quetiapine-fumarate and Hyperglycemia

Topics: Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Dyslipidemias; Humans; Hyperglycemia; Quetiapine Fumarate; Risk Assessment; Treatment Outcome; Weight Gain

Bipolar disorder is a complex mental illness that is frequently both under-diagnosed and under-treated. The symptoms of bipolar disorder can be confused with other medical illnesses or drug effects or may even be overlooked entirely as extreme character traits. The consequences of delayed diagnosis or misdiagnosis are potentially devastating, including loss of employment, impaired relationships and a severely impaired quality of life. This article will review the historic perspectives of bipolar disorder, the diagnostic criteria for the phases of the illness, and the pharmacologic options available to treat this condition. Quetiapine, an atypical antipsychotic, will be reviewed indepth. Based on extensive trial data, reviewed in this article, quetiapine is approved by the US Food and Drug Administration for use as monotherapy or as adjunctive therapy with other mood stabilizers for the treatment of acute manic episodes of bipolar I disorder. Clinical trials describing the efficacy of quetiapine in other phases of bipolar disorder and in other patient populations are also reviewed. A discussion of the drug profile of quetiapine includes its chemistry, availability, pharmacodynamics, pharmacokinetics and metabolism. Preclinical studies, postmarketing surveillance, safety, tolerability and regulatory issues are also evaluated. Finally, potential future directions for quetiapine are discussed, together with a review of key issues in bipolar disorder management and details of the information resources used in preparing this article.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug and Narcotic Control; Drug Monitoring; Drug Therapy, Combination; Expert Testimony; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Hyperglycemia; Lipids; Quetiapine Fumarate

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyskinesias; Haloperidol; Humans; Hyperglycemia; Hyperprolactinemia; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Thioridazine; Weight Gain

Although rare, second-generation antipsychotic drugs cause severe hyperglycemia within several days after the initiation of therapy. Because glucose tolerance exhibits circadian rhythmicity, we evaluated an effect of a dosing-time on quetiapine-induced acute hyperglycemia in mice. A single intraperitoneal dose of quetiapine dosing-time-independently induced insulin resistance in fasted C57BL/6J mice. However, acute hyperglycemic effect was detected only after dosing of the drug at the beginning of an active phase. Under the conditions in which hepatic glucose production was stimulated by pyruvate administration, hyperglycemic effect of quetiapine was dosing-time-independently observed. In addition, the dosing-time-dependent hyperglycemic effect of quetiapine disappeared in the liver-specific circadian clock-disrupted mice in which circadian rhythmicity in hepatic glucose production is deranged. Furthermore, the dosing-time had little impact on the pharmacokinetics of quetiapine in normal mice. These results suggest that quetiapine acutely causes hyperglycemia only when hepatic glucose production elevates. Therefore, quetiapine therapy with once daily dosing at a rest phase might be safer than that at an active phase. Further studies are needed to confirm the hypothesis.

Topics: Animals; Antipsychotic Agents; Blood Glucose; Dose-Response Relationship, Drug; Glucose; Hyperglycemia; Insulin Resistance; Liver; Male; Mice, Inbred C57BL; Mice, Transgenic; Quetiapine Fumarate

Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function.

Topics: Animals; Antipsychotic Agents; Cell Line; Cholecalciferol; Class Ia Phosphatidylinositol 3-Kinase; Data Mining; Databases, Factual; Disease Models, Animal; Glucose Transporter Type 4; Humans; Hyperglycemia; Insulin Resistance; Mice; Quetiapine Fumarate; Signal Transduction; Vitamin D

Topics: Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Dyslipidemias; Humans; Hyperglycemia; Quetiapine Fumarate; Weight Gain

Topics: Aged, 80 and over; Antipsychotic Agents; Cognitive Dysfunction; Delusional Parasitosis; Dementia, Vascular; Female; Humans; Hyperglycemia; Leukoaraiosis; Quetiapine Fumarate

There is increasing concern about the development of diabetes mellitus and associated complications in patients administrating second-generation antipsychotics. Previous reports indicate that the risk of quetiapine, although relatively lower, is not negligible. We report a patient with bipolar disorder who, after treating with low-dose quetiapine, develops newly-onset diabetes and hyperglycemic hyperosmolar state. Clinical manifestations and managements of quetiapine-associated diabetes are addressed, and we recommend routine monitoring of serum glucose after initiating quetiapine treatment at any given dose.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Blood Glucose; Diabetes Mellitus; Dibenzothiazepines; Drug Monitoring; Humans; Hyperglycemia; Male; Osmolar Concentration; Quetiapine Fumarate

Topics: Antipsychotic Agents; Child; Dibenzothiazepines; Female; Humans; Hyperglycemia; Mental Disorders; Quetiapine Fumarate

Topics: Acromegaly; Acute Disease; Adenoma; Adult; Antipsychotic Agents; Basal Ganglia; Brain Ischemia; Chorea; Diabetes Complications; Diabetic Ketoacidosis; Dibenzothiazepines; Dyskinesias; Female; Growth Hormone; Humans; Hyperglycemia; Insulin; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Neoplasms; Quetiapine Fumarate; Syndrome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Contraindications; Diabetes Mellitus; Diagnosis, Differential; Dibenzothiazepines; Humans; Hyperglycemia; Japan; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Research Design; Risk Factors; Schizophrenia

To explore the clinical characteristics of hyperglycemia in patients treated with quetiapine.. A pharmacovigilance survey of spontaneously reported adverse events in quetiapine-treated patients was conducted using reports from the U.S. Food and Drug Administration MedWatch program (January 1, 1997, through July 31, 2002) and published cases using the search terms hyperglycemia, diabetes, acidosis, ketosis, and ketoacidosis.. We identified 46 reports of quetiapine-associated hyperglycemia or diabetes and 9 additional reports of acidosis that occurred in the absence of hyperglycemia and were excluded from the immediate analyses. Of the reports of quetiapine-associated hyperglycemia, 34 patients had newly diagnosed hyperglycemia, 8 had exacerbation of preexisting diabetes mellitus, and 4 could not be classified. The mean +/- SD age was 35.3 +/- 16.2 years (range, 5-76 years). New-onset patients (aged 31.2 +/- 14.8 years) tended to be younger than those with preexisting diabetes (43.5 +/- 16.4 years, p = .08). The overall male:female ratio was 1.9. Most cases appeared within 6 months of quetiapine initiation. The severity of cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. There were 21 cases of ketoacidosis or ketosis. There were 11 deaths.. Atypical antipsychotic use may unmask or precipitate hyperglycemia.. An additional 23 cases were identified since August 1, 2002, the end of the first survey, by extending the search through November 30, 2003, bringing the total to 69.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Child; Child, Preschool; Comorbidity; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Dibenzothiazepines; Female; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Male; MEDLINE; Mental Disorders; Middle Aged; Pharmacoepidemiology; Quetiapine Fumarate; Schizophrenia; Sex Distribution; United States; United States Food and Drug Administration

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypertriglyceridemia; Quetiapine Fumarate; Risk Factors