Long-term Antipsychotic Treatment Research Articles

The Therapeutic Potential of Dalbergia pinnata (Lour.) Prain Essential Oil in Alzheimer's Disease: EEG Signal Analysis In Vivo, SH-SY5Y Cell Model In Vitro, and Network Pharmacology.

Alzheimer's disease (AD) is a neurodegenerative disorder that is projected by the WHO to affect over 100 million people by 2050. Clinically, AD patients undergoing long-term antipsychotic treatment often experience severe anxiety or depression in later stages. Furthermore, early-stage AD manifests with weakened α waves in the brain, progressing to diminished α and β waves in late-stage disease, reflecting changes in emotional states and disease progression. In this study, EEG signal analysis revealed that inhalation of Dalbergia pinnata (Lour.) Prain essential oil (DPEO) enhanced δ, θ, α and β wave powers in the frontal and parietal lobes, with a rising trend in the β/α ratio in the temporal lobe. These findings suggest an alleviation of anxiety and an enhancement of cognitive functions. Treatment of the AD SH-SY5Y (human neuroblastoma cells) cell model with DPEO resulted in decreased intracellular levels of Aβ, GSK-3β, P-Tau, IL-1β, TNF-α, IL-6, COX-2, OFR, and HFR, alongside reduced AchE and BchE activities and increased SOD activity. Network pharmacology analysis indicated a potential pharmacological mechanism involving the JAK-STAT pathway. Our study provides evidence supporting DPEO's role in modulating anxiety and slowing AD pathological progression.

Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia.

Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder. To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder. South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests. A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; P < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; P < 0.0001), and higher persistence (82% vs 64%; P < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, P = 0.90; 3.68 vs 2.96 emergency department visits, P = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; P < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort (P < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; P = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; P < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; P < 0.0001). Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.

Why do patients want medication free treatment for psychosis? An explorative study on reasons for applying to medication free programs

BackgroundA focus on patient’s and service user’s perspectives regarding long-term antipsychotic treatment led to a declaration from the Norwegian Ministry of Health in 2015 to offer treatment without psychotropic medication in mental health as a voluntary option in all four health care regions. In the northernmost region, a 6-bed inpatient ward unit was established, uniquely designed to give people with severe mental illness the possibility to choose such treatment. Only voluntary admissions were accepted. The aim of the present study was to explore the motivation for applying for medication free treatment among patients with several years of treatment history due to psychosis.MethodWe performed nineteen semi-structured, in-depth interviews with persons having at least one admission at the medication free treatment ward during the period 01.01.17 – 17.10.2021. The interviews were recorded, transcribed and analysed using computer-assisted qualitative data analysis software (NVivo). Systematic Text Condensation was applied, with analysis of data from the first interview. Exploration of connections, similarities and nuances was performed through axial coding with continuous comparison of data and memo writing, followed by focused coding identifying core concepts.ResultsAll participants had a diagnosis of severe mental illness and a history of use of antipsychotics throughout many years. The motivation to apply for medication free treatment was complex. Negative experiences with medication were described, but also positive. Many had tried to taper off before, but described this as a lonely and difficult process. Five core concepts were formed and developed from the participants’ narratives: 1) Medication experiences, 2) Developing illness, 3) Treatment in general, 4) Social life and 4) Growing up.ConclusionThe concept of medication free treatment represents a salutogenetic hope for change, closely linked to self-efficacy and an experience of mastery. Potential conflicts concerning guidelines or evidence on medication does not come forward as important. Support from family and professionals is crucial, in contrast to the feeling of being alone when hoping for change. Motivational factors are closely linked to the concept of recovery, where interaction happens on both an individual and a structural level.

Sex-Specific Effects of Long-Term Antipsychotic Drug Treatment on Adipocyte Tissue and the Crosstalk to Liver and Brain in Rats.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of 12 weeks of drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined, as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males, with slightly higher adipocyte area values in both males and females under clozapine treatment. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol-medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine treatment. IR-ß expression changed sex-specifically in the clozapine-medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-treated females. Taken together, clozapine and haloperidol had a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined, and probably in their effect on liver metabolism.

A randomized, prospective, active-controlled study comparing intramuscular long-acting paliperidone palmitate versus oral antipsychotics in patients with schizophrenia at risk of violent behavior

ObjectivePaliperidone palmitate (PP) is an effective long-acting antipsychotic injection, but its impact on the behavior of schizophrenia patients with dangerous tendencies requires further investigation. This study aims to explore the effects of long-term antipsychotic treatment on this population in the community. MethodsThis 49-week, randomized controlled trial was conducted across 21 communities in Wuhan and enrolled 134 schizophrenia patients at risk for violent behavior. With a fixed block size of 10, participants were randomly assigned to receive either intramuscular PP 1-month formulation (PP1M) or oral antipsychotic medication (OAP) at a 1:1 ratio. Changes in patients' risk for violent/aggressive behavior, family burden, social, and cognitive functioning were measured using VRAPP, MOAS, PANSS, FBS, PSP, and RBANS scales from baseline to endpoint. Longitudinal data from multiple repeated measures were analyzed using linear mixed-effects models. ResultsThe study protocol was completed by 77.6% of the patients overall. Significant improvements were observed in the risk assessment scores, MOAS total score, PANSS total score, PSP total score, and FBS total score of patients in the PP1M group from baseline to the end of treatment (all P < 0.05). Importantly, compared to patients in the OAP group, the improvements in these measures were also significantly greater in the PP1M group. Commonly observed AEs, such as hyperprolactinemia (70.3% vs. 62.65%) and muscle tension (45.3% vs. 57.8%), were considered to be the PP-related AEs. Nonetheless, the differences between the two groups did not reach statistical significance, and no new safety concerns emerged. ConclusionsOur study suggests that PP long-acting injection (LAI) is a safe and effective treatment option for community-dwelling schizophrenia patients with impulsive violence and risky behaviors.

Risk of developing avascular necrosis of the femoral head and neck among patients with bipolar disorder: A nationwide cohort study

Background and objectivesThe association between bipolar disorder (BD) and avascular necrosis of the femoral head and neck (AVNHNF) remains unclear. We aimed to investigate the risk of AVNHNF among different polarity of BD. MethodsBetween 2001 and 2010, patients with BD were selected from the Taiwan National Health Research Database. The controls were individuals without severe mental disorder who were matched for demographic, medical and psychiatric comorbidities. Cox regression analysis was used to estimate the risk of AVNHNF, with adjustments for demographics, comorbidities, exposure to corticosteroids, and all-cause clinical visits. ResultsA total of 84,721 patients with BD and 169,442 controls were included. Patients with BD demonstrated a 1.92-fold (95% of confidence interval: 1.21–3.04) higher risk of AVNHNF compared with the controls. The risk was increased to 7.91-fold (4.32–14.49) in patients with severe BD compared with the controls. Importantly, patients with severe bipolar depression were associated with a 14.23-fold higher risk of AVNHNF compared with the controls, while those with sever bipolar mania were associated with a 3.55-fold higher risk. Compared with the controls with alcohol use disorder (AUD), patients with BD and comorbid AUD were associated with a 2.0-fold higher risk of AVNHNF. Finally, long-term use of atypical antipsychotics was associated with a decreased risk of AVNHNF). ConclusionClinicians should be aware of the increased risk of AVNHNF among patients with BD. This increased risk was associated with disorder severity, polarity, and comorbidity with AUD, and attenuated by long-term atypical antipsychotic treatment.

Mental Health Staff's Perspectives on Tapering of Antipsychotic Medication: A Focus Group Study.

Contemporary practices of long-term antipsychotic maintenance treatment for schizophrenia are being challenged, and clinicians must consider the possibilities of reducing long-term maintenance use. However, research indicates that people with schizophrenia receive little support from mental health staff to reduce antipsychotic medication. This article reports a study which aimed to investigate interdisciplinary mental health staff's accounts of tapering of antipsychotic medication and to explore different positions that mental health staff assign to themselves and others. Six focus groups were conducted with 39 mental health staff from outpatient clinics, inpatient units, forensic mental health units, and community mental health services. The data analysis combined analyses of the interactions during focus groups and the thematic content. Results were considered from a discourse analytic perspective considering the function and consequence of accounts applied by the mental health staff. The mental health staff accounted for their perspectives on tapering from the following three distinctive positions: 1) No, patients will eventually realize that they need the medication, 2) Yes, but tapering means running a big risk of relapse in symptoms, and 3) Yes, we need to welcome risks to support personal recovery. Our findings indicated that there was reluctance among interdisciplinary mental health staff to let service users make decisions and limited possibilities for people with schizophrenia to have their request for tapering of their antipsychotic medication met by mental health staff.

The role of the gut microbiome in weight-gain in schizophrenia patients treated with atypical antipsychotics: Evidence based on altered composition and function in a cross-sectional study

ObjectivesWe aimed to explore the interconnection between the weight-gain in schizophrenia patients with atypical antipsychotic treatment and gut microbiome. MethodsThis study employed a cross-sectional design, encompassing a total of 88 schizophrenia patients with long-term atypical antipsychotic treatment. The 16S rRNA gene sequencing was used to identify gut microbiome contents. ResultsNo significant differences in alpha diversity between normal-weight and overweight schizophrenia treated with atypical antipsychotics. The beta diversity analysis showed that overweight patients clustered tightly while normal-weight patients clustered widely. For taxonomic composition, overweight patients had a lower relative abundance in Porphyromonadaceae at family level and Butyrivibrio at genus level, but higher relative abundance in Ruminococcus2 and Clostridium_XIVa at genus level than normal-weight patients. Function prediction revelated that four pathways (including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection and Meiosis-yeast) were significantly different between groups. Correlation analysis indicated that Klebsiella, Butyrivibrio, Unassigned, Methanosphaera, Holdemania, Anaerotruncus were negatively, while Veillonella was positively correlated with BMI in patients. ConclusionOur findings offer evidence that perturbations in the gut microbiome composition, encompassing taxa such as Porphyromonadaceae, Butyrivibrio, Ruminococcus2, and Clostridium_XIVa, in conjunction with distinct functional pathways including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection, and Meiosis-yeast, might contribute to the weight-gain in schizophrenia treated with atypical antipsychotics.

Kynurenine pathway dynamics in patients with schizophrenia spectrum disorders across the disease trajectory

The aim of this study was to evaluate how schizophrenia spectrum disorders (SSD) and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum levels of tryptophan (Trp) metabolites. A total of 112 adults (54 first-episode psychosis [FEP] patients and 58 control subjects [CSs]) participated in the study. The investigated changes in the metabolite levels appeared against a background of persistent increase in BMI and waist circumference among the patients. Regarding the kynurenine (KYN) pathway, the strongest changes were seen in AP-naïve FEP patients. Trp, KYN, kynurenic acid (KYNA), and anthranilic acid (ANT) levels were significantly reduced in blood samples from patients in the early stage of the disease. Furthermore, 3-OH-kynurenine (3-HK) and quinolinic acid (QUIN) levels were somewhat lower in these patients. Most of these changes in the KYN pathway became weaker with AP treatment. The levels of serotonin and its metabolite 5-HIAA tended to be higher at 5.1 years in patients showing the relation of elevated serotonin turnover to increased BMI and waist circumference. The similar trend was evident for the ratio between xanthurenic acid (XA) and KYNA with strong link to the elevated BMI. Altogether, the present study supports the role of Trp-metabolites in the development of obesity and metabolic syndrome in SSD patients.

The effects of sigma-1 agonist fluvoxamine on experimental induced tardive dyskinesia model in rats

Tardive dyskinesia (TD) is a persistent involuntary complex movement disorder that is known to occur with long-term antipsychotic treatment. Despite being a well-recognized complication of this treatment, its symptoms are often masked by the antipsychotic agents, only to become apparent upon reducing or terminating the treatment. In an effort to advance our understanding of TD pathophysiology and to identify potential therapies, the current study aimed to establish an animal model of TD by administering haloperidol to rats and to evaluate the efficacy of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), in ameliorating TD symptoms. The study compared the behavioral and biochemical parameters of rats that were treated with either fluvoxamine, tetrabenazine, haloperidol, or saline (control group). The biochemical parameters of interest included the brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), superoxide dismutase (SOD), and malondialdehyde (MDA). To achieve the study objectives, 32 male Wistar Albino rats were assigned to four different groups. The control group received physiological saline for six weeks. The haloperidol group received 1 mg/kg/ip haloperidol for the first three weeks, followed by two weeks of saline. The haloperidol+fluvoxamine group received 1 mg/kg/ip haloperidol for the first three weeks, followed by 30 mg/kg/ip fluvoxamine. The haloperidol+tetrabenazine group was administered 1 mg/kg/ip haloperidol for the first three weeks, followed by 5 mg/kg/ip tetrabenazine. Behavioral assessments of the rats were performed by measuring vacuous chewing movements. Subsequently, samples were collected from the hippocampus, striatum, and frontal lobe tissues of the rats, and BDNF, NGF, SOD, and MDA levels were measured. The results of the study demonstrated significant differences between the groups with respect to behavioral observations. Furthermore, SOD levels in the hippocampus, as well as BDNF, NGF, and SOD levels in the striatum of the haloperidol+fluvoxamine group were significantly higher than those observed in the haloperidol group. Conversely, MDA levels in the hippocampus were significantly lower in the haloperidol+fluvoxamine group than in the haloperidol group. These findings provide evidence of the beneficial effects of fluvoxamine, acting as a sigma-1 agonist, in treating TD symptoms induced experimentally. The observed benefits were supported by the biochemical investigations performed on brain tissue samples. Therefore, fluvoxamine may be considered as a potential alternative treatment for TD in clinical practice, although further research is needed to corroborate these findings.

A Systematic Review of the Need for Guideline Recommendations; Slow Tapering vs. Maintenance Dose in Long-Term Antipsychotic Treatment: 2022.

The act of discontinuing the antipsychotic medication may be directlyassociated with relapse. This relationship might be due to adaptations that continue to exist after treatment is stopped, such as dopaminergic hypersensitivity. Therefore, more progressive weaning off antipsychotic medication may help reduce the likelihood of relapse when the medication is stopped. As there is a need to gradually reduce or stop using antipsychotic medication, our team tried to conduct a more in-depth search to give further answers to the suggested recommendations. Around 192 articles were gathered for our research, but we could only narrow our search to 36, which were further filtered, and eight were used.We went through all of the pertinent information available until May 2022 and reviewed it to determine the risks associated with prolonged antipsychotic usage and abrupt cessation in the psychotic spectrum of diseases. PubMed, Google Scholar, and Psychiatry Online were the databases used, and the keywords that were looked for and utilized were antipsychotics, tapering, relapse, maintenance dosage, schizophrenia, and psychosis. The recurrence incidence was high in patients in whom antipsychotics were stopped and in whom the dosage was quickly lowered.Patients who were gradually weaned off their antipsychotic medication and kept on the lowest effective dose had a much lower risk of experiencing a relapse. We suggest more studies, including randomized clinical trials and monitoring, considering the enhancement of guidelines for the total cessation of antipsychotic medication use.

A Marked Low-Grade Inflammation and a Significant Deterioration in Metabolic Status in First-Episode Schizophrenia: A Five-Year Follow-Up Study.

The objective of this study was to evaluate how schizophrenia spectrum disorders and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum level of acylcarnitines (ACs), cytokines and metabolic biomarkers and to characterize the dynamics of inflammatory and metabolic changes in the early course of the disorder. A total of 112 adults participated in the study (54 patients with first-episode psychosis (FEP) and 58 control subjects). Biomolecule profiles were measured at the onset of first-episode psychosis and 0.6 years and 5.1 years after the initiation of APs. The results of the present study confirmed that specific metabolic–inflammatory imbalance characterizes AP-naïve patients. Short-term (0.6-years) AP treatment has a favourable effect on psychotic symptoms, as well as the recovery of metabolic flexibility and resolution of low-level inflammation. However, 5.1 years of AP treatment resulted in weight gain and increased serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon-γ, hexoses, acetylcarnitine, short-chain ACs (C3, C4) and long-chain ACs (C16:2, C18:1, C18:2). In conclusion, despite the improvement in psychotic symptoms, 5.1 years of AP treatment was accompanied by a pronounced metabolic–inflammatory imbalance, which was confirmed by the presence of enhanced pro-inflammatory activity and increased obesity with changes in the metabolism of carbohydrates, lipids, and their metabolites.

Effects of Antipsychotic Medications and Illness Duration on Brain Features That Distinguish Schizophrenia Patients.

Previous studies have reported effects of antipsychotic treatment and illness duration on brain features. This study used a machine learning approach to examine whether these factors in aggregate impacted the utility of MRI features for differentiating individual schizophrenia patients from healthy controls. This case-control study used patients with never-treated first-episode schizophrenia (FES, n = 179) and long-term ill schizophrenia (LTSZ, n = 30), with follow-up of the FES group after treatment (n = 71), a group of patients who had received long-term antipsychotic treatment (n = 93) and age and sex-matched healthy controls (n = 373) for each patient group. A multiple kernel learning classifier combining both structural and functional brain features was used to discriminate individual patients from controls. MRI features differentiated untreated FES (0.73) and LTSZ (0.83) patients from healthy controls with moderate accuracy, but accuracy was significantly higher in antipsychotic-treated FES (0.94) and LTSZ (0.98) patients. Treatment was associated with significantly increased accuracy of case identification in both early course and long-term ill patients (both p < .001). Effects of illness duration, examined separately in treated and untreated patients, were less robust. Our results demonstrate that initiation of antipsychotic treatment alters brain features in ways that further distinguish individual schizophrenia patients from healthy individuals, and have a modest effect of illness duration. Intrinsic illness-related brain alterations in untreated patients, regardless of illness duration, are not sufficiently robust for accurate identification of schizophrenia patients.

Elevated osteopontin and IFNy serum levels and increased neutrophil-to-lymphocyte ratio are associated with the severity of symptoms in schizophrenia

IntroductionInflammation and immune dysregulation could contribute to the pathogenesis of schizophrenia. Osteopontin (OPN) is a key cytokine-like molecule in cellular immune response and it can directly modulate the cytokine expression and survival of microglia. Furthermore, its mRNA expression is elevated in first episode psychosis. Imbalance of T-helper subtypes could also represent a vulnerability factor for schizophrenia.ObjectivesThe aim of this study was to evaluate the relevance of T-helper subtype associated cytokines, OPN and NLR in the assessment of the severity of schizophrenia.Methods22 patients with schizophrenia were assessed for the intensity of their symptoms by PANSS and CGI scores. Serum OPN, IFNy, IL-10 and IL-8 concentrations were measured by ELISA kits and NLR was calculated from blood count. Statistical evaluation was performed using Mann-Whitney U test, Student’s t test and Spearman correlation.ResultsWe found significant correlation between the level of OPN and PANSS-total, PANSS-general scores. IFNy level and NLR showed significant correlation with PANSS-total, PANSS-positive, PANSS-general and CGI score. Antipsychotic therapy only had significant effects on NLR and OPN levels, both of which were significantly reduced after long-term antipsychotic treatment.ConclusionsOur results indicate that elevated OPN and IFNy concentrations, and increased NLR are associated with severe symptoms in schizophrenia and suggest the importance of Th1 subtype in patients with high PANSS-positive and PANSS-general score. Antipsychotic treatment had significant effects on the level of OPN and NLR, but not on the level of IFNy. Overall our results strengthen the inflammation hypothesis of schizophrenia.DisclosureNo significant relationships.

Treatment Effect of Long-Term Antipsychotics on Default-Mode Network Dysfunction in Drug-Naïve Patients With First-Episode Schizophrenia: A Longitudinal Study.

Background: The maintenance of antipsychotic treatment is an efficient way to prevent the relapse of schizophrenia (SCZ). Previous studies have identified beneficial effects of antipsychotics on brain structural and functional abnormalities during mostly the acute phase in SCZ, but seldom is known about the effects of long-term antipsychotics on the brain. The present study focused on the long-term antipsychotic effect on the default mode network (DMN) dysfunction in SCZ. Methods: A longitudinal study of the functional connectivity (FC) of 11 DMN subdivisions was conducted in 86 drug-naive first-episode patients with SCZ at the baseline and after a long-term atypical antipsychotic treatment (more than 6 months) based on the resting-state functional magnetic resonance image. In total, 52 patients completed the follow-up of clinical and neuroimaging investigations. Results: At the baseline, relative to healthy controls, altered connectivities within the DMN and between the DMN and the external attention system (EAS) were observed in patients. After treatment, along with significant relief of symptoms, most FC alterations between the DMN and the EAS at the baseline were improved after treatment, although the rehabilitation of FC within the DMN was only observed at the link between the posterior cingulate cortex and precuneus. Greater reductions in negative and positive symptoms were both related to the changes of DMN-EAS FC in patients. Conclusion: Our findings provide evidence that maintenance antipsychotics on SCZ is beneficial for the improvement of DMN-EAS competitive imbalance, which may partly contribute to the efficient relapse prevention of this severe mental disorder.

Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors.

People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all-cause and suicide-related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide-related mortality risk in incident schizophrenia samples. All-cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all-cause mortality (RR=1.62, 95% CI: 1.47-1.80, n=3). Antipsychotics were protective against all-cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59-0.84, n=11), with largest effects for second-generation long-acting injectable anti-psychotics (SGA-LAIs) (RR=0.39, 95% CI: 0.27-0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34-0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39-0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44-0.63, n=4). Antipsychotics were also protective against natural cause-related mortality, yet first-generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural-cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long-term maintenance antipsychotic treatment and appropriate/earlier use of SGA-LAIs and clozapine could reduce this mortality gap.

Initiation of quarterly palmitate paliperidone in French clinical practice: Results from the observational, cross-sectional OPTIMUS study.

Long-term antipsychotic treatment is key to a positive clinical outcome in schizophrenia. Recent guidelines recommend the prescription of long-acting antipsychotic formulations (LAIs) as early as the first episode in patients with schizophrenia. The OPTIMUS study evaluated real-world use of a new three-monthly paliperidone palmitate formulation (PP3M) in France. For this observational cross-sectional study, all French psychiatrists were invited to enrol patients who had initiated PP3M in the previous 4 months. Snapshot data were collected at a routine consultation, without any modification of clinical practice. This population of 350 patients with schizophrenia started on PP3M predominantly included single men, living independently with a diagnosis of schizophrenia for a median of 9.3 years. Demographic characteristics were broadly comparable to those reported in other studies on LAIs. Investigators cited treatment simplification (96.9%) and patient comfort (93.3%) as the most common reasons for switching to PP3M; enhancing adherence was mentioned less often (61.1%) with most patients previously considered as adherent, and a majority of them expressing a positive attitude to their treatment. One-third of patients accepted the psychiatrist's proposal to initiate PP3M treatment without any discussion, and relatives were involved in the therapeutic decision-making process in only 23.7% of cases. After initiation, few changes were seen in professional follow-up frequency or concomitant pharmacological and non-pharmacological treatment modalities except for a decrease in antipsychotic polytherapy. PP3M is mostly prescribed in adherent patients with fairly stable schizophrenia, and the longer dosing interval does not substantially affect patient care.

Treatment of tardive dystonia due to risperidone use with single-dose botulinum toxin

Late-onset dystonia occurs after long-term antipsychotic treatment or after discontinuation of treatment. Being young, male gender, mental retardation, and mood disorder are risk factors. By considering the dystonic complaints and psychotic symptoms of the patient who had a diagnosis of schizoaffective disorder and had risperidone 8 mg/day tablet use for 3 months, it was planned to continue treatment with clozapine. When the dystonic complaints did not improve, botulinum toxin was applied and recovery was achieved. In most cases, botulinum toxin can provide a dramatic improvement in the treatment of tardive dystonia, which is very difficult to treat and causes significant loss of functionality and poor quality of life. For this reason, botulinum toxin application should come to mind in the treatment of tardive dystonia.

Chronic Use of Antipsychotics in Schizophrenia: Are We Asking the Right Question?

There is an ongoing debate about the potential risks and benefits of long-term antipsychotic treatment in schizophrenia. The data for and against the chronic use of these medicines is mostly indirect, either from observational studies potentially exposed to reverse causation bias or randomized controlled studies that do not cover beyond 2–3 years. We propose that perseverating on the question of what positive or negative outcomes are causally associated with chronic antipsychotic treatment may not lead to better answers than the limited ones that we have, given the limited feasibility of more conclusive studies. Rather, we argue that addressing the research question of the risks and benefits of antipsychotic discontinuation from a perspective of personalized medicine, can be more productive and meaningful to people living with schizophrenia. To this end, research that can quantify the risk of relapse after treatment continuation for a given individual should be prioritized. We make the case that clinically feasible neuroimaging biomarkers have demonstrated promise in related paradigms, and that could be offering a way past this long debate on the risks and benefits of chronic antipsychotic use.

Association of the First Antipsychotic Treatment Duration With the Re-Initiation of Treatment in Schizophrenia: A National Health Insurance Data-Based Study

Objectives: The optimal duration of maintenance treatment for patients with first-episode schizophrenia (FES) remains unclear. We examined the first antipsychotic treatment duration and its association with re-initiation of treatment using a nationwide claim database.Methods: Data from the Health Insurance Review and Assessment Service database in South Korea for 2007–2016 were used. Linear regression analysis and Cox proportional hazard models were used to evaluate the associations between the duration of the first antipsychotic treatment, time to re-initiation of treatment, and occurrence of treatment re-initiation.Results: Of 30,143 patients with FES, 80.4% (n=24,231) received &lt;2 years of the first antipsychotic treatment. In patients who discontinued treatment (n=23,030), the rate of treatment re-initiation was 74.2% (n=17,086). As the duration of the first antipsychotic treatment increased, the time to re-initiation of treatment decreased (β=-0.146, p&lt;0.001); however, the rate of treatment re-initiation was relatively constant (hazard ratio=1.001, p&lt;0.001).Conclusion: Long-term antipsychotic treatment was not significantly associated with the rate of treatment re-initiation but showed a negative association with the time to re-initiation of treatment. Further research is needed to better understand the optimal treatment duration for FES.