norquetiapine and Psychotic-Disorders

Quetiapine apparently differs from other antipsychotic drugs in terms of its antidepressant activity and efficacy in bipolar depression. The mechanism of this activity is unknown although it may be mediated by its metabolite N-desalkylquetiapine (norquetiapine).. The aim of the study was to analyse the relationships between quetiapine and norquetiapine plasma concentrations and clinical improvement in depressive and anxious symptoms.. This was a prospective observational study. Recruited patients were evaluated during a clinical post-acute phase. Patients were recruited from patients hospitalized in the Psychiatric Department of Ospedale Maggiore Policlinico of Milan, Italy. After discharge they were followed-up as outpatients. The study involved 41 outpatients (23 males, 18 females; age >18 years) diagnosed as affected by schizophrenia (17 patients), borderline personality disorder (eight patients) or bipolar depression (16 patients) on the basis of the Diagnostic and Statistical Manual of Mental Disorders, fourth text revision (DSM-IV-TR) criteria. Patients were prescribed 50-800 mg of quetiapine (Seroquel®). Patients were evaluated after discharge from the psychiatric department (baseline, T0), after 15 days (T1) and after 3 months (T2) using the Brief Psychiatry Rating Scale (BPRS) with particular reference to the dimensions of depression (items 5, 9 and 13) and anxiety (items 1, 2 and 6). Plasma quetiapine and norquetiapine concentrations were determined by means of high-performance liquid chromatography at T2.. There was a significant improvement in the mean BPRS total score, as well as in the dimensions of anxiety and depression. The bipolar patients only showed a significant curvilinear relationship described by a second-order polynomial model between the plasma norquetiapine/quetiapine concentration ratio and the improvement in depression at T2. There was a significant negative linear correlation between the norquetiapine/quetiapine ratio and anxiety in all of the patients.. The results of this study confirm the efficacy of quetiapine on both anxious and depressive symptoms. Norquetiapine has a specific effect on anxiety and depressive symptoms, showing a correlation between plasma concentrations and clinical efficacy only in patients with bipolar depression.

Topics: Adult; Antipsychotic Agents; Anxiety; Depression; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate

The aim of this study was to investigate the steady-state pharmacokinetic, safety, and tolerability profiles of immediate-release quetiapine administered by similar dose-escalation regimens in pediatric and adult populations with psychotic or mood disorders.. Pediatric patients aged 10-17 years were titrated to a quetiapine dose of 200 mg twice daily (b.i.d. on days 5-7, 400 mg b.i.d. on days 11-12, with a final 400-mg dose on day 13. In a separate trial, adult patients aged 18-45 years were titrated to a quetiapine dose of 200 mg b.i.d. on days 4-6, 400 mg b.i.d. on days 10-11, with a final 400-mg dose on day 12. Concentrations of quetiapine and three metabolites (quetiapine sulfoxide, 7-hydroxy quetiapine, and norquetiapine) were quantified in plasma and urine. Adverse events, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests were evaluated throughout the studies.. In both pediatric and adult populations, plasma concentrations of quetiapine and norquetiapine increased proportionately as the dose was escalated from 200 mg b.i.d. to 400 mg b.i.d. There were no age-related differences in the dose-normalized quetiapine plasma concentration-time curve (AUC(SS)) and maximum plasma concentration (C(SS,max)). Quetiapine was rapidly absorbed after 200-mg and 400-mg doses in pediatric patients [median t(max) (time to maximum plasma concentration) 1.5 hours, both doses] and adult patients (median t(max) 1.0 hour and 1.2 hours, respectively). The mean quetiapine t(1/2) (terminal elimination half-life) was approximately 6 hours for pediatric and 5 hours for adult patients. Norquetiapine displayed a similar median t(max) and a longer t(1/2) compared with quetiapine. Quetiapine was well tolerated, with no serious adverse events and no unexpected events reported.. Pediatric and adult populations demonstrated similar pharmacokinetic, safety, and tolerability profiles for quetiapine administered by dose escalation. The predictability in quetiapine concentration profiles for children aged 10 years to adults suggests that no dosage adjustment may be required when treating patients of these ages.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Area Under Curve; Child; Dibenzothiazepines; Electrocardiography; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate