quetiapine-fumarate and Hypertriglyceridemia

Pancreatitis is a very rare adverse effect of quetiapine treatment, with only 5 cases of quetiapine-associated pancreatitis reported in the English literature to date. Herein, we report one patient who developed severe hypertriglyceridemia (>1000 mg/dL) after quetiapine administration, resulting in acute pancreatitis. An analysis of the underlying pathogenic mechanisms and a review of relevant literature are also presented. Clinicians should be aware of the potentially life-threatening metabolic disturbances and/or pancreatitis associated with quetiapine therapy.

Topics: Acute Disease; Bipolar Disorder; Dibenzothiazepines; Humans; Hypertriglyceridemia; Pancreatitis; Quetiapine Fumarate

Topics: Antipsychotic Agents; Delirium; Humans; Hypertriglyceridemia; Infant; Off-Label Use; Quetiapine Fumarate

Second-generation antipsychotics have well-known metabolic side effects such as hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric and flank pain associated with nausea, and was noted to have elevated triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological parameters revealed neutropenia with pancytopaenia. The patient was started on conservative management for acute pancreatitis, and on intravenous insulin and oral gemfibrozil for lowering of his triglycerides. He gradually improved and was transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and leucocyte counts normalised at discharge and he was transitioned to ziprasidone. The combination of hypertriglyceridaemia, worsening hyperglycaemia and neutropenia made us suspect quetiapine as the causative agent. Medications cause only 0.1-7% of acute pancreatitis cases, with quetiapine implicated in only five-reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or 11.29 mmol/L) has been reported in <10 patients.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Humans; Hypertriglyceridemia; Male; Middle Aged; Pancreatitis; Quetiapine Fumarate; Treatment Outcome

A 27-year-old man treated with quetiapine for anxiety disorder developed hypertriglyceridaemia-induced acute pancreatitis and diabetic ketoacidosis. He was otherwise physically healthy with no family history of hyperlipidaemia. Despite aggressive intensive therapy he died of multiorgan failure within 36 h from initial presentation. While second-generation antipsychotics are well known to be causally linked to diabetes and hyperlipidaemia, this is to my knowledge the first-described case of a fatal triad of extreme hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine. Clinicians should be aware of this rare clinical presentation since rapid progression to multiorgan failure can occur. Early supportive therapy should be initiated. Lactescent serum and ketoacidosis in severe acute pancreatitis should not be overlooked-initiate insulin therapy and possibly plasmapheresis in case of extreme hypertriglyceridaemia.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed Diagnosis; Diabetic Ketoacidosis; Diagnosis, Differential; Dibenzothiazepines; Dose-Response Relationship, Drug; Fatal Outcome; Humans; Hypertriglyceridemia; Male; Pancreas; Pancreatitis, Acute Necrotizing; Phobic Disorders; Psychotic Disorders; Quetiapine Fumarate; Tomography, X-Ray Computed

We report a case of fatal acute pancreatitis caused by severe hypertriglyceridaemia in a 27-year-old male who was treated with quetiapine. The blood samples were milk-like with markedly elevated triglycerides (> 55 mmol/l). Computer tomography revealed a severe pancreatitis without bile stones or cholestasis. In spite of treatment the patient's condition rapidly worsened and he died 48 hours after admission. We discuss the option of treating hypertriglyceridaemia-induced pancreatitis with apheresis.

Topics: Adult; Antipsychotic Agents; Fatal Outcome; Humans; Hypertriglyceridemia; Male; Pancreatitis; Quetiapine Fumarate; Tomography, X-Ray Computed

Polyunsaturated fatty acids (PUFAs) are bimodally distributed in acute schizophrenia, suggesting two endophenotypes. We intended to characterize these endophenotypes clinically. Our a priori hypothesis was that low PUFA patients have more negative symptoms.. Patients (aged 18-39) with schizophrenia, schizoaffective or schizophreniform disorders were recruited at hospital admission during an acute episode. The baseline Positive and Negative Syndrome Scale, vital signs and biochemical variables were measured in 97 patients with available RBC PUFA levels. Adjustment for multiple testing was not performed.. The median Negative Subscale score was higher (p=0.04) in the low PUFA (25 points, n=30) than in the high PUFA group (19 points, n=67). Among 95 patients with measurements of serum triglycerides, hypertriglyceridaemia was more prevalent (p=0.009) among low PUFA patients (66%) than high PUFA patients (36%). PUFA modified the effect of antipsychotics on triglycerides (p=0.046). Serum glucose and mean corpuscular haemoglobin were higher (p=0.03, 0.001, respectively) in low PUFA than in high PUFA patients. Low PUFA men were heavier (p=0.04) than high PUFA men.. During an acute episode of schizophrenia, patients with low RBC PUFA have more negative symptoms and more metabolic and haematological abnormalities than those with high PUFA. This indicates that PUFA levels define two clinically distinct endophenotypes of the disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Clozapine; Dibenzothiazepines; Endophenotypes; Erythrocytes; Fatty Acids, Unsaturated; Female; Humans; Hypertriglyceridemia; Linear Models; Logistic Models; Male; Obesity; Olanzapine; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Dibenzothiazepines; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Humans; Hypercholesterolemia; Hypertriglyceridemia; Male; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Valproic Acid

Topics: Antipsychotic Agents; Cholesterol; Dibenzothiazepines; Humans; Hypertriglyceridemia; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia, Paranoid; Triglycerides

Second-generation antipsychotics can cause lipid elevations at a greater rate than older typical antipsychotics. This risk may not be equivalent amongst the second-generation antipsychotics. We conducted a computerized, retrospective, nonrandomized, case-control analysis of 6331 patients receiving antipsychotics. For each patient, the first prescription for at least 60 continuous days for four antipsychotics [haloperidol (HALD), olanzapine (OLANZ), quetiapine (QUET), or risperidone (RISP)] was analyzed for total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), and triglycerides (TGL). Mean HDL was lower during OLANZ treatment than with RISP (P = 0.03) or QUET (P = 0.001). TGL were higher during OLANZ (P = 0.0007) or QUET treatment (P = 0.006) than RISP. In dichotomous analyses, odds ratios on the percentage of participants having abnormal cholesterol (P = 0.0003), low-density lipoprotein (P = 0.001), or TGL (P = 0.0001) during medication were in the order: OLANZ > QUET > RISP > HALD. For HDL, the results were less robust but the percentage of participants were in the order: OLANZ>RISP = HALD = QUET. In treatment-emergent analyses of patients without lipid abnormalities during an unmedicated baseline period, there was a greater risk of developing new HDL abnormality with OLANZ than RISP (P<0.05). In conclusion, treatment with RISP or HALD was associated with a more favorable lipid profile than with OLANZ or QUET.

Topics: Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Dibenzothiazepines; Dyslipidemias; Female; Haloperidol; Humans; Hypertriglyceridemia; Male; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risk Assessment; Risperidone; Time Factors; United States; United States Department of Veterans Affairs

Topics: Adult; Amisulpride; Antipsychotic Agents; Appetite; Dibenzothiazepines; Dose-Response Relationship, Drug; Eating; Female; Humans; Hyperprolactinemia; Hypertriglyceridemia; Quetiapine Fumarate; Recurrence; Schizophrenia, Paranoid; Sulpiride

The goal of this study was to select some genes that may serve as good candidates for future studies of the direct effects (not explained by obesity) of some antipsychotics on hyperlipidemia. A search for single-nucleotide polymorphisms (SNPs) that may be associated with these direct effects was conducted. From a published cross-sectional sample, 357 patients on antipsychotics were genotyped using a DNA microarray with 384 SNPs. A total of 165 patients were taking olanzapine, quetiapine or chlorpromazine which may directly cause hypertriglyceridemia or hypercholesterolemia. Another 192 patients taking other antipsychotics were controls. A two-stage statistical analysis that included loglinear and logistic models was developed to select SNPs blindly. In a third stage, physiological knowledge was used to select promising SNPs. Known physiological mechanisms were supported for 3 associations found in patients taking olanzapine, quetiapine or chlorpromazine [acetyl-coenzyme A carboxylase alpha SNP (rs4072032) in the hypertriglyceridemia model, and for the neuropeptide Y (rs1468271) and ACCbeta, (rs2241220) in the hypercholesterolemia model]. These genes may be promising candidates for studies of the direct effects of some antipsychotics on hyperlipidemia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cross-Sectional Studies; Dibenzothiazepines; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Lipids; Male; Olanzapine; Oligonucleotide Array Sequence Analysis; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

We report a case of a 29-year-old man with schizoaffective disorder in which diabetes mellitus and hypertriglyceridemia developed with quetiapine (Seroquels). We reviewed the literature on the relationship between antipsychotic therapy and development of metabolic disorders and found serious concerns. This case demonstrates the importance of a careful monitoring of glucose and other metabolic parameters in patients receiving atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Diabetes Mellitus; Dibenzothiazepines; Humans; Hypertriglyceridemia; Male; Psychotic Disorders; Quetiapine Fumarate; Risk Factors

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

Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Hyperlipidemias; Hypertriglyceridemia; Lipids; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Retrospective Studies