverse events that may arise.

Clozapine-Induced Microseizures, Orofacial Dyskinesia, and Speech Dysfluency in an Adolescent with Treatment Resistant Early Onset Schizophrenia on Concurrent Lithium Therapy.

Clozapine is an atypical antipsychotic used in the treatment of refractory schizophrenia. It has a well-known side effect profile, including agranulocytosis, decreased seizure threshold, and tardive dyskinesia. In addition, numerous case reports have described clozapine-induced stuttering in adults. However, there has been only one previous case report describing it in the adolescent population. In addition, concurrent lithium therapy has been shown to enhance the neurotoxic effects of antipsychotics and lower the seizure threshold. Here, we report on the development of clozapine-induced microseizures, orofacial dyskinesia, and stuttering in a 17-year-old adolescent male with treatment of refractory early onset schizophrenia on clozapine and concurrent lithium therapy. The patient's symptoms of schizophrenia responded well to the clozapine regimen. However, with the escalating dose of clozapine, the patient developed speech dysfluency in the form of stuttering and perioral twitching. An electroencephalogram confirmed seizure activity. Due to similarities with tardive dyskinesia, symptoms of microseizures induced by atypical antipsychotics may not be accurately diagnosed. A multidisciplinary treatment of speech dysfluency is of particular importance in the adolescent schizophrenic patients, who are expected to have longer duration of lifetime exposure to antipsychotics and in whom peer group interaction is crucial for normal personal and social development.

Levetiracetam-induced transaminitis in a young male with traumatic brain injury.

Levetiracetam is a commonly prescribed antiepileptic drug for seizure prophylaxis in patients with traumatic brain injury (TBI). Levetiracetam metabolism has been reported to be non-dependent on hepatic cytochrome P450 (CYP450) isoenzyme system. Furthermore, levetiracetam and its metabolites are reported to be eliminated from systemic circulation via renal excretion. Therefore, due to its well-known renal clearance mechanism with no dosage adjustments recommended for hepatic impairment, levetiracetam is often chosen as the drug of choice in patients with suspected or ongoing hepatic dysfunction. Furthermore, monitoring of liver enzymes is often not considered to be critical in levetiracetam therapy. However, hepatotoxicity is still possible with levetiracetam. Here, we report on an 18-year-old male with TBI who developed transaminitis with levetiracetam therapy which resolved following the discontinuation of levetiracetam. A close monitoring of liver enzymes and early recognition of hepatotoxicity is still necessary and critical to preventing major sequelae stemming from levetiracetam-induced hepatotoxicity.

Concomitant Use of Topiramate Inducing Neutropenia in a Schizophrenic Male Stabilized on Clozapine.

This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient's psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient's laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner.