A validated method for the determination of quetiapine fumarate tablets in human plasma by UPLC-MS/MS and its application to a pharmacokinetic study in healthy Chinese subjects.

A rapid, highly specific and sensitive UPLC-MS/MS method was developed for the determination of Quetiapine Fumarate, a therapeutic drug for various psychiatric disorders, in human plasma. The samples were pretreated using a protein precipitation method, followed by chromatographic separation using a column (Kinetex C18, 2.6µm 50*2.1mm) equipped with an ESI source and MRM mode mass spectrometer. In the validation results of the method, the analyte quetiapine showed a peak at approximately 1.0 minute and exhibited good linearity within the concentration from 2.5 to 2000ng/mL. The intra- and inter-batch precision CV% were within the range of -1.3% to 7.7% and precision of intra- and inter-batch were below 15.0%. Furthermore, this method demonstrated low matrix effects and high recovery rates. The quetiapine plasma sample solution remained stable at room temperature for 25 hours and following 4 freeze-thaw cycles. The prepared samples remained stable in the autosampler (The temperature control of the autosampler was 5oC) for 185 hours and after four freeze-thaw cycles at -20oC and -70oC for 40 days. The present work effectively employed this approach to investigate the pharmacokinetics of orally administered quetiapine fumarate tablets in a cohort of healthy Chinese individuals, both in a fasting state and after a meal.

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.

BACKGROUND: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown. METHODS: In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures. RESULTS: Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P = 0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments. CONCLUSIONS: In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.).

Uso de antipsicóticos atípicos no tratamento da esquizofrenia no Sistema Único de Saúde do Brasil: estudo de coorte, 2008-2017 / Uso de antipsicóticos atípicos en el tratamiento de la esquizofrenia en el Sistema Único de Salud de Brasil: estudio de 2008 a 2017 / Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017

Objective: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. Methods: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. Results: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. Conclusion: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Objetivo: investigar las características sociodemográficas y clínicas de los usuarios de antipsicóticos atípicos, atendidos por el Componente Especializado de Asistencia Farmacéutica (CEAF) para el tratamiento de la esquizofrenia en Brasil, de 2008 a 2017. Métodos: estudio de cohorte retrospectivo utilizando registros de autorizaciones de trámites de alta complejidad del Sistema de Información Ambulatorio del SUS, de todos los estados brasileños. Resultados: de los 759.654 usuários identificados, el 50,5% era del sexo feminino de la región Sudeste (60,2%), diagnosticadas con esquizofrenia paranoide (77,6%). Hubo una mayor prevalencia de risperidona (63,3%) entre niños y adolescentes; de olanzapina (34,0%) en adultos; y quetiapina (47,4%) en ancianos. Alrededor del 40% de los niños/adolescentes estaba bajo uso no autorizado de antipsicóticos según la edad. La adherencia al CEAF fue alta (82%), y la deserción a los seis meses fue del 24%. Conclusión: los hallazgos amplían el conocimiento sobre el perfil sociodemográfico y clínico de los usuarios y destacan la práctica del uso off-label.

Objetivo: investigar características sociodemográficas e clínicas de usuários de antipsicóticos atípicos assistidos pelo Componente Especializado da Assistência Farmacêutica (CEAF), para tratamento da esquizofrenia no Brasil, de 2008 a 2017. Métodos: estudo de coorte retrospectivo utilizando registros das autorizações de procedimentos de alta complexidade do Sistema de Informações Ambulatoriais do Sistema Único de Saúde, de todos os estados brasileiros. Resultados: dos 759.654 usuários, 50,5% eram do sexo feminino, da região Sudeste (60,2%), diagnosticados com esquizofrenia paranoide (77,6%); observou-se maior prevalência de uso da risperidona (63,3%) entre crianças/adolescentes; de olanzapina (34,0%), em adultos; e quetiapina (47,4%), nos idosos; cerca de 40% das crianças/ adolescentes estavam sob uso off-label de antipsicóticos segundo a idade; a adesão ao CEAF foi alta (82%), e o abandono em seis meses foi de 24%. Conclusão: os achados ampliam o conhecimento sobre perfil sociodemográfico e clínico dos usuários e destacam a prática do uso off-label.

CYP2D6 Genotyping and Antipsychotic-Associated Extrapyramidal Adverse Effects in a Randomized Trial of Aripiprazole Versus Quetiapine Extended Release in Children and Adolescents, Aged 12-17 Years, With First Episode Psychosis.

PURPOSE/BACKGROUND: The aim of this study was to examine the association between genetically predicted CYP2D6 phenotypes and extrapyramidal symptoms (EPSs). METHODS/PROCEDURES: Data from the Tolerability and Efficacy of Antipsychotics trial of adolescents with first-episode psychosis randomized to aripiprazole versus quetiapine extended release were studied. Extrapyramidal symptom assessments included the Simpson-Angus Scale and the Barnes Akathisia Rating Scale. Patients were CYP2D6 genotyped. Plasma concentrations of antipsychotics and antidepressants were analyzed. FINDINGS/RESULTS: One hundred thirteen youths (age, 12-17 years; males, 30%; antipsychotic naive, 51%) were enrolled. Poor metabolizers had a significantly higher dose-adjusted aripiprazole plasma concentration (±SD) compared with normal metabolizers at week 4 (24.30 ± 6.40 ng/mL per milligram vs 14.85 ± 6.15 ng/mL per milligram; P = 0.019), but not at week 12 (22.15 ± 11.04 ng/mL per milligram vs 14.32 ± 4.52 ng/mL per milligram; P = 0.067). This association was not found in the quetiapine extended release group. No association between CYP2D6 genotype groups and global Barnes Akathisia Rating Scale score or Simpson-Angus Scale score was found in any of the treatment arms. IMPLICATIONS/CONCLUSIONS: Our results do not support routine use of CYP2D6 testing as a predictor of drug-induced parkinsonism or akathisia risk in clinical settings. Further studies with larger samples of CYP2D6 poor metabolizers are needed.

Can Quetiapine Prolong the Antidepressant Effect of Ketamine?: A 5-Year Follow-up Study.

PURPOSE: Ketamine, a noncompetitive, high-affinity antagonist of the N-methyl-d-aspartate-type glutamate receptor, has a rapid effect in patients with treatment-resistant disorder, but many patients who respond to intravenous ketamine relapse within several days. The objective of this study was to examine the long-term outcome of patients' mood 5 years after ketamine treatment. METHODS: Sixteen electroconvulsive therapy referrals received at least 1 intravenous ketamine treatment in addition to their stable antidepressant medications. Depression was evaluated using the Inventory of Depressive Symptomatology-Clinician-Rated, Hamilton Rating Scales for Depression, and Montgomery-Åsberg Depression Rating Scale. Anxiety was measured using the Hamilton Rating Scale. RESULTS: Of 16 patients treated, 6 achieved complete remission, 3 partially responded, and 7 did not respond. At baseline, all patients were treated with antidepressants, 14 patients were also treated with neuroleptics, of whom 5 patients were treated with quetiapine. The time to relapse in the 5 patients taking quetiapine was significantly longer than in patients who were taking other neuroleptics (965.83 ± 824.68 vs 80.5 ± 114.3, Z = 7.001, P = 0.0001). At the 5-year follow-up, 3 of the patients taking quetiapine maintained their remission. Overall levels of depression and anxiety at all times were improved in comparison to baseline. CONCLUSIONS: Our follow-up results suggest that the combination of quetiapine and ketamine can prolong time to relapse after ketamine treatment in patients with treatment-resistant disorder.

Therapeutic potential of TAK-071, a muscarinic M1 receptor positive allosteric modulator with low cooperativity, for the treatment of cognitive deficits and negative symptoms associated with schizophrenia.

The selective activation of the muscarinic M1 receptor (M1R) may be a promising approach for treating cognitive impairment associated with cholinergic dysfunction. We previously reported that low cooperativity (α-value) is associated with a favorable cholinergic side effect profile of M1R positive allosteric modulators (M1 PAMs), as well as being a crucial factor for the cognitive improvement observed after combining M1 PAMs with donepezil, in rodents. In this study, we preclinically characterized TAK-071, a novel M1 PAM with low cooperativity (α-value = 199), as a new therapy for schizophrenia. We tested TAK-071 in the offspring of polyriboinosinic-polyribocytidylic acid-treated dams, which is a maternal immune activation model of schizophrenia. TAK-071 improved sociability deficits and working memory in this model. In a genetic mouse model of schizophrenia, miR-137 transgenic (Tg) mice, TAK-071 improved deficits in working memory, recognition memory, sociability, and sensorimotor gating. Patients with schizophrenia usually take several antipsychotics to treat positive symptoms. Thus, we also investigated the combined effects of TAK-071 with currently prescribed antipsychotics. Among the 10 antipsychotics tested, only olanzapine and quetiapine showed M1R antagonistic effects, which were counteracted by TAK-071 at possible effective concentrations for cognitive improvement in vitro. Moreover, haloperidol did not affect the ability of TAK-071 to improve working memory in miR-137 Tg mice, suggesting a low risk of losing efficacy when combined with dopamine D2 receptor antagonists. In conclusion, TAK-071 can exert beneficial effects on social behavior and cognitive function and could be a new therapy for schizophrenia.

The stability of quetiapine oral suspension compounded from commercially available tablets.

Quetiapine fumarate (QF) is an atypical antipsychotic used off-label for the treatment of delirium in critically-ill infants and children. For the treatment of pediatric populations or patient populations with trouble swallowing tablets, an oral suspension would be an ideal dosage formulation. However, there are no liquid formulations of QF commercially available. Therefore, a compounded oral suspension prepared from the commercial QF tablets is widely used in clinical settings. The extemporaneous preparation of QF compounded oral suspension changes the formulation from a solid form to a liquid form. Thus, the stability of QF compounded oral suspension should be critically evaluated to guide pharmacists for administration and storage of QF compounded oral suspensions. However, the stability of the nonaqueous oral QF suspension was not measured. The objective of this study was to develop QF compounded oral suspensions at 10 mg/mL by using commercial QF tablets in two readily available aqueous vehicles (Ora-Sweet and Ora-Blend) and measure their stability at both room temperature and under refrigeration. Physical stability of the QF compounded suspensions were evaluated by appearance and odor. Chemical stability of the QF compounded suspensions were evaluated based on pH, degradation, drug content and the amount of the drug dissolved in the vehicles. An HPLC method was validated and used to evaluate QF compounded suspensions over 60 days. In addition to the total drug in the suspensions, the dissolved drug in the vehicles was also measured during the stability testing and evaluated as a stability parameter. Overall, QF suspension prepared in Ora-Blend was preferable, demonstrating a superior 60-day stability at both room temperature and refrigerated storage.

Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report.

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 CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient's pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.

Successful diagnosis and treatment of pulmonary aspergillosis-related malignant catatonia using propofol and quetiapine: A case report.

INTRODUCTION: Malignant catatonia (MC) is a movement disorder syndrome characterized by immobility, rigidity, and consciousness disorders that develops in association with mental and physical diseases. It is often fatal due to hyperthermia, rhabdomyolysis, and acute kidney injury. Its clinical symptoms are similar to those of another disorder, neuroleptic malignant syndrome (NMS), and it is often difficult to distinguish between the 2 disorders. PATIENT CONCERNS: An Asian woman in her 60s with history of schizophrenia. She was admitted to our hospital because of symptoms such as fever, unconsciousness, and muscle rigidity. Blood tests showed kidney injury and high creatinine kinase levels. DIAGNOSES: At the time of admission, she had been diagnosed with NMS complicated by pulmonary aspergillosis and was undergoing treatment although there was no improvement. INTERVENTIONS: Subsequently, the administration of propofol, a gamma-aminobutyric acid A agonist, markedly improved the symptoms, and the diagnosis was corrected to MC. At the beginning of her hospitalization, she received dantrolene, bromocriptine, amantadine, and L-3,4-dihydroxyphenylalanine as treatment for NMS, but her symptoms did not improve. With propofol, which is used for sedation, her catatonic symptoms improved markedly. Quetiapine administration further improved the symptoms, and it eventually resolved completely. OUTCOMES: The patient's MC was in remission. Prolonged intensive care management resulted in a decline in activities of daily living, and she required rehabilitation at another hospital. CONCLUSION: This is the first report of MC with suspected involvement of pulmonary aspergillosis. MC differs from NMS, in that it is treated more effectively with gamma-aminobutyric acid A agonists. Although benzodiazepines are the first choice for the diagnosis and treatment of MC, they are ineffective for majority of patients with schizophrenia. However, even in such cases, propofol and quetiapine are effective, and they facilitate diagnosis and treatment.

Dose-response association of acute-phase quetiapine treatment with risk of new-onset hypothyroidism in schizophrenia patients.

AIMS: To assess association between quetiapine treatment and risk of new-onset hypothyroidism in schizophrenia patients. METHODS: We conducted a retrospective cohort study in a tertiary hospital in China between January 2016 and December 2018. Schizophrenia patients with normal thyroid tests at admission were included. Hypothyroidism, which was defined as thyroid-stimulating hormone >4.20 mU/L and free thyroxine <12.00 pmol/L, or on L-thyroxine prescriptions, was the outcome measure, and quetiapine treatment between admission and subsequent thyroid test was the exposure measure of this study. Adjusted relative risks and 95% confidence intervals were used to assess the independent association of quetiapine treatment with risk of new-onset hypothyroidism. The dose-response association was further analysed by 3 quetiapine doses: low (≤<=0.2 g/d), medium (0.2-0.6 g/d), and high (>0.6 g/d). RESULTS: A total of 2022 eligible patients were included in the final analysis. Sixty patients (15.0%) in the quetiapine group developed hypothyroidism, while 56 patients (3.5%) in the nonquetiapine group developed hypothyroidism. Relative risk (95% confidence interval) of developing hypothyroidism for quetiapine use was 4.01 (2.86-5.64) after adjusting for several potential confounding factors. A strong dose-response association between quetiapine use and risk of developing hypothyroidism was observed: adjusted relative risks (95% confidence intervals) were 1.00 (0.25-2.59), 4.22 (2.80-6.25) and 5.62 (3.66-8.38), respectively, for low-, medium- and high-dose quetiapine, as compared with no quetiapine. CONCLUSION: Acute phase quetiapine treatment for schizophrenia patients was strongly associated with increased risk of developing new-onset hypothyroidism, with a clear dose-response association.

Association of Low-Dose Quetiapine and Diabetes.

Importance: Quetiapine has been associated with increased risk of type 2 diabetes when used in medium or high doses for the treatment of severe mental disorders. It is not known whether low doses, commonly used off-label for sedative-hypnotic purposes, are also associated with increased risk of type 2 diabetes. Objective: To investigate whether there is an association between prescription of low-dose quetiapine and the risk of type 2 diabetes. Design, Setting, and Participants: This cohort study examined nationwide Danish health registers for data regarding new users of quetiapine (n = 185 938) or selective serotonin reuptake inhibitors (SSRIs) (n = 1 031 920) who were aged 18 years or older between January 1, 1998, and December 31, 2018. Individuals with schizophrenia or bipolar disorder were excluded. Quetiapine-initiators were matched 1:1 with initiators of SSRIs, using a high-dimensional propensity score (hdPS). Maximum follow-up was 5 years. Association with cumulative dose was investigated, using a case-control approach nested among quetiapine users. Data analysis was performed from May to September 2020. Exposures: Dispensing of quetiapine or SSRIs. Quetiapine prescriptions were limited to tablet strengths of 25 mg and 50 mg to focus on low-dose use. Main Outcomes and Measures: Incident type 2 diabetes was defined as first filling of an antidiabetic medication, first register diagnosis of type 2 diabetes or first hemoglobin A1C measurement greater than or equal to 6.4% (≥48 mmol/mol). Incidence rates (IRs), incidence rate ratios (IRRs), and number-needed-to-harm (NNH) were calculated for full and matched cohorts using as-treated and intention-to-treat approaches. Odds ratios (ORs) were calculated for the association with cumulative quetiapine dose. Results: Altogether, 896 285 patients were included in the full cohort; 538 164 (60%) were female and the median (interquartile range) age was 47 (33-67) years. There were 57 701 low-dose quetiapine initiators and 838 584 SSRI initiators. The matched cohort consisted of 54 616 pairs. In as-treated analyses, the incidence of type 2 diabetes during treatment with low-dose quetiapine (425 cases) was 9.59 cases/1000 person-years (PY) (95% CI, 8.72-10.5/1000 PY), which was slightly higher than for SSRI users (8462 cases; IR, 8.13/1000 PY; 95% CI, 7.96-8.30/1000 PY), resulting in a significant IRR of 1.18 (95% CI, 1.07-1.30) and NNH of 684 (95% CI, 418-1873). However, the between-group difference was nonsignificant in the hdPS-matched cohort (IR, 9.49 vs IR, 9.58; IRR, 0.99; 95% CI, 0.87-1.13). The case-control analysis found no dose-response association of low-dose quetiapine with diabetes (OR for doubling of the cumulative dose: 1.02; 95% CI, 0.95-1.09; P = .54), but in sensitivity analyses higher daily doses were associated with diabetes (all tablet strengths: OR, 1.08; 95% CI, 1.03-1.13). Conclusions and Relevance: In this cohort study, use of low-dose quetiapine was not associated with excess risk of type 2 diabetes in comparison with SSRIs.

The effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic paraventricular nucleus.

Antipsychotics, including amisulpride (AMI), quetiapine (QUE), aripiprazole (ARI), and olanzapine (OLA), are used to treat mental illnesses associated with psychotic symptoms. The effect of these drugs on c-Fos expression in vasopressinergic (AVP) and oxytocinergic (OXY) neurons was studied in the hypothalamic paraventricular nucleus (PVN) of rats. The presence of c-Fos in AVP and OXY perikarya was investigated in seven PVN cells segregations: the anterior (Ant), dorsal cup (Dc), wing-shaped (Wi), periventricular zone (Pe), circle-shaped core (Co) and shell of core (Sh), and the posterior (pPVN) after an acute treatment with AMI-20 mg/kg, QUE-15 mg/kg, ARI-10 mg/kg, and OLA-5 mg/kg/bw in rats. Ninety min after treatments, the animals were sacrificed by transcardial perfusion with fixative and the PVN area sliced into 35 µm thick coronal sections for immunohistochemistry. The c-Fos was processed by avidin-biotin-peroxidase complex intensified with nickel-enhanced 3,3'-diaminobenzidine tetrahydrochloride. Visualization of AVP- and OXY-synthesizing neurons was achieved by a fluorescent marker Alexa Flour 568. The c-Fos-AVP and c-Fos-OXY colocalizations were evaluated from c-Fos stained sections merged with AVP or OXY ones. AMI, QUE, ARI, and OLA, single administration distinctly increased the c-Fos expression in each of the PVN cells segregations. QUE induced the highest magnitude of activation of AVP and OXY neurons, while OLA and AMI had only moderate effects. Incontestable variabilities detected in c-Fos expression in PVN AVP and OXY neurons extend the knowledge of selected antipsychotics extra-striatal actions and may also be helpful in a presumption of their possible functional impact.

Effects of Quetiapine on Neural Tube Development in the Early Stage of Chicken Embryos.

AIM: To investigate the effects of quetiapine exposure on neural tube development in early stage chicken embryos. MATERIAL AND METHODS: Eighty-four fertilised specific pathogen-free chicken eggs were divided into four equal groups (groups 1?4). Three experimental groups (groups 2, 3 and 4) and a single control group (group 1) were used. Each egg in group 2 (n=21) was injected with 20 ?L of saline after 30 hours of incubation. Eggs in groups 3 and 4 were injected with 0.02 ml of a solution containing 400 and 800 ?g of quetiapine dose, respectively. Incubation was continued until the end of 72 hours. All embryos were then removed from the eggs and histopathologically examined. RESULTS: Normal development and the closed neural tubes were shown in 18, 16, 13 and 9 embryos in groups 1 2, 3 and 9, respectively, of the 84 embryos incubated. Open neural tubes were found in one, three and five embryos in groups 2, 3 and 5, respectively. Also, developmental anomalies were found in three, four, five and seven embryos in groups 1, 2, 3 and 4, respectively. Moreover, no significant relationship between NTD and quetiapine exposure had been found. CONCLUSION: Quetiapine has no significant effect on the occurrence of neural tube defects in the chicken embryo model.

A case of extended-release Quetiapine causing recurrent low-grade fevers.

This case highlights recurrent low-grade fevers caused by extended-release Quetiapine (Quetiapine XR), a previously unreported side effect, in a patient with Schizophreniform Disorder. While there have been case reports of Quetiapine causing neuroleptic malignant syndrome, there is paucity of data specifically describing recurrent low-grade fevers, with no other accompanying symptoms, caused by Quetiapine XR.

Neutropenia in Incarcerated Adolescents Secondary to Intranasal Quetiapine Misuse.

Objective: Between April 2015 and May 2016, a number of young males incarcerated at a Youth Justice center in New South Wales, Australia, were noted to have unexplained and significant neutropenia. None of the adolescents were prescribed quetiapine; however, it was prescribed for other young people in the center for this time period. The authors undertook a case series review to investigate the cause of this neutropenia. Methods: Case series review, including review of all pathology, electrocardiograms, medication charts, and medical file notes. Results: Quetiapine was used in the center; however, none of the young people with neutropenia were prescribed quetiapine (or any other medication causing neutropenia). During the assessments of these young people, it was found that the administration of quetiapine had changed during this time period to using pulverized quetiapine powder, administered after hours to young people when there were no health center staff available to supervise. On questioning, two neutropenic young people admitted to "snorting" diverted quetiapine powder. All instances of neutropenia resolved once the medication was removed from the center. Conclusions: Quetiapine has a high potential for abuse, especially in custodial settings. Quetiapine should never be crushed as this increases the potential for diversion, misuse, and serious side effects. Quetiapine misuse should be considered part of the differential diagnosis of unexplained neutropenia, especially in a setting where the drug is available.

Lurasidone, olanzapine, and quetiapine extended-release for bipolar depression: A systematic review and network meta-analysis of phase 3 trials in Japan.

AIM: This systematic review and random-effect model, network meta-analysis of the phase 3 trials in Japan assessed the efficacy and safety profile of lurasidone compared with olanzapine and quetiapine extended-release (QUE-XR) for the treatment of bipolar depression. METHODS: The study included double-blind, randomized, placebo-controlled, phase 3 trials in Japan that included patients with bipolar depression. Outcomes included response rate (primary), remission rate (secondary), improvement of Montgomery-Åsberg Depression Rating Scale (MADRS) total score, discontinuation rates, and incidence of individual adverse events. RESULTS: Three studies were included (n = 1223). Lurasidone and olanzapine but not QUE-XR were superior to placebo in response rate [risk ratio (95% credible interval): lurasidone = 0.78 (0.66, 0.92); olanzapine = 0.84 (0.71, 0.99); QUE-XR = 0.87 (0.73, 1.03)]. Lurasidone, olanzapine and QUE-XR were superior to placebo in remission rate [lurasidone = 0.90 (0.83, 0.98); olanzapine = 0.87 (0.77, 0.99); QUE-XR = 0.84 (0.73, 0.98)] and the improvement of MADRS total score. There were not differences in discontinuation rates between each antipsychotic and placebo. Compared with placebo, lurasidone was higher incidence of akathisia, and increased body weight and blood prolactin level; olanzapine was higher incidence of somnolence and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels; QUE-XR was higher incidence of extrapyramidal symptoms, akathisia, somnolence, dry mouth, constipation and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels. CONCLUSIONS: Our results suggested although the efficacy of three SGAs was similar, there were the differences in the safety profile among the SGAs.

Anabolic steroids-induced delirium: A case report.

INTRODUCTION: Anabolic steroids are commonly used by athletes, body builders, and young adults to improve muscle strength. Deleterious effects of anabolic steroids on physical health are well-established. Psychiatric aspects are of particular importance and include psychosis, delirium, mania, depression, and aggression. We describe the case of a young gentleman who was managed as a case of androgenic steroid induced delirium. PATIENT CONCERN: A 33-year-old gentleman presented with increased aggression, hostility, and destructive impulses. He was a regular user of testosterone propionate, testosterone cyprionate and trenbolone acetate up to 200 mg daily in injectable form. His mental status examination showed labile effect, flight of ideas and persecutory delusions. Physical examination was positive for atrophic testes. Laboratory results showed a decreased plasma testosterone level of 9.59 nmol/l (10.4-37.4 nmol/l). Sex Hormone Binding Globulin was 23.8 nmol/l (18.3-54.1 nmol/l) and bioavailable testosterone was 5.110 nmol/l (4.36-14.30 nmol/l). DIAGNOSIS: He was diagnosed as a case of anabolic steroids induced delirium. INTERVENTIONS AND OUTCOME: Patient was treated with regular haloperidol and quetiapine after which his sensorium, speech and behavior improved. He was discharged on haloperidol 7.5 mg and quetiapine 700 mg daily. CONCLUSION: The purpose of this case report is to emphasize on the neuropsychiatric effects and management of anabolic steroids manifested by delirium, increased aggression, hostility, and destructive impulses.

Aparición de clínica obsesiva tras infarto cerebrovascular. a propósito de un caso / Onset of obsessive symptoms after a cerebrovascular stroke. with regard to a case

Se presenta el caso clínico de un paciente de 72 años sin antecedentes psiquiátricos previos que ingresa en el Servicio de Neurología por infarto cerebral en territorio vertebrobasilar. Durante el ingreso presenta elevada ansiedad secundaria a una ideación obsesiva de contenido erótico con intensa repercusión emocional y conductual. Se inicia tratamiento sintomático con Quetiapina, observándose mejoría progresiva del cuadro hasta la total recuperación del paciente. En el presente artículo se revisa la relación entre las diferentes áreas anatómicas cerebrales y la aparición de clínica obsesiva

A 72 year old male without previous psychiatric history is admitted to the neurology department due to vertebrobasilar stroke. During the stay, the patient manifests a high level of anxiety related to the onset of an erotic obsessive idea with an intense emotional and behavioural repercussion. Symptomatic treatment with quetiapine was started, with a progressive improvement of the symptoms until it's complete resolution. In the present article, we aim to review the relationship between the different brain anatomical areas and the onset of obsessive symptoms

Esquema de tratamiento escalonado no opioide para reducir la adicción a la morfina: reporte de un caso / Non-opioid staircase treatment scheme to reduce morphine addiction: a case report

Los opiáceos son sustancias que se utilizan en la práctica clínica por sus propiedades analgésicas. Sin embargo, se ha visto que estos medicamentos generan adicción y dependencia, lo cual es un riesgo para los pacientes de no existir un adecuado control y seguimiento por parte del personal de salud. Reportamos el caso de una paciente mujer joven con adicción crónica a la morfina la cual acudió al establecimiento de salud por presentar mialgias, diaforesis y escalofríos. Fue estabilizada en la emergencia y diagnosticada con un Síndrome de Abstinencia secundaria a su adicción. Debido a que el establecimiento no contaba con los fármacos de elección para esta enfermedad, la paciente fue dada de alta con la siguiente terapéutica: ácido valproico, gabapentina, mirtazapina y quetiapina. Al momento de realizado este reporte, la paciente estaba cursando su cuarto mes de tratamiento con una mejoría clínica considerable. Presentamos el caso debido a la importancia de poder manejar otros esquemas de tratamiento para esta enfermedad

Opioids are substances that are commonly used in clinical practice because of their analgesic properties. However, there is evidence that these drugs generate addiction and dependence, becoming a risk for the patients in the absence of adequate control and following by health professionals. We report the case of a young female patient with a chronic addiction to morphine who arrived to the health facility due to myalgia, diaphoresis and chills. She was stabilized in the emergency service and diagnosed with Opioid Withdrawal Syndrome. Due to the fact that the establishment did not have the first line therapy, the patient was discharged from the hospital with the following medication: valproic acid, gabapentin, mirtazapine and quetiapine. At the time of this report, the patient was in her fourth month of treatment with considerable clinical improvement. We present this case due to the importance of being able to handle other therapeutic schemes for this disease