Antipsychotics In Schizophrenia Research Articles

The impact of COVID-19 public health measures on the utilization of antipsychotics in schizophrenia in Manitoba – A population-based study

PurposeDuring the COVID-19 pandemic, public health measures were implemented, yet it is unknown whether these measures affected medication access in those with schizophrenia (SCZ). This study aimed to assess whether the antipsychotic utilization in SCZ changed during the pandemic. MethodsWe used dispensed prescription drug data from the Canadian province of Manitoba in individuals with SCZ using linked administrative data from the Manitoba Population Research Data Repository. The quarterly incident and prevalent dispensation of antipsychotics at two periods were compared with the expected trend (April 1, 2015 to April 1, 2020 and 2021) using linear autoregression. We stratified the primary results by age and sex and examined multiple subgroups. ResultsThere were 9045 individuals with SCZ in the first fiscal quarter of 2020. The prevalent use of the most common antipsychotics were: olanzapine (206.7/1000), risperidone (190.8/1000), quetiapine (174.4/1000), and clozapine (100.9/1000). The overall prevalent use of antipsychotics remained stable during the pandemic compared with the expected trend. A significant decrease in the incident use in April–June 2020 (estimate: -1.3, 95%CI:-2.2,-0.3) was noted compared with the expected. A significantly higher incidence of atypical antipsychotics (estimate: 1.4, 95%CI: 0.2,2.5) and risperidone separately (estimate: 1.8, 95%CI: 0.2,3.3) was noted in 2021 compared with expected. ConclusionThis study found a decline in the receipt of antipsychotics for people with SCZ during the initial implementation of COVID-19 public health measures, particularly on the overall incidence. Future work on investigating the impact of these trends on SCZ outcomes is needed to inform future pandemic-related policies.

All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis.

Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66-0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66-0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63-0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59-1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66-0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.

An online evidence-based dictionary of common adverse events of antidepressants: a new tool to empower patients and clinicians in their shared decision-making process

BackgroundAdverse events (AEs) are commonly reported in clinical studies using the Medical Dictionary for Regulatory Activities (MedDRA), an international standard for drug safety monitoring. However, the technical language of MedDRA makes it challenging for patients and clinicians to share understanding and therefore to make shared decisions about medical interventions. In this project, people with lived experience of depression and antidepressant treatment worked with clinicians and researchers to co-design an online dictionary of AEs associated with antidepressants, taking into account its ease of use and applicability to real-world settings.MethodsThrough a pre-defined literature search, we identified MedDRA-coded AEs from randomised controlled trials of antidepressants used in the treatment of depression. In collaboration with the McPin Foundation, four co-design workshops with a lived experience advisory panel (LEAP) and one independent focus group (FG) were conducted to produce user-friendly translations of AE terms. Guiding principles for translation were co-designed with McPin/LEAP members and defined before the finalisation of Clinical Codes (CCs, or non-technical terms to represent specific AE concepts). FG results were thematically analysed using the Framework Method.ResultsStarting from 522 trials identified by the search, 736 MedDRA-coded AE terms were translated into 187 CCs, which balanced key factors identified as important to the LEAP and FG (namely, breadth, specificity, generalisability, patient-understandability and acceptability). Work with the LEAP showed that a user-friendly language of AEs should aim to mitigate stigma, acknowledge the multiple levels of comprehension in ‘lay’ language and balance the need for semantic accuracy with user-friendliness. Guided by these principles, an online dictionary of AEs was co-designed and made freely available (https://thesymptomglossary.com). The digital tool was perceived by the LEAP and FG as a resource which could feasibly improve antidepressant treatment by facilitating the accurate, meaningful expression of preferences about potential harms through a shared decision-making process.ConclusionsThis dictionary was developed in English around AEs from antidepressants in depression but it can be adapted to different languages and cultural contexts, and can also become a model for other interventions and disorders (i.e., antipsychotics in schizophrenia). Co-designed digital resources may improve the patient experience by helping to deliver personalised information on potential benefits and harms in an evidence-based, preference-sensitive way.

Neurogenetics: Precision Medicine-Based Approaches to Neurological Disorders with an Emphasis on Addressing Alzheimer’s Disease and Schizophrenia

There exist over 600 neurological conditions, each characterized by unique pathologies tailored to individual patients. Over the past two decades, advances in biotechnology have propelled the field of neurogenetics forward. This progress has illuminated therapeutic targets and methodologies tailored to the specific needs of each patient. Current treatment options primarily encompass therapies and conventional medications like cholinesterase inhibitors for Alzheimer’s disease and antipsychotics for schizophrenia. However, these treatments often address symptoms or general targets rather than the precise underlying causes. Precision medicine has emerged as a promising approach in both animal and human clinical trials. Examples include the identification of specific genetic variations linked to Alzheimer's risk and progression, as well as the application of multigenic pharmacogenomics-guided therapies for schizophrenia patients. This review paper delves into the role of precision medicine in neurogenetics, focusing on neural stem cells, induced pluripotent stem cells (iPSCs), genetic profiling, and pharmacogenetics within the contexts of Alzheimer’s disease and schizophrenia. By evaluating current achievements alongside existing challenges, this paper underscores precision medicine as a pivotal strategy for effectively targeting neurological disorders.

Relationship between functional connectivity and weight-gain risk of antipsychotics in schizophrenia

BackgroundThe mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia. MethodsFifty-five individuals with schizophrenia (final N = 54) were divided into groups based on previously reported AP weight-gain risk (no APs/low risk [N = 19]; moderate risk [N = 17]; high risk [N = 18]). Resting-state functional magnetic resonance imaging (fMRI) was completed after an overnight fast (“fasted”) and post-meal (“fed”). Correlations between AP weight-gain risk and functional connectivity were assessed at the whole-brain level and in reward- and eating-related brain regions (anterior insula, caudate, nucleus accumbens). ResultsWhen fasted, greater AP weight-gain risk was associated with increased connectivity between thalamus and sensorimotor cortex (pFDR = 0.021). When fed, greater AP weight-gain risk was associated with increased connectivity between left caudate and left precentral/postcentral gyri (pFDR = 0.048) and between right caudate and multiple regions, including the left precentral/postcentral gyri (pFDR = 0.001), intracalcarine/precuneal/cuneal cortices (pFDR < 0.001), and fusiform gyrus (pFDR = 0.008). When fed, greater AP weight-gain risk was also associated with decreased connectivity between right anterior insula and ventromedial prefrontal cortex (pFDR = 0.002). ConclusionsAPs with higher weight-gain risk were associated with greater connectivity between reward-related regions and sensorimotor regions when fasted, perhaps relating to motor anticipation for consumption. Higher weight-gain risk APs were also associated with increased connectivity between reward, salience, and visual regions when fed, potentially reflecting greater desire for consumption following satiety.

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model.

The available antipsychotics for schizophrenia (SZ) only reduce positive symptoms and do not significantly modify SZ neurobiology. This has raised the question of the robustness and translational value of methods employed during drug development. Electroencephalography (EEG)-based measures like evoked and spontaneous gamma oscillations are considered robust translational biomarkers as they can be recorded in both patients and animal models to probe a key mechanism underlying all SZ symptoms: the excitation/inhibition imbalance mediated by N-methyl-D-aspartate receptor (NMDAr) hypofunction. Understanding the effects of commercialized atypical antipsychotics on such measures could therefore contribute to developing better therapies for SZ. Yet, the effects of such drugs on these EEG readouts are unknown. Here, we studied the effect of the atypical antipsychotic aripiprazole on the gamma-band auditory steady-state response (ASSR), spontaneous gamma oscillations and behavioral features in a SZ rat model induced by the NMDAr antagonist MK-801. Interestingly, we found that aripiprazole could not normalize MK-801-induced abnormalities in ASSR, spontaneous gamma oscillations or social interaction while it still improved MK-801-induced hyperactivity. Suggesting that aripiprazole is unable to normalize electrophysiological features underlying SZ symptoms, our results might explain aripiprazole's inefficacy towards the social interaction deficit in our model but also its limited efficacy against social symptoms in patients.

Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data

There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence. We conducted network meta-analyses using individual participant data from Swedish and Finnish national registries and aggregate data from RCTs. The target population was adults (age >18 and <65 years) with schizophrenia and schizoaffective disorder with stabilised symptoms. We analysed each registry separately to obtain hazard ratios (HRs) and 95% CIs for relapse within 6 months post-antipsychotic initiation as our main outcome. Interventions studied were antipsychotics, no antipsychotic use, and placebo. We compared HRs versus a reference drug (oral haloperidol) between registries, and between registry individuals who would be eligible and ineligible for RCTs, using the ratio of HRs. We synthesised evidence using network meta-analysis and compared results from our network meta-analysis of real-world data with our network meta-analysis of RCT data, including oral versus long-acting injectable (LAI) formulations. Finally, we conducted a joint real-world and RCT network meta-analysis. We included 90 469 individuals from the Swedish and Finnish registries (mean age 45·9 [SD 14·6] years; 43 025 [47·5%] women and 47 467 [52·5%] men, ethnicity data unavailable) and 10 091 individuals from 30 RCTs (mean age 39·6 years [SD 11·7]; 3724 [36·9%] women and 6367 [63·1%] men, 6022 White [59·7%]). We found good agreement in effectiveness of antipsychotics between Swedish and Finnish registries (HR ratio 0·97, 95% CI 0·88-1·08). Drug effectiveness versus no antipsychotic was larger in RCT-eligible than RCT-ineligible individuals (HR ratio 1·40 [1·24-1·59]). Efficacy versus placebo in RCTs was larger than effectiveness versus no antipsychotic in real-world (HR ratio 2·58 [2·02-3·30]). We found no evidence of differences between effectiveness and efficacy for between-drug comparisons (HR ratio vs oral haloperidol 1·17 [0·83-1·65], where HR ratio >1 means superior effectiveness in real-world to RCTs), except for LAI versus oral comparisons (HR ratio 0·73 [0·53-0·99], indicating superior effectiveness in real-world data relative to RCTs). The real-world network meta-analysis showed clozapine was most effective, followed by olanzapine LAI. The RCT network meta-analysis exhibited heterogeneity and inconsistency. The joint real-world and RCT network meta-analysis identified olanzapine as the most efficacious antipsychotic amongst those present in both RCTs and the real world registries. LAI antipsychotics perform slightly better in the real world than according to RCTs. Otherwise, RCT evidence was in line with real-world evidence for most between-drug comparisons, but RCTs might overestimate effectiveness of antipsychotics observed in routine care settings. Our results further the understanding of the generalisability of RCT findings to clinical practice and can inform preferential prescribing guidelines. None.

Efficacy and safety of clozapine combination with different antipsychotics in schizophrenia: a systematic review

Schizophrenia is a severe and chronic mental disorder, where antipsychotics are used as the main therapy. Antipsychotics are commonly used in combination, especially in refractory patients. Clozapine is one of antipsychotics that is often used in combination with other antipsychotic to achieve more effective treatment. However, the effectiveness and safety of the clozapine combination are still inconclusive. This review aimed to evaluate the efficacy and safety evidence of clozapine combination therapy with different other antipsychotics. Relevant articles were collected from Google Scholar, Scopus, and PubMed, and published in 2000-2020. Five studies concerning the effectiveness and safety of clozapine in combination with different other antipsychotics were evaluated. No significant difference in the effectiveness of clozapine in combination with other antipsychotics was observed in 4 studies. No significant difference in the safety of all clozapine combinations was observed in 3 studies. Only 2 studies reported that the clozapine-atypical antipsychotic combination (clozapine-aripiprazole) is more tolerable compared to the clozapine-typical antipsychotic. In conclusion, the efficacy and safety of clozapine in combination with different other antipsychotics have not been definitively conclusive, yet.

Systematic Selection of Antipsychotics in Schizophrenia: A Binary Search Approach Based on Efficacy and Side Effects

Systematic Selection of Antipsychotics in Schizophrenia: A Binary Search Approach Based on Efficacy and Side Effects

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs

QuestionThis umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.Study selection and analysisFollowing the Preferred Reporting Items for Systematic Reviews...

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial

BackgroundIt remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia.MethodsThis multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively.ResultsAt week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%).ConclusionsSymptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks.Trial registrationThis study was registered on Clinicaltrials.gov (NCT03451734).

Change of prescription for patients with schizophrenia or major depressive disorder during admission: real-world prescribing surveys from the effectiveness of guidelines for dissemination and education psychiatric treatment project

BackgroundPolypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge.MethodsData on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups.ResultsFor both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients.ConclusionsIt is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures.Trial registrationThe study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).

Effects of varenicline on the serum levels of olanzapine in male patients with Schizophrenia: a randomized controlled trial.

Smoking in patients with Schizophrenia is more common than in the general population. Varenicline, a partial agonist at α4β2 nicotinic acetylcholine receptors, is an effective smoking cessation pharmacotherapy in patients with Schizophrenia. However, its effects on the serum levels of antipsychotics in Schizophrenia are understudied. This study investigated the impact of smoking cessation with varenicline on the serum concentration of olanzapine in patients with Schizophrenia. Adult smokers with Schizophrenia were enrolled in a 12-week course of varenicline and placebo for smoking cessation. The serum concentration of olanzapine was measured at baseline and weeks 1, 2, 4, 8, and 12. Data were analyzed with the generalized additive mixed model. During the 12-week study, the results indicated that olanzapine concentrations increased nonlinearly in the varenicline and placebo groups. Threshold effect analysis suggested that the olanzapine concentrations increased over time until the turning point (week 4). However, there was no significant difference between the two treatment groups. Varenicline showed safety and efficacy in smoking cessation in people with Schizophrenia.

Studies Point to Benefits of Early Treatment With Long-Acting Antipsychotics

Back to table of contents Previous article Next article Clinical & ResearchFull AccessStudies Point to Benefits of Early Treatment With Long-Acting AntipsychoticsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:23 Nov 2022https://doi.org/10.1176/appi.pn.2022.12.10.39AbstractPatients with schizophrenia who were prescribed oral antipsychotics for less than three years saw greater symptom improvements when switching to long-acting injectable formulations than those who had been taking the oral medications longer.iStock/Rawf8Numerous studies have pointed to the benefits of long-acting injectable antipsychotics (LAIs) at reducing the risk of symptom relapse, hospitalizations, and other adverse outcomes in patients with schizophrenia. A pair of recent studies provide evidence that switching from oral antipsychotics to LAIs within the first two to three years of a diagnosis may provide the greatest benefit.One study involved data collected from Taiwan’s national health insurance on over 19,000 people aged 16 to 65 who had a schizophrenia diagnosis, were taking oral antipsychotics, and were hospitalized for acute psychosis between 2002 and 2005. Among this group, Joni Yu-Hsuan Shao, Ph.D., a professor of biomedical informatics at Taipei Medical University in Taiwan, and colleagues identified 678 patients who were switched from oral antipsychotics to an LAI during hospitalization and who continued to receive the LAI at least 12 months after discharge; 312 received LAIs within three years of their first oral antipsychotic prescription (early stage of treatment), while 366 transitioned following three or more years of oral medication use (late stage of treatment).As described in the Journal of Clinical Psychiatry, each of these patients was matched to a patient of similar age, sex, hospitalization date, and psychiatric comorbidities who continued taking oral antipsychotics following discharge from the hospital. All patients were followed up from their date of hospitalization until the end of the study period (December 31, 2015) or death, whichever came first. During this period the researchers recorded all instances of rehospitalizations (psychiatric or other medical), psychiatric emergency room (ER) visits, or death.Early LAI switchers had the following:37% reduced risk of psychiatric hospitalization.44% reduced risk of any hospitalization.42% reduced risk of a psychiatric ER visit.51% reduced risk of death by any cause.The reductions in adverse health outcomes were not seen in patients who were switched during the late stage of illness; in fact, patients who switched to LAIs in the late stage of treatment had a 34% increased risk of psychiatric rehospitalization during the follow-up period compared with patients who stayed on oral antipsychotics.“These real-world data demonstrated that LAIs in the early stage of treatment of hospitalized patients increased disease control and had long-term benefits,” Shao and colleagues wrote.The other study was published in JAMA Network Open and conducted by Yue Wei, M.P.H., of the University of Hong Kong and colleagues. The investigators used health records data to identify 23,719 individuals diagnosed with schizophrenia between 1993 and 2019 who were prescribed at least one oral and LAI antipsychotic during this time. They compared the health outcomes of these patients during periods while taking oral antipsychotics with periods while taking LAIs.As expected, patients had lower rates of emergency department visits, hospitalizations, and suicide attempts while taking an LAI antipsychotic relative to their time taking an oral antipsychotic. The benefits were more pronounced for those who began taking LAI antipsychotics within two years of a schizophrenia diagnosis; compared with periods they were taking the oral medication, these patients had the following:76% reduced risk of a psychiatric hospitalization.65% reduced risk of any hospitalization.33% reduced risk of an emergency department visit.72% reduced risk of a suicide attempt while on an LAI.Shao said these findings support the critical period hypothesis, which posits that schizophrenia-related deterioration is particularly aggressive in the two to five years after the first episode of psychosis.The Shao study was supported by the Bali Psychiatric Center, Taiwan. The Wei study was supported by The Excellent Young Scientists Fund of the National Natural Science Foundation of China. ■Resources“Long-term Outcomes of Early Use of Long-Acting Injectable Antipsychotics in Schizophrenia”“Association of Long-Acting Injectable Antipsychotics and Oral Antipsychotics With Disease Relapse, Health Care Use, and Adverse Events Among People With Schizophrenia” ISSUES NewArchived

Dried Blood Spot (DBS) as a useful tool to improve clozapine, aripiprazole and paliperidone treatment: From adherence to efficiency

IntroductionTherapeutic Drug Monitoring (TDM) of antipsychotics in schizophrenia is a powerful tool that allows tailoring the treatment in an individualized approach. Our goals are to develop and validate a Dried Blood Spot (DBS) method for monitoring some commonly used antipsychotics (aripiprazole, clozapine, and paliperidone) and to evaluate its usefulness as a compliance biomarker, as well as in drug-dose adjustment to personalize the antipsychotic treatment to improve its efficacy and safety. Methods31 first-psychotic episode (FEP) and schizophrenia patients were included; 5 refer to naïve FEP who started antipsychotic treatment; 26, to patients with more than one episode and under antipsychotic treatment: aripiprazole (7 cases), clozapine (17), paliperidone (11). For DBS sample collection, 25μl of capillary blood were placed in the spot of a FTA™DMPK-C-card. After completely dryness, antipsychotics were extracted and analyzed by a validated UHPLC-MS/MS-method. DBS antipsychotic results were compared with those obtained in venous blood/plasma. ResultsAripiprazole, paliperidone and clozapine showed from good to excellent correlations between concentrations in venous blood and DBS capillary blood (r2, from 0.500 to 0.721). The correlation between conventional plasma and DBS concentrations for paliperidone, aripiprazole, clozapine, and their metabolites were moderate, suggesting that optimal drug target concentrations should be established for DBS. ConclusionsIn this study, for aripiprazole, dehydroaripiprazole, paliperidone, clozapine and desmethylclozapine, DBS has provided good analytical performance for TDM. Thus, DBS sampling can offer a great alternative over conventional sampling for plasma measurement. The assay provides good analytical performances for TDM and clinical research applicability, suggesting that DBS is a promising clinical application in TDM in psychiatry.

Associations between antipsychotic use, substance use and relapse risk in patients with schizophrenia: real-world evidence from two national cohorts.

Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid substance use disorder (SUD) is very sparse, and non-existent on the prevention of the development of SUDs in patients with schizophrenia. To compare the real-world effectiveness of antipsychotics in schizophrenia in decreasing risk of developing an initial SUD, and psychiatric hospital admission and SUD-related hospital admission among patients with an SUD. Two independent national cohorts including all persons diagnosed with schizophrenia (N = 45 476) were followed up for 22 (Finland: 1996-2017) and 11 (Sweden: 2006-2016) years. Risk of developing an SUD was calculated with between-individual models, and risks of psychiatric and SUD-related hospital admission were calculated with within-individual models, using Cox regression and adjusted hazard ratios (aHRs) for using versus not using certain antipsychotics. For patients with schizophrenia without an SUD, clozapine use (Finland: aHR 0.20, 95% CI 0.16-0.24, P < 0.001; Sweden: aHR 0.35, 95% CI 0.24-0.50, P < 0.001) was associated with lowest risk of developing an initial SUD in both countries. Antipsychotic polytherapy was associated with second lowest risk (aHR 0.54, 95% CI 0.44-0.66) in Sweden, and third lowest risk (aHR 0.47, 95% CI 0.42-0.53) in Finland. Risk of relapse (psychiatric hospital admission and SUD-related hospital admission) were lowest for clozapine, antipsychotic polytherapy and long-acting injectables in both countries. Results were consistent across both countries. Clozapine and antipsychotic polytherapy are most strongly associated with reduced risk of developing SUDs among patients with schizophrenia, and with lower relapse rates among patients with both diagnoses.

DRD3 Ser9Gly polymorphism and treatment response to antipsychotics in schizophrenia: A meta-analysis

The association between dopamine D3 receptor (DRD3) Ser9Gly polymorphism and treatment response to antipsychotic drugs (APDs) in schizophrenia (SCZ) has been widely reported with inconsistent results, thus we performed an updated meta-analysis to derive a more precise estimation of the relationship. PubMed, Cochrane Library, Medline, Embase, CNKI, Weipu and Wanfang databases were searched for eligible studies published until March 2022. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the associations in four genetic models. A total of 13 studies with 1769 patients were included in this meta-analysis. Our findings suggested that Ser9Gly polymorphism was significantly associated with treatment response to APDs in SCZ in allele model (Ser vs Gly, OR = 0.72, 95 % CI = 0.58–0.89, P = 0.002), recessive model (Ser/Ser vs Ser/Gly + Gly/Gly, OR = 0.55, 95 % CI = 0.36–0.86, P = 0.008) and co-dominant model (Ser/Ser vs Gly/Gly, OR = 0.57, 95 % CI = 0.33–0.99, P = 0.045) in Caucasians, but not in Asians. meta-regression revealed that the associations were not confounded by mean age, male ratio and treatment duration (P > 0.05). In summary, our results indicated the DRD3 Ser9Gly may influence the efficacy of APDs in specific genetic models, of which Ser allele and Ser/Ser genotype contributed to poor treatment response in Caucasians.

Cardiovascular diseases and use of antipsychotics in schizophrenia: a review

RESUMO Objetivo Realizar uma revisão de escopo a respeito dos efeitos adversos cardiovasculares e metabólicos associados ao uso de antipsicóticos em pessoas com o diagnóstico de esquizofrenia. Métodos Foi realizada uma revisão de escopo utilizando-se da base de dados PubMed, com descritores MeSH relacionados às doenças cardiovasculares e antipsicóticos. Foram encontrados 976 artigos, os quais foram filtrados por títulos, seguidos dos resumos e, na sequência, lidos na íntegra. Ao final, foram selecionados 71 artigos para a análise. Resultados O uso de antipsicóticos típicos e atípicos para tratamento da esquizofrenia associa-se a alterações glicêmicas e lipídicas, síndrome metabólica, hipertensão, ganho de peso e morbidade cardiovascular. Os estudos evidenciaram a existência de subdiagnóstico e subtratamento de doenças crônicas nessa população. A mortalidade por doença cardiovascular demonstrou aumento considerável nos pacientes em tratamento com agentes antipsicóticos, em comparação com a população geral. Conclusão Alguns fatores dos antipsicóticos, ainda não completamente determinados na psicofarmacologia, vêm se mostrando relacionados a maior risco de distúrbios metabólicos, comportamentais e intrínsecos às pessoas diagnosticadas com esquizofrenia, os quais podem agravar o curso clínico de tais doenças. Reconhece-se a necessidade de aprimorar o acompanhamento e o diagnóstico de doenças cardiovasculares e metabólicas entre pessoas com diagnóstico de esquizofrenia em tratamento com antipsicóticos típicos e atípicos.

Symptomatic versus disease-modifying effects of psychiatric drugs.

Drugs can be divided into two major categories, symptomatic and disease modifying. This review explores whether and how psychiatric drugs fall into one or the other of those categories, and the implications of those results for clinical practice and research in psychopharmacology. Narrative review. Most psychiatric drugs have only short-term effects of improving active symptoms. They do not show long-term benefits for the underlying disease, such as improving the course of illness and improving mortality. Evidence is provided for this claim in the treatment literature of antidepressants for depressive illness and antipsychotics for schizophrenia. Developing truly beneficial drugs for disease modification also is limited by the poor clinical and biological validity of Diagnostic and Statistical Manual diagnoses as well as the use of invalid falsely positive maintenance efficacy randomized discontinuation trial designs. Current psychopharmacology is limited mostly to symptomatic effects, not transformative treatments for the diseases underlying those symptoms. A change in approach is needed in psychopharmacology practice and research, focusing on long-term disease modification rather than short-term symptom improvement.

Long-term Outcomes of Early Use of Long-Acting Injectable Antipsychotics in Schizophrenia.

Background: Long-acting injectable antipsychotics (LAIs) may potentially benefit patients requiring psychiatric hospitalization during the early stages of schizophrenia. However, few studies have compared the long-term effectiveness between patients who switched to LAIs and those who remained on oral antipsychotics (OAPs).Methods: Using the Taiwan National Health Insurance Research Database, we constructed a population-based cohort with 19,813 new OAP users with ICD-9-CM-defined schizophrenia who were hospitalized from 2002 to 2005. Within this cohort, 678 patients who switched to LAIs during their hospitalization were identified. The LAI group was matched to patients who remained on OAPs (n = 678). The LAI cohort was further subdivided for analysis into patients who switched to LAIs within 3 years of OAP initiation ("an early stage") and those who switched after 3 years ("a late stage"). Conditional Cox regressions and conditional negative binomial regressions were used to estimate the risk of death and the number of hospital visits between the two groups.Results: During the 13-year study period, 312 patients switched to LAIs within the first 3 years of OAP initiation. All- and natural-cause mortalities in these patients were significantly lower than in those who remained on OAPs. The hazard ratios (HRs) for all- and natural-cause mortalities were 0.49 (95% confidence interval [CI], 0.27-0.87) and 0.30 (95% CI, 0.15-0.60), respectively. No significant decrease associated with LAIs was observed in unnatural-cause mortality. Patients receiving LAIs had lower risks of rehospitalization (incidence rate ratio [IRR] = 0.56, 95% CI, 0.45-0.69), psychiatric hospitalization (IRR = 0.63, 95% CI, 0.50-0.81), and psychiatric emergency room visits (IRR = 0.58, 95% CI, 0.45-0.75) compared to patients who remained on OAPs. Use of LAIs in the late stage of treatment did not decrease the risk of relapse or mortality.Conclusions: Switching to LAIs during the first 3 years of treatment improved antipsychotic adherence, decreased relapses, and reduced long-term mortality. Our results provide evidence to support the benefits of early LAI treatment in schizophrenia.