Quetiapine Group Research Articles

Effects of long-term therapy with quetiapine and olanzapine on parameters of immunity and cytokine levels in patients with schizophrenia

IntroductionThe study of effects of long-term antipsychotic therapy in patients with schizophrenia is relevant.ObjectivesTo study effects of long-term antipsychotic therapy on parameters of immunity and cytokine levels in patients with schizophrenia.MethodsWe examined 20 schizophrenic patients, who received quetiapine (group 1) and 17 - olanzapine (group 2) for more than 6 months before admission in the hospital as the main anti-recurrence therapy. Persons aged 20-63 years with length of the follow-up of the disease ≥1 year were included. The investigations included: phenotyping of immunocompetent cells into CD differentiation clusters by flow cytometry; mitogen-induced, spontaneous production of cytokines (IL2, IFN-γ, IL-4, TNF-α) were identified with use of kits for enzyme-linked immunosorbent assay (ELISA).ResultsIt was shown that patients of group 1 in comparison with group 2 were characterized by lower values of СD3- lymphocytes (p=0.049), higher values of the spontaneous production of IFN-γ (p=0.01), mitogen-induced production of IL-2 (p=0.043) and IL-4 (p=0.059). In all examined low level of mitogen-induced of IFN-γ (p=0.0001) and TNFα (p=0.002; p=0.0001), high level of spontaneous production of TNFα (p=0.001) were revealed in relation to control.ConclusionsIt was found that the acute period of schizophrenia after prolonged treatment with atypical antipsychotics is accompanied by immunological imbalance and dysregulation of the cytokine system. More severe immune disorders when hospitalized during the exacerbation period were revealed in patients who had been receiving antipsychotic therapy with the atypical antipsychotic quetiapine for a long time. This can be associated with the features of the mechanism of action of atypical antipsychotics.DisclosureNo significant relationships.

Efficacy of quetiapine for delirium prevention in hospitalized older medical patients: a randomized double-blind controlled trial

BackgroundDelirium is a common disorder among hospitalized older patients and results in increased morbidity and mortality. The prevention of delirium is still challenging in older patient care. The role of antipsychotics in delirium prevention has been limited. Therefore, we conducted a trial to investigate the efficacy of quetiapine use to prevent delirium in hospitalized older medical patients.MethodsThis study was a randomized double-blind controlled trial conducted at Ramathibodi Hospital, Bangkok, Thailand. Patients aged ≥65 years hospitalized in the internal medicine service were randomized to quetiapine 12.5 mg or placebo once daily at bedtime for a maximum 7-day duration. The primary end point was delirium incidence. Secondary end points were delirium duration, length of hospital stay, ICU admission, rehospitalization and mortality within 30 and 90 days.ResultsA total of 122 patients were enrolled in the study. Eight (6.6%) left the trial before receiving the first dose of the intervention, whereas 114 (93.4%) were included in an intention-to-treat analysis allocated to the quetiapine or placebo group (n = 57 each). The delirium incidence rates in the quetiapine and placebo groups were 14.0 and 8.8% (OR = 1.698, 95% CI 0.520–5.545, P = 0.381), respectively. Other endpoints in the quetiapine and placebo groups were the median length of hospital stay, 6 (4–8) days versus 5 (4–8) days (P = 0.133), respectively; delirium duration, 4 (2.3–6.5) versus 3 (1.5–4.0) days (P = 0.557), respectively; ICU admission, 3 (5.3%) patients from both groups (P = 1.000); and mortality in the quetiapine and placebo groups, 1 (1.8%) versus 2 (3.5%) at 30 days (P = 0.566) and 7 (12.3%) versus 9 (15.8%) days at 90 days (P = 0.591). There were no significant differences in other outcomes. None of the participants reported adverse events.ConclusionsQuetiapine prophylaxis did not reduce delirium incidence in hospitalized older medical patients. The use of quetiapine to prevent delirium in this population group should not be recommended.Trial registrationThis trial was retrospectively registered with the Thai clinical trials registry (TCTR) at clinicaltrials.in.th (TCTR20190927001) on September 26, 2019.

Comparison of the Effectiveness of Haloperidol Injection and Oral Quetiapine to Control Delirium in Patients in the Emergency Department and Intensive Care Unit – A Randomized Clinical Trial

Background: Delirium is a psychiatric syndrome observed among patients with critical psychiatric disorders. Haloperidol is now one of the first-line drugs for the treatment of delirium. However, quetiapine can be considered as an appropriate substitute in patients with a high risk of extrapyramidal symptoms or long QT syndrome. Objectives: This study aimed to compare the effectiveness of intramuscular haloperidol and oral quetiapine to control delirium in patients in the emergency department and intensive care unit. Methods: This randomized clinical trial was performed during 2017-2018 on patients with delirium who were referred to the emergency department and intensive care unit of Imam Reza Hospital (referral center), Mashhad, Iran. Patients were divided into two groups of 100 patients per group through a random allocation technique . In this study, 5 mg of intramuscular haloperidol every 12 hours and 25 mg of oral quetiapine were prescribed daily for the patients in the control and intervention groups, respectively. The delirium severity score of each patient was evaluated before and three days after the intervention through Delirium Rating Scale-Revised-98. Results: In this study, the mean±SD age of participants was 60.2±14.1 years. The findings indicated that no significant difference was observed between haloperidol (22.7±1.9) and quetiapine (22.7±2.2) groups in terms of the baseline delirium severity score (P=0.95). The mean delirium severity scores of patients in haloperidol and quetiapine groups were 25.6±2.1 and 25.2±2.5, respectively. Based on the obtained results, the difference between the delirium severity scores of both groups was not statistically significant (P=0.24). Conclusion: Based on the results, oral quetiapine has a similar effect as intramuscular haloperidol and can be used as a substitute to this medicine for controlling the symptoms of patients with delirium.

Treatment of chronic insomnia with atypical antipsychotics: results from a follow-up study.

ObjectiveSecond generation (atypical) antipsychotics are increasingly being used for treatment of insomnia, but there is little evidence to show long-term efficacy of these medication. This follow-up study was designed to assess patients with chronic insomnia who were treated with atypical antipsychotics.Material and MethodsIn this follow-up study, forty patients with chronic insomnia were evaluated between 2016 and 2018 following after one year of treatment with two atypical antipsychotic drugs of olanzapine and quetiapine in two groups in the sleep disorders research center of Kermanshah University of Medical Science in Iran. The Pittsburgh Sleep Quality Questionnaire (PSQI) and 5 consecutive nights of Actigraphy were utilized to evaluate both subjective and objective measures of sleep quality. Lastly, sleep quality before and after treatment and comparisons of sleep quality between the two groups were performed.ResultsNine male participants comprised olanzapine group (n=22) and six male participants comprised the quetiapine group (n=18). The average age in the olanzapine group was 45.23±10.18 and the average age in the quetiapine group was 46.33±7.99. Results showed total PSQI score improved significantly in both groups (p<0.05), while the actigraphy results showed only significant improvement in sleep quality parameters in the quetiapine group (p<0.05).ConclusionTwo atypical antipsychotics drugs of olanzapine and quetiapine have long-term efficacy in managing chronic insomnia. More improvements in objective sleep quality with quetiapine is promising for patients with chronic insomnia. Further research to evaluate long-term adverse effects of atypical antipsychotic drugs is recommended.

Hospitalization Risk for Adults with Bipolar I Disorder Treated with Oral Atypical Antipsychotics as Adjunctive Therapy with Mood Stabilizers: A Retrospective Analysis of Medicaid Claims Data

Background: Atypical antipsychotics (AAPs) with mood stabilizers are recommended as a first-line treatment for patients with bipolar disorder. No studies have compared the inpatient health care resource utilization for patients with bipolar disorder treated with lurasidone as adjunctive therapy with mood stabilizers compared with other oral AAPs. Objective: To compare the risk of hospitalization for adult Medicaid beneficiaries with bipolar I disorder when treated with lurasidone compared with other oral AAPs as adjunctive therapy with mood stabilizers. Methods: This retrospective cohort study used the MarketScan Research Databases Multi-State Medicaid Database (IBM, Armonk, NY) claims data to assess patients with bipolar I disorder between January 1, 2014, and June 30, 2019. Adult patients who initiated oral AAP treatment with mood stabilizers (index date) and who were continuously enrolled 12 months before (pre-index) and 24 months after (post-index) the index date were included. Treatment categories assigned by patient-month included lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone with mood stabilizers; no/minimal treatment; AAP monotherapy; and other. Marginal structural models were performed to estimate the all-cause and psychiatric hospitalization rates and hospital length of stay associated with each adjunctive AAP therapy by controlling for both time-invariant and time-varying confounders. Results: Adults with bipolar I disorder (N = 11,426; mean age = 39.4 years; female=73%) treated with an adjunctive oral AAP with mood stabilizers during the index month were categorized into lurasidone (12%), aripiprazole (17%), olanzapine (7%), quetiapine (32%), risperidone (11%), ziprasidone (7%), or other (15%) treatment groups. The adjusted odds of all-cause and psychiatric hospitalization were significantly higher for olanzapine (all causes: adjusted odds ratio [aOR] = 1.59; 95% CI, 1.13-2.25; psychiatric: aOR = 1.61, 95% CI, 1.12-2.32), quetiapine (all-causes: aOR = 1.27, 95% CI, 1.01-1.58; psychiatric: aOR = 1.28, 95% CI, 1.02-1.59), and ziprasidone (all-causes: aOR = 1.68, 95% CI, 1.05-2.66; psychiatric: aOR = 1.55, 95% CI, 1.02-2.35) compared with lurasidone with mood stabilizers. The adjusted odds of all-cause and psychiatric hospitalizations were numerically lower for lurasidone compared with aripiprazole. The all-cause hospital length of stay per 100 patient-months was significantly higher for olanzapine (20.3 days) and quetiapine (16.0 days) compared with lurasidone (12.2 days, both P values < 0.05). Conclusions: In a Medicaid population, adults with bipolar I disorder treated with lurasidone as adjunctive therapy with mood stabilizers had significantly lower all-cause and psychiatric hospitalization rates compared with olanzapine, quetiapine, and ziprasidone. Fewer hospitalizations may reduce the economic burden associated with bipolar disorder. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Mortality and morbidity following postoperative use of short‐term, low‐dose quetiapine vs risperidone in patients with diabetes: Analysis using a national inpatient database

Short-term, low-dose quetiapine is used to treat postoperative delirium and insomnia. Quetiapine is contraindicated for patients with diabetes in Japan because there have been several case reports of diabetic ketoacidosis (DKA) in patients receiving long-term, high-dose quetiapine. However, because safety of short-term, low-dose quetiapine remains controversial, it is prescribed for patients with diabetes in real-world clinical practice. The present study aimed to compare in-hospital mortality and morbidity between short-term, low-dose quetiapine and risperidone in postoperative patients with diabetes. We used a national inpatient database in Japan to perform a retrospective cohort study. We identified hospitalized patients with diabetes who underwent scheduled elective surgery and received oral quetiapine 200 mg/d or less or oral risperidone 4 mg/d or less within 7 days of surgery between July 2010 and March 2018. We performed one-to-one propensity score-matched analyses to compare outcomes between patients with quetiapine and risperidone. The primary outcome was in-hospital mortality. The secondary outcome was infectious complications (pneumonia, urinary tract infection, surgical site infection, and sepsis). Propensity score matching created 665 pairs of patients who received quetiapine or risperidone. The primary outcome was observed in 19 (2.9%) of the quetiapine group and 11 (1.7%) of the risperidone group (relative risk, 1.27; 95% confidence interval, 0.97-1.68; P = .14). The secondary outcome did not differ significantly between the groups. In terms of mortality and infectious outcomes, safety of quetiapine and risperidone may be comparable.

Quetiapine treatment for cannabis use disorder

BackroundPharmacotherapy for cannabis use disorder (CUD) is an important unmet public health need. MethodsIn a 12-week randomized double-blind placebo-controlled trial, the efficacy of quetiapine (300 mg nightly) for the treatment of CUD was tested in 130 outpatients. Weekly cannabis use was categorized into three groups: heavy use (5−7 days), moderate use (2–4 days) and light use (0–1 days). ResultsAt baseline both groups were considered heavy users (using days per week: median = 7.0; interquartile range (IQR): 6.5−7.0; daily dollar value: median = $121.4; IQR: 73.8–206.3). The week-by-treatment interaction was marginally significant (χ2(2) = 5.56, P = .06). With each week, the odds of moderate compared to heavy use significantly increased in the quetiapine group (OR=1.17, P < .0001), but not significantly in the placebo group (OR=1.05, P = .16). The odds of light versus heavy use did not significantly differ over time (P = .12). Treatment was also associated with reduced cannabis withdrawal symptoms by 10.4% each week (95% CI: 8.9–11.8). No serious adverse events occurred during the study and no evidence of development of a movement disorder was detected. Adverse effects were not significantly different between the quetiapine and placebo treatment arms. ConclusionsThe use of quetiapine to treat CUD was associated with an increased likelihood of heavy frequency use transitioning to moderate use, but not light use. The clinical significance of reductions in cannabis use, short of abstinence warrants further study.

The neuroprotective effect of quetiapine in critically ill traumatic brain injury patients.

Quetiapine is an atypical antipsychotic commonly used in critical care. Cellular and animal models demonstrated its novel anti-inflammatory properties in traumatic brain injury (TBI). Our study aimed to assess the effect of quetiapine on outcomes in critically ill TBI patients. We hypothesize that quetiapine improves neurological outcomes. The Multiparameter Intelligent Monitoring in Intensive Care database was queried, and all adult (age, ≥18 years) isolated TBI patients (extracranial Abbreviated Injury Scale, < 2) admitted to the intensive care unit for a period of >48 hours. Patients were stratified into quetiapine (+) and no-quetiapine (-) groups. Propensity score matching was performed (1:2 ratio). Outcome measures were intensive care unit length of stay, discharge Glasgow Coma Scale (GCS), and mortality. A subanalysis was performed for patients who underwent intracranial pressure (ICP) monitoring to ascertain the effect of quetiapine dose on ICP, and cerebral perfusion pressure (CPP). Survival curves and regression analyses were performed. A matched cohort of (quetiapine, 116 vs. no-quetiapine, 232) patients was obtained. Mean ± SD age was 65 ± 21 years, median head Abbreviated Injury Scale was 3 (3-4), and median GCS was 10 (9-16). The median quetiapine dose given was 50 (25-125) mg. Patients who received quetiapine had lower mortality (17.2% vs. 27.6%; p = 0.03) and a higher median GCS at discharge (12 [11-14] vs. 11 [10-13]; p < 0.04) but no difference in intensive care unit length of stay (4.1 days vs. 4.7 days; p = 0.75) or discharge to skilled nursing facility (34.5% vs. 31.9%; p = 0.63). On subanalysis of patients who received quetiapine, 40% had ICP monitoring. Higher doses of quetiapine were independently associated with progressively lower ICP (β = -0.022 mm Hg/mg of quetiapine; p = 0.01) and higher CPP (β = 0.031 mm Hg/mg quetiapine; p = 0.01). Quetiapine may decrease mortality and improve neurological outcomes in critically ill TBI patients. It has a dose-dependent effect to decrease ICP and increase CPP. Quetiapine may be a potential therapeutic modality in critically ill TBI patients, but further studies are required to explore these mechanisms. Systematic Review, level III.

Efficacy and Safety of Quetiapine for Pediatric Bipolar Depression: A Systematic Review of Randomized Clinical Trials.

Quetiapine is a second-generation antipsychotic (SGA) approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia, mania, and aggression in children and adolescents. It is also commonly used as an off-label medication to treat children and adolescents with bipolar depression, although the FDA has not approved quetiapine for this purpose. We conducted a systematic review of randomized clinical trials (RCTs) using the MEDLINE database and included two studies that met our inclusion criteria. Both RCTs were eight-week short-term studies that involved patients of 10-18 years of age with a Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of bipolar disorder, depressed type. The mean difference in the Children's Depression Rating Scale-Revised (CDRS-R) score and the response and remission rates in the quetiapine group were not statistically significant when compared to the placebo group. A high placebo response rate proved that quetiapine was no better than the placebo in treating pediatric bipolar depression. Quetiapine proved to be a relatively safe drug with the most common side effects being headache, somnolence, gastric upset, and weight gain. There was a significant increase in triglyceride levels, but no other metabolic effects were reported. This calls for future studies with larger sample sizes and improved methodology to explore the efficacy of quetiapine and other SGAs for the management of pediatric bipolar depression.

Quetiapine for delirium prophylaxis in high-risk critically ill patients

BackgroundDelirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. MethodsThe study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. ResultsThe incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). ConclusionsThe findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

COMPARISON OF THE EFFECT OF QUETIAPINE WITH HALOPERIDOL IN TREATMENT OF DELIRIUM IN ICU PATIENTS

Introduction: Delirium is a relatively common disorder in ill patients. Haloperidol, a first-generation antipsychotic, is known to be the main treatment, but it has extrapyramidal side effects, whereas quetiapine is a second-generation antipsychotic and lacks these effects. In a recent study, we compared the effects of quetiapine with haloperidol in the treatment of delirium symptoms. Materials and methods: This study was a clinical trial performed on patients with delirium. Patients were randomly divided into two groups, one group receiving haloperidol 2.5 mg daily and the other group receiving 25 mg daily quetiapine. Sedation status of patients was determined based on RASS scoring criteria and disease severity according to APACHE II criteria and finally data were analyzed by SPSS 20 software. Results: The mean age of patients in quetiapine and haloperidol group was 59.83 with standard deviation of 16.51 and 64.90 with standard deviation of 21.34 years (p-value = 0.308). The ratio of male to female in the quetiapine and haloperidol group was 19 to 11 and 21 to 9, respectively (p-value = 0.392). Patients in quetiapine group had significantly better RASS and disease severity than patients in haloperidol group (p-value = 0.001). Conclusion: According to the results, it is concluded that the use of quetiapine can not only be effective in improving sedation status and severity of disease in patients with delirium, but also better than haloperidol.

Role of Glucuronidation Pathway in Quetiapine Metabolism: An In vivo Drug-Drug Interaction Study between Quetiapine and Probenecid.

Background:Uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes play a significant role in the metabolism of quetiapine, and coadministration with a UGT inhibitor/inducer drug may change its pharmacokinetic profile.Objective:The objective of this study was to assess the impact of probenecid, a UGT enzyme inhibitor, on the pharmacokinetic profile of quetiapine.Materials and Methods:Twelve treatment-naïve, 7-week-old male Sprague–Dawley rats (weighting 161 ± 22 g) were randomly and equally divided into control, quetiapine-alone and quetiapine plus probenecid groups. The quetiapine plus probenecid group received a single oral dose of probenecid (50 mg/kg) followed by 50 mg/kg of quetiapine; the quetiapine-alone group only received 50 mg/kg of quetiapine. Blood samples (0.2 ml) were collected from all rats after 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 h of the drug administration in heparinized tubes. The pre-established liquid chromatography–mass spectrometry method was utilized to ascertain the plasma concentration of quetiapine and the control group was used to prepare the controlled standard.Results:Significant pharmacokinetic differences were observed between the quetiapine-alone and quetiapine plus probenecid groups in terms of Cmax (392 ± 209 vs. 1323 ± 343 ug/L, respectively, P = 0.004), AUC0-∞ (P = 0.04) and Tmax (P = 0.004). Further, in the combined drug group, there was a decrease in drug clearance (CL/F) (from 27 ± 11 to 16 ± 3 L/h/kg; P = 0.005) and an increase in the volume of distribution (Vd) (P = 0.01), but there was no significant difference between both groups in terms of half-lives (P = 0.27). No significant within-group variability of pharmacokinetic parameters was observed (P = 0.25).Conclusion:The results of this animal study suggest that glucuronidation by UGT enzyme system may also play an important role in quetiapine metabolism, which, if proven in future human studies, would imply that the bioavailability and pharmacokinetic parameters of quetiapine may require alterations when co-administered with probenecid to avoid development of quetiapine toxicity.

Efficacy of Low-Dose Prophylactic Quetiapine on Delirium Prevention in Critically Ill Patients: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study.

Purpose: To evaluate the efficacy of short-term low-dose quetiapine for delirium prevention in critically ill patients. Methods: In this prospective, a single-center, randomized, double-blind, placebo-controlled trial, adult patients who were admitted from July 2015 to July 2017 to a medical intensive care unit (ICU) of a tertiary teaching hospital affiliated to Seoul National University were included. Quetiapine (12.5 mg or 25 mg oral at night; N = 16) or placebo (N = 21) was administered according to randomization until ICU discharge or the 10th ICU day. The primary endpoint was the incidence of delirium within the first 10 ICU days. Secondary endpoints included the rate of positive Confusion Assessment Method for the ICU (CAM-ICU) (the number of positive CAM-ICU counts/the number of total CAM-ICU counts), delirium duration, successful extubation, and overall mortality. Result: The incidence of delirium during the 10 days after ICU admission was 46.7% (7/15) in the quetiapine group and 55.0% (11/20) in the placebo group (p = 0.442). In the quetiapine group, the rate of positive CAM-ICU was significantly lower than in the placebo group (14.4% vs. 37.4%, p = 0.048), delirium duration during the study period was significantly shorter (0.28 day vs. 1.83 days, p = 0.018), and more patients in the quetiapine than in the placebo group were weaned from mechanical ventilation successfully (84.6% vs. 47.1%, p = 0.040). Conclusions: Our study suggests that prophylactic use of low-dose quetiapine could be helpful for preventing delirium in critically ill patients. A further large-scale prospective study is needed.

Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies

IntroductionPsychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies. MethodsRetrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available. ResultsForty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P = 0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P < 0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR < 1 before day 43, HR > 1 after day 43; P = 0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P = 0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P = 0.001). ConclusionAccounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.

Dopamine D2 Receptor Occupancy Estimated From Plasma Concentrations of Four Different Antipsychotics and the Subjective Experience of Physical and Mental Well-Being in Schizophrenia: Results From the Randomized NeSSy Trial.

Impaired subjective well-being in schizophrenia patients treated with antipsychotics has often been linked inter alia to the antidopaminergic effects of medication. Thus, it is important to capture the association between striatal dopamine D2 receptor occupancy (D2-RO) and global subjective well-being. We examined this association using data from our multicenter, randomized, double-blind Neuroleptic Strategy Study (NeSSy). An innovative double randomization process was used for allocation of patients to the specific treatment groups. Plasma drug concentrations were measured after 6 and 24 weeks of treatment to obtain the estimated D2-RO (eD2-RO) relative to literature values. We made an exploratory analysis of associations between eD2-RO and subjective well-being scores. One hundred two blood samples from 69 patients were available for the analysis. Because of the lack of a satisfactory occupancy model for quetiapine, only haloperidol, flupentixol, and olanzapine treatment groups were pooled, whereas aripiprazole data were analyzed separately, because of its partial agonistic properties. In the pooled antagonist group, eD2-RO correlated negatively with the summarized well-being score. In a more detailed analysis, this association could be confirmed for all first-generation antipsychotic-treated patients, but not for the separate second-generation antipsychotic groups. In the aripiprazole group, higher eD2-RO was associated with impaired physical well-being, but had no association with mental well-being. Our results suggest that high plasma levels and consequently high occupancy at D2 receptors are disadvantageous for subjective well-being, as distinct from the objective extrapyramidal side effects. To minimize patients' malaise, which disfavors adherence, implementation of therapeutic drug monitoring in the clinical routine may be useful.

Evaluation of Second Generation Antipsychotics, as Augmentative Plan, in Treatment-Resistant Obsessive-Compulsive Disorder

Introduction: Since around half of the patients with obsessive-compulsive disorder do not respond efficiently to current serotonin- reuptake inhibitors, the objective of the present study was to compare the effectiveness and safety of quetiapine against aripiprazole in patients with obsessive-compulsive disorder, who had not responded successfully to fluvoxamine. Methods: Forty-four patients with obsessive-compulsive disorder, who had not responded efficaciously to fluvoxamine, at maximum dose (300 milligrams per day) and duration (twelve weeks), were allocated randomly in a double-blind assessment to take quetiapine (n=22) or aripiprazole (n=22), plus their serotonin-reuptake inhibitor for twelve weeks. While treatment response was evaluated by the Yale- Brown Obsessive-Compulsive Scale (YBOCS), as the main outcome scale, Clinical Global Impressions-Severity Scale (CGI-S) was also used as an ancillary measure. Results: 54.54% of patients in the quetiapine group and 27.27% of them in the aripiprazole group responded partially to the abovementioned on treatment adds. According to the findings, the YBOCS score dropped from 31.18+/-4.93 to 27.97+/-3.71 (p&lt;0.01), and 33.27 +/- 3.90 to 30.72+/-4.67 (p &lt; 0.06), for quetiapine and aripiprazole, respectively. In this regard, no substantial alteration regarding CGI-S was evident in each of the aforementioned groups. Conclusion: This assessment indicated that patients with treatment-resistant obsessivecompulsive disorder could benefit more from adding quetiapine, in comparison with aripiprazole, to their current serotonergic medication.

Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for non-systematic adverse events

BackgroundAdverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials or across sources for a single trial may produce inconsistent information about the adverse events associated with interventions.MethodsWe compared the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports (CSRs)) of trials for two drug-indications—gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting.ResultsWe identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.”ConclusionsSelection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study.

Comparison of the association of risperidone and quetiapine with deteriorating performance in walking and dressing in subjects with Parkinson's disease: a retrospective cohort study using administrative claims data.

This retrospective cohort study was performed to investigate the association between risperidone and deteriorating performance in walking and dressing in subjects with Parkinson's disease using the Japanese Diagnosis Procedure Combination data. These data include inpatient claims including information from the time of admission to discharge from 89 acute phase National Hospitals in Japan. The data were evaluated by implementing the inverse probability of treatment weighting, using propensity scores estimated from the clinical characteristics of subjects prescribed risperidone or quetiapine. The generalized estimation equation was used to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). In total, 304 subjects were eligible for participation, and were hospitalized between April 2012 and March 2017 (108 and 196 for risperidone and quetiapine groups, respectively). The performance of walking deteriorated at discharge, with 22.2% and 10.2% recorded at admission for the risperidone and quetiapine groups (aRR, 1.7; 95% CI, 0.9 to 3.4), respectively. The performance of dressing also deteriorated: 24.1% and 10.7% in the risperidone and quetiapine groups (aRR, 1.9; 95% CI, 1.04 to 3.7), respectively. These results suggest an association between risperidone and deteriorating performance in dressing in subjects with Parkinson's disease in comparison with quetiapine.

Changes in inflammation with treatment for bipolar II depression: Pilot trial data on differential effects of psychotherapy and medication

ObjectivesLimited prospective data, mostly focused on bipolar I disorder, suggests that pro-inflammatory cytokines are elevated in abnormal mood states. We evaluated whether treatment normalizes peripheral markers of inflammation in bipolar II disorder. MethodsUsing data from a randomized clinical trial of Interpersonal and Social Rhythm Therapy (IPSRT) + quetiapine vs. IPSRT + placebo for bipolar II depression, we examined whether these treatments for bipolar II depression impact inflammatory cytokines and whether observed changes in cytokines are associated with changes in depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD-17). ResultsCytokine values were available for 33 participants who completed baseline and 20-week follow-up visits. After excluding those with CRP values > = 10 mg/L, there were 27 patients available for analysis (IPSRT + quetiapine N = 10, IPSRT + placebo N = 17). Baseline measure of inflammation did not appear to moderate treatment response, nor was change in HRSD-17 score correlated with changes in cytokines. Those who received IPSRT + quetiapine had significantly greater increases in IL-6 (p = 0.02) and TNF-α (p = 0.04), even after adjusting for changes in body mass index, than the IPSRT alone group. Descriptively, the quetiapine group showed increases in pro-inflammatory and decreases in anti-inflammatory cytokines and the psychotherapy group showed reduced pro-inflammatory cytokines. ConclusionsDespite both groups showing depression improvement, this small study suggests a more pro-inflammatory cytokine profile over time with quetiapine plus psychotherapy compared to psychotherapy alone. Elevated risk of cardiovascular morbidity and mortality among those with bipolar II disorder underscores the importance of delivering treatments that do not exacerbate these risk factors.

Preventative effects of aripiprazole and quetiapine on seizure and lethality in a mice cocaine toxicity model: an experimental study.

ObjectiveTo assess the effectiveness of pre-treatment with aripiprazole and quetiapine to prevent acute cocaine toxicity in a mouse model of cocaine toxicity.MethodsThis experimental study included three groups (n = 25 per group) of mice that were intraperitoneally injected with normal saline solution, 10 mg/kg quetiapine or 10 mg/kg aripiprazole 15 min before 105 mg/kg cocaine hydrochloride. When the cocaine administration was completed, researchers blinded to the study groups observed the mice in terms of seizures and death for a further 30 min.ResultsIn the cocaine + quetiapine group, the mean ± SE time to the first seizure was 10.80 ± 2.27 min and seizure activity was detected in 18 mice (72%) by the end of the 30 min. In the cocaine + aripiprazole group, the mean ± SE time to the first seizure was 18.10 ± 1.94 min and seizure activity was detected in 15 mice (60%) by the end of the 30 min. When compared with the control group, there was a significant difference between the cocaine + quetiapine and cocaine + aripiprazole groups in terms of seizure activity. Survival time was increased in the cocaine + aripiprazole group compared with the control and cocaine + quetiapine groups.ConclusionQuetiapine and aripiprazole pre-treatment reduced seizure activity and delayed the onset of seizures compared with the control group.