quetiapine-fumarate and norquetiapine

Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.

Topics: Animals; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Evaluation, Preclinical; Humans; Quality of Life; Quetiapine Fumarate

Quetiapine, originally developed as an antipsychotic, demonstrates efficacy in clinical studies of schizophrenia, bipolar mania and depression, major depressive disorder and generalized anxiety disorder. This broad spectrum of efficacy was not predicted from the preclinical pharmacology of quetiapine. Binding studies in vitro show that quetiapine and its major active human metabolite, norquetiapine, have moderate to high affinity for dopamine D2 and serotonin 5-HT2A receptors, while norquetiapine alone has high affinity for the norepinephrine transporter (NET). This positron emission tomography (PET) study measured NET occupancy in human subjects treated with extended-release quetiapine (quetiapine XR) at doses relevant in the treatment of depression. PET measurements using the specific NET radioligand (S,S)-[(18)F]FMeNER-D2 were performed before and after quetiapine XR treatment at 150 and 300 mg/d for 6-8 d in nine healthy males (aged 21-33 yr). Regions of interest were defined for the thalamus, using the caudate as reference region. NET occupancy was calculated using a target:reference region ratio method. Plasma concentrations of quetiapine and norquetiapine were monitored during PET measurements. Following quetiapine XR treatment, the mean NET occupancy in the thalamus was 19 and 35%, respectively, at quetiapine XR doses of 150 and 300 mg/d. The estimated plasma concentration of norquetiapine corresponding to 50% NET occupancy was 161 ng/ml. This is the first demonstration of NET occupancy by an antipsychotic in the human brain. NET inhibition is accepted as a mechanism of antidepressant activity. NET occupancy may therefore contribute to the broad spectrum of efficacy of quetiapine.

Topics: Administration, Oral; Adult; Antidepressive Agents; Antipsychotic Agents; Biotransformation; Delayed-Action Preparations; Dibenzothiazepines; Healthy Volunteers; Humans; Magnetic Resonance Imaging; Male; Norepinephrine Plasma Membrane Transport Proteins; Positron-Emission Tomography; Quetiapine Fumarate; Radioligand Assay; Thalamus; Young Adult

Cumulative evidence indicates that neuropeptides play a role in the pathophysiology of schizophrenia. Early data showed increased neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from schizophrenia patients and data from rodents show that antipsychotic drugs modulate NPY levels in and release from selected rat brain regions. In view of these findings we investigated whether the atypical antipsychotic quetiapine, originally used as an antipsychotic but subsequently shown to be efficient also in major depressive disorder and in both poles of bipolar disorder, would affect NPY-like immunoreactivity (-LI), and corticotropin-releasing hormone (CRH)-LI levels in CSF of schizophrenia patients. NPY-LI and CRH-LI in CSF were determined in 22 patients with schizophrenia. Lumbar puncture was performed at baseline and again after 4 wk of quetiapine treatment (600 mg/d). Patients were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at weekly intervals. Quetiapine treatment was associated with a significant increase in NPY-LI (p<0.001) and decrease in CRH-LI (p<0.01). Stepwise multiple regression analysis revealed that ΔNPY-LI and ΔCRH-LI levels predicted 63% (p<0.001) of the variability of the ΔPANSS total score, ΔNPY-LI 42% (p<0.05) of the ΔPANSS anxiety items (G2) and ΔCRH-LI 40% (p=0.05) of the ΔPANSS depression items (G6). These results suggest that while quetiapine's effects on monoamines are probably related to its antipsychotic properties, the modulation of NPY and CRH accounts for its antidepressant and anxiolytic effects and can be markers of response.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Corticotropin-Releasing Hormone; Dibenzothiazepines; Electrocardiography; Electroencephalography; Female; Humans; Male; Middle Aged; Neuropeptide Y; Quetiapine Fumarate; Regression Analysis; ROC Curve; Schizophrenia; Tandem Mass Spectrometry; Treatment Outcome; Young Adult

Quetiapine is an established drug for treatment of schizophrenia, bipolar disorder, and major depressive disorder. While initially manufactured as an immediate-release (IR) formulation, an extended-release (XR) formulation has recently been introduced. Pharmacokinetic studies show that quetiapine XR provides a lower peak and more stable plasma concentration than the IR formulation. This study investigated if the pharmacokinetic differences translate into different time curves for central D₂ dopamine receptor occupancy. Eleven control subjects were examined with positron emission tomography (PET) and the radioligand [11C]raclopride. Eight subjects underwent all of the scheduled PET measurements. After baseline examination, quetiapine XR was administered once-daily for 8 d titrated to 300 mg/d on days 5-8, followed by 300 mg/d quetiapine IR on days 9-12. PET measurements were repeated after the last doses of quetiapine XR and IR at predicted times of peak and trough plasma concentrations. Striatal D₂ receptor occupancy was calculated using the simplified reference tissue model. Peak D₂ receptor occupancy was significantly higher with quetiapine IR than XR in all subjects (50 ± 4% and 32 ± 11%, respectively), consistent with lower peak plasma concentrations for the XR formulation. Trough D₂ receptor occupancy was similarly low for both formulations (IR 7 ± 7%, XR 8 ± 6%). The lower peak receptor occupancy associated with quetiapine XR may explain observed pharmacodynamic differences between the formulations. Assuming that our findings in control subjects are valid for patients with schizophrenia, the study supports the view that quetiapine, like the prototype atypical antipsychotic clozapine, may show antipsychotic effect at lower D₂ receptor occupancy than typical antipsychotics.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Basal Ganglia; Binding, Competitive; Biotransformation; Carbon Radioisotopes; Cross-Over Studies; Delayed-Action Preparations; Dibenzothiazepines; Drug Administration Schedule; Humans; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Quetiapine Fumarate; Raclopride; Radiography; Radioligand Assay; Receptors, Dopamine D2; Sweden; Young Adult

While many drug poisonings are successfully treated with specific antidotes, intoxications with tricyclic antidepressants and/or atypical neuroleptics still represent a major challenge. Besides conventional approaches, a new hemoadsorption device might represent an opportunity for therapeutic detoxification.. We report a 64-year-old female patient who attempted suicide by ingesting an unknown dose of quetiapine. Following application of all available standard diagnostic and therapeutic measures, she was admitted to the intensive care in a deeply somnolent state. Gastroscopy was performed necessitating analgo-sedation, intubation, and mechanical ventilation. Since quetiapine is in principle not dialysable, CytoSorb hemoadsorption was commenced resulting in a clear and rapid decrease in plasma levels of quetiapine and its metabolite norquetiapine over the next few hours. The next day, analgesia was stopped, the patient became alert, and cooperative so that she could be extubated without issues. CytoSorb blood purification therapy was discontinued after 2 days. One day later, the patient was transferred to a psychiatric clinic.. We were able to quickly and efficiently reduce quetiapine and norquetiapine to non-toxic serum levels and to stabilize a critical situation using CytoSorb. Therefore, in the absence of a proven beneficial treatment regimen, the use of CytoSorb might represent an alternative for life-threatening complications of quetiapine intoxication. In particular, intoxications caused by lipophilic agents should be further evaluated.

Topics: Antidepressive Agents, Tricyclic; Antidotes; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Middle Aged; Quetiapine Fumarate

Quetiapine is an atypical antipsychotic drug, frequently found in post-mortem samples. The quantitative determination of active metabolites may help in the interpretation of the potential toxic effects of the parent drug and its role in death. A fully validated LC-MS/MS method was developed for the identification and quantification of quetiapine and two main metabolites (N-desalkylquetiapine and 7-hydroxyquetiapine) in blood, biological fluids and tissues. Then, the distribution of analytes in different matrices was evaluated. LODs of 0.9, 0.3 and 0.3ng/mL were calculated for quetiapine, N-desalkylquetiapine and 7-hydroxyquetiapine respectively; while a LOQ at the concentration of 10.0ng/mL was defined for the three analytes. 13 post-mortem positive real cases have been included in the experiment. The results revealed that quetiapine and N-desalkylquetiapine might undergo a significant post-mortem redistribution, while 7-hydroxyquetiapine is less affected by this factor. N-desalkylquetiapine could be found in blood in relatively high concentrations in comparison to those of quetiapine; therefore, it should be always advisable to measure both the analytes. The analysis of tissues could provide additional data on potential intoxication with quetiapine.

Topics: Adipose Tissue; Adult; Aged; Antipsychotic Agents; Bile; Brain Chemistry; Chromatography, Liquid; Dibenzothiazepines; Female; Forensic Toxicology; Humans; Kidney; Limit of Detection; Liver; Lung; Male; Middle Aged; Muscle, Skeletal; Postmortem Changes; Quetiapine Fumarate; Spleen; Tandem Mass Spectrometry; Tissue Distribution; Young Adult

Quetiapine, an atypical antipsychotic drug, is used for the treatment of schizophrenia and acute mania. Although a previous report showed that quetiapine blocked hERG potassium current, quetiapine has been considered relatively safe in terms of cardiovascular side effects. In the present study, we used the whole-cell patch-clamp technique to investigate the effect that quetiapine and its major metabolite norquetiapine can exert on human cardiac sodium channels (hNa

Topics: Action Potentials; Dibenzothiazepines; Heart; HEK293 Cells; Humans; Long QT Syndrome; Membrane Potentials; Myocardium; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Quetiapine Fumarate; Sodium Channel Blockers

Quetiapine is effective in treating depressive symptoms in major depressive disorder and bipolar disorder, but the mechanisms underlying its antidepressants effects are unknown. Norquetiapine, a metabolite of quetiapine, has high affinity for norepinephrine transporter, which might account for its therapeutic efficacy.. In this study, we used positron emission tomography with (S,S)-[11C]O-methyl reboxetine to estimate norepinephrine transporter density and assess the relationship between norepinephrine transporter occupancy by quetiapine XR and improvement in depression in patients with major depressive disorder (n=5) and bipolar disorder (n=5). After the baseline positron emission tomography scan, patients were treated with quetiapine XR with a target dose of 150 mg in major depressive disorder and 300 mg in bipolar disorder. Patients had a second positron emission tomography scan at the end of week 2 and a final scan at week 7.. Norepinephrine transporter density was significantly lower in locus ceruleus in patients compared with healthy subjects. Further, there was a significant positive correlation between quetiapine XR dose and norepinephrine transporter occupancy in locus ceruleus at week 2. The norepinephrine transporter occupancy at week 2 in hypothalamus but not in other regions predicted improvement in depression as reflected by reduction in MADRS scores from baseline to week 7. The estimated dose of quetiapine XR associated with 50% norepinephrine transporter occupancy in hypothalamus at week 2 was 256 mg and the estimated plasma levels of norquetiapine to achieve 50% norepinephrine transporter occupancy was 36.8 µg/L.. These data provide preliminary support for the hypothesis that norepinephrine transporter occupancy by norquetiapine may be a contributor to the antidepressant effects of quetiapine.

Topics: Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hypothalamus; Locus Coeruleus; Male; Middle Aged; Norepinephrine Plasma Membrane Transport Proteins; Positron-Emission Tomography; Quetiapine Fumarate; Reboxetine; Young Adult

Topics: Antidepressive Agents; Cloning, Molecular; Dibenzothiazepines; Dose-Response Relationship, Drug; ERG1 Potassium Channel; HEK293 Cells; Humans; Quetiapine Fumarate

Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine.. We evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant-like and anxiolytic-like drug action.. Norquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5-HT1A receptors, and the anxiolytic-like activity of norquetiapine in rat punished responding was blocked by the 5-HT1A antagonist, WAY100635.. Quetiapine and norquetiapine have multiple in vitro pharmacological actions, and results from preclinical studies suggest that activity at NET and 5-HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Conditioning, Operant; Dibenzothiazepines; Disease Models, Animal; Helplessness, Learned; Humans; Immobility Response, Tonic; Male; Mice; Norepinephrine Plasma Membrane Transport Proteins; Piperazines; Punishment; Pyridines; Quetiapine Fumarate; Radioligand Assay; Rats; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists

The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficacy in schizophrenia, bipolar, major depressive and general anxiety disorders, but to also have a possible anti-inflammatory effect, which could be important in the treatment of the inflammatory aspects of psychiatric diseases. Male C57BL/6 mice were given either quetiapine (i.p. 10mg/kg), its main active metabolite norquetiapine (i.p. 10mg/kg), or saline as a vehicle control, once a day for 14days. On the 14th day, this dose was followed by a single dose of either LPS (i.p. 1mg/kg) or saline. 24h post LPS short-term recognition memory and anhedonia behaviour were measured using the Y-maze and saccharin preference test respectively. Immediately following behavioural testing, mice were culled before serum, prefrontal cortex and hippocampal analysis of cytokine levels was conducted. It was found that LPS challenge led to increased serum and brain cytokine levels as well as anhedonia, with no significant effect on recognition memory. Quetiapine and norquetiapine both increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the pro-inflammatory cytokine IFN-γ in serum 4h post LPS. Within the brain, a similar pattern was seen in gene expression in the hippocampus at 4h for Il-10 and Ifn-γ, however norquetiapine led to an increase in Il-1β expression in the PFC at 4h, while both drugs attenuated the increased Il-10 in different regions of the brain at 24h. These effects in the serum and brain, however, had no effect on the observed LPS induced changes in behaviour. Both quetiapine and its metabolite norquetiapine appear to have a partial anti-inflammatory effect on IL-10 and IFN-γ following acute LPS challenge in serum and brain, however these effects did not translate into behavioural changes.

Topics: Anhedonia; Animals; Antipsychotic Agents; Behavior, Animal; Brain Chemistry; Cytokines; Dibenzothiazepines; Gene Expression; Hippocampus; Inflammation; Interferon-gamma; Interleukin-10; Lipopolysaccharides; Male; Memory, Short-Term; Mice; Mice, Inbred C57BL; Prefrontal Cortex; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Depression; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

Quetiapine is an atypical antipsychotic agent for the treatment of schizophrenia, acute mania, and acute bipolar depression. The antidepressive response is considered to be mediated by the metabolite norquetiapine (N-desalkylquetiapine), and the aim of this study was to develop an LC-MS/MS method to measure concentrations of these compounds in human plasma.. Following one step liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a Sunfire C18 column (50mm×2.1mm, 5μm). The retention times were 2.12, 2.24, 2.12 and 2.19min for quetiapine, norquetiapine and their respective stable labeled internal standards, respectively. Cycle time was 4min. Selected reaction monitoring (SRM) in positive ion mode was used for quantitation.. The present method exhibited a linear dynamic range of 0.5-500ng/ml for quetiapine and 0.6-600ng/ml for norquetiapine. The applicable range was extended by dilution up to 5-fold with blank matrix. The accuracy and precision for quetiapine were <103.0% and 8.8%, for norquetiapine were <108.8% and 11.1%, respectively.. A rapid, sensitive, and robust LC-MS/MS method for quantifying quetiapine and its metabolite norquetiapine levels in human plasma was validated and successfully applied to samples from schizophrenic patients in clinical pharmacokinetics studies.

Topics: Antipsychotic Agents; Blood Chemical Analysis; Chromatography, Liquid; Dibenzothiazepines; Humans; Limit of Detection; Quetiapine Fumarate; Spectrometry, Mass, Electrospray Ionization; Time Factors

Quetiapine has been recently approved as an add-on therapy in the treatment of major depressive disorders in the case of inadequate response to antidepressant monotherapy. Thereby the antidepressant potential is attributed to the N-demethylated metabolite norquetiapine (NQ). The aim of this cross-sectional analysis was to relate quetiapine (Q) doses to serum concentrations of Q and its active metabolite and clinical effects.. Data were obtained from patients who had been treated with different antidepressants and augmented under naturalistic conditions with Q for whom blood level measurements were requested.. For this analysis, 105 depressed patients were included who had been augmented with Q. The mean daily doses of Q were 222 ± 125 mg. Doses correlated significantly (P < 0.001) with the highly variable serum concentrations of both Q and NQ. Median serum concentrations of Q and NQ were 46 ng/mL (25th to 75th percentile 20-91 ng/mL) and 59 ng/mL (25th to 75th percentile 26-133 ng/mL), respectively. Concentrations per dose ranged from 0.10 to 0.58 ng·ml·mg for Q and from 0.17 to 0.59 ng·ml·mg for NQ. Most patients (55%) received comedications in addition to the antidepressant drug and Q. According to the clinical global impressions scale, 60% of the patients were either much (36%) or very much improved (24%). Receiver-operating characteristic analysis revealed no significant differences of serum concentrations between responders and nonresponders for NQ (P = 0.835) but a trend for Q (P = 0.056).. Due to marked variability of Q and NQ concentrations in the blood, therapeutic drug monitoring may be helpful to identify pharmacokinetic peculiarities. The lack of correlation between serum concentrations of NQ and clinical improvement casts doubts on the concept that NQ is the pharmacologically active principle for the augmentation therapy.

Topics: Antidepressive Agents; Antipsychotic Agents; Cross-Sectional Studies; Depressive Disorder, Major; Dibenzothiazepines; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies

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