quetiapine-fumarate and Drug-Related-Side-Effects-and-Adverse-Reactions

Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression.. We conducted a systematic review and network meta-analysis. We searched for randomised controlled trials comparing pharmacological interventions with each other or placebo in adults with acute bipolar depression (type I, type II, or not otherwise specified), excluding those with substance misuse, unipolar depression, or schizophrenia, in MEDLINE, Embase, PsycINFO, Google Scholar, Cochrane Library, Web of Knowledge, CINAHL, and LILACS from database inception up to April 13, 2023. Criteria for eligibility were a duration of 2-16 weeks with masked outcome assessments, and we included combination, add-on design, and monotherapy studies. The co-primary outcomes were depressive symptoms, examined with standardised mean differences (SMDs), and manic switch, examined with odds ratios (ORs). We also investigated dropouts due to any reason, inefficacy, adverse events, and important side-effects as secondary outcomes. The confidence in the evidence was evaluated using Confidence-In-Network-Meta-Analysis (CINeMA). The study was registered with PROSPERO, CRD42020171726.. We analysed data from 101 randomised controlled trials covering 20 081 participants, 8063 men (41·7%) and 11 263 women (58·3%; sex not available in four studies), mean age 41·0 years (range of means 28·7-53·6 years), and 68 medications and placebo. Ethnicity data were not available. With moderate confidence in the evidence, olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were more efficacious than placebo in reducing depressive symptoms, with SMDs ranging from 0·41 (95% CI 0·19-0·64) for olanzapine plus fluoxetine to 0·16 (0·03-0·29) for lamotrigine. Several other drugs might also be efficacious, but the confidence in the evidence was very low to low. Antidepressants as a class seem to be efficacious, but had a higher risk for manic switch compared to antipsychotics. Medications differed in their side-effect profiles.. This is, to our knowledge, the largest network meta-analysis of pharmacotherapy for bipolar depression to date. Olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were found to be more efficacious than placebo in adults with acute bipolar depression, with good confidence in the evidence, and to differ in their side-effect profiles. These findings can inform evidence-based care and the development of treatment guidelines internationally.. None.

Topics: Adult; Bipolar Disorder; Depression; Drug-Related Side Effects and Adverse Reactions; Female; Fluoxetine; Humans; Lamotrigine; Lurasidone Hydrochloride; Male; Middle Aged; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate

We examined systematic adverse events (AEs) in Part 1 (of 2) of a study describing the assessment and reporting of AEs in clinical trials.. We examined 52 public and nonpublic data sources about trials of quetiapine for bipolar depression using data from the Multiple Data Sources study. We extracted and compared information about systematic AEs (i.e., AEs assessed for all participants) in six prespecified domains: cardiovascular, cholesterol, endocrine, extrapyramidal symptoms, mania, and weight.. Eligible trials did not assess and report the same systematic AEs, and most results were not available in public sources. Overall, public sources reported 159 results, of which 92 of 159 (58%) included sufficient statistical information to calculate the treatment effect and its precision. Nonpublic sources reported 636 results; 630 of 636 (99%) reported sufficient statistical information.. Systematic AEs were defined and analyzed in many ways, which led to many numerical results. Most systematic AEs were not mentioned in public sources. To minimize bias, methods for defining and analyzing potential AEs should be prespecified in trial registers and protocols. All trial results should be publicly available so that stakeholders can compare benefits and AEs. Trials could report core sets of AEs to facilitate decision-making.

Topics: Bipolar Disorder; Data Accuracy; Drug-Related Side Effects and Adverse Reactions; Gabapentin; Humans; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

We examined nonsystematic adverse events (AEs) in Part 2 (of 2) of a study describing the assessment and reporting AEs in clinical trials.. We examined 21 trials of gabapentin for neuropathic pain (52 sources) and seven trials of quetiapine for bipolar depression (80 sources) using data from the Multiple Data Sources study. We extracted and compared information about nonsystematic AEs (i.e., AEs that were not assessed for every participant), including AEs categorized as "serious." We recorded whether AEs were grouped by anatomic or physiological system.. Trials of the same drug reported information about different AEs. Information in public sources was inadequate for decision-making. No public source reported all AEs, or all serious AEs, identified in nonpublic sources about the same trial. Of trials with only public sources, 2/15 (13%) gabapentin and 0/3 (0%) quetiapine trials grouped AEs by anatomic or physiological system.. Public sources contained little information about nonsystematic AEs, including serious AEs. Grouping might make nonsystematic AEs easier to detect; however, most public sources did not report grouped AEs. Standards are needed to improve the collection and reporting of nonsystematic AEs so that stakeholders can use trials to assess the balance of potential benefits and harms.

Topics: Bipolar Disorder; Data Accuracy; Drug-Related Side Effects and Adverse Reactions; Gabapentin; Humans; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

The anticonvulsant valproic acid and the atypical antipsychotics olanzapine and quetiapine provide synergistic mood-stabilising, antidepressant and antipsychotic activities in the treatment of bipolar and schizoaffective disorders. Existing literature shows that pharmacokinetic and pharmacodynamics drug-drug interactions (DDIs) possibly occur with the use of such a combination. Clinical reports of a possible interaction between the drugs leading to an increased risk of adverse drug reactions have also emerged. The main objective of this paper is to review the incidence of DDIs between the anticonvulsant and the antipsychotics, to postulate the possible mechanisms of the interaction and to establish whether certain target populations are at an increased susceptibility to such interactions. The usefulness of therapeutic drug monitoring (TDM) of the antipsychotics to monitor for an interaction was also assessed. A systematic database search was carried out using the search engine provided by PubMed using the following key words: olanzapine, quetiapine, valproic acid, pharmacokinetic drug-drug interaction, bipolar disorder, therapeutic drug monitoring.. Evidence of a possible clinically relevant DDI between valproic acid and both antipsychotics has been uncovered. A possible mechanism for the interactions has been postulated, and the importance of TDM has been discussed.. Further research is required to determine whether DDIs occur with the concurrent use of valproic acid and olanzapine or quetiapine, and to investigate the potential of TDM as a clinical tool in improving pharmacotherapy and preventing toxicity.

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Humans; Olanzapine; Quetiapine Fumarate; Valproic Acid

Bipolar disorder is a common, recurrent, and chronic condition associated with significant morbidity and reduced longevity mainly due to the depressive pole of the illness. Despite the great need for effective therapies, relatively few randomized controlled trials have been conducted and, to date, only two agents have been approved by the United States Food and Drug Administration for treatment of bipolar depression (olanzapine/fluoxetine combination and quetiapine). Quetiapine is the first approved monotherapy for treatment of bipolar depression, and an extended-release (XR) form of quetiapine is now available. This once-daily, bioequivalent formulation represents a useful alternative for patients who cannot tolerate twice-daily, immediate-release (IR) quetiapine. Here, we summarize the evidence supporting the efficacy of quetiapine for treatment of bipolar depression, and also review the similarities and differences between the two formulations. Additional research on longer-term use of quetiapine XR is needed to establish the durability of therapeutic effects and tolerability over months or years of therapy, both alone and in combination with other mood stabilizers. Studies on the potential utility of lower doses of quetiapine XR and head-to-head studies to evaluate relative efficacy and cost-effectiveness also are needed.

Topics: Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Drug-Related Side Effects and Adverse Reactions; Humans; Medication Adherence; Quetiapine Fumarate; Therapeutic Equivalency; Treatment Outcome

Quetiapine, a dibenzothiazepine derivative, is an atypical antipsychotic, multireceptor antagonist that has a preclinical profile similar to clozapine. Randomized studies have demonstrated the efficacy of quetiapine relative to placebo in the treatment of acute relapse and the long-term management of schizophrenia. Quetiapine is generally well tolerated relative to other antipsychotic medications, although side effects include sedation, orthostatic hypotension, anticholinergic and metabolic side effects. The purpose of this article is to critically review the current literature on quetiapine with an emphasis on emergent themes and key findings in the use of this agent for the treatment of schizophrenia. There are also continued efforts to understand, predict and manage the side-effect risk with quetiapine.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; Humans; Practice Patterns, Physicians'; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Clinical trials with healthy volunteers are a useful model for evaluating safety and tolerability, without the interference of concomitant diseases and drugs. The present study aims to improve our understanding of antipsychotic-related adverse reactions (ARs) and their possible association with common genetic variants of pharmacodynamic proteins such as neurotransmitter receptors/transporters.. A total of eight polymorphisms located in seven pharmacodynamic-related genes (SCL6A4, MDR1, 5HT2A, DRD2, DRD3, COMT and GRIN2B) were genotyped in a cohort of 211 healthy volunteers who received a single dose of risperidone (1 mg), olanzapine (5 mg) or quetiapine (25 mg).. Interestingly, a significant association was found between the incidence of neurological ARs and specific polymorphisms in key genes (DRD2 and SCL6A4).. Genetic variants in pharmacodynamic genes could represent valuable markers of AR risk and antipsychotic safety. Original submitted 7 February 2013; Revision submitted 3 June 2013.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers, Pharmacological; Dibenzothiazepines; Drug-Related Side Effects and Adverse Reactions; Female; Genotype; Healthy Volunteers; Humans; Huntingtin Protein; Male; Nerve Tissue Proteins; Olanzapine; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone

To assess dosing, efficacy, and tolerability of quetiapine fumarate in drug-naive first-episode psychosis.. We present a prospective, randomized, controlled, single-center, double-blind, fixed-dose, 4-week comparison study of 200 mg/day versus 400 mg/day of quetiapine in 141 drug-naive acutely ill first-episode psychosis patients (diagnosed according to DSM-IV) aged 15 to 25 years. The double-blind 4-week trial (Part 1) was followed by a single-blind, naturalistic, flexible-dose 8-week period (Part 2). The main outcome measures were symptomatic change, functioning, and tolerability. Data were collected from July 2003 until January 2006.. The estimated time trends of the linear mixed-effects modeling indicated that efficacy between the 2 treatment groups in Part 1 was similar for most outcome measures except for 5 measures: the Scale for the Assessment of Negative Symptoms (SANS) anhedonia-asociality subscale (p = .011), the Social and Occupational Functioning Assessment Scale (p = .020), the Global Assessment of Functioning scale (p = .070), the SANS affective flattening or blunting subscale (p = .051), and the Udvalg for Kliniske Undersogelser total (p = .056), suggesting that the 200-mg group improved more for the SANS anhedonia-asociality subscale, whereas the 400-mg group showed a slight deterioration. Social and global functioning also improved more in the 200-mg group than in the 400-mg group. Part 2 of the study revealed that, independent of the initial target dose, when clinicians were able to adjust the dose flexibly, the dose at 12 weeks was similar between groups and averaged 268 mg/day.. Our study in acutely ill drug-naive first-episode psychosis patients suggests that quetiapine is a safe and well-tolerated antipsychotic medication. In contrast to multiepisode patients, dosing should be more conservative in untreated new-onset cases. An initial dose of 250 to 300 mg/day of quetiapine is proposed as a primary target dose in drug-naive first-episode psychosis patients.. clinicaltrials.gov Identifier: NCT00449397.

Topics: Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Linear Models; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate

Retrospective studies using spontaneous reporting system databases have provided a great understanding of adverse drug reactions (ADRs) in the real world, complementing the data obtained from randomized controlled trials. However, there have been few reports on large-scale epidemiological studies on the adverse effects of antipsychotics in Asia.. This study aimed to investigate the characteristics of antipsychotic ADRs using a nationwide pharmacovigilance database.. Data were collected from the Korea Adverse Event Reporting System database between 2010 and 2019. The study subjects were selected using the International Classification of Disease codes for diseases related to psychosis and Electronic Data Interchange codes for amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. The causality assessment of "possible," "probable," or "certain" by the World Health Organization-Uppsala Monitoring Center System causality category was selected. All data were descriptively analyzed.. In total, 5067 adverse events associated with antipsychotic drugs were reported. The antipsychotics that commonly resulted in ADRs were quetiapine (47.7%), olanzapine (11.3%), and clozapine (10.7%). Serious ADRs were most commonly observed with clozapine. Gastrointestinal and central nervous system problems occurred within a month when ADRs were classified according to the time of onset. In contrast, metabolic and bone marrow-related symptoms occurred after long-term use. Sedation and nausea were the most common ADRs in children and adolescents, whereas constipation and dizziness were common in adults and the elderly.. This study extends our knowledge of antipsychotic ADRs in the Asian population.

Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Clozapine; Drug-Related Side Effects and Adverse Reactions; Haloperidol; Humans; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

Polypharmacy increases the risk of potential drug-drug interactions (pDDIs). This retrospective analysis was conducted to detect pDDIs and adverse drug reactions (ADRs) among older adults with psychiatric disorder, and identify pDDIs with clinical significance.. A retrospective analysis was carried out based on the medical records of older adults with psychiatric disorders. Data on demographic characteristics, substance abuse, medical history, and medications were extracted. The Lexi-Interact online database was used to detect pDDIs. The minimal clinically important difference (MCID) was set as the change in the Treatment Emergent Symptom Scale (TESS) score between admission and discharge. The median and interquartile ranges were used for continuous variables, and frequencies were calculated for dichotomous variables. Poisson regression was implemented to determine the factors influencing the number of ADR types. The influencing factors of each ADR and the clinical significance of the severity of the ADR were analysed using binary logistic regression. P < 0.05 was considered statistically significant.. A total of 308 older adults were enrolled, 171 (55.52%) of whom had at least 1 pDDI. Thirty-six types of pDDIs that should be avoided were found, and the most frequent pDDI was the coadministration of lorazepam and olanzapine (55.5%). A total of 26 ADRs induced by pDDIs were identified, and the most common ADR was constipation (26.05%). There was a 9.4 and 10.3% increase in the number of ADR types for each extra medical diagnosis and for each extra drug, respectively. There was a 120% increase in the number of ADR types for older adults hospitalized for 18-28 days compared with those hospitalized for 3-17 days. There was an 11.1% decrease in the number of ADR types for each extra readmission. The length of hospitalization was a risk factor for abnormal liver function (P < 0.05). The use of a large number of drugs was a risk factor for gastric distress (P < 0.05) and dizziness and fainting (P < 0.05). None of the four pDDIs, including coadministrations of olanzapine and lorazepam, quetiapine and potassium chloride, quetiapine and escitalopram, and olanzapine and clonazepam, showed clinical significance of ADR severity (P > 0.05).. pDDIs are prevalent in older adults, and the rate is increasing. However, many pDDIs may have no clinical significance in terms of ADR severity. Further research on assessing pDDIs, and possible measures to prevent serious ADRs induced by DDIs is needed to reduce the clinical significance of pDDIs.

Topics: Aged; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Lorazepam; Mental Disorders; Olanzapine; Quetiapine Fumarate; Retrospective Studies

Recent pharmacological studies indicated that the modulation of tripartite-synaptic transmission plays important roles in the pathophysiology of schizophrenia, mood disorders and adverse reactions. Therefore, to explore the mechanisms underlying the clinical and adverse reactions to atypical antipsychotics, the present study determined the effects of the sub-chronic administration of quetiapine (QTP: 3~30 μM) on the protein expression of 5-HT7 receptor (5-HT7R), connexin43 (Cx43), cAMP level and intracellular signalling, Akt, Erk and adenosine monophosphate-activated protein kinase (AMPK) in cultured astrocytes and the rat hypothalamus, using ultra-high-pressure liquid chromatography with mass spectrometry and capillary immunoblotting systems. QTP biphasically increased physiological ripple-burst evoked astroglial D-serine release in a concentration-dependent manner, peaking at 10 μM. QTP enhanced the astroglial signalling of Erk concentration-dependently, whereas both Akt and AMPK signalling's were biphasically enhanced by QTP, peaking at 10 μM and 3 μM, respectively. QTP downregulated astroglial 5-HT7R in the plasma membrane concentration-dependently. Protein expression of Cx43 in astroglial cytosol and intracellular cAMP levels were decreased and increased by QTP also biphasically, peaking at 3 μM. The dose-dependent effects of QTP on the protein expression of 5-HT7R and Cx43, AMPK signalling and intracellular cAMP levels in the hypothalamus were similar to those in astrocytes. These results suggest several complicated pharmacological features of QTP. A therapeutically relevant concentration/dose of QTP activates Akt, Erk and AMPK signalling, whereas a higher concentration/dose of QTP suppresses AMPK signalling via its low-affinity 5-HT7R inverse agonistic action. Therefore, 5-HT7R inverse agonistic action probably plays important roles in the prevention of a part of adverse reactions of QTP, such as weight gain and metabolic complications.

Topics: AMP-Activated Protein Kinases; Animals; Connexin 43; Dibenzothiazepines; Drug-Related Side Effects and Adverse Reactions; Proto-Oncogene Proteins c-akt; Quetiapine Fumarate; Rats; Receptors, Serotonin

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).

Topics: Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Drug-Related Side Effects and Adverse Reactions; Exanthema; Humans; Japan; Lamotrigine; Lithium Carbonate; Olanzapine; Quetiapine Fumarate; Risperidone

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the

Topics: Alleles; Antipsychotic Agents; Cytochrome P-450 CYP2D6; Drug-Related Side Effects and Adverse Reactions; Genetic Association Studies; Genetic Variation; Genotype; Humans; Male; Middle Aged; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Quetiapine Fumarate; Severity of Illness Index

We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c.421 non-CA/AA genotypes (P-value: 0.008). Multivariate analysis revealed that the ABCG2 c.421 CA/AA genotype was found associated to a higher hazard (P-value: 0.004) of developing adverse drug reactions classified as metabolism and nutrition disorders. The ABCB1 2677TT/3435TT genotype had a statistically significant lower aripiprazole Ct/ds if compared with patients with others ABCB1 genotypes (P-value: 0.026). Information obtained on ABCB1 and ABCG2 gene variants may result useful to tailor treatments with these drugs in Caucasian pediatric patients.

Topics: Adolescent; Aripiprazole; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Child; Child, Preschool; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Drug-Related Side Effects and Adverse Reactions; Female; Genotype; Humans; Male; Neoplasm Proteins; Olanzapine; Pediatrics; Polymorphism, Genetic; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

Topics: Antidepressive Agents; Antimanic Agents; Bipolar Disorder; Carbamazepine; Delirium; Depression; Dose-Response Relationship, Drug; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Electroconvulsive Therapy; Female; Humans; Lithium Compounds; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported in the European Summary of Product Characteristics (SPCs). The ADE report database at Danish Medicines Agency was searched for all quetiapine ADRs involving individuals (<18 years) in the period 1997-2015. Fifteen ADE case reports were retrieved, scrutinized, and categorized. The average age was 14.8 years (range 10-17 years) and six patients were boys. The main reported ADEs were (i) endocrine, for example, hyperprolactinemia and hyperthyroidism, (ii) cardiac, for example, tachycardia and QT prolongation, (iii) neurological, for example, seizures and cerebral hemorrhage, and (iv) psychiatric, for example, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns.

Topics: Adolescent; Adverse Drug Reaction Reporting Systems; Age Factors; Antipsychotic Agents; Case-Control Studies; Child; Databases, Factual; Denmark; Drug-Related Side Effects and Adverse Reactions; Dystonia; Female; Humans; Hypotension, Orthostatic; Male; Quetiapine Fumarate; Tachycardia; Treatment Outcome

To characterise quetiapine reported adverse drug events (ADEs) in older Australians in terms of type, frequency, severity and outcome, and to compare these characteristics with those of younger Australians.. Basic descriptive analyses were used to examine patient characteristics. The characteristics of reported ADEs were compared between older and younger Australians using odds ratios and chi-squared tests.. The most frequently reported ADEs in older people were nervous system disorders (23.7%). There were significantly more reports of skin and subcutaneous ADEs and hepatobiliary ADEs for older people than for younger people. More severe ADEs were reported in older people with death more likely to occur in older than in younger people CONCLUSION: Significant differences between older and younger people in terms of reported ADEs, severity and mortality were found. There is a need for further prospective studies in older people on quetiapine to confirm the findings of this study.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Australia; Chi-Square Distribution; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Odds Ratio; Quetiapine Fumarate; Risk Factors; Severity of Illness Index; Young Adult

The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics.. This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression.. Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up.. Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and treatment factors predicted an increased risk of TD.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Quetiapine Fumarate; Risperidone

The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years.. Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP.. A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions.. The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Aged, 80 and over; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Carbamazepine; Causality; Dibenzothiazepines; Drug-Related Side Effects and Adverse Reactions; Female; Galactorrhea; Humans; Lamotrigine; Logistic Models; Male; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Switzerland; Triazines; Valproic Acid; Weight Gain; Young Adult

To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes.. Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality.. Nursing homes in the United States.. 75,445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥ 65, were eligible for Medicaid, and lived in a nursing home in 2001-5.. Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders.. Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine.. Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Cause of Death; Comorbidity; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Epidemiologic Methods; Female; Haloperidol; Humans; Male; Medical Assistance; Mortality; Nursing Homes; Quetiapine Fumarate; Risperidone; United States

We investigated the change of antipsychotic treatment of elderly persons with dementia after several publications indicated an association between use of antipsychotics and cerebrovascular events in this population.. Twice a year, the complete medication, age, diagnosis and gender of all inpatients in 30 German psychiatric sites is collected anonymously in a data base for statistical analysis.. The treatment changed for the benefit of Quetiapine and Haloperidol. The use of both Risperidone and Olanzapine decreased markedly.. The antipsychotic treatment changed due to critical publication. But, the evidence for the risk profile is still a matter of debate.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Alzheimer Disease; Antipsychotic Agents; Cerebral Infarction; Dibenzothiazepines; Drug Therapy, Combination; Drug Utilization; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Female; Germany; Humans; Male; Practice Patterns, Physicians'; Publication Bias; Quetiapine Fumarate; Risk; Risperidone

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Central Nervous System Agents; Dibenzothiazepines; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Humans; Lamotrigine; Lithium Compounds; Quetiapine Fumarate; Treatment Outcome; Triazines

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Breast Feeding; Depression, Postpartum; Depressive Disorder; Dibenzothiazepines; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Fluvoxamine; Humans; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors