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Objectives: The current study uses longitudinal data from the National Alzheimer's Coordinating Center (NACC) to assess the effects of antipsychotic medication use on changes in cognitive functioning among adults in the United States. Methods: Linear mixed models were conducted that included study visits, days between visits, sex, age, education, and medical history (i.e. diabetes, seizures, traumatic brain injury, stroke, and Parkinson's disease). The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to create variables assessing changes in psychotic symptoms, manic symptoms, and agitation/disinhibition. Results: The results indicated that starting an antipsychotic medication was associated with a greater decline in semantic fluency (Fruit and Vegetable Naming), processing speed (Digit Symbol and Trail Making Test, Part A), and cognitive flexibility (Trail Making Test, Part B). Conversely, stopping an antipsychotic medication was protective against declines in the same cognitive skills. The effect of antipsychotic medications on cognitive functioning did not appear to differ by reported changes in psychiatric symptoms after adjusting for false discovery. Conclusion: The results suggest that prescribers should consider discontinuance of an antipsychotic if the patient is reporting cognitive problems and their symptoms are manageable off the medications. The findings hope to spark future research into the effects of antipsychotic use on biomarkers of progressive dementias (e.g. Alzheimer's disease). [ABSTRACT FROM AUTHOR]

Objectives: To describe nursing home (NH) characteristics associated with antipsychotic use and test whether associations changed after implementation of the National Partnership to Improve Dementia Care's antipsychotic reduction initiative (ARI). Methods: Longitudinal quasi-experimental design using data from multiple sources and piecewise linear mixed models were used for statistical analyses. Results: There was a significant decrease in monthly antipsychotic use across the study period (pre-ARI b = −0.0003, p <.001; post-ARI b = −0.0012, p <.001), which held after adjusting for NH characteristics. Registered nurse hours (b = −0.0026, p <.001), licensed practical nurse hours (b = −0.0019, p <.001), facility chain membership (b = −0.0013, p <.01), and health inspection ratings (b = −0.0003, p >.01) were associated with decreased antipsychotic use. Post-ARI changes in associations between NH characteristics and antipsychotic use were small and not statistically significant. Conclusions: Decreases in antipsychotic use were associated with most NH characteristics, and associations persisted post-ARI. Further research is warranted to examine the interactions between ARI policy and NH characteristics on antipsychotic prescribing, as well as other NH factors, such as facility prescribing cultures and clinical specialty of staff. Clinical Implications: Decreases in monthly antipsychotic use were observed following the ARI. The decreases in monthly antipsychotic use were associated with most NH characteristics, and these associations persisted during the post-ARI period. [ABSTRACT FROM AUTHOR]

Antipsychotics are frequently used for inpatients with alcohol withdrawal syndromes (AWS). While there is evidence on the effects of these medications in other settings there is little data on the mortality rate associated with these drugs for the treatment of AWS) We utilized the national COSMOS Epic database to identify inpatients with AWS. We then assessed the mortality rate for adult patients with or without the use of anti-psychotics along with subsets of patients based on age, gender, race, and ethnicity. We identified 233,821 patients of whom 26% received antipsychotic agents. The mortality rate was 1.5%. Patients aged 60 or over and those who received typical antipsychotic agents had a higher mortality rate. The use of typical antipsychotic agents is associated with a higher mortality rate. The use of any antipsychotic agent in patients aged 60 or over is associated with an increased mortality rate. Further study of this effect is warranted. [ABSTRACT FROM AUTHOR]

Paliperidone Palmitate is the only antipsychotic that has been developed in three different intramuscular long-acting injectable (LAI) dosing regimen: monthly (PP1M), quarterly (PP3M), and from 2020 also twice-yearly (PP6M). The latter was approved for the maintenance treatment of adults with schizophrenia and clinically stabilized with PP1M or PP3M. Data from studies evaluating efficacy in the maintenance treatment of schizophrenia with PP6M are reviewed. Since no post-marketing safety studies are currently available, data from spontaneous reporting system databases, FAERS and Eudravigilance, are analyzed and the reported treatment-emergent adverse events of PP6M are discussed. The efficacy of PP6M is comparable to that of PP3M in terms of relapses prevention in patients with schizophrenia previously stabilized on PP3M or PP1M. Also, the maintenance of clinical efficacy in the long term has been demonstrated. Data from pharmacovigilance analyses, as well as from phase 3 studies, show that PP6M is generally well tolerated, consistently with PP3M safety data. PP6M allows a longer dosing interval than any other LAI antipsychotics, potentially reducing nonadherence and disease relapses. In future, an increase in the prescription rates of PP6M is expected and real-world efficacy and tolerability studies will be conducted. [ABSTRACT FROM AUTHOR]

We systematically reviewed extant studies evaluating the efficacy and tolerability of xanomeline and xanomeline-trospium (KarXT) for treatment of adults with schizophrenia. In accordance with PRISMA guidelines, articles were systematically searched for in databases and clinical trial registries. A total of 4 preclinical trials and 3 randomized controlled trials (RCTs) were included in this review. A 4-week RCT observed a difference of 24.0 points (SD 21.0) in the Positive and Negative Syndrome Scale (PANSS) total score between xanomeline and placebo groups (p = 0.039). A 5-week RCT observed PANSS total score changes from baseline to week 5, including −17.4 and −5.9 points in KarXT and placebo groups, respectively (LSMD −11.6 points; 95% CI −16.1 to −7.1; p < 0.001; d = 0.75). Another 5-week RCT observed PANSS total score changes from baseline to week 5, including −21.2 (SE 1.7) and −11.6 (SE 1.6) points in KarXT and placebo groups, respectively (LSMD −9.6; 95% CI −13.9 to −5.2; p < 0.0001; d = 0.61). Side effects include constipation, nausea, vomiting, dyspepsia, and dry mouth. KarXT offers an innovative non-D2 blocking approach, representing a promising treatment avenue for schizophrenia. [ABSTRACT FROM AUTHOR]

Antipsychotic polypharmacy is prevalent, however literature on antipsychotic polypharmacy during treatment among patients with dual diagnosis is largely non-existent. This study aims to investigating the extent of antipsychotic polypharmacy dual diagnosis patients during hospitalisations. Utilizing cohort data from an integrated dual diagnosis in-patient facility from patients hospitalized between 1 March 2012, to 31 December 2016, we compared the mean antipsychotic medication administered at admission and discharge and examined covariate associations with logistic regressions. The study identified 907 hospital admissions, of which 641 were the first for each patient during the period. At admission, 74.1% received antipsychotics; polypharmacy spanned psychiatric disorders. categories. Patients with affective or personality spectrum disorders were less likely to have antipsychotic polypharmacy upon admission compared to those with psychosis spectrum disorders. 2013–2016 admissions presented less polypharmacy than 2012. Mean antipsychotic numbers remained unchanged for >30-day hospitalizations. Patients admitted without antipsychotic polypharmacy with an affective spectrum disorder or aged 41–50 or over 51 years old were less likely to be discharged with antipsychotic polypharmacy when compared to patients with psychosis spectrum disorder or aged 18–30 years old. Approximately three-quarters of admitted patients were treated with antipsychotic medication. Antipsychotic polypharmacy was observed across all psychiatric disorder categories, indicating potential off-label use. Addressing antipsychotic polypharmacy during treatment is challenging, even for specialised facilities. Rational antipsychotic prescribing, deprescribing protocols, and further prescription pattern research are needed. [ABSTRACT FROM AUTHOR]

Developing novel antipsychotic mechanisms of action and repurposing established compounds for the treatment of schizophrenia is of utmost importance to improve relevant symptom domains and to improve the risk/benefit ratio of antipsychotic compounds. Novel trial design concepts, pathophysiology-based targeted treatment approaches, or even the return to old values may improve schizophrenia outcomes in the future. In this review of the clinical trial landscape in schizophrenia, we present an overview of the challenges and gaps in current clinical trials and elaborate on potential solutions to improve the outcomes of people with schizophrenia. The classic parallel group design may limit substantial advantages in drug approval or repurposing. Collaborative approaches between regulatory authorities, industry, academia, and funding agencies are needed to overcome barriers in clinical schizophrenia research to allow for meaningful outcome improvements for the patients. [ABSTRACT FROM AUTHOR]

IntroductionMethodResultsDiscussionInformed consent is the process whereby individuals make decisions about their medical care. Information provision, presumption of capability and absence of coercion are three fundamental assumptions required to provide informed consent. Informed consent may be complex to achieve in the context of antipsychotic prescribing. This systematic review aimed to explore challenges relating to informed consent processes in antipsychotic prescribing in the UK.This was a systematic review of the literature relating to informed consent in antipsychotic prescribing in community settings. Data were analysed using Framework analysis.Twenty-eight articles were included. Information provision has been perceived as lacking for a long time. Capacity has often not been assumed and loss of capacity has sometimes been viewed as permanent. Power imbalances associated with prescriber status and legal framework surrounding the Mental Health Act can blur lines between coercion and persuasion.Challenges relating to process of informed consent in antipsychotic prescribing have persisted throughout the last few decades. People prescribed antipsychotics need to be made aware of their effects in line with current research. Further research is required to develop models for best practices for informed consent. [ABSTRACT FROM AUTHOR]

Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. CA activators (CAAs) are becoming increasingly important in the biomedical field since enhancing CA activity may have beneficial effects at neurological level. Here, we investigate selected antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants (TCAs) as potential activators of human CAs I, II, IV, and VII. Our findings indicate that these compounds are more effective at activating hCA II and VII compared to hCA I and IV. Overall, hCA VII was the most efficiently activated isoform, particularly by phenothiazines and TCAs. This is especially relevant since hCA VII is the most abundant isoform in the central nervous system (CNS) and is implicated in neuronal signalling and bicarbonate balance regulation. This study offers additional insights into the pharmacological profiles of clinically employed drugs and sets the ground for the development of novel optimised CAAs. [ABSTRACT FROM AUTHOR]

The purpose of the study was to determine the effect of combination therapy involving opioids, steroids, benzodiazepines, anticholinergics, and antihistamines on antipsychotics efficacy for delirium. The study included adult inpatients receiving end-of-life palliative care and diagnosed with hyperactive delirium. Changes in delirium symptoms were assessed using the Intensive Care Delirium Screening Checklist (ICDSC). A retrospective analysis was conducted on 97 patients with ICDSC scores of =4, comparing the scores before and after antipsychotic administration. A mean score <4 sustained for 3 days after antipsychotics administration was considered effective. The mean days with ICDSC <4 within a 3-day period were evaluated as well. The efficacy of antipsychotics was compared between cases with and without the use of opioids, steroids, benzodiazepines, anticholinergics, and antihistamines. The results revealed no significant differences in the efficacy of antipsychotics for delirium when used in conjunction with opioids (odds ratio 0.614, 95% CI [0.179-2.105]), benzodiazepines (0.387, [0.108-1.390]), steroids (1.258, [0.276-5.746]), or anticholinergics (2.085, [0. 148-29.458]). Additionally, no significant differences were observed in the mean days with ICDSC <4 within 3-day period. Although opioids, benzodiazepines, steroids, anticholinergics, and antihistamines are recognized as delirium risk factors, their use for symptom relief in patients with delirium may not affect antipsychotic efficacy. [ABSTRACT FROM AUTHOR]

This nationwide retrospective cross-sectional study examines the prevalence of antipsychotic polypharmacy (APP) and demographic, forensic, and clinical factors associated with its practice among Greenlandic forensic psychiatric patients. We collected data from electronic patient files, court documents, and forensic psychiatric assessments. We defined APP as two or more concurrent prescriptions of antipsychotic medication. The study population of 74 patients had a mean age of 41.4 years, and 61 were men. All included patients had either schizophrenia or another ICD-10 F2-diagnosis. We used unpaired t-tests and Chi2 or Fisher's exact test. The prevalence of APP was 35% (n = 26), and there was a significant association between APP and a prescription of clozapine (Chi2, p = 0.010), olanzapine (Fisher's test, p = 0.003), and aripiprazole (Fisher's test, p = 0.013). Furthermore, we found a significant association between APP and prescription of a first-generation antipsychotic (FGA) (Chi2, p = 0.011). Despite recommendations in guidelines, the use of APP is common practice. The majority of forensic psychiatric patients suffer from severe psychiatric disorders, often with other comorbidities, including substance use disorder. The severity and complexity in mental health render forensic psychiatric patients at high risk of APP treatment. Further knowledge on APP use is crucial to secure and further improve the psychopharmacological treatment for this group of patients. [ABSTRACT FROM AUTHOR]

Schizophrenia is a psychotic disorder and one of the most severe and impactful mental illnesses. Sexual dysfunction is highly prevalent in patients with schizophrenia but remains underdiagnosed and undertreated. Sexual dysfunction is frequently attributed to antipsychotics which may reduce medication adherence, but negative symptoms can also reduce sexual drive. This review provides an overview of the current knowledge about sexual dysfunction in patients with schizophrenia. The authors first review the literature concerning the mechanisms of sexual dysfunction and explore the impact of antipsychotics on sexual function. Finally, they present the available non-pharmacological and pharmacological treatment strategies for sexual dysfunction in patients with schizophrenia. Sexual dysfunction in patients with schizophrenia is still underrated by clinicians despite having a negative impact on the quality of life and therapeutic adherence. Antipsychotic treatment is still perceived as a major cause of sexual impairment. Psychiatrists must be aware of this condition and actively question the patients. A comprehensive approach, addressing pharmacological and non-pharmacological aspects, is fundamental for managing sexual dysfunction in schizophrenia. Pharmacological strategies include (1) Serum-level adjustment of the antipsychotic dose, if possible (2) switching to a well-tolerable antipsychotic (aripiprazole, brexpiprazole) and (3) adding a coadjuvant drug (phosphodiesterase-5 inhibitors). [ABSTRACT FROM AUTHOR]

Objective: The aim of this review is to analyse the literature regarding studies centred on the clinical outcome of individuals affected by schizophrenia and treated with various antipsychotics, and then switched to orally administered partial D2-dopamine agonists (PD2A): Aripiprazole (ARI), brexpiprazole (BREX) or cariprazine (CARI). Method: A PubMed literature search was performed on 16 February 2021, and updated on Jan 26, 2022 for literature on antipsychotic switching in individuals affected by schizophrenia. Literature was included from 2002 onward. Six strategies were defined: Abrupt, gradual and cross-taper switch, and 3 hybrid strategies. The primary outcome was all-cause discontinuation rate per switch strategy per goal medication. Results: In 10 reports on switching to ARI, 21 studies with different strategies were described, but there were only 4 reports and 5 strategies on switching to BREX. Only one study about CARI was included, but it was not designed as a switch study. The studies are difficult to compare due to differences in methodology, previous antipsychotic medication, doses of the introduced P2DA and study duration. Conclusion: This analysis did not reveal evidence for a preferable switching strategy. A protocol should be developed which defines optimal duration, instruments to be used, and the timing of the exams. [ABSTRACT FROM AUTHOR]

The challenges posed by treatment-resistant schizophrenia and depressive symptoms have led to ongoing difficulties despite the availability of antipsychotics and antidepressants. This review addresses the potential of amisulpride analogs, particularly SEP-4199, in addressing these challenges through enhanced efficacy and reduced side effects. This review focuses on the pharmacological profile of amisulpride analogs, exemplified by LB-102 and its derivative SEP-4199. PubMed gathered articles (up to 10 March 2023) on 'amisulpride,' 'schizophrenia,' 'bipolar disorder,' and 'major depressive disorder;' ClinicalTrials.gov tracked SEP-4199 and LB-102 trials. LB-102, a newly identified N-methylated analog of amisulpride, exhibits enhanced lipophilicity at lower doses, as demonstrated in a phase 1 study, indicating significant promise for therapeutic applications. The discovery of SEP-4199, a non-racemic analog composed of R- and S-enantiomers in an 85:15 ratio, is discussed, emphasizing its potential to enhance antidepressant effects while minimizing extrapyramidal side effects via selective D2 receptor binding. Recent phase 2 trials have demonstrated SEP-4199's efficacy in treating depressive symptoms in bipolar disorder I, capitalizing on D2-mediated anti-anhedonic and D3-mediated reward effects. The development of SEP-4199 presents a potential breakthrough for managing depressive symptoms in bipolar disorder I. Further exploration of D2 and D3 receptor-mediated effects could lead to improved treatment strategies. [ABSTRACT FROM AUTHOR]

To survey trends of antipsychotic use during pregnancy and examine the associations between the use of quetiapine or any antipsychotic and adverse obstetric and neonatal outcomes. Birth register study of 36,083 women who gave birth at Kuopio University Hospital, Finland, between 2002 and 2016. Obstetric and neonatal outcomes between women using quetiapine (N = 152) or any antipsychotic (N = 227) were compared to controls (N = 35,133). Altogether 246 (0.7%) women used antipsychotic medications during pregnancy and 153 (62,2%) of these women used quetiapine. Antipsychotic usage increased from 0.4% to 1.0% during the 15-year follow-up. Women using antipsychotics were more likely to smoke, drink alcohol, use illicit drugs, use other psychotropic medications, and have higher pre-pregnancy body mass index. Quetiapine use was associated with higher risk of increased postpartum bleeding in vaginal delivery (aOR 1.65; 95%CI 1.13–2.42), prolonged neonatal hospitalization (≥5 days) (aOR 1.54; 95%CI 1.10–2.15), and higher placental to birth weight ratio (PBW ratio) (aB 0.009; 95%CI 0.002–0.016). Use of any antipsychotic was associated with a higher risk of gestational diabetes mellitus (aOR 1.64; 95%CI 1.19–2.27), increased postpartum bleeding in vaginal delivery (aOR 1.50; 95%CI 1.09–2.07), prolonged neonatal hospitalization (≥5 days) (aOR 2.07; 95%CI 1.57–2.73), and higher PBW ratio (aB 0.007; 95%CI 0.001–0.012). The use of antipsychotic medications increased among Finnish pregnant women from 2002 to 2016. Pregnant women using antipsychotics appear to have a higher risk for some adverse pregnancy and birth outcomes and may benefit from more frequent maternity care follow-ups. [ABSTRACT FROM AUTHOR]

Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other than their action at D2 receptors. Pharmacologically, they are 5HT2 antagonists and D3 and 5HT1A partial agonists but with little or no alpha-adrenergic, anticholinergic or antihistaminic activity. They also share a long duration of action. Clinically, D2 partial agonists are effective antipsychotics and generally have useful antimanic and antidepressant activity. They are usually well tolerated, causing akathisia and insomnia only at the start of treatment, and are non-sedating. These drugs also share a very low risk of increased prolactin and of weight gain and accompanying metabolic effects. They may also have a relatively low risk of tardive dyskinesia. There is some evidence that they are preferred by patients to dopamine antagonists. Individual dopamineD2 partial agonists have much in common and as a group they differ importantly from dopamine D2 antagonists. Dopamine D2 partial agonists should be considered a distinct class of antipsychotics. D2 partial agonists share many pharmacological and clinical properties D2 partial agonists differ in several important respects from D2 antagonists D2 partial agonists should be considered a discrete class of antipsychotics [ABSTRACT FROM AUTHOR]

The open dialogue (OD) approach includes the need-adapted use of psychiatric medication in treating first-episode psychosis (FEP), but there is limited information on how psychiatric medications are actually used in OD-based services. This study aims to analyse long-term medication dispensing patterns among FEP cohort treated according to the OD. The OD cohort consisted of people who received treatment for FEP in the Finnish Western Lapland catchment area at a time of OD implementation (n=61). The comparison group included people whose FEP treatment commenced outside the catchment area during the mid-1990s (n=1378). Data were gathered from national registers from onset to the end of the 10-year follow-up or death. A non-confirmatory descriptive comparison was performed to evaluate the usage patterns and cumulative exposure to psychiatric medication. Under OD, a smaller proportion had been dispensed benzodiazepines, antidepressants, and neuroleptics. Persons who had received these medications did not differ in cumulative exposure. In both groups, most of those who received neuroleptics in the first follow-up years continued using medication throughout follow-up. OD may assist in detecting FEP patients who can manage without neuroleptics, thus minimizing iatrogenic effects. Due to the observational design, further studies are required to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Psychiatric patients' human rights are often violated when forced treatment orders are issued. We assessed the records for 30 consecutive petitions for mental health commitment in which an involuntary medication order was requested, from Anchorage, Alaska. In 29 cases, the commitment petition was granted. The forced medication order was granted in 27 of the 30 cases. In 26 cases, in violation of previous Supreme Court rulings, the patients' desires, fears, wishes and experiences were ignored even when the patients were afraid that the neuroleptics might kill them or when they had experienced serious harms such as tardive dyskinesia. The ethical and legal imperative of offering a less intrusive treatment was also ignored. Benzodiazepines were not offered. Psychotherapy was not offered or mentioned in 15 cases. The providers claimed, contrary to the evidence, that psychotherapy does not work. The legal procedures can best be characterized as a sham, in which the patients are defenseless. The power imbalance and abuse were extreme, and several of the psychiatrists who argued for forced treatment obtained court orders for administering drugs and dosages that were dangerous. We suggest forced medication be abandoned. [ABSTRACT FROM AUTHOR]

To investigate the patterns and trends of suspected suicides and suicide attempts involving antipsychotic or sedative-hypnotic medications reported to United States poison centers. Data from the National Poison Data System for 2000 through 2021 were retrospectively analyzed. There were 972,975 suspected suicides and suicide attempts with antipsychotics or sedative-hypnotics ranked as the primary substance reported to poison centers from 2000–2021, averaging 44,226 cases annually. Most (85.6%) cases occurred among individuals >19 years old, females accounted for 63.5% of cases, and 51.8% were single-substance exposures. The rate of reported exposures per 100,000 United States population increased significantly from 27.2 in 2000 to 49.1 in 2008 (P < 0.0001), then plateaued to 49.6 in 2016 (P = 0.1497), followed by a significant decrease to 38.7 in 2021 (P < 0.0001). Individuals 13–19 years old demonstrated the greatest increase in rate from 28.4 in 2000 to 79.6 in 2021 (P < 0.0001). Approximately half (48.8%) of primary substance exposures were benzodiazepines, followed by antipsychotic medications (36.7%) and other types of sedative/hypnotic/anti-anxiety or antipsychotic medications (14.6%). Most primary substance exposures were admitted to a critical care or non-critical care unit (43.3%) or directly to a psychiatric facility (27.9%), and 36.1% were associated with in a serious medical outcome, including 1,330 deaths. Individuals >49 years old were more likely to experience a serious medical outcome (relative risk = 1.25, 95% CI: 1.24–1.26), including death (relative risk = 3.06, 95% CI: 2.74–3.41), or be admitted to a critical care or non-critical care unit (relative risk = 1.24, 95% CI: 1.23–1.24) than younger individuals. Suspected suicides and suicide attempts involving antipsychotic or sedative-hypnotic medications increased during the 22-year study period, especially among individuals 13–19 years old, and these cases often had severe clinical consequences. Based on the characteristics and trends identified in this study, increased prevention efforts are warranted to help prevent these suspected suicides and suicide attempts. [ABSTRACT FROM AUTHOR]

Aripiprazole is an antipsychotic with a partial agonism of dopamine D2 and D3 receptors. This differential mechanism implies a rigorous appraisal of the appropriate therapeutic strategies in certain situations. To answer currently unsolved clinical questions about the use of oral and long-acting injectable (LAI) aripiprazole, we present here an expert consensus from 12 Spanish psychiatrists and a pharmacologist with extensive experience in the use of this antipsychotic. Through one face-to-face session and online collaboration, we reached consensus and established practical recommendations based on scientific evidence and clinical experience. We classified the available scientific literature according to SIGN system and attributed a level of evidence to each reviewed article. The recommendations were divided according to (i) chronological dimension (based on previous treatments, including patients naïve or not to antipsychotic treatment and maintenance regimen), and (ii) dimension related to therapeutic options, comprising switches to aripiprazole and the most used combinations with this antipsychotic. We recommend considering aripiprazole as first treatment option in the early stages of schizophrenia and in patients with affective symptoms and contemplating a switch to aripiprazole LAI in all candidate patients. Importantly, switches from other antipsychotics should consider previous antipsychotic history and exposure to aripiprazole. Aripiprazole can be considered as first treatment option in early stages of schizophrenia and in patients with significant affective symptoms. Aripiprazole LAI shows better adherence than oral aripiprazole and could be considered in all candidate patients. Before switching to aripiprazole, detailed information about previous antipsychotic history should be gathered. Switch to aripiprazole should be managed differently for aripiprazole naïve and non-naïve patients. Rigorous and controlled studies on antipsychotics in real clinical practice should be carried out. [ABSTRACT FROM AUTHOR]

Evidence from treatment trials shows that the most effective pharmacological treatment for Psychotic Major Depression (PMD) is combined antidepressant and antipsychotic pharmacotherapy. This study investigates the use of antidepressant and antipsychotic treatment for PMD in clinical practice and examines how treatment profiles correlate with demographic and clinical symptoms. Anonymised electronic health records of 2,837 individuals with PMD were followed up for 12-months post-diagnosis in a historic open cohort design. The use of antidepressants and antipsychotics, alone or in combination, were described using frequency statistics. Demographic and clinical characteristics associated with each treatment were assessed using logistic regression analyses. Antidepressant and antipsychotic combination pharmacotherapy was the most used treatment for PMD with 69.9% users, compared to antidepressant monotherapy (10.9%) and antipsychotic monotherapy (10.3%). The remaining 8.9% of individuals did not receive antidepressant or antipsychotic treatment. The presence of delusions was strongly associated with the use of antipsychotics, both alone (odds ratio =3.99, 95% confidence intervals = 2.72–5.83, p<.001) and in combination with antidepressants (OR = 2.7, 95% CI = 2.09–3.67, p<.001), rather than antidepressant treatment alone. Combined antidepressant and antipsychotic pharmacotherapy is the most common treatment of PMD in clinical practice, showing that clinical practice is in line with evidence from treatment research. [ABSTRACT FROM AUTHOR]

Post-psychotic depression (PPD) after a FEP (first-episode psychosis) differs from other depressive symptoms in chronic schizophrenia in its aetiology, symptomatology, and prognostic implications. The objective was to search if any pharmacological or non-pharmacological interventions have proven to be effective on depressive symptoms after a FEP. for this systematic review we systematically searched and screened PubMed for articles published from August 1975 to October 15, 2020, with the terms: treatment AND first-episode psychosis OR post-psychotic OR post-schizophrenic AND depression. we identified 139 articles of which 20 met the inclusion criteria. These interventions were then categorized into four subgroups (antipsychotics, antidepressants, psychological and miscellaneous) this review has several limitations. The reviewed studies were heterogeneous as to assessments, interventions, and samples; furthermore, only one study had PPD in FEP as its primary outcome. to our knowledge, this is the first review of PPD in a FEP's treatment. PPD continues to be a diagnostic and therapeutic challenge. The available evidence for the use of treatment whether pharmacological or non-pharmacological is limited. However, certain approaches such as online therapy and treatment with n-3 polyunsaturated fatty acids (PUFA) show promising results. It could be of interest for future studies to focus not only on the treatment of PPD but also on the diagnostic heterogeneity of the sample and the adaptation of the content of the intervention to the individual. [ABSTRACT FROM AUTHOR]

High rates of opioid overdose and suicide among the 50+ age group call for an examination of suicidal intent in overdose incidents. Using 2015–2020 National Poison Data System opioid poisoning cases aged 50+ (n = 83 153), we examined the types of opioids and other substances associated with suspected suicides compared to intentional misuse/abuse without suicidal intent. During the six years, prescription opioid cases decreased, while illicit opioid cases increased. Among both types of opioid poisoning cases, the proportions of suspected suicides decreased and those of intentional misuse/abuse without suicidal intent increased. However, due to the large increase in illicit opioid cases, the number of suspected suicide cases involving illicit opioids increased. Multivariable analyses showed that among prescription opioids, acetaminophen with opioid (IRR = 1.17, 95% CI = 1.11–1.24) and tramadol (IRR = 1.12, 95% CI = 1.06–1.47) were associated with higher risk of suspected suicides than intentional misuse/abuse without suicidal intent. Among illicit opioid cases, fentanyl poisoning cases were associated with lower risk of suspected suicides (IRR = 0.40, 95% CI = 0.17–0.94). Of other medications, use of benzodiazepines and antipsychotics was consistently associated with higher risk of suspected suicides in both prescription and illicit opioid cases. Alcohol and cocaine were also associated with higher risk of suspected suicide. Along with continued reductions in opioid prescribing, more effective monitoring of individual patient misuse/abuse behaviors and suicide risk assessment are needed. Healthcare professionals should also review other prescription medications frequently co-prescribed with opioids that may have additive effects on suicidal behaviors among older adults. [ABSTRACT FROM AUTHOR]

Psychotropic drugs such as antipsychotics may prolong the QTc interval, increasing the risk of torsades de pointes (TdP) and sudden cardiac death. To assess QTc prolongation by psychotropic drugs, an electrocardiogram (EKG) is usually recorded before and after starting treatment. Circadian variations in the QTc interval have been described but have not been adequately studied in patients taking psychotropic drugs. In psychiatric clinical practice, EKGs before and after treatment initiation are often compared, without considering the time of day at which the two EKGs are recorded. To determine whether there is a circadian change in the QTc interval in patients treated with psychotropic drugs, we evaluated the EKGs of a group of patients treated with psychotropic drugs (85% on antipsychotics) and the EKGs of a group of patients that were not treated with medications. In each group, we compared the EKGs recorded before 11:00 am with those recorded after 5:00 pm. The QTc value was significantly longer in the group treated with psychotropic drugs than in the group without drugs at both morning and evening evaluations (p ≤ 0.001). In each group, a statistically significant difference was found between the EKGs recorded before 11:00 a.m. and the EKGs recorded after 5:00 p.m. In patients treated with medications, the mean QTc in the morning was 453.3 ± 25.4 while the mean QTc in the afternoon was 428.4 ± 24.7 (p < 0.0001). In patients who were not receiving any medication, the morning mean QTc was 422.4 ± 22.6 while the mean afternoon QTc was 409.4 ± 19.6 (p = 0.002). These results suggest that a circadian variation in QTc is observed both in patients taking psychotropic drugs and in patients not taking medication. We conclude that any comparison of EKGs to test the effect on QTc of a medication, should be referred to EKGs recorded at the same time of day. [ABSTRACT FROM AUTHOR]

Schizophrenia is a psychiatric disorder that affects 1% of the world population and is treated with antipsychotics, which may induce important biochemical and hematological alterations. Since it is necessary to verify the safety of new molecules with antipsychotic potential, the present study aimed to evaluate the oral toxicity of PT-31, a putative α2-adrenoreceptor agonist, after acute (2000 mg/kg) and repeated doses (28 days) gavage treatment, in three different doses: minimum effective dose in animal models (10 mg/kg), twice the dose (20 mg/kg), and four times the dose (40 mg/kg), as recommended by the OECD guidelines. Balb/C female adult mice were used, and biochemical, hematological, and histopathological analyses were performed. PT-31 10 and 20 mg/kg did not cause biochemical alterations related to hepatic and renal toxicity, and neither altered glycemic and lipid profiles. The preclinical dose of PT-31 also did not promote mice histopathological changes in the liver, kidney, and brain. In the hematimetric parameters, PT-31 only increased HGB at 20 mg/kg, and MCH and MCHC at 40 mg/kg. However, all the tested doses of PT-31 showed platelet increase, which must be better investigated. Therefore, further studies are needed to investigate the safety of PT-31 as a potential antipsychotic drug. [ABSTRACT FROM AUTHOR]

Objective: Bupropion is one of the few medications with an FDA indication for smoking cessation. This is of particular significance due to the high co-morbidity of tobacco use disorder in patients with schizophrenia spectrum and other psychotic disorders. We sought to determine whether historical suggestions of bupropion's pro-dopaminergic activity lead prescribers to withhold bupropion in populations receiving antipsychotic medications. Methods: The prevalence in clinical practice of the combination of bupropion and 10 antipsychotic formulations was determined by a computer review of the Genoa Healthcare database for all prescribers at 10 participating community mental health centers. Actual prevalence was compared with expected prevalence using the test of proportions. A Bonferroni correction for multiple comparisons was included. Results: Clozapine, p = 0.0004, and the microsphere formulation of risperidone, p = 0.0045, were prescribed with bupropion significantly less often that chance. None of the other eight antipsychotic formulations were prescribed significantly differently than chance. Conclusions: The co-prescription of bupropion and antipsychotic medication may be affected by historical misconceptions regarding bupropion's purportedly pro-dopamine properties. Viable options for the treatment of tobacco use disorder should not be discounted prematurely in patients with schizophrenia spectrum and other psychotic disorders. We suggest further study on the safety and efficacy of the combination of bupropion and antipsychotic medication is needed. [ABSTRACT FROM AUTHOR]

Abstract Background Aims Methods Results Conclusions Antipsychotic medications (APs) are used for people with psychosis diagnoses and, increasingly for other problems and groups.This study examines how APs are prescribed, from the perspective of recipients.757 people, from 30 countries, responded to questions about their experiences with APs, in an online survey.Most (70%) were told nothing about adverse effects. Fewer than 2% recalled being told about the risks of diabetes, suicidality, sexual dysfunction, or reduced life span. None recalled being told about reduced brain volume or withdrawal effects. Only 28% recalled being offered other treatments; with only 14% offered talking therapies. 46% were not told how long to take the APs; and, of those who were told something, 48% were told to take them forever. Most respondents (76%) were not told how APs work. Only 19% were satisfied with the prescribing process, and only 25% reported a good, or very good, relationship with the prescriber. Information, satisfaction with the process, and the prescriber relationship were all positively related to three self-reported outcomes: reduction of problems the drugs were prescribed for, general helpfulness, and quality of life.Steps need to be taken to ensure people prescribed antipsychotics are fully informed, especially about adverse effects and alternatives. [ABSTRACT FROM AUTHOR]

There is a lack of robust epidemiological evidence on antipsychotic (AP) use in patients with agitation in Alzheimer's disease (AD). Authors studied AP use in patients with AD and agitation and compared their use with patients with other or no neuropsychiatric symptoms (NPS). A retrospective cohort study in the UK Clinical Practice Research Datalink, included patients with AD between January 1st, 2015, and December 31st, 2017. AP use was compared between patients with agitation, other types of NPS and no NPS. There were 24,464 patients with AD, median follow-up of 1.1 years (interquartile range [IQR] 0.5–2.1), and median age 83 years (78–88). A larger percentage of patients with agitation (n = 2432) were prescribed APs (38.2%) than other NPS (n = 13,076, 20.4%) and no NPS (n = 11,816, 12.2%). Compared to patients with no NPS, adjusted hazard ratios for AP use were 3.45 (95% CI 2.86–4.17) for patients with agitation and 1.31 (95% CI 1.19–1.44) for patients with other NPS. Among users of APs, the treatment discontinuation rate at six months was 44.8% in patients with agitation (other NPS 57.1%; no NPS 63.5%). Patients with AD and agitation were frequently prescribed APs and for long periods in routine clinical practice in the UK. The high real-life usage of APs suggests that physicians prefer using APs for the treatment of agitation despite recommendations against their long-term use. These data support a need for AP therapies that better address known safety concerns with currently used APs to treat agitation in elderly patients with AD. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify independent predictors of satisfaction with antipsychotics in patients with schizophrenia spectrum disorders treated in a mental health catchment area. Observational analytical study of patients (n = 150) recruited through a convenience sampling method from five mental health units. Satisfaction with the antipsychotic as a medication was evaluated using the Treatment Satisfaction Questionnaire for Medication (TSQM). Therapeutic alliance was assessed by the Working Alliance Inventory Short Form (WAI-S). Patient-perceived participation in decision-making was assessed using COMRADE (Combined Outcome Measure for Risk communication And treatment Decision making Effectiveness). A multiple linear regression analysis was performed to identify variables independently associated with the TSQM 'Global Satisfaction' total score. Two variables – age and higher level of self-perceived participation in treatment decision-making – were directly, significantly, and independently associated (β coefficient values: 0.209 and 0.432, respectively) with a higher TSQM Global satisfaction score. In addition, the severity of psychotic symptoms was inversely associated with satisfaction (β coefficient value: −0.205) (R2 = 0.355; R2 adj. = 0.291; F(13) = 5.554; p < 0.01). These findings suggest that involving the patient in treatment decision-making and optimising the treatment to reduce symptoms, especially in younger patients, could increase satisfaction with antipsychotic treatment. Patient involvement in shared decision-making is relevant for treatment satisfaction. Current evidence suggests that improving the doctor–patient relationship optimises antipsychotics outcomes. Self-perceived participation in decision-making predicts satisfaction with antipsychotic medication. Types of antipsychotics do not determine consistent differences in satisfaction. [ABSTRACT FROM AUTHOR]

Second generation antipsychotics (SGAs) induce weight gain and dyslipidemia, albeit with important intervariability. Insulin-like growth factor binding protein (IGFBP)-2 is proposed as a circulating biomarker negatively associated with waist circumference and hypertriglyceridemia. Thus, we tested whether metabolic alterations developed upon the use of SGAs are associated with plasma IGFBP-2 levels. A cross-sectional study was performed in 87 men newly diagnosed with schizophrenia and administered for approximately 20 months with olanzapine or risperidone as their first antipsychotic treatment. Plasma IGFBP-2 concentration, anthropometric data, as well as glucose and lipid profiles were determined at the end of the treatments. IGFBP-2 levels were similar between patients using olanzapine or risperidone and were negatively correlated with waist circumference, insulin sensitivity, and plasma triglycerides (TG). A higher proportion of men with a hypertriglyceridemic (hyperTG) waist phenotype was found in patients with IGFBP-2 levels lower than 220 ng/mL (43% for olanzapine and 13% for risperidone) compared to those with IGFBP-2 above this threshold (10% and 0%, respectively). IGFBP-2 may have a role in altering metabolic risk in schizophrenic patients using SGAs. Longitudinal studies are required to evaluate whether IGFBP-2 can predict the development of a hyperTG waist phenotype in this population. [ABSTRACT FROM AUTHOR]

Delusional parasitosis (DP) is a psychiatric condition characterized by an individual's persistent belief that she or he is infested with pathogens when no such infestation is medically present. Family education on safety is needed before discharge due to the high risk of self-injury when patients try to rid themselves of the parasite. We present the case of a woman who presented twice with self-inflicted injury with a foreign body to the head to eliminate supposed tapeworms in her brain; she declined antipsychotic medication and psychiatric referral after the first emergency department visit only to come back with a more serious injury requiring a frontoparietal craniotomy. This clinical situation underscores the importance of psychiatric assessment to ascertain a patient's risk to themselves. Neuroimaging should be considered in the evaluation of elderly patients presenting with new-onset psychiatric complaints. [ABSTRACT FROM AUTHOR]

Antipsychotic long acting injections (LAI) allow a range of dosage intervals to be administered. Short intervals can be inconvenient for patients and staff. There are few clinical reasons for using them yet this is common practice. This study aimed to examine the feasibility of reducing LAI frequency with service user consent. The study took place in a community mental health team in the north of England. A specialist mental health pharmacist reviewed records of all service users on LAI and drew up an action plan. Each service user then met with the consultant psychiatrist for medication review. Nineteen out of thirty service users on LAI had intervals less than the maximum licensed. The frequency was reduced in eight cases. After 6 months follow–up, there was no deterioration in symptoms. In nine cases, antipsychotic doses were also reduced as a result of the review. Where a service user is prescribed a LAI with a short dosage interval consideration should be given to increase the interval. This can free up service user and staff time. A medication focused review can also lead to other benefits such as dosage reduction. [ABSTRACT FROM AUTHOR]

Introduction: Antipsychotics are widely prescribed for patients with schizophrenia. The Brazilian public health system provides these patients free of charge to patients and it is pertinent to evaluate their benefits. Objective: To evaluate the effectiveness of olanzapine and risperidone in the treatment of patients with schizophrenia in the real-world and assessing risk factors for their discontinuation through a national non-concurrent cohort with 16 years of follow-up. Methods: Three SUS administrative databases were integrated by deterministic-probabilistic linkage. After patients were matched (1:1) for psychiatric hospitalization, year of receiving the antipsychotic, sex, and age, considering either olanzapine or risperidone at study entry. Kaplan-Meier was used to estimate the cumulative probabilities of discontinuation of treatment and associated factors were identified. Sensitivity analyses were performed. Results: 3416 pairs of patients were included. Olanzapine had a longer time until discontinuation of treatment (p = 0.021), and risperidone had a higher risk of discontinuation (p = 0.021). Among patients persistent for at least 24 months, there was no statistically significant difference. Conclusion: Olanzapine demonstrated superior real-world effectiveness over risperidone, in terms of survival and psychiatric hospitalization. This superiority was not sustained in all analyses. [ABSTRACT FROM AUTHOR]

Exposure and clinical response to CNS drugs are largely variable. AGNP guidelines suggest therapy individualisation with therapeutic drug monitoring of plasma concentrations and pharmacogenetic testing. We present the retrospective analysis of the last 5 years' data collected in real life settings as indirect evidence of the applications of the AGNP guidelines in the routine clinical management of psychiatric patients requiring pharmacologic treatments. Plasma concentrations were quantified using a liquid chromatography/tandem mass spectrometry method. Genomic DNA was isolated using an automatic DNA extraction system. All genotypes were determined by Real-Time PCR. We collected a total of 4582 requests for TDM and 212 requests for pharmacogenetic analysis. A wide distribution in the trough concentrations was observed for most drugs indicating a high interpatient variability. Nearly 45% of the samples had trough levels below the minimum effective drug concentrations set by the AGNP guidelines; only 8% of the samples had high concentrations. For pharmacogenetics analysis, among antipsychotics, clozapine, haloperidol and aripiprazole were the most requested (78%); while for antidepressants SSRIs were the most frequently prescribed. These data suggest that physicians are becoming more confident with the laboratory pharmacologic tools to optimise treatments and/or that the pharmacological treatment of patients with psychiatric disorders is becoming more challenging. TDM and PGx might significantly contribute to the rational selection of the best drug and best dose in individual cases. [ABSTRACT FROM AUTHOR]

Anecdotal evidence suggests a substantial proportion of individuals with cocaine use disorder do not report craving during inpatient detoxification. To examine prevalence and clinical correlates of consistent absence of cocaine craving among inpatients during detoxification. We hypothesized that craving absence would be associated with less severity of cocaine use, depression, and anxiety. Alternative explanations were also explored. Craving absence (i.e., non-cravers) was defined as a daily score of zero across two separate craving visual analogue scales in each of the inpatient days. Participants scoring ≥1 on ≥1 day were considered cravers. Severity of cocaine use disorder as well as in-treatment depression and anxiety were assessed. Alternative contributors included presence of cocaine and other substances in urine at admission, in-treatment prescription of psychotropic medications, treatment motivation, executive function, interoception, and social desirability. Eighty-seven participants (78.2% males) met criteria as either non-cravers (n = 29; 33.3%) or cravers (n = 58; 66.7%). Mean length of admission in non-cravers and cravers was, respectively, 10.83 and 13.16 days. Binary logistic regression model showed that non-cravers scored significantly lower than cravers on cocaine use during last month before treatment (OR, 95% CI; 0.902, 0.839–0.970), in-treatment depression (OR, 95% CI; 0.794, 0.659–0.956), and in-treatment prescribing of antipsychotics (OR, 95% CI; 0.109, 0.014–0.823). Model prediction accuracy was 88.9%. One in three patients undergoing inpatient detoxification experienced absence of craving, linked to less pretreatment cocaine use, better mood, and decreased administration of antipsychotics. Findings may inform pretreatment strategies and improve treatment cost-effectiveness. [ABSTRACT FROM AUTHOR]

The primary aims of this study were to determine if oxcarbazepine is a safely tolerated option for treatment of psychiatric symptoms in children and whether its use facilitates dose modification of other psychotropic medications. A retrospective chart review was completed using data extracted from the electronic medical record of a large outpatient child psychiatry clinic. A total of 507 of 740 children prescribed oxcarbazepine for psychiatric indications for 3 months or more had adequate data to assess clinical responses and medication outcomes. Most patients prescribed oxcarbazepine experienced clinically significant control of irritability/anger, mood stabilization, aggressive outbursts, impulsivity, or anxiety, with over 80% achieving at least maintenance symptom control. In all, 51% and 25% fully discontinued second- or third-generation antipsychotic or antidepressant medication, respectively, after starting oxcarbazepine; 8% discontinued oxcarbazepine for nonresponse, while 9% stopped oxcarbazepine because of emergent side effects. In patients fully discontinuing or reducing the second- or third-generation antipsychotic dose by 50% or more, improvements in body mass index were observed. Oxcarbazepine may prove to be an appropriate alternative to antipsychotic and antidepressant medications for treating psychiatric symptoms in children and adolescents. In particular, it may be a more metabolically neutral psychotropic medication. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic-induced sexual dysfunction is a common complaint among patients with psychotic disorders. However, few papers have discussed its impact on treatment adherence. Aims: The aim of the study was to determine the prevalence of antipsychotic induced sexual dysfunction in patients with schizophrenia and schizoaffective disorder and assess its impact on treatment adherence. Methods: Nighty-five outpatients treated with antipsychotics for at least four weeks were recruited. Sexual dysfunction was assessed using a questionnaire inspired from the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ). An Arabic version of the Medication Adherence Rating Scale (MARS) was used to assess treatment adherence. Results: The prevalence of sexual dysfunction was 57.9%, of which 65.5% attributed it to treatment. Reduced desire was the mostly reported sexual dysfunction in males and females. Number, dose and duration of antipsychotics were not associated with sexual dysfunction. MARS score was associated with the presence of sexual dysfunction (p = 0.0001) and its attribution to antipsychotic medication (p = 0.0003), the latter being an independent associated variable (p = 0.001). Conclusion: Sexual dysfunction is prevalent in patients with schizophrenia and schizoaffective disorder treated with antipsychotic drugs. Clinicians should ask about sexual dysfunction and discuss its different causes with patients in order to improve adherence. [ABSTRACT FROM AUTHOR]

Introduction: The ziprasidone analogue lurasidone is approved for the treatment of schizophrenia and bipolar disorder for adults and children older than 10 years. Small studies and case reports suggest lurasidone overdose is not generally associated with major adverse effects, but no large sample has been published. Objective: To describe intentional lurasidone overdoses reported to poison centers. Methods: Retrospective analysis of single-substance intentional lurasidone ingestions from the National Poison Data System (NPDS) from 2011 to 2018. Results: There were 1753 single-substance intentional overdoses. Average age was 28.6 years (SD = 13.3 years) and 1199 (68.4%) of patients were female. Most cases (86.6%) were coded as suspected suicide. Regarding final management site, 1143 (65.2%) were discharged or admitted to psychiatric facilities; 328 (18.8%) were admitted, half of whom were admitted to critical care units (CCUs). Major effect was coded in 12 (0.7%), moderate effect in 259 (14.8%), minor effect in 531 (30%), and no effect in 614 (35%). There were no deaths. For cases for which dose information was available, there was not a statistically significant difference between median doses when analyzed by clinical effect. Most common adverse effects were drowsiness (449, 25.6%), tachycardia (254, 14.5%), vomiting (121, 6.9%), and hypertension (115, 6.6%). Most cases had either no therapy reported, or therapy was recommended by the poison center but confirmed not to have been administered (1010, 57.6%). Of the 164 patients admitted to CCUs, 80 (48.8%) received either no therapy or intravenous fluids alone. Discussion: These data suggest major effects are uncommon from lurasidone overdose. Despite a high rate of admission to CCUs, a substantial proportion received no critical therapies. Conclusions: This report demonstrates intentional lurasidone overdoses reported to poison centers generally have a favorable clinical course. [ABSTRACT FROM AUTHOR]

In 2011, the authors published an algorithm summarizing practice guidelines related to the use of long-acting antipsychotics (LAIs) called the Québec Algorithme Antipsychotique à Action Prolongée (QAAPAPLE), and proposed that it be revised every 5–10 years to update it according to most recent scientific knowledge. Therefore, a re-evaluation of the algorithm was conducted to determine which recommendations were still relevant and which needed modification. The authors conducted a two-fold approach: a review of the literature to include new evidence since 2011 (controlled trials, meta-analyses, and practice guidelines); and a participatory component involving electronic surveys, conferences, encounters with opinion leadres, and patients' representatives. Overall, prescribers tended to make decisions based on personal experience and conversations with colleagues rather than consulting evidence-based guidelines. To test if the algorithm was useful worldwide, it was presented in the United Arab Emirates, where the feedback was in agreement with the algorithm and its limitations. Since its initial publication, the QAAPAPLE algorithm has been updated to guide clinicians on the use of LAIs. The new algorithm has also been assessed outside Canada to test its generalizability worldwide, and indicated its flexibility, efficiency, and user-friendliness in order to guide clinicians on the use of LAIs. [ABSTRACT FROM AUTHOR]

The prevailing studies were carried out to formulate and optimize the quetiapine transdermal matrix patch by the usage of Box–Behnken design for ameliorated bioavailability when contrasted with conventional drug delivery. The Box–Behnken design with three-level and three-factor was utilized to explore the intermingle impact of critical attributes on tensile strength, in vitro drug release, and flux. Optimized formulation was characterized for Fourier transform infrared, differential scanning calorimetry, in vivo pharmacokinetics, and skin irritation along with stability studies. The inference of the finalized batch (F14) depicted the flux of 51.81 ± 0.32 µg/h/cm2, TS of 6.46 ± 0.56 MPa, and the % drug release after 20 h of 82.98 ± 1.48% with no remarkable variation even after 6 months stability studies. Correlation between predicted and the observed values of the dependent variables was very closer. Optimized quetiapine transdermal patch did not exert any symptoms of skin irritation. The bioavailability of quetiapine was enhanced almost 4.59 times after topical delivery when contrasted with the conventional dosage form. The outputs of the research work divulged that the developed matrix patch of quetiapine for transdermal drug delivery can be a propitious opportunity that affords effective treatment of schizophrenia. The oral route is not suitable for the drugs having extensive first-pass metabolism which leads to reduced bioavailability. For the parenteral route, invasiveness causes the patient noncompliance while sterility contributes to the cost factor. Moreover, the treatment of schizophrenic patients is a challenging task for caregivers and doctors. Hence, the transdermal patch of quetiapine was developed to bypass the biotransformation of drugs and thereby to enhance the bioavailability as well as to provide sustained drug delivery which ultimately reduces the dosage frequency. [ABSTRACT FROM AUTHOR]

Objectives: Tardive dyskinesia (TD) unlike acute dystonia may be irreversible. This study investigated the effects of oral cannabidiol (CBD) on haloperidol-induced vacuous chewing movement (VCM) model of TD. Methods: There were six experimental groups with different combinations of oral cannabidiol with 5 mg/kg of haloperidol given orally. Behavioural assays and FBS were measured. VCMs were assessed after the last dose of medication. Blood for oxidative stress assays was collected on the 8th day after the administration of the last dose of medication. Results: This study found that CBD co-administration with haloperidol attenuated the VCMs and increased motor tone produced by haloperidol. CBD alone at 5 mg/kg appears to have anxiolytic properties but may not be as effective as haloperidol which exhibited a greater anxiolytic effect at 5 mg/kg. Treatment with CBD alone at 5 mg/kg also appeared to enhance brain DPPH scavenging activity. Conclusions: We confirmed that CBD can ameliorate motor impairments produced by haloperidol. Our data suggest that CBD can be combined with haloperidol to prevent the emergent of extrapyramidal side effects and long-term movement disorders, such as acute dystonic disorder and TD. [ABSTRACT FROM AUTHOR]

Objectives: The management of psychiatric illness in HIV-infected patients is clinically challenging because of the risk of potential drug–drug interactions. Here, we aimed to measure the antidepressant and/or antipsychotic drug concentrations in HIV-infected patients during routine outpatient visits. Methods: Six hundred HIV-infected patients were screened during the first 15 months after the introduction of our outpatient polytherapy management service in a search for subjects treated with psychotropic drugs for at least 3 months. The distribution of psychotropic drug concentrations in HIV-infected patients was compared with that observed in a control group of HIV-negative patients monitored over the same period. Results: The search identified 82 HIV-infected patients concomitantly receiving antiretroviral and psychotropic drug treatment, 55% of whom had plasma psychotropic drug concentrations that were below minimum effective levels. The same result was found in only 26% of the samples taken from HIV-negative patients. These results were not affected by patients' gender, age, adherence to therapies or drug–drug interactions. Conclusions: A higher rate of sub-therapeutic antidepressant and/or antipsychotic drugs concentrations were found in HIV-infected patients. The creation of multidiscliplinary specialist teams may contribute to improving the management of such complex patients. [ABSTRACT FROM AUTHOR]

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation. Of 36 included trials, 27 were suitable for inclusion in NMA, and no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilizers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES = 0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes. This study provides the most comprehensive evidence of augmenters' effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimize treatment choices. Although conclusions are limited by paucity of, and heterogeneity between, trials as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine. [ABSTRACT FROM AUTHOR]

Background: Certain antipsychotics are known to cause QTc interval prolongation, which has been associated with increased risk of arrhythmia and sudden death. Previous studies have investigated whether there is an association between oral antipsychotic dose and QTc interval prolongation, however only few have examined the association between antipsychotic plasma concentrations and QTc interval. Material and methods: We performed a cross-sectional study with 22 forensic psychiatric in-patients. We measured the plasma concentration of the prescribed antipsychotics and performed an ECG simultaneously. We used Bazett's formula to calculate QTc and defined QTc as prolonged when: >460 ms for women and >450 ms for men. Results: Seventy-seven percent (n = 17) of the subjects were men (mean age = 40 years) and 91% (n = 20) were diagnosed with schizophrenia. QTc's ranged from 369 to 437 ms. Patients receiving QTc prolonging drugs had significantly greater QTc interval compared to patients receiving non-prolonging drugs. Weak to moderate negative correlations were found between QTc interval and both defined daily dose (DDD) and antipsychotic plasma concentration. There was no statistical difference between the correlations for DDD and plasma concentration versus QTc interval. Conclusion: We did not find a stronger association between antipsychotic plasma concentration and QTc than between antipsychotic dose and QTc. We suggest close monitoring with regular electroencephalogram's until the development of a better marker for predicting the risk of cardiac arrhythmia. [ABSTRACT FROM AUTHOR]

Background: The main purpose of this study was to assess possible modifications of cognitive performance among schizophrenia patients treated with long-acting injectable antipsychotics (LAIs) of second generation anti-psychotics (SGAs). Our hypothesis is that the shift from the oral formulation to the LAI formulation of SGAs drugs improves the cognitive performance. The secondary objective was to carry out a head to head comparison of two different SGA-LAI treatments [i.e., 1-month Paliperidone Palmitate (PP1M), monthly Aripiprazole (Ari-LAI)] in our study with an independent and real-world setting. Methods: The sample comprised 32 participants who were consecutively recruited over 12 months. Seventeen patients treated with Ari-LAI and 10 treated with PP1M completed psychopathological, neuropsychological and functional assessments. Group differences were explored through chi-squared and t-tests, as appropriate. GLM Repeated Measures were used to study variations of cognitive performance along 12 months and to test differences between drugs. Results: We found an effect of time on the outcomes investigated but this did not depend on the type of LAI used. Conclusions: In comparison with the previous oral treatment with SGAs, patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI. Furthermore, there were no differences between the SGA-LAI regimens. The main purpose of this study was to assess possible modification of cognitive performance of patients with Schizophrenia treated with second generation long-acting injectable antipsychotics (SGA-LAIs). The secondary objective was to carry out a head to head comparison of two different SGA-LAIs: Paliperidone Palmitate 1-Month (PP1M) and Aripiprazole Monthly (Ari-LAI). Patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI. There were no differences between the SGA-LAI regimens. From a practical point of view, switching to LAI formulation seems to produce further social and cognitive improvements in patients who had already benefitted from oral SGA therapy. [ABSTRACT FROM AUTHOR]

Background: Both amisulpride and olanzapine are leading treatments for schizophrenia in China. This study aimed to investigate the long-term cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China.Methods: A decision-analytic Markov model was developed to simulate the lifetime clinical and economic outcomes of schizophrenia treatment from the healthcare payer perspective. The long-term costs and QALYs were estimated. Sensitivity analyses were performed to explore the impact of variance of parameters on the results.Results: Treatment with amisulpride provided an effectiveness gain of 16.59 QALYs at an average cost of USD 25,884 whereas olanzapine resulted in 16.38 QALYs at a cost of USD 34,839 over a lifetime horizon. One-way sensitivity analysis suggested that the most sensitive variable was the unit cost of olanzapine. In a probabilistic sensitivity analysis based on a Monte Carlo simulation with a lifetime horizon, the probability of amisulpride being cost-effective was 99.8% at a willingness-to-pay threshold of USD 9,322, the GDP per capita in China 2018. A scenario analysis with updated olanzapine unit cost suggested an ICER of 7,857 USD/QALY.Conclusions: Amisulpride is likely to be a cost-effective option with increased effectiveness compared with olanzapine in the treatment of schizophrenia patients in China. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to examine the association of country of residence with body mass index (BMI) between Mexican and Colombian patients exposed to antipsychotics. We hypothesize that there will be a significant association between country of residence and BMI and that Mexican patients will have higher BMI than their Colombian counterparts. Design: The International Study of Latinos on Antipsychotics (ISLA) is a multisite, international, cross sectional study of adult Latino patients exposed to antipsychotics in two Latin American Countries (i.e. Mexico and Colombia). Data were collected from a total of 205 patients (149 from Mexico and 56 from Colombia). The sites in Mexico included outpatient clinics in Mexicali, Monterrey and Tijuana. In Colombia, data were collected from outpatient clinics in Bogotá. For this study we included patients attending outpatient psychiatric community clinics that received at least one antipsychotic (new and old generation) for the last 3 months. A linear regression model was used to determine the association of country of residence with BMI for participants exposed to an antipsychotic. Results: After controlling for demographics, behaviors, biological and comorbid psychiatric variables, there was a significant difference between Colombia vs. Mexico in the BMI of patients exposed to antipsychotics (β = 4.9; p < 0.05). Conclusion: Our hypotheses were supported. These results suggest that differences in BMI in patients exposed to antipsychotics in Mexico and Colombia may reflect differences in prevalence of overweight/obesity at the population level in the respective countries, and highlights the involvement of other risk factors, which may include genetics. [ABSTRACT FROM AUTHOR]

Introduction: Despite increased interest in the pharmacotherapy of bipolar disorder during pregnancy and the postpartum period, management of the disorder during these critical periods in a woman's life remains challenging. Areas covered: The authors review the effect of pregnancy and the postpartum period on the course of bipolar disorder, describe adverse pregnancy and birth outcomes, and discuss the pharmacotherapy of bipolar disorder during and after pregnancy. Expert opinion: When treating women with bipolar disorder of childbearing age, clinicians should consider the possibility of pregnancy. Pre-conception counseling should be an integral part of the overall plan to manage bipolar disorder during and after pregnancy. Peripartum management of bipolar disorder is challenging and requires balancing of risks associated with the use of drugs and the potentially deleterious effects of untreated bipolar disorder on the fetus/child. Formulation of personalized treatment requires knowledge of both current (episode type, symptom severity, psychiatric comorbidity, and safety concerns) and historical (episode frequency, response to drugs and psychotherapy, and the effect of reproductive events including pregnancy and postpartum period) factors. Close monitoring is essential for early detection and management of mood episodes. Routine safety assessments are necessary to identify women at risk of harming themselves or the newborn. [ABSTRACT FROM AUTHOR]