Antipsychotics In Treatment Of Schizophrenia Research Articles

Short-term antipsychotic treatment reduces functional connectivity of the striatum in first-episode drug-naïve early-onset schizophrenia

BackgroundThe striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients. MethodsWe recruited 49 first-episode drug-naïve EOS patients to have resting-state functional magnetic resonance imaging scans at baseline and after 8 weeks of treatment with antipsychotics, along with baseline scanning of 34 healthy controls (HCs) for comparison purposes. We examined the FC values between each seed in striatal subregion and the rest of the brain. The Positive and Negative Syndrome Scale (PANSS) was applied to measure psychiatric symptoms in patients. ResultsCompared with HCs at baseline, EOS patients exhibited weaker FC of striatal subregions with several brain regions of the salience network and default mode network. Meanwhile, FC between the dorsal caudal putamen (DCP) and left supplementary motor area, as well as between the DCP and right postcentral gyrus, was negatively correlated with PANSS negative scores. Furthermore, after 8 weeks of treatment, EOS patients showed decreased FC between subregions of the putamen and the triangular part of inferior frontal gyrus, middle frontal gyrus, supramarginal gyrus and inferior parietal lobule. ConclusionsDecreased striatal FC is evident, even in the early stages of schizophrenia, and enhance our understanding of the neurodevelopmental abnormalities in schizophrenia. The findings also demonstrate that reduced striatal FC occurs after antipsychotic therapy, indicating that antipsychotic effects need to be accounted for when considering striatal FC abnormalities in schizophrenia.

Rho kinase inhibitors ameliorate cognitive impairment in a male mouse model of methamphetamine-induced schizophrenia

Schizophrenia (SCZ) is a severe psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive deficits. Current antipsychotic treatment in SCZ improves positive symptoms but has major side effects and little impact on negative symptoms and cognitive impairment. The pathoetiology of SCZ remains unclear, but is known to involve small GTPase signaling. Rho kinase, an effector of small GTPase Rho, is highly expressed in the brain and plays a major role in neurite elongation and neuronal architecture. This study used a touchscreen-based visual discrimination (VD) task to investigate the effects of Rho kinase inhibitors on cognitive impairment in a methamphetamine (METH)–treated male mouse model of SCZ. Systemic injection of the Rho kinase inhibitor fasudil dose-dependently ameliorated METH-induced VD impairment. Fasudil also significantly suppressed the increase in the number of c-Fos–positive cells in the infralimbic medial prefrontal cortex (infralimbic mPFC) and dorsomedial striatum (DMS) following METH treatment. Bilateral microinjections of Y-27632, another Rho kinase inhibitor, into the infralimbic mPFC or DMS significantly ameliorated METH-induced VD impairment. Two proteins downstream of Rho kinase, myosin phosphatase-targeting subunit 1 (MYPT1; Thr696) and myosin light chain kinase 2 (MLC2; Thr18/Ser19), exhibited increased phosphorylation in the infralimbic mPFC and DMS, respectively, after METH treatment, and fasudil inhibited these increases. Oral administration of haloperidol and fasudil ameliorated METH-induced VD impairment, while clozapine had little effect. Oral administration of haloperidol and clozapine suppressed METH-induced hyperactivity, but fasudil had no effect. These results suggest that METH activates Rho kinase in the infralimbic mPFC and DMS, which leads to cognitive impairment in male mice. Rho kinase inhibitors ameliorate METH-induced cognitive impairment, perhaps via the cortico-striatal circuit.

Early Non-Response to Antipsychotic Treatment in Schizophrenia: A Systematic Review and Meta-Analysis of Evidence-Based Management Options.

Early non-response is a well-established prognostic marker but evidence-based and consistent recommendations to manage it are limited. The aim of this systematic review and meta-analysis was to generate evidence-based strategies for the management of schizophrenia patients with early non-response to 2 weeks of antipsychotic treatment. We conducted a systematic review and meta-analysis of randomized trials comparing antipsychotic dose escalation, switch, augmentation and continuation in individuals with study-defined early antipsychotic treatment non-response. Eligibility criteria were (1) clinical trials of primary psychosis treating for at least 2 weeks with antipsychotic monotherapy with study-defined operationalized criteria for early non-response; and (2) randomization to at least two of the following treatment strategies: dose escalation, switch, augmentation, or treatment continuation. Information sources were Pubmed, PsycINFO, and EMBASE, and risk of bias was assessed using Jadad scores. Results were synthesized using random-effects meta-analysis, comparing each intervention with treatment continuation for total symptom change as the primary outcome, generating standardized mean differences (SMDs) and 95% confidence intervals (CIs). Studies meeting the selection criteria but providing insufficient data for a meta-analysis were presented separately. We screened 454 records by 1 August 2022, of which 12 individual datasets met the inclusion criteria, representing 947 research participants. Of those studies, five provided data to include in the meta-analysis (four with early non-response at 2 weeks, one at 3 weeks). Early non-response was defined within a timeline of 2 weeks in eight datasets, with the remaining datasets ranging between 3 and 4 weeks. The rates of early non-response ranged between 72.0 and 24.1%, and the endpoint ranged within 4-24 weeks post randomization. Quality was good (i.e., Jadad score of ≥3) in 8 of the 12 datasets. Overall, three studies compared antipsychotic switch versus continuation and two compared antipsychotic switch versus augmentation, in both cases without significant pooled between-group differences for total symptom severity (n=149, SMD 0.18, 95% CI -0.14 to 0.5). Individually, two relatively large studies for antipsychotic switch versus continuation found small advantages for switching antipsychotics for total symptom severity (n=149, SMD -0.49, 95% CI -1.05 to -0.06). One relatively large study found an advantage for dose escalation, although this finding has not been replicated and was not included in the meta-analysis. None of the alternatives included antipsychotic switch to clozapine. Despite robust accuracy of early antipsychotic non-response predicting ultimate response, the evidence for treatment strategies that should be used for early non-response after 2-3 weeks is limited. While meta-analytic findings were non-significant, some individual studies suggest advantages of antipsychotic switch or dose escalation. Therefore, any conclusions should be interpreted carefully, given the insufficient high-quality evidence.

MSR93 A Systematic Review of Current Evidence and Gaps on the Impact of Oral Antipsychotic Treatments in Schizophrenia

Schizophrenia, a complex disease with no current cure, affects about 1% of the US population. The burden of schizophrenia is significantly impacted due to heterogeneity observed across medications’ adherence, efficacy, safety, economic, and effectiveness outcomes. The study goal is to provide an in-depth review of studies that describe the clinical, economic, and humanistic outcomes associated with oral medications in schizophrenia.

Unmet needs with antipsychotic treatment in schizophrenia and bipolar I disorder: patient perspectives from qualitative focus groups

BackgroundSchizophrenia (SZ) and bipolar I disorder (BD-I) are chronic mental health disorders often treated with antipsychotic medications. This qualitative study sought to better understand disease burden and treatment experiences with oral antipsychotic medications in participants living with SZ or BD-I.MethodsSix 90-min focus groups were conducted with participants diagnosed with SZ or BD-I. Trained moderators facilitated discussions using a semistructured guide. Participants described symptoms, impacts of disease, and experiences with oral antipsychotic medications, whether favourable or unfavourable.ResultsAmong participants with SZ (n = 15; 3 groups, 5 per group), 53% were male and 33% were white, with a mean of 18.6 years since diagnosis. Of participants with BD-I (n = 24; 3 groups, 8 per group), 33% were male and 42% were white, with a mean of 13.0 years since diagnosis. Participants described numerous symptoms of their illnesses that impacted relationships and daily life, including effects on emotional health, the ability to work, and encounters with law enforcement. Previous antipsychotic medications were deemed effective by 14/15 (93%) participants with SZ and 12/16 (75%) participants with BD-I. Most participants with SZ (13/15; 87%) or with BD-I (16/24; 67%) reported discontinuing their antipsychotic medication at some point. Side effects were a common reason for discontinuing or switching medications for participants with SZ (8/15; 53%) and for those with BD-I (11/24; 46%). The most common side effects reported in both cohorts were weight gain, drowsiness, sexual problems, and neurologic symptoms. Side effects negatively affected quality of life, leading to serious health problems and issues with self-esteem.ConclusionsPeople living with SZ or BD-I cited a range of favourable and unfavourable experiences with oral antipsychotic medications. Most participants reported that their antipsychotics were effective at controlling their symptoms, but multiple side effects impacted their quality of life, caused additional serious health problems, and often led to discontinuation of or switching antipsychotics. Findings from this study contribute to a better understanding of patients’ experiences with antipsychotics and highlight a need for new medications with favourable benefit/risk profiles.

New Atypical Antipsychotics in the Treatment of Schizophrenia and Depression.

Schizophrenia and depression are heterogeneous disorders. The complex pathomechanism of the diseases imply that medication responses vary across patients. Many psychotropic drugs are available but achieving optimal therapeutic effect can be challenging. The evidence correlates well with clinical observations, suggesting that new atypical antipsychotic drugs are effective against negative and cognitive symptoms of schizophrenia, as well as against affective symptoms observed in depression. The purpose of this review presents the background and evidence for the use of the new second/third-generation antipsychotics (aripiprazole, cariprazine, lurasidone, asenapine, brexpiprazole, lumateperone, pimavanserin) in treatment of schizophrenia and depression. We have first provided a brief overview of the major neurobiological underpinnings of schizophrenia and depression. We then shortly discuss efficacy, safety and limitations of ongoing pharmacotherapy used in depression and schizophrenia. Mainly, we have focused this review on the therapeutic potential of new atypical antipsychotic drugs—currently existing—to be effective in psychotic, as well as in affective disorders.

Late-Onset Dyskinesia Occurring During Antipsychotic Treatment for Schizophrenia: Management of Tardive Dyskinesia Based on the Latest Knowledge

Tardive dyskinesia is a drug-induced involuntary movement related to long-term use of dopamine receptor-blocking agents. If there is no improvement upon discontinuation or change in the causative drug, treatment needs to be initiated. The most effective drug is the vesicular monoamine transporter 2 selective inhibitor. Other drugs, such as clonazepam, amantadine, yokukansan, and Ginkgo biloba extract, may be effective in some patients. Botulinum toxin treatment and deep brain stimulation are potential treatment options for patients with tardive dyskinesia that is refractory to the aforementioned agents. Optimal treatment should be selected while monitoring for mental illnesses.

Late-Onset Dyskinesia Occurring During Antipsychotic Treatment for Schizophrenia: Treatments for Tardive Dyskinesia

Tardive dyskinesia is recognized as buccolingual dyskinesia, but also includes various involuntary movements, such as chorea, dystonia, myoclonus, and tremor. Tardive dyskinesia can be treated depending on the type of movement disorder present. Antipsychotics causing tardive dyskinesia should be reduced in dosage or should be discontinued. However, the treatment of schizophrenia is important, and neurologists must treat tardive dyskinesia in collaboration with psychiatrists taking care of patients with tardive dystonia. Various treatments, such as VMAT-2 inhibitors or tetrabenazine, reserpine, dopamine receptor antagonists, botulinum toxin therapy, anticholinergic agents, or deep brain stimulation, are trialed, depending on the type of movement disorder and the degree of severity of the disorder.

The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment.

BackgroundFor decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 (DISC1) is a gene implicated in the etiology of schizophrenia, and we have found elevated levels of the D2R-DISC1 complex in the postmortem brain tissue of patients with schizophrenia.MethodsWe used coimmunoprecipitation to measure D2R-DISC1 complex levels in peripheral blood samples from patients with schizophrenia and unaffected controls in 3 cohorts (including males and females) from different hospitals. We also used label-free mass spectrometry to conduct proteomic analysis of these samples.ResultsLevels of the D2R-DISC1 complex were elevated in the peripheral blood samples of patients with schizophrenia from 3 independent cohorts, and were normalized with antipsychotic treatment. Proteomic analysis of the blood samples from patients with high D2R-DISC1 complex levels that were normalized with antipsychotic treatment revealed a number of altered proteins and pathways associated with D2R, DISC1 and the D2R-DISC1 complex. We identified additional proteins and pathways that were associated with antipsychotic treatment in schizophrenia, and that may also be novel targets for schizophrenia treatment.LimitationsSample sizes were relatively small, but were sufficient to detect associations between D2R-DISC1 levels, schizophrenia and treatment response. The relevance of leukocyte changes to the symptoms of schizophrenia is unknown. The coimmunoprecipitation lanes included several nonspecific bands.ConclusionLevels of the D2R-DISC1 complex were elevated in patients with schizophrenia and reduced with antipsychotic treatment. This finding reinforces the independent role of each protein in schizophrenia. Our results enhanced our understanding of the molecular pathways involved in schizophrenia and in antipsychotic medications, and identified novel potential molecular targets for treating schizophrenia.

Uric Acid Potential Role in Systemic Inflammation and Negative Symptoms After Acute Antipsychotic Treatment in Schizophrenia.

Uric acid (UA) has been shown to have neuroprotective or neurotoxic properties, in relation to specific tissues and diseases that have been studied. Previous studies provided contradictory results on the role of UA in schizophrenia as a neurodegenerative disorder. The aim of this brief report was an additional analysis of UA sera levels in different phases of schizophrenia. Here, 86 patients with first-episode psychosis (FEP) vs. 45 patients with schizophrenia in relapse (SC in relapse) vs. 35 healthy control subjects (HC) were studied before and 1 month after antipsychotic therapy. Further, we aimed to explore the possible correlation of UA with scores presenting clinical features and with serum concentrations of the proinflammatory cytokines interleukin (IL)-6 and IL-17. When comparing the data between all three groups, we did not find significant differences in UA levels, either before or after the applied therapy. Also, comparing sera concentrations of UA in every single group, the analysis did not reveal statistically significant differences between FEP patients, but statistically, a significant difference was found in SC in relapse before and after treatment (334.71 ± 116.84 vs. 289.37 ± 109.15 μmol/L, p = 0.05). Uric acid serum levels correlated with negative sub-score (p = 0.001, r = 0.306), general sub-score (p = 0.015, r = 0.236), and total PANSS score (p = 0.009, r = 0.3) after 1 month of therapy. We have established a statistically significant positive correlation between serum concentrations of UA and IL-6 in exacerbation (p = 0.01, r = 0.220) and with IL-17 after treatment and in the stabilization of psychosis (p = 0.01, r = 0.34), suggesting potential cascades in different phases of schizophrenia that potentiate inflammation.

Trauma and resistance to antipsychotic treatment in schizophrenia: A narrative review

This review explored whether trauma exposure is associated with poorer response to antipsychotic treatment in schizophrenia patients. A systematic search identified eight studies, of which five reported an association between trauma and non-remission of psychotic symptoms (n = 4) or treatment-resistant schizophrenia (TRS, n = 1). Although evidence supporting the link between trauma and resistance to antipsychotic treatment is scarce, trauma history should be systematically investigated in all persons with TRS, as there is a growing body of evidence showing that schizophrenia patients benefit from therapies for post-traumatic symptoms.

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.

Complete blood count inflammatory markers in treatment-resistant schizophrenia: Evidence of association between treatment responsiveness and levels of inflammation

Accumulating evidence suggests that the variable response to antipsychotic treatment in schizophrenia reflects distinct biological subtypes. The pathophysiology of schizophrenia is associated with alteration in the immune system which can be measured with complete blood count (CBC) markers of systemic inflammation, including the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). While previous research suggested a decrease in CBC inflammatory markers following treatment, it is unknown if treatment or response to treatment is associated with CBC markers in treatment-resistant schizophrenia. Here, we retrospectively analyzed the CBC at admission and discharge in schizophrenia inpatients classified as treatment-responsive, treatment-resistant, and ultra-treatment-resistant. Despite similar NLR at admission, the subtypes manifested different changes in NLR during treatment resulting in significant differences at discharge. Only the treatment-responsive group presented a significant decrease in inflammatory markers after treatment. Additionally, we found that the responsive group had a higher PLR at admission and was the only subgroup to demonstrate a significant reduction following treatment. In sum, our results support the idea that persistent inflammation is a biological trait marker of treatment resistance in schizophrenia.

Long-Acting Injectable Antipsychotic Treatment in Schizophrenia and Co-occurring Substance Use Disorders: A Systematic Review

Objectives: Co-occurring substance use disorders (SUDs) among individuals with schizophrenia are a prevalent and complex psychiatric comorbidity, which is associated with increased symptom severity, worsened illness trajectory and high rates of treatment non-adherence. Recent evidence suggests that the use of long-acting injectable (LAI) antipsychotics may provide an effective treatment option for individuals with this dual-diagnosis.Methods: A systematic review of the literature was conducted using the databases PubMed, PsychInfo and Google Scholar for English-language studies, investigating the use of LAIs in co-occurring schizophrenia and substance use disorders (SCZ-SUDs).Results: Eight reports [one case study (n = 1), one case series (n = 8), three open-label retrospective studies (n = 75), and three randomized controlled trials (n = 273)] investigated the use of LAI antipsychotics in 357 participants with SCZ-SUDs [alcohol use disorder: 5 studies, n = 282; cocaine use disorder: 5 studies, n = 85; amphetamine use disorder: 1 study, n = 1; cannabis use disorder: 3 studies, n = 160; opioid use disorder: 3 studies, n = 19; methylenedioxymethamphetamine (MDMA) use disorder: 2 studies, n = 9; ketamine use disorder: 1 study, n = 4] and were included in this systematic review. Findings indicate significant improvements in substance use related outcomes across 7 of 8 studies, while in 6 of 8 studies, significant improvements in psychopathology-related outcomes were reported.Conclusions: LAI antipsychotics may be an efficacious intervention option for the treatment of SCZ-SUDs. However, varying methodological rigor, generally small sample sizes and heterogeneity of samples, settings, substances of abuse, tested LAIs and comparators, as well as psychosocial cotreatments and level of reported detail across studies requires that these findings be considered preliminary and interpreted with caution. Further research is required to better understand the effects of LAIs among individuals with SCZ-SUDs.

Association of 5-HTR2A T102C and A-1438G polymorphisms with clinical response to atypical antipsychotic treatment in schizophrenia: A meta-analysis

Associations of serotonin 2A receptor (5-HTR2A) gene polymorphisms with clinical response to atypical antipsychotics (AAPs) treatment in schizophrenia (SCZ) were inconsistent. Thus we conducted a meta-analysis to investigate more reliable estimates. The Cochrane Library, Embase, PubMed, Weipu, CNKI and Wanfang databases were searched for eligible studies published up to September 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in four genetic models. Subgroup analyses were performed by ethnicity and antipsychotic type. Meta-regression was used to evaluate the potential effects of confounding variables. In total, 19 studies were included for the meta-analysis, of which 17 studies containing 2359 patients were identified for T102C polymorphism and 7 studies containing 1408 patients for A-1438G polymorphism. The results showed that A-1438G polymorphism was significantly associated with clinical response to AAPs treatment in SCZ in four genetic models (allele model, A vs. G, OR = 1.87, 95% CI = 1.05–3.33, P = 0.034; recessive model, AA vs. GA + GG: OR = 1.79, 95% CI = 1.17–2.72, P = 0.007; dominant model, AA + GA vs. GG: OR = 3.40, 95% CI = 1.15–10.10, P = 0.027; co-dominant model, AA vs. GG: OR = 3.44, 95% CI = 1.07–11.10, P = 0.039) in Asians, but not in Caucasians. When stratified by antipsychotic type, A-1438G polymorphism was related to the efficacy of olanzapine in recessive model (AA vs. GA + GG, OR = 1.85, 95% CI = 1.18–2.90, P = 0.007), but not in other models. However, neither four genetic models nor subgroup analyses of T102C polymorphism were found any significant associations with AAPs response (P > 0.05). Meta-regression revealed that no association was confounded by mean age, male ratio, treatment duration and illness duration (P > 0.05). The present meta-analysis indicated that 5-HTR2A A-1438G polymorphism, but not T102C polymorphism, was significantly associated with AAPs response in SCZ, especially in Asians and olanzapine-treated patients.

Antipsychotic treatment effects and structural MRI brain changes in schizophrenia.

Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

The use of antipsychotics in targeted therapy of schizophrenia — prospects and challenges (for example, amisulpride).

Personalized medicine is an innovative approach that takes into account the biological, social and psychological characteristics of people in the development of preventive drugs and treatment of diseases. The goals of personalized medicine in psychiatry are to anticipate a person’s susceptibility to disease, achieve accurate diagnosis, and facilitate a favorable response to treatment. This article analyzes the information presented in the literature on use of antipsychotics in treatment of schizophrenia from the standpoint of personalized medicine with the aim to draw up recommendations for improving the effectiveness of psychotic symptoms therapy and set the vector for further scientific research in this direction. Despite the existence of many international and local guidelines and protocols for antipsychotic therapy, there is still the problem of early determination of which antipsychotic will be effective and safe for a particular patient — before the most effective drug is determined, patients are usually treated with various antipsychotics. In the treatment of schizophrenia, no antipsychotic drug or dosage is universal. Therefore, to maximize the useful effect and minimize the risk of side effects, numerous individual characteristics of each individual user must be considered. In particular, such characteristics as sex, age, clinical features (dominant symptoms, time of onset of symptoms and their intensity), comorbid mental and somatic disorders, presence/absence of bad habits, response to previous therapy (in case of such) should be taken into account. Given the possibility of flexible dosage of amisulpride and its significant effectiveness in reducing various groups of symptoms in various categories of patients, it has the potential for widespread use in personalized psychiatry. Key words personalized medicine, atypical antipsychotics, effectiveness of therapy

Long-term Continuity of Antipsychotic Treatment for Schizophrenia: A Nationwide Study.

Schizophrenia often requires long-term treatment with antipsychotic medication. This study aims to measure the continuity of antipsychotic treatment over the course of illness in schizophrenia, as well as factors involved in the interruption of treatment. For this, we followed up a national cohort of first-episode psychosis patients in Finland for up to 18 years. Stratified Cox proportional hazards regressions were conducted for "within-participant" risk of discontinuation of subsequent treatments compared to the first, and by specific antipsychotic compared to oral olanzapine, the most prescribed antipsychotic in this cohort. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated. Among 3343 participants followed up for a mean of 8 years (SD = 4.93), the median number of continuous treatment episodes was 6 (interquartile range [IQR] = 3-11) with a median duration of 11.4 months (IQR = 5.3-25.6). In the first year after diagnosis, the incidence rate of treatment discontinuation was 30.12 (95% CI = 29.89-30.35) events per 100 participant-years, decreasing to 8.90 (95% CI = 8.75-9.05) in the 10th year. The risk of discontinuation progressively decreased over successive treatment episodes (aHR = 0.30; 95% CI = 0.20-0.46 for episodes after the 15th compared to the first). Individuals were 67% less likely to interrupt treatment with long-acting injectable than oral antipsychotics (aHR = 0.33; 95% CI = 0.27-0.41). Treatment for schizophrenia over the long term is often characterized by recurrent cycles of interruptions and reintroductions of antipsychotic medication, which is typically not recommended by management guidelines. Greater utilization of long-acting injectable formulations earlier in the course of illness may facilitate the continuity of antipsychotic treatment in schizophrenia.

Pharmacotherapy management of schizophrenia for family physicians.

Canadian family physicians likely encounter 1 or 2 new patients per year with signs or symptoms of schizophrenia.[1][1] Although antipsychotic treatment of schizophrenia is generally the responsibility of a psychiatrist, family physicians play an important role in the long-term management of

Long-Term Continuity of Antipsychotic Treatment for Schizophrenia: A Nationwide Study

Background: Schizophrenia often requires long-term treatment with antipsychotic medication. This study aims to measure the continuity of antipsychotic treatment over the course of illness in schizophrenia, as well as factors involved in the interruption of treatment. Methods: Cohort study of individuals in Finland recently diagnosed with schizophrenia, and followed up between 2000 and 2018. Stratified Cox proportional hazards regressions were conducted for “within-participant” risk of discontinuation of subsequent treatments compared to the first, and by specific antipsychotic compared to oral olanzapine, the most commonly prescribed antipsychotic. Adjusted Hazards Ratios (aHR), 95% Confidence Intervals (95%CI) were calculated. Outcomes: Among 3,343 participants followed up for a mean of 8 years (Standard Deviation (SD)=4·93), the median number of continuous treatment episodes was 6 (Inter Quartile Range [IQR]=3-11) with a median duration of 11·4 months (IQR=5·3-25·6). In the first year after diagnosis, the incidence rate of treatment discontinuation was 30·12 (95%CI=29·89-30·35) events per 100 participant-years, decreasing to 8·90 (95%CI=8·75-9·05) in the tenth year. The risk of discontinuation progressively decreased over successive treatment episodes (aHR= 0·30; 95% CI=0·20-0·46 for episodes after the 15th compared to the 1st). Individuals were 67% less likely to interrupt treatment with long-acting injectable than oral antipsychotics (aHR=0·33; 95% CI=0·27-0·41). Interpretation: Treatment for schizophrenia over the long-term is often characterized by recurrent cycles of interruptions and reintroductions of antipsychotic medication, which is typically not recommended by management guidelines. Interventions in the early phase of illness and greater utilization of long-acting injectable formulations may facilitate the continuity of antipsychotic treatment in schizophrenia. Funding Statement: This study was funded with departmental support of the Zucker Hillside Hospital (Glen Oaks, NY), the Department of Clinical Neuroscience, Karolinska Institutet (Stockholm, Sweden), and the Academy of Finland (Grants: 315969, 320107, for HT). Declaration of Interests: Dr Rubio has been a consultant or has received speaker/consulting honoraria from: Lundbeck, Teva, Medscape. He has also received royalties from UpToDate, and grant support from Alkermes. Dr Taipale reports personal fees from Janssen-Cilag. Dr. Correll has been a consultant and/or advisor to or has received honoraria from: Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, IntraCellular Therapies, Janssen/JJ is a member of advisory board for Lundbeck, and has received grants from the Stanley Foundation and Sigrid Juselius Foundation. Dr. Tiihonen, Dr. Tanskanen and Dr. Taipale have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their employing institution. Ethics Approval Statement: Permissions were granted by pertinent institutional authorities at the Finnish National Institute for Health and Welfare (permission THL/847/5.05.00/2015), the Social Insurance Institution of Finland (65/522/2015), and Statistics Finland (TK53-1042-15).