Search

Objectives Cure for severe depression in elderly patients with psychotic symptoms should consider not only the results of major depression but also the nature of antidepressants and their side effects. Psychiatric disability is higher in patients who have greater deterioration in neurological function. Methods In addition to reviewing antidepressant discontinuation syndrome and depressive disorder, this study describes an elderly woman with mild depression that developed into major depression, related to high suspicion of delirium, diagnosed based on patient history, physical health examination, neurological examinations, family history, and laboratory data, with subsequent treatment plan. Results The treatment results and prognosis indicate that patients with paroxetine antidepressant deactivation may enable early use of low-dose quetiapine with less anticholinergic and extrapyramidal side effects for the treatment of depression in elderly patients with psychotic symptoms. The poor prognostic factors for patients were chronic environmental stress (poverty) and lack of a social support system. Although the patient lived with her children and grandchildren, she rarely received care. Hence, it was not possible to monitor her condition and medication intake. Conclusions The consensus is that the abrupt discontinuation of short half-life selective serotonin reuptake inhibitors (SSRIs), such as paroxetine can be associated with transient symptomatology, much of which is of a serotonergic nature. Psychotic-like symptoms have also been reported in both controlled trials and large patient databases.

Background: Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response. Methods: We analyzed data from two similar 24-weeks comparative effectiveness trials, with a combined sample of 770 participants randomized to two different lithium doses, quetiapine (300 mg/day), or standard treatment without lithium. Glucose, lipids and vital signs were measured before and after 24 weeks of treatment. We calculated several cardiovascular risk scores, assessed baseline correlations and compared the four treatment arms via multiple linear regression models. Results: Higher cholesterol and LDL levels were associated with greater depression severity, showing differential correlations to specific symptoms, particularly agitation, low energy and suicidality. Those randomized to quetiapine showed a significant worsening of cardiometabolic markers during the 24-week trial. Neither baseline nor change in lipid levels correlated with differential treatment response. Limitations: Study duration was short from the perspective of cardiometabolic risk markers, and all treatment arms included patients taking adjunct antipsychotics. The trials compared quetiapine to lithium, but not to other medications known to affect similar risk factors. Conclusions: Treatment with 300 mg/day quetiapine for 24 weeks, representing a short and common dose course, resulted in increased cardiometabolic risk markers, emphasizing the importance of monitoring during mood-stabilizing treatment. The symptom-specific associations are in line with previous studies in unipolar depression, suggesting a cardiometabolic-depression link that needs to be further studied in bipolar depression.

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p

Summary Introduction The drugs used to treat psychiatric illnesses are known as antipsychotics. Antipsychotics have a higher incidence of adverse drug reactions including extrapyramidal side effects and several other metabolic disorders. The main objective of the study is to assess the changes in anthropometric parameters of metabolic risk in patients with severe mental disorders initiated with antipsychotic drug therapy. Materials and methods A prospective observational study was carried out in the psychiatric inpatient unit of a tertiary care teaching hospital for eight months. Eligible patients were enrolled and their baseline and follow-up anthropometric measurements such as body weight, body mass index (BMI), fat index, and waist-hip ratio were taken before and after six weeks of therapy. The changes were documented and analyzed. Results and Discussion The most commonly prescribed antipsychotics were olanzapine, clozapine, risperidone and quetiapine. A considerable mean increase in the body weight of 4.5 kg with a mean increase in body mass index of 1.7 kg/m2, percentage body fat of 1.84% and the waist-hip ratio of 0.027 was observed among patients treated with olanzapine. Similarly, patients who were prescribed with clozapine also revealed a significant increase in the mean body weight of 4.7 kg, an increase in BMI of 1.75 kg/m2, 0.07 of waist-hip ratio and a percentage body fat of 1.4%. On analysis, patients treated with quetiapine and risperidone also showed significant changes in the anthropometric parameters. Conclusion The overall comparison and statistical analysis of different anthropometric parameters suggest that the changes observed within the parameters were a result of antipsychotic drug therapy.

Objective To describe pharmacological and non-pharmacological practices for delirium, carried out by psychiatry residents and psychiatrists in Colombia. Methods An anonymous survey was conducted based on the consensus of experts of the Liaison Psychiatry Committee of the Asociacion Colombiana de Psiquiatria [Colombian Psychiatric Association] and on the literature review. It was sent by email to the association members. Results 101 clinicians participated. Non-pharmacological preventive measures such as psychoeducation, correction of sensory problems or sleep hygiene are performed by 70% or more. Only about 1 in 10 participants are part of an institutional multi-component prevention programme. The preventive prescription of drugs was less than 20%. Regarding non-pharmacological treatment, more than 75% recommend correction of sensory difficulties, control of stimuli and reorientation. None of the participants indicated that the care at their centres is organised to enhance non-pharmacological treatment. 17.8% do not use medication in the treatment of delirium. Those who use it prefer haloperidol or quetiapine, particularly in hyperactive or mixed motor subtypes. Conclusions The practices of the respondents coincide with those of other experts around the world. In general, non-pharmacological actions are individual initiatives, which demonstrates the need in Colombian health institutions to commit to addressing delirium, in particular when its prevalence and consequences are indicators of quality of care.

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo/manic episodes (termed predominant hypo/manic polarity). We examined the associations between staging and predominant polarity with measures of illness burden and treatment outcome utilizing data from a six-month comparative effectiveness trial of lithium and quetiapine in bipolar disorder (Bipolar CHOICE). We used number of self-reported lifetime mood (depressive and hypo/manic) episodes as a proxy for staging and ratio of depressive to manic episodes to define predominant polarity. Polarity and staging were correlated with several measures of burden of illness. Childhood abuse was correlated with more lifetime mood episodes, while more depressive episodes and depressive polarity were correlated with more anxiety disorder comorbidity. Depressive polarity was also correlated with more past trials of psychotropics, particularly antidepressants. However, neither staging nor predominant polarity moderated the randomized treatment effect of lithium vs. quetiapine. Number of depressive episodes in the past year was identified as a potential predictor of overall worse treatment outcome, regardless of medication condition. In conclusion, though staging and predominant episode polarity correlated with several measures of illness burden, they were not associated with differential treatment outcomes. This could be because many of our patients presented for treatment at advanced stages of illness and further highlights the need for early intervention in bipolar disorder.

Background Delirium 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. Methods The 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. Results The 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). Conclusions The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Background Treatment-resistant depression (TRD) is considered a common clinical condition often associated with relevant suicidal ideation and characterized by a severe functional impairment lifetime. Among the available drugs for the TRD treatment, second-generation antipsychotics (SGAs) have been reported as effective. In this context, the aim of this study was to review the clinical studies evaluating the efficacy of SGAs as add-on therapy in TRD. Methods A comprehensive search on PubMed, Medline and PsychINFO of all randomized clinical trials (RCTs) assessing the augmentation with antipsychotics in TRD, published from January 2000 until March 2020, was performed. Sixteen RCTs studies met the inclusion criteria. Results The reviewed studies showed that the add-on therapy with aripiprazole could be beneficial in the treatment of TRD. Furthermore, RCTs on quetiapine augmentation support its use in TRD, especially when comorbid anxiety or insomnia are present. The effects of risperidone and olanzapine as add-on in TRD were less studied, but preliminary data indicated an efficacy respect to placebo, making them a possible therapeutic option in TRD. Limitations The lack of consistency in the definition of TRD together with the small sample sizes and the heterogeneity of antipsychotics dosages used in the reviewed RCTs may have limited the strength of evidences obtained. Conclusion Overall, the available RCTs studies seem to support the hypothesis that the augmentation with SGAs, in particular aripiprazole and quetiapine, is a valid therapeutic option for TRD. However, to improve the therapeutic outcome of patients with TRD, larger and more homogeneous RCTs are needed.

The use of antipsychotic medications (APMs) could be different among countries due to availability, approved indications, characteristics and clinical practice. However, there is limited literature providing comparisons of APMs use among countries. To examine trends in antipsychotic prescribing in Taiwan, Hong Kong, Japan, and the United States, we conducted a cross-national study from 2002 to 2014 b y using the distributed network approach with common data model. We included all patients who had at least a record of antipsychotic prescription in this study, and defined patients without previous exposure of antipsychotics for 6 months before the index date as new users for incidence estimation. We calculated the incidence, prevalence, and prescription rate of each medication by calendar year. Among older patients, sulpiride was the most incident [incidence rate (IR) 11.0–23.3) and prevalent [prevalence rate (PR) 11.9–14.3) APM in Taiwan, and most prevalent (PR 2.5–3.9) in Japan. Quetiapine and haloperidol were most common in the United States (IR 8.1–9.5; PR 18.0–18.4) and Hong Kong (PR 8.8–13.7; PR 10.6–12.7), respectively. The trend of quetiapine use was increasing in Taiwan, Hong Kong and the United States. As compared to older patients, the younger patients had more propensity to be prescribed second-generation APM for treatment in four countries. Trends in antipsychotic prescribing varied among countries. Quetiapine use was most prevalent in the United States and increasing in Taiwan and Hong Kong. The increasing use of quetiapine in the elderly patients might be due to its safety profile compared to other APMs.

Case Presentation A 52-year-old man, current smoker with a 50 pack-year history, presented to our department with cough, yellow sputum, and localized right chest pain. Chest radiograph revealed a large mass in the right upper lobe. He denied the presence of fever, night sweats, or weight loss. He has a medical history of COPD and anxiety disorder. He was receiving long-acting beta agonists/long-acting muscarinic antagonists as a treatment for COPD and quetiapine 100 mg for anxiety disorder.

Background Dengue is a common mosquito-borne viral infection worldwide. Manic episode due to dengue encephalopathy is a rare complication of this infection. Patients with brain lesion may be more susceptible to developing extrapyramidal symptoms (EPS) from antipsychotics. Here, we present the first reported case of the use of alpha-2 adrenergic receptor (α2AR) agonists, clonidine and tizanidine, in bipolar disorder due to encephalopathy. Case summary A 23-year-old Thai man diagnosed with bipolar disorder due to dengue encephalopathy had persistent manic symptoms for 7 months. He failed to respond to sodium valproate 1,500 mg/day and quetiapine 800 mg/day, and had antipsychotic-induced EPS from haloperidol, risperidone, and quetiapine. After adjunct α2AR agonists (clonidine 0.9 mg/day, and then switch to tizanidine 12 mg/day due to drowsiness) to sodium valproate (1,500 mg/day) and quetiapine (800 mg/day), EPS disappeared, and manic symptoms were in remission after 1 year of follow-up. Conclusion Clonidine and tizanidine may provide substantial efficacy and safety when used as an adjunctive treatment for manic episode due to encephalopathy. In addition, clonidine and tizanidine may decrease antipsychotic-induced EPS, and this may result in a better tolerability of medications.

Hyponatraemia is the most common electrolyte disturbance in the elderly. It can be asymptomatic or produce a spectrum of symptoms, particularly in the central nervous system, such as altered state of consciousness, lethargy, headache, seizures and gait disturbances, all of which are a common reason for consultation in this population. This condition has a high impact on the functionality of the patient given the need for multiple hospital stays, as well as on mortality. Its aetiology is multifactorial and its most common causes include low salt intake, chronic diseases such as kidney disease and heart failure, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is commonly caused by the chronic use of certain drugs, such as antidepressants, diuretics and antipsychotics, which are the most forgotten in clinical practice. The following clinical case presents the diagnostic approach of hyponatraemia and the importance of the medical history as a key tool to detect the aetiology of this clinical entity.

Schizophrenia is a severe brain disorder with an excess morbidity and mortality partly due to a higher incidence of metabolic disturbances and cardio-vascular events. The exposure to antipsychotic treatment has been observed linked to these metabolic abnormalities. This study explores the metabolic effects of aripiprazol, quetiapine and ziprasidone in drug-naïve patients with a first-episode of psychosis, at long-term. Two-hundred and two patients with first-episode of psychosis were included in the study. Patients were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Clinical, sociodemographic and anthropometric measures, as well as lipid and glyceamic parameters, were recorded at baseline and after three years of initiating antipsychotic treatment. Body weight and BMI increased significantly after 3 years of follow-up (F = 35.0, p, The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507; Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004; SENY Fundació Research Grant CI 2005–0308007; and Fundación Marqués de Valdecilla API07/011.

Highlights • COVID-19 patients with psychiatric disorders should be managed on a personalized basis. • Risks of pharmacological interaction are not absolute and should be contextualized. • Essential psychopharmacological ongoing treatments should be maintained. • Most psychotropic drugs should be reduced 25–50% if given with lopinavir/ritonavir. • Dose titration should be progressive and with ECG monitoring if cardiotoxic risk., Background : The management of coronavirus disease 2019 (COVID-19) in patients with comorbid psychiatric disorders poses several challenges, especially regarding drug interactions. Methods : We report three representative case-scenarios on patients with psychiatric disorders and COVID-19 to provide a practical approach based on the existing literature and the clinical experience of an expert team in consultation-liaison psychiatry. Case-centered recommendations : Psychopharmacological ongoing treatments should be prioritized and most doses should be reduced 25–50% of original dose if the patient receives lopinavir/ritonavir, with some exceptions including quetiapine, asenapine, olanzapine, sertraline, lamotrigine, bupropion, and methadone. If the psychopharmacological usual doses are in the low-to-median range levels, a dose change during COVID-19 drugs co-administration is not recommended, but only ECG and clinical monitoring of adverse effects and drug levels if required. Furthermore, when introducing a psychopharmacological drug, dose titration should be progressive, with ECG monitoring if cardiotoxic interactions are present. (A) In agitated delirium, olanzapine is recommended as first-line antipsychotic and quetiapine should be avoided. (B) In severe mental illness (SMI), essential treatments should be maintained. (C) In non-SMI with depressive/anxiety symptoms, psychological support should be provided and symptoms identified and treated. Limitations : Most recommendations on pharmacological interactions provide only a limited qualitative approach and quantitative recommendations are lacking. Conclusions : Patients with psychiatric disorders and COVID-19 should be managed on a personalized basis considering several clinical criteria and, should not be excluded from receiving COVID-19 treatments. Risks of pharmacological interaction are not absolute and should be contextualized, and most psychopharmacological treatments should include an ECG with special attention to QTc interval.

Background Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder. Methods The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response. Results Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms. Conclusions Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history.

Background Sleep walking (SW) is a parasomnia behavior characterized by repetitious occurrence of ambulation during a partial arousal from non-rapid eye movement (NREM) sleep. Sleep-related eating (SRE) is one of the complex sleep behaviors that may accompany SW. Emerging evidence suggests that NREM parasomnias can be associated with atypical antipsychotic medication use. Methods We present a case series (n = 5) and a systematic review of the literature of cases of SW, with or without SRE (n = 23), associated with atypical antipsychotic use. Results Twenty-eight cases of SW, with and without SRE, with a mean age of 44.8 years (S.D. = 15.04) and a male predominance (75%; n = 21) were identified. Quetiapine was the most commonly implicated medication with SW and SRE (n = 14). Remission from SW/SRE was noted in all cases with measures including antipsychotic dosage reduction, discontinuation of medication, switching to an alternate medication, and use of continuous positive airway pressure (CPAP) for comorbid obstructive sleep apnea (OSA) treatment. Conclusions Sleep walking (SW), with or without sleep related eating (SRE), can be a rare but reversible side effect associated with use of atypical antipsychotics. More research is warranted to elucidate the mechanisms underlying SW and SRE associated with atypical antipsychotic use.

We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention.

Background The aim of this study was to evaluate quetiapine-associated pulmonary complications (PC) in critically injured trauma patients. Methods Injured adults admitted during 2016 to the ICU at a Level I trauma center were analyzed. Outcomes were evaluated by competing risks survival analysis. Results Of 254 admissions, 40 (15.7%) had PC and 214 (84.3%) were non-events. PC patients were more severely injured, had longer hospital stays and were more likely to die. Patients administered quetiapine were more likely to develop PC and acquire PC earlier than those without quetiapine. Quetiapine was a positive risk factor for PC (sHR 2.24, p = 0.013). Stratification by ventilator use revealed non-ventilated patients administered quetiapine had the highest risk for PC (sHR 4.66, p = 0.099). Conclusions Quetiapine exposure in critically injured trauma patients was associated with increased risk of PC. Guidelines for treatment of delirium with quetiapine in critically injured trauma patients should account for this risk.

Background Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior. Methods We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures. Results On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting at 2 weeks (group x time, F8,3052= 2.9, p = 0.003 for body weight, F8,3052= 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F1,2770= 2.0, p = 0.002), BMI (F1,2767= 2.0, p = 0.002), and waist circumference (women only, F25,1621= 2.9, p Limitations Bipolar CHOICE was not designed to study anthropometric outcomes. Conclusions Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline.

Psychotic and compulsive symptoms in Parkinson disease are highly prevalent and associated with poor outcomes and greater caregiver burden. When acute, delirium should be ruled out or treated accordingly. When chronic, comorbid systemic illnesses, dementia, and psychiatric disorders should be considered. Reduction and discontinuation of anticholinergics, amantadine, dopamine agonists, and levodopa as tolerated, as well as adjunctive clozapine or quetiapine are frequently effective to manage Parkinson disease psychosis. Pimavanserin appears effective but is not widely available, and more experience is needed. Dopamine agonist discontinuation is usually successful for impulse control disorders, but requires frequent monitoring, documentation, and caregiver involvement.

Purpose Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration–approved OAAs in a real-world setting. Methods This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up. Findings The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488–16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05–2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04–2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779–35,353] vs $23,851 [18,907–28,795]; medical, $19,343 [16,294–22,392] vs $12,013 [7488–16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694–11,795; P = 0.009) than in brexpiprazole users. Implications Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.

Quetiapine is a common atypical antipsychotic used to treat mental disorders such as schizophrenia, bipolar disorder, and major depressive disorder. There has been increasing number of reports describing its cardiotoxicity. However, the molecular mechanisms underlying quetiapine-induced myocardial injury remain largely unknown. Herein, we reported a novel cell death type, quetiapine-induced necroptosis, which accounted for quetiapine cardiotoxicity in mice and proposed novel therapeutic strategies. Quetiapine-treated hearts showed inflammatory infiltration and evident fibrosis after 21-day continuous injection. The specific increases of protein levels of RIP3, MLKL and the phosphorylation of MLKL showed that quetiapine induced necroptotic cell death both in vivo and in vitro. Pharmacologic blockade of necroptosis using its specific inhibitor Necrostatin-1 attenuated quetiapine-induced myocardial injury in mice. In addition, quetiapine imbalanced the endocannabinoid system and caused opposing effects on two cannabinoid receptors (CB1R and CB2R). Specific antagonists of CB1R (AM 281, Rimonabant), but not its agonist ACEA significantly ameliorated the heart histopathology induced by chronic quetiapine exposure. By contrast, specific agonists of CB2R (JWH-133, AM 1241), but not its antagonist AM 630 exerted beneficial roles against quetiapine cardiotoxicity. The protective agents (AM 281, Rimonabant, AM 1241, and JWH-133) consistently inactivated the quetiapine-induced necroptosis signaling. Quetiapine bidirectionally regulates cannabinoid receptors and induces myocardial necroptosis, leading to cardiac toxic effects. Therefore, pharmacologic inhibition of CB1R or activation of CB2R represents promising therapeutic strategies against quetiapine-induced cardiotoxicity.

According to the American Geriatrics Society (AGS) Beers criteria, most atypical antipsychotic (AAPs) are inappropriate in patients with Parkinson's disease (PD) due to the risk of worsening Parkinsonian symptoms. This study evaluated the risk of pneumonia associated with inappropriate AAP use in elderly nursing home residents with PD. The study population encompassed older adults aged 65 years or older with a diagnosis of PD and with comorbid depression who started the AAP medication. Appropriate AAPs were defined as aripiprazole, clozapine or quetiapine according to 2015 Beers criteria, and inappropriate AAPs included olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone. Cox regression analyses involved propensity score-matched users of inappropriate and appropriate AAPs to examine the association between AAP use and risk of pneumonia. The mean age of patients in propensity-matched cohort (n = 12,076) was 82.15 years (SD = 6.97). The pneumonia incidence rates were 37.19 and 45.92 per person-year in appropriate and inappropriate AAP groups, respectively. Multivariable Cox regression analyses revealed increased risk of pneumonia [Hazard Ratio (HR) 1.20 (1.08–1.34)] for nursing home residents who were taking inappropriate compared to those taking appropriate AAP. In sensitivity analyses, the pneumonia risk was 1.28 (1.12–1.47) for risperidone vs. quetiapine and 1.29 (1.06–1.57) for olanzapine vs. quetiapine. The risk of pneumonia was significantly higher for patients with PD who used inappropriate AAP in comparison to appropriate AAP group in all analyses. This investigation warrants further attention regarding safety of atypical antipsychotics in PD.

Objectives Limited 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. Methods Using 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). Results Cytokine 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. Conclusions Despite 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.

Introduction Understanding hospitalization in Lewy body dementia (LBD) is a known knowledge gap. We aimed to identify common causes, medication profiles, complications, and outcomes of hospitalization in LBD. Methods A retrospective cohort study investigated details of academic medical center hospitalizations over a two-year period for patients with LBD. Data collected included demographics, home medications, pre-hospital living status, reason for admission, admission service, inpatient medications, complications, and discharge status. Non-parametric statistics assessed associations between variables and length of stay. Odds of a change in living situation based on admission variables was calculated. Results The study included 178 hospitalizations (117 individuals). Neuropsychiatric symptoms were the most common admission reason (40%), followed by falls (24%) and infection (23%). Patients were usually admitted to medicine services; neurology or psychiatric consultations occurred less than 40% of the time. Antipsychotics were administered during 38% of hospitalizations. Use of antipsychotics other than quetiapine or clozapine was associated with longer length of stay and increased odds of discharge to a higher level of care. One-third of hospitalizations resulted in transition to a higher level of care; 15% ended in hospice care or death. Conclusion The most common reasons for hospitalization in LBD are potentially modifiable. Opportunities for improved care include increased involvement of neurological and psychiatric services, delirium prevention strategies, and reduced antipsychotic use. Clinicians should counsel patients and families that hospitalizations in LBD can be associated with end of life. Research is needed to identify strategies to prevent hospitalization and optimal standards for inpatient care. Funding Lewy body dementia research at the University of Florida is supported by the University of Florida Dorothy Mangurian Headquarters for Lewy Body Dementia and the Raymond E. Kassar Research Fund for Lewy Body Dementia.

Background In contrast to over 30 studies reporting neurotoxicity associated with the first-generation antipsychotics (FGAs), several published studies have reported multiple neuroprotective effects associated with the second generation antipsychotics (SGAs). This prompted us to conduct a review of the reported neuroprotective mechanisms of the SGA class of antipsychotics compared to the FGAs. Methods A PubMed search was conducted using the keywords antipsychotic, neuroprotection, neuroplasticity, neurogenesis, neurotoxicity, toxicity, brain volume, neuroinflammation, oxidative stress, myelin, and oligodendrocyte. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. Results Animal, cell culture, and human clinical studies were identified. Twenty-four reports met the criteria for the search. All studies included at least one SGA (aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, perospirone, quetiapine, risperidone, and/or ziprasidone). A few also included FGAs as a comparator (predominantly haloperidol). All studies demonstrated at least one neuroprotective mechanism of one or more SGAs, while some studies also showed that FGAs ranged from having no neuroprotective effects to actually exerting neurotoxic effects leading to neuronal death. Conclusions A review of the literature suggests that in addition to their antipsychotic efficacy and low motoric side effects, SGAs exert measurable neuroprotective effects mediated via multiple molecular mechanisms and often in a dose-dependent manner. The neuroprotective effects of SGAs range from preventative to restorative and may play a salutary role in ameliorating the neurodegenerative effects of psychosis.

Second-generation antipsychotics are associated with moderate benefits in terms of improved schizophrenia symptoms, but also with higher rates of side-effects such as excessive weight gain (WG); a consensus on their efficacy has not been reached. To date, no study has evaluated the interplay of treatments and side-effects in a single framework, which is a critical step to clarify the role of side-effects in explaining the efficacy of these antipsychotics. We used recent methods for mediation and interaction to clarify the role of WG in explaining the effects of second-generation drugs on schizophrenia symptoms. We used data from 1460 participants in the CATIE trial, assigned to either perphenazine (first-generation comparison drug), olanzapine, quetiapine, risperidone, or ziprasidone. The primary outcome was an individual's score on the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia after 9 months, separately evaluated as positive (PANSS+), negative (PANSS−), and total PANSS score. WG after 6 months was investigated as a potential mediator and effect modifier. Results showed that, by limiting WG, patients would benefit of a considerably better improvement in terms of PANSS symptoms. In the scenario of weight change being controlled between −2% and 1% for all participants, patients assigned to olanzapine would experience the highest significant improvements in both PANSS+ (−2.66 points; 95% CI: −4.98, −0.35), PANSS− (−1.59; 95% CI: −4.31, 1.14), and total PANSS (−6.11; 95% CI: −13.13, 0.92). In conclusion, occurrence of excessive WG hampers the potentially beneficial effects of second-generation antipsychotics, thus suggesting future directions for treatment and interventions.

Background Various agents for augmentation of serotonin reuptake inhibitors have been investigated for treatment-resistant obsessive-compulsive disorder (OCD). We aimed to comprehensively compare different augmentation agents for treatment-resistant OCD in adults. Methods PubMed, Embase, Web of Science, CENTRAL, the WHO's ICTRP, and ClinicalTrials.gov were searched on February 20, 2018. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcome was efficacy measured by the Yale-Brown Obsessive Compulsive Scale. The secondary outcomes were tolerability (side-effect discontinuation) and acceptability (all cause discontinuation). Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). Results Thirty-three articles with 34 trials (1216 patients) were included. Memantine (MD, −8.94; 95% CI, −14.42 to −3.42), risperidone (−4.47, −8.75 to −0.17), topiramate (−6.05, −10.89 to −1.20), lamotrigine (−6.07, −11.61 to −0.50), and aripiprazole (−5.14, −9.95 to −0.28) were significantly superior to placebo. Antipsychotic (−4.09, −6.22 to −1.93) and glutamatergic (−5.22, −7.53 to −2.84) agents were significantly superior to placebo. Considerable heterogeneity was found across studies, and baseline symptom severity was identified as a significant moderator. After baseline severity adjustment, quetiapine (−5.00, −8.59 to −1.29) and olanzapine (−8.28, −15.34 to −1.13) became significantly superior to placebo. Conclusions Our study supports the use of antipsychotic or glutamatergic agents as augmentation agents for treatment-resistant OCD. Topiramate, lamotrigine, aripiprazole, olanzapine, risperidone, memantine, and quetiapine are alternative augmentation drugs; however, a definitive conclusion of the best drug remains undetermined because of the considerable heterogeneity and limited numbers of studies and patients for each agent.

Schizophrenia and schizoaffective disorder are chronic and debilitating psychiatric disorders. The present study was designed to determine DNA damage in patients with schizophrenia and schizoaffective disorder to assess the roles of oxidative metabolism and DNA repair mechanisms in this process, to assess the contribution of drugs, and thus to demonstrate the differences between schizophrenia and schizoaffective disorder. Thirty schizophrenia and 30 schizoaffective disorder patients, each having at least five years of disease history, aged between 18 and 60 years with no physical or neurological diseases, and 30 healthy volunteers participated in the study. Psychometric scales were applied, and 5 ml of blood was taken from all participants. The DNA damage was measured in lymphocytes by the comet assay method; the total oxidative parameters by ELISA; OGG1 and NEIL1 gene expressions by real-time PCR; and the role of drugs by in vitro assays. The most important finding in this study was that patients with schizophrenia had significantly greater DNA damage than schizoaffective disorder patients and the controls. This study also provides evidence of high oxidative stress statuses and inadequate DNA repair capacities in patients with schizophrenia. Moreover, psychotropic drugs did not induce any DNA damage to the lymphocytes according to in vitro analyses. The use of clozapine and adequate repair processes of the patients were the decisive factors in the prevention of DNA damage. The results of this study provide a reexamination of schizoaffective disorder within the schizophrenia spectrum and indicate that schizoaffective disorder may be considered a different diagnostic category. © 2018 Elsevier B.V.

Background Disturbances in thyroid function have been associated with use of psychotropic drugs, including antipsychotics. Still, the thyroid function in relation to commonly prescribed antipsychotic drugs and polypharmacy is not fully known. We investigated thyroid function associated with use of antipsychotics in patients with psychotic disorders compared with healthy controls. Methods We included 1345 patients and 989 healthy controls from the Thematically Organized Psychosis (TOP) study, recruiting participants between 18 and 65 years of age in the Oslo-area. All patients underwent a thorough clinical investigation and assessment of medication data. Thyroid function was determined from plasma levels of free thyroxin (fT4) and thyroid-stimulating hormone (TSH). Multiple linear regression analyses were performed to evaluate the association between thyroid parameters and use of antipsychotics, and monotherapy users of olanzapine, quetiapine, aripiprazole or risperidone (N = 473) were investigated separately. Results We found lower levels of fT4 (median 13.70 vs 14.00, p Conclusions Our findings indicate an association between use of antipsychotics and lower fT4. Clinicians should be aware that patients using quetiapine, olanzapine or antipsychotics in psychotropic polypharmacy are especially at risk.

Background: We aimed to investigate the association between congenital malformations and exposure to Second generation antipsychotics (SGAs) during the entire period of pregnancy. Methods: We used data from the Korean National Health Insurance (NHI) claims-based database. This study included data from all registered pregnancies in Korea between 1 January 2008 and 31 December 2018 in women aged 18 to 49 years (n=4,620,019). SGAs were divided into 3 groups, according to their risk of prolactin elevation: 1) the prominent prolactin elevation group (risperidone, paliperidone, amisulpride, zotepine); 2) the moderate prolactin elevation group (olanzapine, ziprasidone); and 3) the non–prolactin elevation group (quetiapine, aripiprazole). Findings: Our primary cohort consisted of 4 620 019 completed pregnancies, with linked records to 4 457 399 live-born infants. There were 4 834 women (0·11%) who were prescribed SGAs during pregnancy. The overall relative risk of congenital malformation 1.45 (95% CI, 1·33–1·57) in those who used SGAs during pregnancy compared to those who did not use SGAs during the observation period. The relative risk of congenital malformation was 1·25 (95% CI, 1·11–1·41) in those who used SGAs during pregnancy compared to those who used SGAs during the observation period but not during pregnancy. Women who used SGAs from the prominent prolactin elevation group during pregnancy had significantly increased risks of congenital malformation. Interpretation: Exposure to SGAs during pregnancy is associated with an increased risk of congenital malformation, regardless of the trimester of exposure and SGAs with a higher prolactin level increases the risk of malformations. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The study was conducted following the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of the HIRA (No. 2020-097).

Different therapeutic strategies are used for lowering prolactin concentrations in patients with psychotic disorders with antipsychotic-induced hyperprolactinaemia. We aimed to examine the evidence from open-label studies and randomized clinical trials (RCTs) that studied four prolactin-lowering therapeutic strategies in people with psychotic disorders and hyperprolactinaemia: 1) switching to prolactin-sparing antipsychotics; 2) adding aripiprazole; 3) adding dopamine agonists; and 4) adding metformin. RCTs were included in a meta-analysis. Effect sizes (Hedges' g) of prolactin reductions with each strategy were calculated. Withdrawal rates were also considered. We identified 26 studies. Nine studies explored switching antipsychotic treatment to aripiprazole (n = 4), olanzapine (n = 1), quetiapine (n = 2), paliperidone palmitate (n = 1) or blonanserin (n = 1). Twelve studies tested the addition of aripiprazole. Six studies explored the addition of cabergoline (n = 3), bromocriptine (n = 2) or terguride (n = 1). We also found one meta-analysis testing the addition of metformin to antipsychotic treatment but no other individual studies. A meta-analysis could only be performed for the addition of aripiprazole, the strategy with the best level of evidence. Five RCTs testing the addition of aripiprazole yielded a significant reduction in prolactin concentration compared to placebo (N = 3) or maintaining antipsychotic treatment (N = 2): Hedges' g was −1.35 (CI 95%: −1.93 to −0.76, p < 0.001). The three placebo-controlled RCTs for aripiprazole addition showed similar withdrawal rates for aripiprazole (10.1%) and placebo (11.5%), without significant differences in the meta-analysis. Our study suggests that, in terms of levels of evidence, adding aripiprazole is the first option to be considered for lowering prolactin concentrations in patients with schizophrenia and hyperprolactinaemia.

Background: Antipsychotics remain the first choice of treatment for post-stroke psychosis, despite an increased risk of mortality reported in elderly patients. We aimed to compare the mortality risk among antipsychotics in elderly patients with stroke using the stroke registry for external adjustment. Methods: We conducted a retrospective cohort study to identify patients aged above 65 years who were admitted for stroke in the National Health Insurance Database (NHID) from 2002 to 2014. The first date of antipsychotic use after the stroke hospitalization was defined as the index date. Covariates including diseases, medications and external information on smoking, BMI, stroke severity and disability, that were unavailable in the NHID were obtained from the linked Multicenter Stroke Registry (MSR) and used for propensity score calibration (PSC). The main outcome was one-year all-cause mortality Findings: Stroke patients in the NHID prescribed with haloperidol, quetiapine and risperidone numbered 22 235, 28 702 and 8 663, respectively. In the PSC-adjusted analyses, haloperidol [adjusted hazard ratio (aHR) = 1.22; 95% CI 1.18–1.27] and risperidone (aHR = 1.31; 95% CI 1.24–1.38) users had a higher mortality risk than quetiapine users. Haloperidol and risperidone exhibited a dose-response relationship with mortality risk after controlling for confounders. When the dosage was higher than 0.5 defined daily dose (DDD), haloperidol and risperidone users had a significant mortality risk as compared with those taking a lower dose. The sensitivity analyses showed similar patterns. Interpretation: In post-stroke elderly patients, quetiapine would be favored over risperidone and haloperidol at doses higher than 0.5 DDD. When haloperidol or risperidone is indicated, starting with a lower dose is suggested to avoid excess risk. Funding Statement: This research was supported in part by the Ministry of Science and Technology, Taiwan [grant number MOST 107-2320-B-006-035]. Declaration of Interests: The authors declare they have no conflict of interest with respect to this research study and paper. Ethics Approval Statement: The research protocol was approved by the Institutional Review Board of National Cheng Kung University Hospital (IRB No. A-EX-106-016).

Anxiety is common in women during the perinatal period, manifests with various symptoms and severity, and is associated with significant maternal morbidity and adverse obstetric and neonatal outcomes. Given the intimate relationship and frequency of contact, the obstetric provider is positioned optimally to create a therapeutic alliance and to treat perinatal anxiety. Time constraints, absence of randomized controlled trials, mixed quality of data, and concern for potential adverse reproductive outcomes all limit the clinician's ability to initiate informed risk-benefit discussions. Clear understanding of the role of the obstetric provider in the identification, stabilization, and initiation of medication and/or referral to psychotherapy for women with perinatal anxiety disorders is critical to maternal and neonatal wellbeing. Informed by our clinical practice as perinatal psychiatric providers, we have provided a concise summary of current research on the approach to the treatment of perinatal anxiety disorders in the obstetric setting that includes psychotherapy and supportive interventions, primary and adjuvant psychiatric medication, and general prescribing pearls. Medications that we examined include antidepressants, benzodiazepines, sedative-hypnotics, antihistamines, quetiapine, buspirone, propranolol, and melatonin. Further research into management of perinatal anxiety, particularly psychopharmacologic management, is warranted.

Background Successful medication management for bipolar disorder requires clinicians to monitor and adjust regimens as needed, to achieve maximum effectiveness and patient adherence. This study aims to measure the prevalence of indications for medication adjustment at visits for bipolar disorder treatment; the frequency with which physicians recommend medication adjustments; and how strongly the indications predict the adjustments. Methods Data included 3,094 visits for 457 patients in Bipolar CHOICE, a comparative effectiveness study that compared treatment with lithium versus quetiapine. A set of indications for adjustment was matched to reports of whether the physician recommended a medication adjustment at that visit, and what type. Associations between indication and adjustment were examined using bivariate tests and hierarchical logistic mixed effects models. Results Medication adjustment was recommended at 63% of the visits where one of the indications was present, and at 53% of all visits. In multivariable analyses, adjustment was more likely to be recommended if there was an indication of non-response or side effects, for patients who started on quetiapine rather than lithium, or for patients who were female, married, employed or more educated. Limitations The study's cross-sectional design implies that observed associations could result from confounding variables. Also, the CHOICE trial placed certain restrictions on physicians’ medication choices, although this is not likely to have resulted in major alterations of prescribing patterns. Conclusions Clinical inertia may help explain the lack of any adjustment recommendation at 37% of the visits where one of the indications was present. Other explanations could also apply, such as watchful waiting.

Children and adolescents with schizophrenia are a particularly vulnerable group. Thus, we integrated all the randomized evidence from the available antipsychotics used for this subgroup by performing a network-meta-analysis and pairwise meta-analysis using a random-effects model. We searched multiple databases up to Nov 17, 2016 (final update search in PubMed: Dec 12, 2017). The primary outcome was efficacy as measured by overall change/endpoint in symptoms of schizophrenia. Secondary outcomes included positive and negative symptoms, response, dropouts, quality of life, social functioning, weight gain, sedation, prolactin, extrapyramidal side effects (EPS) and antiparkinsonian medication. Twenty-eight randomized controlled trials (RCTs) with 3003 unique participants (58% males; mean age 14.41 years) published from 1967 to 2017 were identified. Clozapine was significantly more effective than all other analyzed antipsychotics. Nearly all antipsychotics were more efficacious compared to placebo, but ziprasidone showed no efficacy. In terms of preventing weight gain, molindone, lurasidone and ziprasidone were benign. The highest weight gain was found for clozapine, quetiapine and olanzapine. Most antipsychotics had some sedating effects. Risperidone, haloperidol, paliperidone and olanzapine were associated with prolactin increase. There were evidence gaps for some drugs and many outcomes, especially safety outcomes. Most of the comparisons are based only on one study or just on indirect evidence. Nevertheless, the available direct and indirect evidence showed that the treatment effects were similar compared to findings in adult patients with schizophrenia.

Background There is uncertainty about the required duration of long-term antipsychotic maintenance medication after a first episode of psychosis. Robust predictors of relapse after discontinuation are yet to be identified. The present study aimed to determine the proportion of young people who discontinue their antipsychotic medication after a first episode of psychosis, the proportion who experience relapse, and predictors of relapse. Methods A retrospective study of all individuals presenting to the Early Psychosis Prevention and Intervention Centre between 01/01/11 and 31/12/13 was conducted. A Cox regression analysis was conducted to identify predictors of relapse. Results A total of 544 young people with a FEP were included. A trial of discontinuation was undertaken by 61% of the cohort. Median duration of antipsychotic medication prior to first trial of discontinuation was 174.50 days. Amongst those trialing discontinuation, 149 (45.8%) experienced relapse in a median follow-up time post discontinuation of 372 days. On multivariate analysis, predictors of relapse were a diagnosis of cannabis abuse disorder (HR: 1.40), and longer duration of antipsychotic medication (HR: 1.05). Conclusion Antipsychotic discontinuation frequently occurs earlier than guidelines recommend. Individuals with a diagnosis of cannabis abuse are more likely to experience relapse and addressing this substance abuse prior to discontinuation could possibly reduce relapse rates.

While impairments of cognition in schizophrenia have the greatest impact on long-term functional outcome, the currently prescribed treatments, antipsychotic drugs (APDs), do not effectively improve cognition. Moreover, while more than 20 years have been devoted to the development of new drugs to treat cognitive deficits in schizophrenia, none have been approved to date. One area that has not been given proper attention at the preclinical or clinical stage of drug development is the chronic medication history of the test subject. Hence, very little is known about how chronic treatment with drugs that affect multiple receptors like APDs influence the response to a potential pro-cognitive agent. Therefore, the purpose of this study was to evaluate the α7 nicotinic acetylcholine receptor (α7 nAChR) partial agonist, tropisetron in rats chronically treated with APDs with distinct pharmacological profiles. Rats were treated orally with either risperidone (2.5 mg/kg/day) or quetiapine (25.0 mg/kg/day) for 30 or 90 days and then an acute injection of vehicle or tropisetron (3.0 mg/kg) was administered before training in a novel object recognition (NOR) task. After a 48 hr delay (when recollection of the familiar object was impaired in vehicle-treated animals) neither 30 nor 90 days of risperidone or quetiapine treatment improved NOR performance. In contrast, tropisetron markedly improved NOR performance in rats treated with either APD for 30 or 90 days. These animal data reinforce the argument that two commonly prescribed APDs are not pro-cognitive agents and that α7 nAChR ligands like tropisetron have potential as adjunctive treatments in schizophrenia.

Objective The risk of gastrointestinal hypomotility (GIHM) with the use of antipsychotic medications in patients with schizophrenia remains inadequately recognized. The aim of this study was to explore the incidence of GIHM and its risks in patients with schizophrenia treated with antipsychotics. Methods We conducted a retrospective cohort study using the National Health Insurance Research Database. We identified adult (≥ 20 years of age) patients with a first-time diagnosis of schizophrenia or schizoaffective disorder in the Registry for Catastrophic Illness Patients during the period from 2001 to 2011. Each subject in the cohort was followed until their corresponding diagnosis of GIHM was made, until the time of death, or to December 31, 2012. The incidence rates of each outcome were calculated. Cox proportional hazards regression with time-dependent covariates for antipsychotics use was employed to evaluate the associations between different types of antipsychotics and the risk of GIHM. Results Our study found that the incidence densities of constipation, ileus, and ischemic bowel disease were 42.5, 4.4, and 0.1 per 1000 person-years. In terms of the risk of hypomotility with the use of antipsychotics, clozapine and quetiapine were significant in developing constipation, with a hazard ratio of 2.15 and 1.34, respectively. High-potency first-generation antipsychotics and clozapine were also significant in the occurrence of ileus, with a hazard ratio of 1.30 and 1.95, respectively. Similar associations were found in an anticholinergic agent subgroup analysis. Conclusion Patients receiving antipsychotics such as high-potency first-generation antipsychotics, clozapine, or quetiapine should undergo proper evaluation and intervention to minimize the disease burden and life-threatening outcomes of treatment.

Antipsychotic drugs are associated with autonomic nervous system (ANS) dysfunction in patients with schizophrenia, but the effects of individual atypical antipsychotic drugs are not clear. This study investigated how four atypical antipsychotic drugs-risperidone, olanzapine, aripiprazole, and quetiapine-differ in their effects on ANS activity. A total of 241 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 90 participants received risperidone, 68 olanzapine, 52 aripiprazole, and 31 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. The quetiapine group showed significantly diminished sympathetic and parasympathetic activity compared with the risperidone and aripiprazole groups and significantly lower sympathetic activity relative to olanzapine. In addition, multiple regression analysis showed that the type of antipsychotic drug significantly influenced ANS activity. We suggest that, among the antipsychotics examined-risperidone, olanzapine, aripiprazole and quetiapine-quetiapine has the strongest effect on ANS activity.

Traumatic brain injury (TBI)-induced agitation and aggression pose major obstacles to clinicians in the acute hospital and rehabilitation settings. Thus, management of these symptoms is crucial. Antipsychotic drugs (APDs) are a common treatment approach for alleviating these symptoms. However, previous preclinical TBI studies have indicated that daily and chronic administration of these drugs (e.g., haloperidol; HAL) can exacerbate cognitive and motor deficits. Quetiapine (QUE) is an atypical APD that differs from many typical APDs, such as HAL, in its relatively rapid dissociation from the D(2) receptor. The goal of this study was to test the hypotheses that intermittent HAL and QUE would not hinder recovery of cognitive and motor function following TBI and that daily QUE would also not impair functional recovery, which would be in contrast to HAL. Seventy anesthetized male rats received either a controlled cortical impact or sham injury and were then randomly assigned to TBI and sham groups receiving HAL (0.5 mg/kg) or QUE (10 mg/kg) intraperitoneally once per day or once every other day and compared to each other and vehicle (VEH) controls. Motor function was assessed by beam balance/walk tests on post-operative days 1-5 and cognitive function was evaluated with a Morris water maze task on days 14-19. No differences were revealed among the sham groups in any task, and hence the data were pooled. No overall differences were detected among the TBI groups, regardless of treatment or administration paradigm [p > 0.05], but all were impaired vs. SHAM controls [p < 0.05]. The SHAM controls also performed significantly better in the cognitive test vs. all TBI groups [p < 0.05]. Moreover, the TBI + continuous HAL group performed worse than the TBI + continuous VEH, TBI + continuous QUE, and TBI + intermittent QUE groups [p < 0.05], which did not differ from one another. Overall, the data suggest that QUE does not exacerbate TBI-induced cognitive and motor deficits, which supports the hypothesis. QUE may prove useful as an alternative APD treatment for management of agitation and aggression after clinical TBI. HAL may also be safe, but only if used sparingly.

Major depressive disorder (MDD) is a highly debilitating condition that is drawing considerable attention due to its high global prevalence and to the fact that treatments are still far from reaching the total number of patients affected. Among available treatment strategies, quetiapine is an important research target, due to antidepressant responses in patients resistant to classical treatments and in animals submitted to protocols that induce depressive-like behaviours. Quetiapine has a broad spectrum of action, within which are many mechanisms that seem to be related to the most effective antidepressant therapeutic responses. In this review, research results related to the pharmacokinetic profile, neurotransmitters, receptors and signalling molecular targets involved in the functional and structural plasticity of key brain regions in MDD are reported and discussed. Moreover, the physiological mechanisms, which are targets of quetiapine and are involved in both MDD and poor therapeutic response, are reported. The main adverse effects observed from therapeutic dosages and overdose are also described. Finally, the main mechanisms underlying the therapeutic response are highlighted.

Aim We examined the first- and second-line pharmacological treatment for delirium to determine which drugs were chosen, how and when second-line drugs were started, and the effectiveness and tolerability of those treatments. Methods A retrospective medical chart review was performed for delirium inpatients referred to the Department of Psychiatry, Hiroshima Citizens Hospital, from October 2011 to September 2012. Clinical diagnoses were based on ICD-10. We compared the baseline severity of delirium, duration needed for improvement, and rescue with antipsychotics between subjects given only first-line drugs and those switched to second-line drugs. Results We studied 194 consecutive patients including 127 men and 67 women whose average age was 76.5 ± 9.8 years. For first-line drugs, trazodone was most frequently prescribed (n = 100, 51.5%), followed by quetiapine (n = 57, 29.4%). Among patients treated with trazodone or quetiapine as first line treatment, 59 of 100 (59%) continued trazodone and 52 of 57 (91.2%) continued quetiapine. Duration needed for improvement did not differ significantly between patients treated with trazodone as a first line drug and those with quetiapine as same. Conclusion Trazodone can be a candidate drug as one of the first line drugs for delirium.

This study aimed to evaluate the efficacy and safety of quetiapine fumarate extended-release (XR) in the treatment of Chinese patients with acute schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non-inferiority randomized study in Chinese patients (n = 388) with schizophrenia randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment. Safety objectives included adverse event (AE) monitoring, laboratory test results, and electrocardiograms. Changes in PANSS total score were -33.4 for quetiapine XR and -35.9 for chlorpromazine (P > 0.05). Least squares mean changes were: positive subscale, -9.9 ± 0.53 and -11.1 ± 0.51; negative subscale, -5.9 ± 0.50 and -6.7 ± 0.48; general psychopathology subscale, -12.9 ± 0.74 and -13.9 ± 0.71; aggression and hostility cluster scores, -4.8 ± 0.33 and -5.4 ± 0.32; and depression cluster scores, -1.8 ± 0.18 and -1.7 ± 0.18, for quetiapine XR and chlorpromazine, respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine, AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for treating acute schizophrenia in Chinese patients and was well tolerated.

Background Bipolar patients experience sleep disturbances during and between mood episodes. Yet the impact of sleep on treatment with different medications has not been fully explored. The purpose of this paper is to explore the potential impact of poor sleep at baseline on outcomes in a randomized effectiveness trial of quetiapine and lithium. Methods The Bipolar CHOICE study was a 6-month, parallel group, multisite randomized controlled trial. Participants with bipolar disorder (N = 482; 59% female and age 18–70 years) received quetiapine or lithium. Patients were allowed to also receive adjunctive personalized treatments, which were guideline-informed, empirically-based medications added to treatment as needed. Medication changes were recorded as necessary clinical adjustments (NCA). Fisher's exact tests, mixed-regression models, and Mann-Whitney U tests were used to assess demographic and clinical characteristics as well as whether sleep disturbance would predict outcomes. Results 63% of patients had baseline sleep disturbance. Individuals with sleep disturbance had worse bipolar illness severity, greater severity of depression, mania, anxiety, irritability, and psychosis, were less likely to have sustained response (17% vs. 29%; adjusted RR: 0.55, 95% CI: 0.38–0.78, p = 0.0006) and had more NCAs (median 0.71 vs. 0.59, p = 0.03). Limitations Our findings were limited by how we defined sleep disturbance, and by how severity of sleep disturbance was assessed with one item with a non-sleep specific measure. Conclusions Baseline sleep disturbance was associated with more severe bipolar symptoms and worse 6-month outcomes. Further research is warranted on improving sleep in bipolar disorder, especially the role of psychosocial interventions.

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.

Objectives The objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs). Study Design and Setting Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic sources (clinical study reports [CSRs] and individual participant data [IPD]). Results We found 21 gabapentin RCTs (74 reports, 6 IPD) and 7 quetiapine RCTs (50 reports, 1 IPD); most were reported in journal articles (18/21 [86%] and 6/7 [86%], respectively). When available, CSRs contained the most trial design and risk of bias information. CSRs and IPD contained the most results. For the outcome domains “pain intensity” (gabapentin) and “depression” (quetiapine), we found single trials with 68 and 98 different meta-analyzable results, respectively; by purposefully selecting one meta-analyzable result for each RCT, we could change the overall result for pain intensity from effective (standardized mean difference [SMD] = −0.45; 95% confidence interval [CI]: −0.63 to −0.27) to ineffective (SMD = −0.06; 95% CI: −0.24 to 0.12). We could change the effect for depression from a medium effect (SMD = −0.55; 95% CI: −0.85 to −0.25) to a small effect (SMD = −0.26; 95% CI: −0.41 to −0.1). Conclusions Disagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.