paliperidone-palmitate and Hyperglycemia

There are no direct comparisons of paliperidone extended-release (ER), aripiprazole and ziprasidone in efficacy and metabolic influence in patients with first-episode schizophrenia.. The present study examined the efficacy and metabolic influence of paliperidone ER, aripiprazole and ziprasidone in patients with first-episode schizophrenia in China.. Subjects were recruited from outpatient and 254 patients entered the trial. These patients received treatment randomly with paliperidone ER, aripiprazole and ziprasidone and were assessed at baseline, 13, 26 and 52 weeks, respectively with Positive and Negative Syndrome Scale (PANSS), 7-item Clinical Global Impressions-Severity (CGI-S), anthropometric (weight, body mass index and waist circumference) and metabolic (fasting blood glucose, HbA1c, cholesterol, high density lipoproteins (HDL), low density lipoproteins and triglycerides) measures.. A total of 203 patients completed the trial. Paliperidone group had significant greater reduction in PANSS than aripiprazole group and ziprasidone group from 13 weeks, although the a reduction in PANSS of each group was more than 20%. There was no difference in CGI-S among the three groups, and all three groups had a significant reduction from baseline in CGI-S. Aripiprazole group increased in weight and body mass index despite no statistical change in waist circumference. Other two groups showed no changes in anthropometric measure. At the end of the study, two glucose metabolic indices (fasting blood glucose and HbA1c) of aripiprazole group were significantly higher than that of baseline. In lipid metabolism, aripiprazole group reduced triglycerides significantly and had no changes in other indices. Paliperidone group reduced HDL and increased triglycerides despite no changes in glucose metabolism. Ziprasidone group also had no significant changes in glucose metabolism, but reduced cholesterol, low density lipoproteins and increased HDL. Furthermore, 22 subjects in three groups reached the diagnostic criteria of metabolic syndrome.. Paliperidone ER, aripiprazole and ziprasidone are effective in treating first-episode schizophrenia, and the ranking of efficacy from high to low is paliperidone ER > aripiprazole > ziprasidone. Paliperidone ER can impair lipid metabolism potentially but had no influence on glucose metabolism. Aripiprazole can damage glucose metabolism and has little influence on lipid metabolism. Ziprasidone is considered an atypical antipsychotic with no evidence of harm to glucose and lipid metabolism.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Body Mass Index; China; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Female; Follow-Up Studies; Humans; Hyperglycemia; Hyperlipidemias; Isoxazoles; Male; Metabolic Diseases; Paliperidone Palmitate; Piperazines; Psychiatric Status Rating Scales; Pyrimidines; Quinolones; Schizophrenia; Thiazoles; Weight Gain; Young Adult

Although paliperidone-related hyperglycemia has been extensively examined, the underlying mechanisms have not yet been elucidated. We investigated the effects of a single intravenous injection of paliperidone (0.2, 0.4, or 0.6 mg/kg) on serum concentrations of glucose and other endogenous metabolites in rats. We also examined the effects of a single intravenous injection of paliperidone (0.4 mg/kg) on AMP-activated protein kinase (AMPK) activity in the hypothalamus and liver. To clarify the relationship between AMPK activity and adrenaline secretion, the effects of berberine, which inhibits hypothalamic AMPK, on paliperidone-induced hyperglycemia were assessed. Significant increases were observed in serum glucose, adrenaline, and insulin concentrations following intravenous injections of paliperidone at doses of 0.4 and 0.6 mg/kg. A propranolol pretreatment attenuated paliperidone-induced increases in serum concentrations of glucose, but not adrenaline. Significant increases were also noted in phosphorylated AMPK concentrations in the hypothalamus following the administration of paliperidone at a dose of 0.4 mg/kg. A berberine pretreatment attenuated paliperidone-induced increases in blood concentrations of glucose, adrenaline, and insulin and phosphorylated AMPK concentrations in the hypothalamus. Collectively, the present results demonstrated that an acute treatment with paliperidone induced hyperglycemia, which was associated with the effects of hypothalamic AMPK activation on the secretion of adrenaline.

Topics: AMP-Activated Protein Kinases; Animals; Berberine; Glucose; Hyperglycemia; Hypothalamus; Insulin; Paliperidone Palmitate; Rats

Clozapine, an antipsychotic developed in 1958, is considered the gold standard and the treatment of choice in treatment-resistant schizophrenia despite its side effects and despite 40-70% of these patients not responding to clozapine. In the last decade, new antipsychotics, such as paliperidone palmitate (PP), have emerged as well as its long acting-injectable (LAI) formulations, available as PP-1-monthly (PP1M) and the newest PP-3-montlhy (PP3M). Despite paliperidone having shown a similar efficacy as others antipsychotics for the treatment of schizophrenia, and that PP3M has been shown to reduce relapses compared to oral formulations, no study has been carried out in treatment-resistant schizophrenia. The aim of our study was to carry out an exploratory evaluation of endocrine and hepatic profiles as well as the concomitant treatments associated to PP3M vs. clozapine, the gold standard, in patients with treatment-resistant schizophrenia. We designed a retrospective study. A total number of 33 patients previously diagnosed as schizophrenics treatment-resistant, who were prescribed clozapine followed by PP1M and PP3M when available, were selected. Demographic data, BMI, hepatic enzymes (glutamic oxaloacetic transaminase, glutamate-pyruvate transaminase and gamma-glutamyl transferase (GGT)], thyroid function (thyroid stimulating hormone), blood platelets and both white and red blood cells as well as the use of concomitant antipsychotics, benzodiazepines and biperiden were compared under treatment with clozapine and PP3M. Antipsychotics and benzodiazepines dosages were compared using by the defined daily dose (DDD) method and haloperidol or diazepam dose equivalents. All statistical analyses were performed using the paired Student t-test for repeated measures. Our data showed that patients under treatment with PP3M showed a significant decrease in BMI (P < 0.01), glucose (P < 0.01), cholesterol (P < 0.05) and triglycerides (P < 0.01) when compared with basal values under treatment with clozapine. Hepatic cholestasis enzyme, GGT, were significantly elevated (P < 0.05) under treatment with clozapine when compared to PP3M. Switching clozapine to PP3M led to a significant lower pharmacological exposure to antipsychotics, by both the DDD (P < 0.05) and haloperidol dose equivalents (P < 0.001) methods without increasing the dose of benzodiazepines while biperiden was more used under PP3M. Finally, antipsychotic monotherapy was higher and less polypharmacy was use

Topics: Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Resistance; Drug Substitution; Dyslipidemias; Female; Humans; Hyperglycemia; Male; Middle Aged; Obesity; Paliperidone Palmitate; Retrospective Studies; Schizophrenia; Spain