Quetiapine Treatment Research Articles

Treatment of bipolar depression: clinical practice vs. adherence to guidelines-data from a Bavarian drug surveillance project.

Pharmacotherapy of bipolar depression (BPD) is confronted with major clinical challenges, like limited evidence-based treatment options, regular cases of treatment resistance, and risk of treatment-emergent affective switches. Medical guidelines can support practitioners to make decisions based on current scientific evidence. The objective of this study is to evaluate to what extent recommendations of the 2019 German S3 guidelines "Diagnosis and Treatment of Bipolar Disorders" are reflected in clinical practice in inpatient treatment. We conducted a descriptive analysis of prescription numbers in 2,627 patients with BPD in a naturalistic inpatient setting analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014-2022. Of the patients, 38% were not administered any drug explicitly recommended for treatment of BPD, that is, quetiapine, lamotrigine, carbamazepine, or olanzapine. Only 6% of the patients received monotherapy with one of those drugs. Of the patients, 34% were administered ≥4 psychotropic drugs simultaneously. Patients received 912 different therapy regimens of mono or combination therapy with mood stabilizers (MS), atypical antipsychotics (AAP), and antidepressants. Of the patients, 72% received an antidepressant and 6% without concomitant prescription of an AAP or MS. Prescription rates of venlafaxine (21% to 14%) and tricyclic antidepressants (9% to 6%) decreased significantly from the first (2014-2016) to the last (2020-2022) observed time period. Of the patients, 60% received an MS. Prescription rate of valproate (22% to 14%) decreased significantly, while lithium prescription increased significantly (29% to 35%). Of the patients, 71% were administered an AAP. Quetiapine was the most prescribed drug overall (43%). Only two patients were administered a combination of olanzapine and fluoxetine. Our results demonstrate a substantial gap between guideline recommendations and current clinical practice. The remarkable heterogeneity in treatment regimens, with no discernible dominant treatment approach, is in part a reflection of the complexity of bipolar disorder but also substantiates the need of comprehensive recommendations regarding combination therapies. Increase in lithium prescription is an encouraging development due to its unique efficacy in maintenance treatment. To improve the quality of clinical practice guideline implementation, more randomized controlled trials shouldbeconducted in the future to prospectively investigate different implementation strategies.

Serum S100B protein and white matter changes in schizophrenia before and after medication

Schizophrenia patients have abnormalities in white matter (WM) integrity in brain regions. S100B has been shown to be a marker protein for glial cells. The atypical antipsychotics have neuroprotective effects on the brain. It is not clear whether antipsychotics can induce S100B changes and improve symptoms by protecting oligodendrocytes. To investigate WM and S100B changes and associations and determine the effect of quetiapine on WM and S100B in schizophrenia patients, we determined serum S100B levels with solid phase immunochromatography and fractional anisotropy（FA）values of 36 patients and 40 healthy controls. Patients exhibited significantly higher serum concentrations of S100B and decreased FA values in left postcentral，right superior frontal，right thalamus, and left inferior occipital gyrus, while higher in right temporal cortex WM compared with healthy controls. Following treatment with quetiapine, patients had decreased S100B and higher FA values in right cerebellum，right superior frontal，right thalamus, and left parietal cortex，and decreased FA values in right temporal cortex WM compared with pre-treatment values. Furthermore, S100B were negatively correlated with PANSS positive scores and positively correlated with FA values in the left postcentral cortex. In addition，the percentage change in FA values in the right temporal cortex was positively correlated with the percentage change in the S100B, percentage reduction in PANSS scores, and percentage reduction in PANSS-positive scores. Our findings demonstrated abnormalities in S100B and WM microstructure in patients with schizophrenia. These abnormalities may be partly reversed by quetiapine treatment.

Quetiapine Oral Solution in Alzheimer's Disease: Efficacy and Dosage Insights from a Real-World Retrospective Study.

Neuropsychiatric symptoms (NPS) are distressing for patients with dementia, often accelerating functional decline and nursing home placement. Medications such as quetiapine are used to alleviate NPS, but their side effects require cautious use. Liquid formulations such as quetiapine oral suspension suit specific populations; however, real-world data on their use in patients with dementia are limited. The purpose of this retrospective, naturalistic study was to provide preliminary data on the effects of treatment with quetiapine oral suspension on behavioral and psychiatric disturbances in Alzheimer's disease (AD) outpatients in Taiwan. Between January 2022 and June 2023, data were collected from outpatients with a diagnosis of probable AD who received treatment with Qting® (quetiapine oral solution 25 mg/ml). Primary outcome measures were changes in Neuropsychiatric Inventory (NPI) total score and its sub-items from baseline to the endpoint. We recruited 66 AD patients with a mean age of 72.1±7.6 years, most of whom were female (69.7%). Twenty-three patients had data on neuropsychological test and NPI scores before and after quetiapine treatment. There was no significant change in global cognitive function from baseline to the endpoint. A significant reduction in NPI total score after quetiapine treatment was noted, while the effect on NPI sub-items was limited. The average maintenance dose was 1.5±0.6 ml. We demonstrated our clinical experience of the use of quetiapine oral solution in AD patients with NPS. Our results showed that quetiapine oral solution treatment significantly improved these symptoms at a relatively low dose.

Predicting quetiapine dose in patients with depression using machine learning techniques based on real-world evidence

BackgroundBeing one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens.MethodsThe study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model.ResultsFour predictors were selected from 38 variables by the univariate analysis (p < 0.05), including quetiapine TDM value, age, mean corpuscular hemoglobin concentration, and total bile acid. Ultimately, the XGBoost algorithm was used to create a prediction model for quetiapine dose that had the greatest predictive performance (accuracy = 0.69) out of nine models. In the testing cohort (62 cases), a total of 43 cases were correctly predicted of the quetiapine dose regimen. In dose subgroup analysis, AUROC for patients with daily dose of 100 mg, 200 mg, 300 mg and 400 mg were 0.99, 0.75, 0.93 and 0.86, respectively.ConclusionsIn this work, machine learning techniques are used for the first time to estimate the dose of quetiapine for patients with depression, which is valuable for the clinical drug recommendations.

Mechanism of cognitive impairment and white matter damage in the MK-801 mice model of schizophrenia treated with quetiapine

Schizophrenia has been linked to cognitive impairment and white matter damage in a growing number of studies this year. In this study, we used the MK-801-induced schizophrenia-like mice model to investigate the effects of quetiapine on behavioral changes and myelin loss in the model mice. The subjects selected for this study were C57B6/J male mice, MK-801 (1 mg/kg/d intraperitoneal injection) modeling for 1 week and quetiapine (10 mg/kg/d intraperitoneal injection) treatment for 2 weeks. Behavioral tests were then performed using the three-chamber paradigm test and the Y maze test. Moreover, western blot, immunohistochemistry, and immunofluorescence were conducted to investigate the changes in oligodendrocyte spectrum markers. In addition, we performed some mechanism-related proteins by western blot. Quetiapine ameliorated cognitive impairment and cerebral white matter damage in MK-801 model mice, and the mechanism may be related to the PI3K/AKT pathways. The present study suggests that quetiapine has a possible mechanism for treating cognitive impairment and white matter damage caused by schizophrenia.

Impact of age, sex and cytochrome P450 genotype on quetiapine and N-desalkylquetiapine serum concentrations: A study based on real-world data from 8118 patients.

To investigate the effect of aging, sex and cytochrome P450 (CYP) genotypes on the exposure of quetiapine (QUE) and the pharmacologically active metabolite N-desalkylquetiapine (NDQ). Patients with serum concentrations of QUE and NDQ were included retrospectively from a therapeutic drug monitoring service. The outcome measures were concentration:dose (C:D) ratios of QUE and NDQ, and NDQ:QUE metabolic ratio. Linear mixed model analyses were used to evaluate the effects of age, sex and, subsequently, CYP2D6/3A genotypes. The average age of the included population (n= 8118 patients) was 44 years (13.5% ≥65 years). The C:D ratio of QUE and NDQ gradually increased in patients aged >50 years compared to those aged 18-30 years, with 28 and 29% increase, respectively, for patients aged >70 years (P< .001). Compared to males, females had 15% lower QUE C:D ratio and 10% higher C:D ratio of NDQ (both P< .001). The NDQ:QUE metabolic ratio was 30% higher in females than in males (P< .001). For females ≥65 years, the NDQ C:D ratio was 36% higher compared to males <65 years (P< .001). A significantly higher NDQ C:D ratio was observed for CYP2D6 intermediate (+7%, P= .012) and poor (+17%, P= .001) compared to normal metabolizers. No effects of CYP3A4*22 and CYP3A5*1 allele variants were observed. This study shows an increase of the QUE and NDQ exposures during aging. Old age, female sex and CYP2D6 allele variants encoding reduced activity are factors associated with high NDQ exposure. Therefore, females ≥65 years carrying CYP2D6 allele variants encoding reduced activity have the highest risk of dose-dependent side effects of NDQ during QUE treatment.

Cardiac adverse events associated with quetiapine: Disproportionality analysis of FDA adverse event reporting system.

Quetiapine, an atypical second-generation antipsychotic drug, is approved for treatment of schizophrenia, bipolar disorder, and depression. Due to the limitations of clinical trials, the association between quetiapine and rare cardiac adverse events (AEs) is still unclear. This study is to evaluate quetiapine-associated cardiac AEs through data mining of FDA Adverse Event Reporting System (FAERS). Reporting odds ratio (ROR) was used to quantify the signals of quetiapine-related cardiac AEs from the first quarter (Q1) of 2018-2022 Q1. Serious and nonserious cases were compared, and signals were prioritized using a rating scale. A total of 1004 cases of quetiapine-associated cardiac AEs were identified, with 31 signals being detected, among which 13 AEs were identified as new and unexpected signals. Besides, nine and 22 cardiac AEs were identified as moderate and weak clinical priority. The median TTO for moderate and weak clinical priority signals were 0 and 4 days, respectively. All of the cardiac AEs had early failure type characteristics, suggesting that most of the patients developed cardiac AEs in a few days after quetiapine treatment, and that the risk of cardiac AEs occurrence would be gradually decreased over time. Our study provided valuable evidence for health-care professionals to mitigate the risk of quetiapine-associated cardiac AEs based on an extensive analysis of a real-world, large-sample FAERS database, and prioritize cardiac AE signals.

Quetiapine Treatment for Post-traumatic Stress Disorder: A Systematic Review of the Literature

Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate clinical response. Second generation antipsychotics are recommended as second-line monotherapy or third-line augmentation strategies and quetiapine appears as one of the most used and promising agents. Up to date, no reviews assessed the efficacy of quetiapine in the treatment of PTSD. We aimed to assess the effectiveness and general safety of quetiapine on PTSD. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting studies that evaluated the efficacy of quetiapine on global or specific PTSD symptomatology. Ten studies (n = 894) were considered eligible for qualitative synthesis: one case report, one case series, one prospective cohort study, 3 open-label trials, 3 retrospective studies, one randomized controlled trial. Quetiapine was effective on global PTSD symptomatology assessed in 6 studies as well as on re-experiencing (4/4 studies), avoidance (4/3 studies) and hyperarousal (4/4 studies), flashbacks (2/2 studies), depressive (4/4 studies), anxiety (1/1 studies), psychotic (3/3 studies), insomnia (4/5 studies), nightmares (3/3 studies) specific symptoms and PTSD domains. Sedation was among the most frequently observed adverse effects and the main cause of drug discontinuation. Preliminary findings support the efficacy of quetiapine in ameliorating symptoms relative to PTSD and its overall safety. However, quetiapine use in PTSD cannot be recommended yet as studies mainly rely on open-label, retrospective studies or case series.

Treatment with the second-generation antipsychotic quetiapine is associated with increased subgenual ACC activation during reward processing in major depressive disorder

BackgroundThe second-generation antipsychotic (SGA) quetiapine is an essential option for antidepressant augmentation therapy in major depressive disorder (MDD), yet neurobiological mechanisms behind its antidepressant properties remain unclear. As SGAs interfere with activity in reward-related brain areas, including the anterior cingulate cortex (ACC) — a key brain region in antidepressant interventions, this study examined whether quetiapine treatment affects ACC activity during reward processing in MDD patients. MethodsUsing the ACC as region of interest, an independent t-test comparing reward-related BOLD response of 51 quetiapine-taking and 51 antipsychotic-free MDD patients was conducted. Monetary reward outcome feedback was measured in a card-guessing paradigm using pseudorandom blocks. Participants were matched for age, sex, and depression severity and analyses were controlled for confounding variables, including total antidepressant medication load, illness chronicity and acute depression severity. Potential dosage effects were examined in a 3 × 1 ANOVA. Differences in ACC-related functional connectivity were assessed in psycho-physiological interaction (PPI) analyses. ResultsLeft subgenual ACC activity was significantly higher in the quetiapine group compared to antipsychotic-free participants and dependent on high-dose quetiapine intake. Results remained significant after controlling for confounding variables. The PPI analysis did not yield significant group differences in ACC-related functional connectivity. LimitationsCausal interpretation is limited due to cross-sectional findings. ConclusionElevated subgenual ACC activity to rewarding stimuli may represent a neurobiological marker and potential key interface of quetiapine's antidepressant effects in MDD. These results underline ACC activity during reward processing as an investigative avenue for future research and therapeutic interventions to improve MDD treatment outcomes.

Brain-gut microbiota multimodal predictive model in patients with bipolar depression

BackgroundThe “microbiota-gut-brain axis” which bridges the brain and gut microbiota is involved in the pathological mechanisms of bipolar disorder (BD), but rare is known about the exact association patterns and the potential for clinical diagnosis and treatment outcome prediction. MethodsAt baseline, fecal samples and resting-state MRI data were collected from 103 BD depression patients and 39 healthy controls (HCs) for metagenomic sequencing and network-based functional connectivity (FC), grey matter volume (GMV) analyses. All patients then received 4-weeks quetiapine treatment and were further classified as responders and non-responders. Based on pre-treatment datasets, the correlation networks were established between gut microbiota and neuroimaging measures and the multimodal kernal combination support vector machine (SVM) classifiers were constructed to distinguish BD patients from HCs, and quetiapine responders from non-responders. ResultsThe multi-modal pre-treatment characteristics of quetiapine responders, were closer to the HCs compared to non-responders. And the correlation network analyses found the substantial correlations existed in HC between the Anaerotruncus_ unclassified，Porphyromonas_asaccharolytica，Actinomyces_graevenitzii et al. and the functional connectomes involved default mode network (DMN),somatomotor (SM), visual, limbic and basal ganglia networks were disrupted in BD. Moreover, in terms of the multimodal classifier, it reached optimized area under curve (AUC-ROC) at 0.9517 when classified BD from HC, and also acquired 0.8292 discriminating quetiapine responders from non-responders, which consistently better than even using the best unique modality. LimitationsLack post-treatment and external validation datasets; size of HCs is modest. ConclusionsMulti-modalities of combining pre-treatment gut microbiota with neuroimaging endophenotypes might be a superior approach for accurate diagnosis and quetiapine efficacy prediction in BD.

Association between quetiapine use and self-harm outcomes among people with recorded personality disorder in UK primary care: A self-controlled case series analysis.

Quetiapine is frequently prescribed to people with personality disorder diagnoses, but this is not supported by evidence or treatment guidelines. To examine associations between periods of quetiapine prescribing and self-harm events in people with personality disorder. Self-controlled case series using linked primary care and hospital records covering the period 2007-2017. We calculated incidence rates and incidence rate ratios (IRRs) for self-harm events during periods when people were prescribed (exposed to) quetiapine, as well as periods when they were unexposed or pre-exposed to quetiapine. We analysed data from 1,082 individuals with established personality disorder diagnoses, all of whom had at least one period of quetiapine prescribing and at least one self-harm episode. Their baseline rate of self-harm (greater than 12 months before quetiapine treatment) was 0.52 episodes per year. Self-harm rates were elevated compared to the baseline rate in the month after quetiapine treatment was commenced (IRR 1.85; 95% confidence interval (CI) 1.46-2.34) and remained raised throughout the year after quetiapine treatment was started. However, self-harm rates were highest in the month prior to quetiapine initiation (IRR 3.59; 95% CI 2.83-4.55) and were elevated from 4 months before quetiapine initiation, compared to baseline. Self-harm rates were elevated throughout the first year of quetiapine prescribing, compared to the baseline rate. However, rates of self-harm reduced in the month after patients commenced quetiapine, compared to the month before quetiapine was initiated. Self-harm rates gradually dropped over a year of quetiapine treatment. Quetiapine may acutely reduce self-harm. Longer-term use and any potential benefits need to be balanced with the risk of adverse events.

Inflammatory markers at baseline correlate with subsequent clinical response to quetiapine in patients with bipolar disorder.

Recent studies proposed the existence of a correlation between patients' inflammatory status and therapy response in bipolar disorder (BD). Here we investigated the correlation between levels of inflammatory markers and quetiapine (QUE) effects in BD patients. In 15 hospitalised BD patients, we investigated changes in inflammatory markers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and cytokines after a 6-week treatment with QUE monotherapy. We found QUE treatment to significantly reduce CRP and IL-6 plasma levels. Moreover, we found higher CRP and IL-6 plasma levels at baseline correlated with better improvement of patients' clinical symptoms. The reported results, although preliminary, could be useful in clinical practice, providing not only markers for QUE response, but also allowing for identification of new targets and new therapies for the treatment of this condition.

Pretreatment Alterations and Acute Medication Treatment Effects on Brain Task-Related Functional Connectivity in Youth With Bipolar Disorder: A Neuroimaging Randomized Clinical Trial.

Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established. A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition. At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls. Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD. Multimodal Neuroimaging of Treatment Effects in Adolescent Mania; https://clinicaltrials.gov/; NCT00893581.

Impaired central set point of thyroid homeostasis during quetiapine treatment in the acute phase of schizophrenia

AimTo evaluate the impact of quetiapine treatment on central set point of thyroid homeostasis in patients with acute phase schizophrenia. MethodsDuring Jan. 2016 to Dec. 2018, we conducted a retrospective cohort study in “the Second Affiliated Hospital of Xinxiang Medical University”. All patients admitted for treatment of schizophrenia being euthyroid at admission and reevaluated for thyroid function during hospitalization were recruited and followed until discharge. Patients treated with mood stabilizers during hospitalization were excluded. Quetiapine use was the exposure measure. The primary outcomes were the parameters of central set point of thyroid homeostasis measured by “thyroid-stimulating hormone (TSH) index” and “thyroid feedback quantile-based index (TFQI)”. Multiple regression models were used to estimate the association between quetiapine exposure and outcomes. ResultsA total of 1302 patients were enrolled in this study. Quetiapine exposure was associated with a more significant decline in the TSH index and TFQI, and the adjusted β and 95% confidence interval (CI) were −0.12 (−0.22, −0.01) and −0.10 (−0.15, −0.05), respectively. A dose-response association between quetiapine exposure and decline in TSH index and TFQI was observed (P < 0.05). Sensitivity analyses restricting to patients under mono-atypical antipsychotic therapy, or selecting patients in the non-quetiapine group matched to quetiapine group yielded similar results. ConclusionQuetiapine was associated with TSH index and TFQI reduction in a dose-response pattern, suggesting that impaired central set point may be involved in the mechanism by which quetiapine affects hypothalamus-pituitary-thyroid axis in acute phase schizophrenia patients.

Quetiapine Combined with Sodium Valproate in Patients with Alzheimer's Disease with Mental and Behavioral Symptoms Efficacy Observation.

Quetiapine combined with sodium valproate is an effective and more suitable drug treatment for Alzheimer's disease. At present, there are relatively few studies on the combined action mechanism of these two drugs. This study has certain practical value. Alzheimer's disease is a multifaceted, highly genetically heterogeneous neurodegenerative disease. The main clinical manifestations are memory loss, abnormal mental behavior, and loss of various cognitive functions. In order to improve the symptoms of patients with Alzheimer's disease, especially those with mental symptoms, this article combines quetiapine and sodium valproate, two commonly used drugs for the treatment of mental illnesses, and applies them to different levels of Alzheimer's and observes the results of the combination's curative effect. This article introduces Alzheimer's disease and its potential mental behaviors in the method section, and it also introduces the mechanism of action of quetiapine and sodium valproate. For the algorithm, this paper introduces a data mining algorithm to understand the effect of drug efficacy. In the experimental part, firstly, it introduces the experimental objects, the proportion of medicines, and the statistical methods. Secondly, this article covers adverse reactions, inflammatory factors and vascular endothelial indicators, Alzheimer's disease performance, MOAS score, treatment effect evaluation, and satisfaction surveys. It can be seen from the experiment that, in mental behavior, the experimental group decreased from 8.2 before treatment to 0.5, and the control group decreased from 7.1 before treatment to 2.6. It can be seen that the scores of the experimental group changed after receiving the treatment of quetiapine combined with sodium valproate.

Metagenomic analysis reveals gut bacterial signatures for diagnosis and treatment outcome prediction in bipolar depression

BackgroundWe aimed to characterize gut microbial alterations in depressed patients with bipolar disorder (BD) following quetiapine monotherapy and explored its potential for disease diagnosis and outcome prediction. MethodsFecal samples were obtained from 60 healthy individuals and 62 patients in acute depressive episodes. All patients received one-month quetiapine treatment after enrollment. The structure of gut microbiota was measured with metagenomic sequencing, and its correlation with clinical profiles and brain function as indicated by resting-state functional magnetic resonance imaging was analyzed. Random forest models based on bacterial species were constructed to distinguish patients from controls, and responders from non-responders, respectively. ResultsBD patients displayed specific alterations in gut microbial diversity and composition. Quetiapine treatment increased the diversity of microbial communities and changed the composition. The abundance of Clostridium bartlettii was negatively associated with age, baseline depression severity, while positively associated with spontaneous neural oscillation in the hippocampus. Tree-based classification models for (1) patients and controls and (2) responders and non-responders showed an area under the curve of 0.733 and 0.800, respectively. ConclusionOur findings add new evidence to the existing literature regarding gut dysbiosis in BD and reveal the potential of microbe-based biomarkers for disease diagnosis and treatment outcome prediction.

The inhibitory effect and mechanism of quetiapine on tumor progression in hepatocellular carcinoma in vivo.

Hepatocellular carcinoma (HCC) is the primary tumor of the liver and the fourth leading cause of cancer‐related death. Recently, several studies indicated the anti‐tumor potential of antipsychotic medicine. Quetiapine, an atypical antipsychotic, is used to treat schizophrenia, bipolar disorder, and major depressive disorder since 1997. However, whether quetiapine may show potential to suppress HCC progression and its underlying mechanism is persisting unclear. Quetiapine has been shown to induce apoptosis and inhibit invasion ability in HCC in vitro. Here, we established two different HCC (Hep3B, SK‐Hep1) bearing animals to identify the treatment efficacy of quetiapine. Tumor growth, signaling transduction, and normal tissue pathology after quetiapine treatment were validated by caliper, bioluminescence image, immunohistochemistry (IHC), and hematoxylin and eosin staining, respectively. Quetiapine suppressed HCC progression in a dose‐dependent manner. Extracellular signal‐regulated kinases (ERKs) and Nuclear factor‐κB (NF‐κB) mediated downstream proteins, such as myeloid leukemia cell differentiation protein (MCL‐1), cellular FLICE‐inhibitory protein (C‐FLIP), X‐linked inhibitor of apoptosis protein (XIAP), Cyclin‐D1, matrix metallopeptidase 9 (MMP‐9), vascular endothelial growth factor‐A (VEGF‐A) and indoleamine 2,3‐dioxygenase (IDO) which involved in proliferation, survival, angiogenesis, invasion and anti‐tumor immunity were all decreased by quetiapine. In addition, extrinsic/intrinsic caspase‐dependent and caspase‐independent pathways, including cleaved caspase‐3, −8, and − 9 were increased by quetiapine. In sum, the tumor inhibition that results from quetiapine may associate with ERK and NF‐κB inactivation.

Direct targeting of wild-type glucocerebrosidase by antipsychotic quetiapine improves pathogenic phenotypes in Parkinson's disease models.

Current treatments for Parkinson’s disease (PD) provide only symptomatic relief, with no disease-modifying therapies identified to date. Repurposing FDA-approved drugs to treat PD could significantly shorten the time needed for and reduce the costs of drug development compared with conventional approaches. We developed an efficient strategy to screen for modulators of β-glucocerebrosidase (GCase), a lysosomal enzyme that exhibits decreased activity in patients with PD, leading to accumulation of the substrate glucosylceramide and oxidized dopamine and α-synuclein, which contribute to PD pathogenesis. Using a GCase fluorescent probe and affinity-based fluorescence polarization assay, we screened 1280 structurally diverse, bioactive, and cell-permeable FDA-approved drugs and found that the antipsychotic quetiapine bound GCase with high affinity. Moreover, quetiapine treatment of induced pluripotent stem cell–derived (iPSC-derived) dopaminergic neurons from patients carrying mutations in GBA1 or LRRK2 led to increased wild-type GCase protein levels and activity and partially lowered accumulation of oxidized dopamine, glucosylceramide, and α-synuclein. Similarly, quetiapine led to activation of wild-type GCase and reduction of α-synuclein in a GBA mutant mouse model (Gba1D409V/+ mice). Together, these results suggest that repurposing quetiapine as a modulator of GCase may be beneficial for patients with PD exhibiting decreased GCase activity.

Quetiapine-Induced Thyroid Dysfunction: A Systematic Review.

Thyroid abnormalities are documented consequences of quetiapine treatment. This may have clinical implications as changes in thyroid hormones may deteriorate a person's affective state. Yet less is known about the clinical factors and underlying mechanisms associated with thyroid hormones on quetiapine therapy. We therefore systematically reviewed the published literature of evidence of quetiapine-induced thyroid abnormalities. We searched MEDLINE, PsycINFO, Google Scholar, and EMBASE for articles in which individuals developed biochemically confirmed thyroid abnormalities (with or without clinical symptoms) while on quetiapine treatment. We included case reports, case series, observational, and experimental studies. We included 32 studies, 20 of which were observational and experimental studies. There were 10 case reports and 1 case series. All the research designs suggested an association between quetiapine and hypothyroidism. However, these findings were limited by the quality of the included studies and the general lack of either a clear temporal relationship or dose response. Quetiapine has been associated with thyroid abnormalities, mainly with hypothyroidism. Drug imputability in these abnormalities is not always clear, and the underlying pathophysiology may include immunological and nonimmunological mechanisms. Large prospective studies are required to clarify this association and to further inform the management of patients treated with quetiapine where hypothyroidism occurs.

A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder.

Objective: To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or mixed episodes in youths with early course bipolar I disorder. Methods: Six-week, randomized, double-blind clinical trial of lithium versus quetiapine for the treatment of adolescents with acute manic/mixed episode. Target dose of quetiapine dose was adjusted to a target dose of 400-600 mg and target serum level for lithium was 1.0-1.2 mEq/L. Primary outcome measure was baseline-to-endpoint change in the Young Mania Rating Scale (YMRS). Secondary outcomes were treatment response (50% or more decrease from baseline in YMRS score) and remission (YMRS score ≤12, Children's Depression Rating Scale-Revised [CDRS-R] total score ≤28 and Clinical Global Impression Bipolar Severity Scale [CGI-BP-S] overall score of ≤3, respectively). Results: A total of 109 patients were randomized (quetiapine = 58 and lithium = 51). Participants in the quetiapine treatment group showed a significantly greater reduction in YMRS score than those in the lithium group (-11.0 vs. -13.2; p < 0.001; effect size 0.39). Response rate was 72% in the quetiapine group and 49% in the lithium group (p = 0.012); no differences in remission rates between groups were observed. Most frequent side effects for lithium were headaches (60.8%), nausea (39.2%), somnolence (27.5%), and tremor (27.5%); for quetiapine somnolence (63.8%), headaches (55.2%), tremor (36.2%), and dizziness (36.2%) were evidenced. Participants receiving quetiapine experienced more somnolence (p < 0.001), dizziness (p < 0.05), and weight gain (p < 0.05). Conclusions: Treatment with both lithium and quetiapine led to clinical improvement. Most study participants in this study experienced a clinical response; however, less than half of the participants in this study achieved symptomatic remission. The head-to-head comparison of both treatment groups showed quetiapine was associated with a statistically significant greater rate of response and overall symptom reduction compared with lithium. Trial registration: clinicaltrials.gov NCT00893581.