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Background Although remission is a priority target in psychosis, reported rates show a marked variation across studies and instability over time. Such variability, partly due to methodology, emphasizes the need to define the optimal assessment procedure, as well as to identify reliable predictors. This study aims to: 1. longitudinally compare remission status according to different criteria; 2. identify predictors of duration and stability. Methods 112 patients with schizophrenia or schizoaffective disorder underwent comprehensive clinical evaluations, with 24-month follow-up. Remission was assessed using three criteria: Remission in Schizophrenia Working Group (RSWG) vs Positive and Negative Syndrome Scale (PANSS) positive and negative scales (PANSS-PN) vs total score (PANSS-T). Kaplan-Meier survival analysis was used for longitudinal comparison, regression models to identify predictors of duration and stability. Results At enrolment 50% of patients were in remission according to RSWG, while only 23.2% reached the other criteria. PANSS-T cumulative remission rates showed the greatest stability. Stable remission according to RSWG criteria was predicted by negative symptoms, while no significant predictors emerged for PANSS-T. Remission duration was predicted by negative, positive and cognitive symptoms and treatment dosage for RSWG criteria, while for PANSS-T the predictors were cognitive symptoms and duration of illness. Conclusion Results are in line with previous literature on remission rates and further support the role of basal clinical predictors. In addition, this study shows that more stringent criteria are more stable over time, suggesting their predictive value and the relevance of their use to optimize evaluations also in clinical settings.

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

Background To summarize the current state of knowledge on antipsychotic treatment strategies for the acute phase and treatment resistance in schizophrenia, we conducted a systematic review of guidelines and algorithms. Methods We conducted a systematic literature search to identify clinical guidelines and algorithms on this topic using MEDLINE and Embase. We extracted information on recommendations for antipsychotic treatment strategies, including those for non-response (i.e., increasing antipsychotic dose and switching to another antipsychotic) and treatment resistance. Results We identified a total of 17 guidelines/algorithms in various countries that were published after 2011. With respect to antipsychotic dose, most of the guidelines (N = 10/11) agreed starting with a low dose or the lowest licensed/effective dose and then titrating the dose upwards. Regarding antipsychotic treatment strategies for non-response, all of the guidelines (N = 9/9) recommended increasing antipsychotic dose towards the upper end of its approved dose range. Five guidelines suggested for increasing beyond the therapeutic dose range in exceptional cases, while overall 10 guidelines including them were negative about such strategy. The vast majority of guidelines (N = 16/17) recommended switching to another antipsychotic for non-response; however, some guidelines mentioned the lack of evidence for these strategies other than the use of clozapine. All the guidelines (N = 17/17) endorsed initiating clozapine after failure to respond to 2 different antipsychotics. Four guidelines endorsed an early use of clozapine, yet as the third antipsychotic. Conclusion The currently available guidelines and algorithms recommended increasing antipsychotic dose and switching to another antipsychotic, particularly clozapine for treatment-resistant schizophrenia, during the acute phase of schizophrenia for non-response.

Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system.This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group.In multivariable analysis, clozapine (hazard ratio=0.43), aripiprazole long-acting injectable (LAI) (hazard ratio=0.71), paliperidone LAI (hazard ratio=0.76), antipsychotic polypharmacy (hazard ratio=0.77), and risperidone LAI (hazard ratio=0.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13), and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine.In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.

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.

Previous studies report that the inhibition of one’s own perspective in favour of acknowledging somebody else’s perspective relates to the neurotypical development of Theory of Mind (ToM) processes. ToM processing seems to be negatively affected in patients diagnosed with schizophrenia (PwS). Different tasks, using different populations, have been used to examine ToM (e.g. Hinting, facial emotion recognition, on-line perspective-taking), making generalizations problematic. We investigated ToM processing, using different paradigms, in one patient group on long-term second-generation antipsychotic treatment for schizophrenia and in neurotypical controls. Methods: Twenty-five patients on treatment with second-generation anti-psychotic medication for schizophrenia for more than ten years and neurotypical controls took part in a Hinting task, a facial emotion recognition task, and an on-line visual computational perspective-taking task. A battery of neuropsychological tests provided the input of a Principal Component Analysis (PCA). Results: Patients performed significantly less effectively than controls on the Hinting Task, and even patients in remittance struggled more with the task. No significant differences in facial emotion recognition between groups were found. The on-line perspective-taking task results revealed that controls, but not patients, presented an intrusion of the other perspective when judging their own perspective (altercentric behaviour). Reaction time results revealed that patients were significantly slower than controls when evaluating the “Other” perspective. The results of the perspective-taking task were examined further by relating them to components from the PCA. Errors in perspective-taking appeared correlated mostly to difficulties in mentalizing and cognitive control (neurotypical participants) and to hinting comprehension skills (patients). Conclusions: Results suggest that mentalizing and cognitive control are relevant functions for perspective-taking and that even after long-term treatment with second-generation antipsychotics, patients still have more difficulties in judging the Other perspective. The facial emotion recognition task suggested that facial emotion recognition is a separate interpretation skill not directly related to ToM

Background: Cognitive deficits are core features of Schizophrenia, showing poor response to antipsychotic treatment, therefore non-pharmacological rehabilitative approaches to such a symptom domain need to be identified. However, since not all patients with Schizophrenia exhibit the same cognitive impairment profile, individualized rehabilitative approaches should be set up. Objectives: We explored the last five-year literature addressing the issue of cognitive dysfunction response to rehabilitative methodologies in Schizophrenia to identify possible predictors of response and individualized strategies to treat such a dysfunction. Conclusion: A total of 76 studies were reviewed. Possible predictors of cognitive rehabilitation outcome were identified among patient-specific and approach-specific variables and a general overview of rehabilitative strategies used in the last five years has been depicted. Studies suggest the existence of multifaced and multi-domain variables that could significantly predict pro-cognitive effects of cognitive rehabilitation, which could also be useful for identifying individual-specific rehabilitation trajectories over time. An individualized rehabilitative approach to cognitive impairment in Schizophrenia is possible if taking into account both patient and approach specific predictors of outcomes.

Background Ethnic variations in pathways to early intervention in psychosis (EIP) have been studied. However, it is important to explore the ethnic variations in response to pharmacological treatment in EIP. Aims To look at ethnic variation in response to antipsychotics. Method Electronic patient records in December 2018 were perused for: Sociodemographic details including ethnicity Prescribed antipsychotic and dosage to which the patient had responded Results White, Black and Asian ethnic groups responded mostly to Olanzapine. The largest proportion of the mixed ethnic group responded to Aripiprazole. The White and Asian groups showed the best responses to Lurasidone at 74 mg. There was a slight response in the mixed and other ethnic groups only at the higher dose of 111 mg. The medication has not been used with any benefit in the Black ethnic group. Conclusion The complex differences highlighted amongst ethnic responses to treatment make a case for multi-centric studies to further explore ethnic differences in early intervention treatments. This will help streamline offered treatments to maximise response in EIP.

Objective: To systematically review the impact of CYP2D6 genetic variation on antipsychotic pharmacokinetics, efficacy, and adverse drug reactions among children and youth. Method: The published li...

Background Impaired sensorimotor gating, commonly measured as disrupted prepulse inhibition (PPI) of the acoustic startle response, has been widely observed in psychotic diseases. However, most PPI studies published so far involve patients with long illness duration and different drug treatments. Few studies have investigated untreated patients at their first episode of psychotic symptoms. Method PPI is an acoustic startle paradigm (30, 60-, 120-ms interstimulus intervals). Startle reactivity and habituation were succesfully assessed in 49 antipsychotic-naive first-episode psychosis (FEP) patients and compared with 35 age- and gender-matched healthy control subjects. Mean age of patients was 28 years and 27 for controls. Patients treated with antipsychotics more than 30 days were not included in the study and twenty-three out of forty-nine patients received antipsychotic treatment with a mean treatment time of 13 days. Results PPI was significantly lower in FEP patients, compared to healthy controls. The PPI deficiency found in these patients was not due to antipsychotic treatment since PPI did not differ between treated (n=23) and untreated patients n=(26). By using the latent curve modeling we identified a delayed habituation in patients treated with antipsychotics, suggesting that antipsychotic treatment should be considered as a confound when investigating habituation in schizophrenia. Conclusions Our results suggest that acute pharmacological treatment does not normalize PPI in FEP patients but should be considered as a confound when investigating habituation in these patients.

Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy., This work was supported by grants from the Stanley Medical Research Institute (SMRI); the Engineering and Physical Sciences Research Council UK (EPSRC); the Dutch Government-funded Virgo consortium (ref. FES0908); the Netherlands Genomics Initiative (ref. 050-060-452); the European Union FP7 funding scheme: Marie Curie Actions Industry Academia Partnerships and Pathways (ref. 286334, PSYCH-AID project); SAF2016-76046-R and SAF2013-46292-R (MINECO) and PI16/00156 (ISCIII and FEDER).

Objective To investigate the gender differences in the efficacy and side effects of three frequently used antipsychotic medicines (risperidone, olanzapine, aripiprazole) for patients with first-episode schizophrenia during the first year of treatment. Methods A total of 569 patients with first-episode schizophrenia were randomly assigned to risperidone, olanzapine, and aripiprazole groups. All patients were treated according to their actual clinical needs. Clinical efficacies were assessed by the Positive and Negative Symptom Scale (PANSS) and side effects were assessed by the Udvalg for Kliniske Undersogelser Side-Effect scale (UKU). All assessments were completed at baseline and at 1, 2, 3, 6, 9, and 12 months. Results Males had higher baseline PANSS total scores and PANSS negative and general pathological scores. No significant interactions were found between treatment time and gender in psychopathology improvements in all three groups. In the end of the first year, female patients receiving risperidone reported more dermatological symptoms (rashes) than males, female patients receiving olanzapine reported more autonomic side effects and dermatological symptoms than males, and female patients receiving aripiprazole reported more psychotic side effects than males. Conclusion Gender differences exhibited in response to antipsychotic treatments for Chinese patients with first-episode schizophrenia. After the first year of antipsychotic treatment, drug-related side effects were more likely presented in female patients than male patients.

Objective: Antipsychotic drugs are widely used for treating patients with first episode of psychosis, targeting threshold psychotic symptoms. The clinical high risk of psychosis is characterized as subthreshold psychotic symptoms and it is unclear whether they can also benefit from antipsychotic drugs treatment. This study attempted to determine whether initiating antipsychotic drugs treatment in the clinical high risk of psychosis phase was superior to initiating antipsychotic drugs treatment in the first episode of psychosis phase, after the 2-year symptomatic and functional outcomes. Method: Drawing on 517 individuals with clinical high risk of psychosis from the ShangHai At Risk for Psychosis program, we identified 105 patients who converted to first episode of psychosis within the following 2 years. Patients who initiated antipsychotic drugs while at clinical high risk of psychosis (CHR_AP; n = 70) were compared with those who initiated antipsychotic drugs during a first episode of psychosis (FEP_AP; n = 35). Summary scores on positive symptoms and the global function scores at baseline and at 2 months, 1 year and 2 years of follow-up were analyzed to evaluate outcomes. Results: The CHR_AP and FEP_AP groups were not different in the severity of positive symptoms and functioning at baseline. However, the CHR_AP group exhibited significantly more serious negative symptoms and total symptoms than the FEP_AP group. Both groups exhibited a significant reduction in positive symptoms and function ( p 2 = 22.270, p Conclusion: For clinical high risk of psychosis, antipsychotic drugs might be not the first choice in terms of long-term remission, which is more reasonable to use at the first episode of psychosis phase.

There is a long-lasting debate regarding the long-term antipsychotic treatment of schizophrenia. The most frequently advocated strategy is continued antipsychotic maintenance treatment (i.e., continuous treatment with a constant dose of antipsychotic medication after symptom remission). Yet, because of the potential side effects of continued antipsychotic medication, other treatment strategies such as targeted intermittent treatment (i.e., stepwise drug discontinuation and early drug intervention in case of prodromal symptoms or early warning signs) have been discussed. In this manuscript, we review recommendations regarding the long-term antipsychotic treatment of schizophrenia from six evidence-based clinical guidelines. In line with the current state of research, all six clinical guidelines recommend continued antipsychotic maintenance treatment. Recommendations regarding other aspects of long-term antipsychotic treatment (e.g., the dosage of antipsychotic medication for long-term treatment, the minimum duration of antipsychotic long-term treatment, and discontinuation strategies) are more vague and heterogeneous. Additionally, we provide clinical case examples to illustrate different course types of patients exposed to targeted intermittent treatment. Finally, we discuss gaps in current clinical guidelines and future research avenues in antipsychotic maintenance treatment.

This review addresses the risks and benefits of long-term maintenance antipsychotic treatment for patients that extends beyond two years. It focuses on framing discussions with patients who are recovering from a first episode. For these patients the evidence strongly supports the benefits over the risk for the first two years. However, both the clinical side effects of antipsychotics and the possible long-term effects of dopamine blocking drugs on the brain require a more nuanced discussion beyond this initial period. In most cases, the decision will be to continue antipsychotics but to consider strategies for mitigating the risks of drugs. This review provides information about the relative risks of dose reduction and intermittent treatment.

Background This survey examined the experiences of people living with schizophrenia who have used oral antipsychotics (APs). Methods Adults with self-reported physician-diagnosed schizophrenia (N=200), who were members of an online research participation panel and reported taking one or more oral APs within the last year, completed a cross-sectional online survey that focused on direct report of their experiences regarding APs (eg, symptoms, side effects, adherence). Descriptive analyses were conducted for the total survey sample and for subgroups defined a priori by experience with specific, prevalent side effects. Results The mean age of the sample was 41.9 (SD=11.0) years, 50% of participants were female, and 32% were nonwhite. Overall ratings were positive for medication effectiveness and convenience but negative for side effects. While most participants reported that APs improved schizophrenia symptoms (92%), 27% reported APs as having done "more harm than good." Almost all participants (98%) reported experiencing side effects of APs, with the most common being anxiety (88%), feeling drowsy/tired (86%), and trouble concentrating (85%). Side effects frequently cited as either "extremely" or "very" bothersome were weight gain (56%), sexual dysfunction (55%), and trouble concentrating (54%). Over 80% reported that side effects had negatively impacted their work and social functioning (eg, social activities or family/romantic relationships). Since initiating treatment, 56% of respondents had stopped taking APs at some point (65% of these due to side effects). Side effects commonly reported as having led to stopping AP treatment were "feeling like a 'zombie'" (22%), feeling drowsy/tired (21%), and weight gain (20%). Conclusion Most participants reported improvements in schizophrenia symptoms associated with the use of APs. However, most participants also reported experiencing numerous bothersome side effects that negatively impacted their work, social functioning, and treatment adherence. Results highlight the unmet need for new APs with favorable benefit-risk profiles.

Objective: By using a self-controlled design, we investigated whether antipsychotic medication exposure was associated with increased pneumonia risk and whether patients receiving clozapine were more likely to develop pneumonia than patients receiving other antipsychotic medications. Methods: Through nationwide health registers, we identified all out-patients with schizophrenia initiating antipsychotic treatment. First, we estimated whether antipsychotic-naïve patients with schizophrenia increased their risk of pneumonia after initiation of either a first- or second-generation antipsychotic medication using a one-year mirror-image model. Afterward, similar analyses were made for individual second-generation antipsychotics. Lastly, the rate of pneumonia for patients initiated on clozapine was compared to patients commenced on other second-generation antipsychotics. Results: In total, 8355 antipsychotic-naïve patients with schizophrenia were initiated on a first-generation antipsychotic medication; 0.95% of the patients had developed pneumonia before exposure, compared to 0.68% after exposure (P = 0.057). Similar findings were made for the 8001 antipsychotic-naïve patients with schizophrenia initiated on second-generation antipsychotic medications, with 0.56% developing pneumonia before exposure compared to 0.55% after exposure (P = 1.00). Second-generation antipsychotic medications did not increase the pneumonia risk, except for risperidone (increased by 0.32%; P = 0.007) and clozapine, which gave the largest absolute increase in pneumonia risk although not significant (increased by 0.64%; P = 0.10). The rate of pneumonia was higher after initiation of clozapine than for other second-generation antipsychotic medications. Conclusion: Most antipsychotic medications were not found to increase the risk of pneumonia. Clozapine exposure might be associated with increased risk of developing pneumonia.

Background We updated our previous systematic review regarding clinical guidelines and algorithms on antipsychotic treatment in the maintenance phase of schizophrenia (doi: 10.1016/j.schres.2011.11.021) to incorporate and synthesize more recent findings to guide clinical practice. Methods We conducted a systematic literature search to identify clinical guidelines and algorithms describing antipsychotic treatment in the maintenance phase of schizophrenia using MEDLINE and Embase. We assessed overall quality of the guidelines/algorithms according to the AGREE II instrument and extracted information on treatment recommendations. Results We identified 20 guidelines/algorithms from various regions, including 11 updated or newly launched ones after the previous systematic review in 2012. All of the guidelines/algorithms satisfied a certain level of quality. Where mentioned, endorsements were sorted into “recommended”, “partially recommended”, or “not recommended”. As for antipsychotic discontinuation strategy, a majority of guidelines/algorithms that mentioned this strategy did not recommend it for multiple-episode schizophrenia (N = 5/6). On the other hand, the guidelines/algorithms tended to shift from “not recommended” to “partially recommended” both for schizophrenia in general (N = 7/13, N = 7/8 for those published after 2013) and first-episode schizophrenia (N = 10/11, N = 7/7 for those published after 2013) regarding this strategy. All guidelines/algorithms (N = 9/9) converged to discourage antipsychotic intermittent/targeted strategy. Similar to antipsychotic discontinuation strategy, all of the updated or new guidelines/algorithms (N = 6/6) endorsed antipsychotic dose reduction/lower dose strategy. Conclusion Recent clinical guidelines and algorithms on antipsychotic maintenance treatment in schizophrenia shifted more toward a possibility of antipsychotic discontinuation and dose reduction/lower dose strategies. Nonetheless, clinicians need to contemplate on the risk-benefit balance of these strategies for individual patients.

Aims: To evaluate the association of relapse and healthcare resource utilization in patients with schizophrenia (SZ), bipolar disorder (BD), or major depressive disorder (MDD) who switched antipsyc...

Two important clinical questions are whether there is a subtype of schizophrenia which responds differently to clozapine relative to other antipsychotics, and whether greater efficacy of clozapine is dependent on the degree of treatment-resistance. The authors address this by examining both variability and magnitude of response in patients treated with clozapine and other antipsychotics for both treatment-resistant schizophrenia (TRS) and non-resistant schizophrenia. Double-blind randomised controlled trials comparing clozapine with other antipsychotics in patients with schizophrenia were identified using five databases. Standard deviations and means of change in total, positive, and negative symptoms were extracted. Variability ratio (VR) and coefficient of variation ratio (CVR) were used to quantify relative variability in symptom change. Hedges’gwas used to quantify mean differences. Ten TRS studies (n = 822) and 29 non-TRS studies (n = 2566) were meta-analysed. Relative variability in change of total symptoms did not differ significantly between clozapine and other antipsychotics in TRS studies (VR = 1.84; 95%CI, 0.85–4.02). These findings were similar with CVR, and for positive and negative symptoms. Clozapine was superior to other antipsychotics in improving total symptoms in both TRS (g = 0.34; 95%CI, 0.13–0.56) and non-TRS (g = 0.20; 95%CI, 0.08–0.32) studies. Furthermore, clozapine was superior in improving positive symptoms in both study groups, but not for negative symptoms. Pooled effect sizes showed no significant difference between TRS and non-TRS studies. These findings do not support a subtype of schizophrenia which responds specifically to clozapine. Clozapine is more effective than other antipsychotics irrespective of treatment-resistance, arguing for its use more generally in schizophrenia. PROSPERO CRD42018086507

Background: The study aimed to examine the antipsychotic treatment effect on the serum S100B and oxidative stress in patients with schizophrenia. Methods: Subjects consisted of patients with schizophrenia of first-episode drug-naive and drug-free acute phases, and met the DSM-IV diagnostic criteria for schizophrenia. All patients were treated with risperidone for eight weeks. Positive and Negative Syndrome Scale (PANSS) was evaluated, and serum levels of S100B and parameters of oxidative stress including total oxidative status (TOS) and malondialdehyde (MDA) were measured before and after antipsychotic treatment. A general linear random-effect model was used for data analysis. Results: Antipsychotic treatment with risperidone reduced the levels of S100B significantly in the first episode drug-naive patients with schizophrenia (Beta=24.89; p=0.0087) and marginally in the drug-free acute phase (Beta=15.65; p=0.093), no significant difference in the effect on S100B between patient groups (p=0.4785). In contrast, antipsychotic treatment increased the levels of MDA in drug-free acute phase schizophrenia (Beta=-6.55; p

IntroductionAripiprazole is hypothesized to have an effect on negative and cognitive symptoms in schizophrenia. Likewise, amisulpride is one of the only second-generation antipsychotics with which an effect on negative symptoms is reported. In the present study, we compare the effect of aripiprazole and amisulpride in initially antipsychotic-naïve patients with first-episode psychoses.MethodsPsychopathology and cognitive measures from two consecutive cohorts of antipsychotic-naïve first episode psychotic patients were obtained before and after 6 weeks of antipsychotic monotherapy with either aripiprazole or amisulpride. Matched healthy controls were included to account for retest effects on the cognitive measures. Analyses of variance (repeated-measures ANOVA) were performed to detect effect of time and possible cohort*time interactions.ResultsLongitudinal data was obtained from 47 and 48 patients treated for 6 weeks with amisulpride or aripiprazole, respectively. For the Wallwork negative symptom dimension, there was a cohort*time interaction [F(1, 93) = 4.29, p = 0.041] and a significant effect of time [F(1, 93) = 6.03, p = 0.016], which was driven by an improvement in patients treated with aripiprazole [t(47) = 4.1, p < 0.001] and not observed in patients treated with amisulpride (p > 0.5). For the eight cognitive measures, no cohort*time interaction was found and neither was cognitive improvement in any of the cohorts when accounting for retest effect.ConclusionPatients treated with aripiprazole improved on negative symptoms, which was not the case for patients treated with amisulpride. This may point to a general effect of a partial D2 receptor agonist on negative symptoms in patients with first-episode psychoses. There was, however, no improvement in cognitive functions.

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

Aim: The aim of this study was to identify the long noncoding RNAs (lncRNAs) associated with schizophrenia (SZ) and the relationships among their expression, antipsychotic efficacy and SZ severity. Method: The diagnostic and predictive value of nine lncRNAs, Gomafu, DISC2, PSZA11, AK096174, AK123097, DB340248, uc011dma.1, ENST00000509804-1 and ENST00000509804-2, was investigated in 48 patients with SZ before and after antipsychotic treatment. Results: Gomafu, AK096174, AK123097, DB340248, uc011dma.1, ENST00000509804-1 and ENST00000509804-2 were individually and collectively associated with, and predictive of, SZ pathogenesis. Moreover, increased expression of plasma AK123097, uc011dma.1 and ENST00000509804-1 levels was reversed after 12 weeks of antipsychotic treatment, which was associated with SZ severity. Conclusion: Seven lncRNAs serve as novel biomarkers for SZ diagnosis and prognosis and three lncRNAs are potential therapeutic targets.

Key Points Question Does prenatal exposure to antipsychotics increase the risk of preterm birth, small for gestational age, attention-deficit/hyperactivity disorder (ADHD), or autism spectrum disorder (ASD)? Findings In this cohort study of 411 251 mother-child pairs, there was not an increased risk of ADHD, ASD, preterm birth, and small for gestational age with prenatal use of antipsychotics. Maternal psychiatric disorders were associated with a significantly increased risk of ADHD and ASD, but not with preterm birth or small for gestational age in neonates. Meaning The findings of this study suggest that there is no association between prenatal exposure to antipsychotics and ADHD, ASD, preterm birth, and small for gestational age; however, underlying maternal psychiatric disorders may be associated with the risk of ADHD and ASD in children., Importance The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear. Objective To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems. Design, Setting, and Participants This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication. Exposures Prenatal antipsychotic exposure. Main Outcomes and Measures Preterm birth (, This cohort study examines the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems.

D-amino acids (DAAs) are indispensable in regulating diverse metabolic pathways. Selective and sensitive detection of DAAs is crucial for understanding the complexity of metabolic processes and managing associated diseases. However, current DAA detection strategies mainly rely on bulky instrumentation or electrochemical probes, limiting their cellular and animal applications. Here we report an enzyme-coupled nanoprobe that can detect enantiospecific DAAs through synergistic energy transfer. This nanoprobe offers near-infrared upconversion capability, a wide dynamic detection range, and a detection limit of 2.2 μM, providing a versatile platform for in vivo noninvasive detection of DAAs with high enantioselectivity. These results potentially allow real-time monitoring of biomolecular handedness in living animals, as well as developing antipsychotic treatment strategies.

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

Background: Most patients with schizophrenia are unable to fulfill their personal and social responsibilities and these are met by their caregivers. The concept of 'burden' has come to the fore for caregivers. Long-acting injectables have been shown to reduce relapse rates, and provide a better level of functionality, but their effect on caregiver burden has not been investigated. Objective: Our aim in this study is to investigate the effect of transition from oral to long-acting antipsychotic treatments on caregiver burden. Other factors that may be related to the burden were also discussed.Setting: This study was performed at Community Mental Health Center of Erzurum Regional Training and Research Hospital.Methods: Caregivers (n:138) of patients diagnosed with schizophrenia for at least one year and who received oral paliperidone or aripiprazole were evaluated at baseline and 1 year after switching to long-acting injectables.Main outcome measure: The Zarit Caregiver Burden Scale (ZCBS) and the Clinical Global Impression-Disease Severity (CGI-S) were administered. Demographic characteristics of caregivers and patients were evaluated.Results: Significant decreases were found in the ZCBS and CGI-S scores after transitioning to long-acting injectable antipsychotics (p

The response to antipsychotic treatment in schizophrenia appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis. Randomised controlled trials comparing placebo and antipsychotics in acute treatment of schizophrenia listed in PubMed, EMBASE and PsycINFO from inception until 30 November 2018 were examined. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges’ g. In addition, individual patient data from two clinical trials was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors. In total, 11,006 articles were identified. Sixty six met inclusion criteria, reporting on 17,202 patients. Compared with placebo, antipsychotic-treated patients demonstrated greater total symptom improvement (g = 0.47, p

Background: Although cannabis use has been linked with schizophrenia in a dose–response pattern, to our knowledge, the relationship between cannabis and schizophrenia has rarely been report...

Antipsychotic treatment may affect brain morphology, and enlargement of the basal ganglia (BG) is a replicated finding. Here we investigated associations between antipsychotic treatment and BG volumes in patients with psychotic and bipolar disorders. We hypothesized that current treatment and, among those medicated, higher dosage, estimated D2R occupancy and being in remission would predict larger BG volumes. Structural covariance analysis was performed to examine if correlations between BG volumes and cortical thickness differed by treatment status. 224 patients treated with antipsychotics; 26 previously treated, 29 never treated and 301 healthy controls (HC) were included from the TOP study cohort (NORMENT, Norway). T1-weighted MR images were processed using FreeSurfer. D2R occupancy was estimated based on serum concentration measurements for patients receiving stable monotherapy. Statistical analyses were adjusted for age, gender and estimated intracranial volume (ICV). We found larger right (p 0.003) and left putamen (p 0.02) and right globus pallidus (GP) (p 0.03) in currently medicated patients compared to HC. Bilateral regional cortical thinning was also observed in currently and previously medicated patients compared to HC. In medicated patients, higher chlorpromazine equivalent dose (CPZ) was associated with larger left GP (p 0.04). There was no association with estimated D2R occupancy (n = 47) or remission status. Lower positive correlation between left putamen volume and cortical thickness of the left lateral occipital cortex was found in medicated patients compared to HC. We replicated the BG enlargement in medicated patients, but found no association with estimated D2R occupancy. Further studies are needed to clarify the underlying mechanisms.

Outpatient diversion programs present an opportunity for severely mentally ill defendants to receive psychiatric treatment and have alleged offenses dismissed by the court. Moreover, the successful completion of pretrial diversion is associated with fewer post-program arrest and jail days. The target patient population for such programs is typically people with schizophrenia spectrum disorders, but the care of such patients in outpatient settings presents challenges for monitoring treatment fidelity, specifically antipsychotic adherence, as low adherence rates are associated with increased rates of recidivism. Presented here is a review of evidence-based strategies that must be employed to track antipsychotic adherence in outpatient diversion programs, including pill counts, use of long-acting injectable antipsychotics, and determination of plasma antipsychotic levels to assess adherence and the adequacy of antipsychotic treatment. Antipsychotic therapy remains the foundation of schizophrenia treatment, but only through the use of all available modalities can clinicians maximize the odds that schizophrenia patients in pretrial diversion maintain psychiatric stability and successfully complete mental health court mandates.

OBJECTIVE To describe the use of pharmacologic treatment in critically ill children treated according to a delirium protocol and compare those treated with antipsychotics to those treated non-pharmacologically. METHODS The study included a retrospective matched cohort describing patients who were pharmacologically treated for delirium compared to those with delirium but not treated in a PICU from December 2013 to September 2015, using a delirium management protocol. Patients were matched by age, sex, diagnosis, mechanical ventilation (MV), and presence of delirium. RESULTS Of 1875 patients screened, 188 (10.03%) were positive for delirium. Of those, 15 patients (8%) were treated with an antipsychotic for delirium. Patients with delirium treated with antipsychotics were younger, had more delirium days (6 vs. 3, p=0.022), longer MV days (14 vs. 7, p=0.017), and longer PICU length of stay (34 vs. 16 days, p=0.029) than in the untreated group. Haloperidol, risperidone, and quetiapine were used in 9, 6, and 2 patients, respectively. Two patients were treated with multiple antipsychotics. Antipsychotic treatment was initiated on day 2 of delirium for 8 of 15 patients (53.3%). Ten patients in the treatment group had improved delirium scores by day 2 of treatment. No significant differences in sedation exposure between groups. No significant adverse effects were reported. CONCLUSIONS No significant adverse events seen in this small cohort of critically ill pediatric patients with delirium treated with antipsychotic therapy. Patients with early-onset delirium refractory to non-pharmacologic treatment may have a more effective response to antipsychotic therapy than patients with late-onset refractory delirium.

Schizophrenia is associated with progressive white matter changes, but it is unclear whether antipsychotic medications contribute to these. Our objective was to characterize effects of short-term treatment with risperidone on white matter diffusion indices.We recruited 42 patients with schizophrenia (30 never treated and 12 currently untreated) and 42 matched healthy control subjects in this prospective case-control neuroimaging study. Patients received a 6-week trial of risperidone. Using diffusion tensor imaging, we assessed microstructural (fractional anisotropy, mean diffusivity, and radial diffusivity) and macrostructural (radial fiber trophy) white matter integrity deficits in unmedicated patients compared with control subjects and change in white matter integrity in patients before and after antipsychotic treatment (mean risperidone dose at end point was 3.73 ± 1.72 mg).At baseline, fractional anisotropy was decreased in the left medial temporal white matter (cluster extent: 123 voxels; Montreal Neurological Institute peak coordinates: x = -51, y = -44, z = -7; α.05), and mean diffusivity was increased in the fusiform/lingual gyrus white matter extending to the hippocampal part of the cingulum (cluster extent: 185 voxels; peak coordinates: x = -27, y = -49, z = 2; α.04) in patients compared with control subjects. Radial diffusivity and macrostructure were not abnormal. None of the diffusion indices showed a significant change after 6 weeks of treatment with both voxelwise and whole-brain white matter analyses.We demonstrate microstructural white matter integrity abnormalities in the absence of macrostructural impairment in unmedicated patients with primarily early-stage schizophrenia. In our data, we found no significant white matter changes after short-term treatment with risperidone.

Long-acting injectable (LAI) antipsychotics are an important treatment option for patients with schizophrenia. Advances and variability in formulation technology have provided several LAI antipsychotic treatment options for schizophrenia, with a wide range of doses and dose intervals. However, clinical reviews of LAIs have not focused on formulation development despite its clinical relevance to injection safety and technique. This article reviews the relationship between formulation technology and clinical practices for LAIs, with a focus on aripiprazole lauroxil, a long-acting atypical antipsychotic indicated for the treatment of schizophrenia. The formulation developed for aripiprazole lauroxil is an aqueous-based suspension suitable for use as a prefilled syringe that, after injection, will release aripiprazole slowly into the plasma. The clinical relationship between the aripiprazole lauroxil formulation and proper injection techniques is explained, including why tapping and shaking the syringe to resuspend the drug particles and rapid injection speed are key steps for best injection practices for this formulation.

Rabbit Syndrome is an uncommon side effect of antipsychotic treatment. Although it is usually associated with typical antipsychotics, it can also be related to atypical antipsychotics. Anticholinergics are the most accepted treatment approach in treating Rabbit Syndrome. Fluvoxamine is a member of selective serotonin reuptake inhibitors and it is a potent agonist of sigma 1 receptors. In this article, we report a Rabbit Syndrome case who has benefited from fluvoxamine, in terms of both depressive disorder and Rabbit Syndrome; and present the data on the effects of sigma 1 agonist fluvoxamine on numerous movement disorders.

Objective: Despite the increasing use of antipsychotic drugs in children and adolescents in many countries, little is known about the treatment duration in this vulnerable population. The present n...

Przedstawiamy przypadek 27-letniego mężczyzny, który bez żadnego powodu dokonał skoku z VII piętra, doznając licznych urazów narządowych. To szokujące dla otoczenia i niezrozumiałe dla samego pacjenta wydarzenie stało się przyczyną ciągu hospitalizacji. Przez długie miesiące był leczony w oddziale intensywnej terapii i rehabilitacyjnym. Zaprzeczał tendencjom samobójczym, nie był w stanie wyjaśnić przyczyny tego skoku. Z powodu objawów depresyjnych był leczony przeciwdepresyjnie, rozpoznano epizod depresji umiarkowany. Następnie wystąpiły u niego objawy psychotyczne, z powodu których był hospitalizowany w oddziałach psychiatrycznych, gdzie podejrzewano schizofrenię. Był leczony przeciwpsychotycznie. Wypisany został z rozpoznaniem ostrych wielopostaciowych zaburzeń z objawami schizofrenii. Czyn ten przywodzi na myśl „zachowanie się wbrew oczekiwaniu”, actio preater expectationem – paragnomen - koncepcję ogłoszoną przez polskiego psychiatrę, prof. Eugeniusza Brzezickiego w latach pięćdziesiątych ubiegłego wieku. Jednocześnie przypadek ten przypomina o tym, że zupełnie bezzasadne, niewytłumaczone żadnymi okolicznościami nagłe zdarzenie związane z uczynieniem sobie bardzo poważnych szkód zdrowotnych może być sygnałem rozpoczynających się zaburzeń psychotycznych, ale niekoniecznie prowadzi do stwierdzenia schizofrenii, jak to sugerował autor pojęcia „paragnomen”.

Pedro Such,1 José Manuel Olivares,2 Lizbeth Arias,1 Mette Troels Berg,1 Jessica Madera3 1Medical Strategy and Communication, H. Lundbeck A/S, Valby, 2500, Denmark; 2Department of Psychiatry, Hospital Álvaro Cunqueiro, Health Research Institute Galicia Sur (IISGS), CIBERSAM, Vigo, Spain; 3Global Medical Affairs, Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, 08540, USACorrespondence: Pedro SuchMedical Strategy and Communication, H. Lundbeck A/S, Ottiliavej 9, Valby, 2500, DenmarkTel +45 3630 1311Email PSU@lundbeck.comBackground: To obtain real-world evidence of functional improvements during atypical long-acting injectable (aLAI) therapy in recent-onset schizophrenia, an online survey was conducted to assess the impact of aripiprazole once-monthly injectable 400 mg (AOM 400; partial D2 receptor agonist) and paliperidone palmitate once-monthly (PP1M; injectable, full D2 receptor antagonist).Methods: Psychiatrists provided data for their 2 most recent AOM 400 patients, 2 most recent PP1M patients. Survey included 2000 patient cases (1000 AOM 400; 1000 PP1M). Eligible patients were aged 18– 35 years, had been diagnosed with schizophrenia within 5 years, received AOM 400 or PP1M continuously for ≥ 6 months according to approved labels (mean durations: 1.6 and 1.7 years with AOM 400 and PP1M, respectively). Assessments included Global Assessment of Functioning (GAF) Scale, Personal and Social Performance Scale, Positive and Negative Syndrome Scale, and Quality of Life Scale. GAF assessments were done retrospectively and also at the time of survey.Results: Baseline mean GAF scores were 43.3 and 43.8 for AOM 400 and PP1M, respectively, indicating serious symptoms/functional impairment in both groups. Mean improvements following AOM 400 and PP1M therapy were 19.7 and 16.3 points, respectively (final scores in mild functional impairment category). Other measures assessing symptoms/functionality/quality of life demonstrated the benefits of long-term aLAI therapy.Conclusion: Schizophrenia patients with serious functional impairment prior to current aLAI treatment showed improvements in functional outcome after AOM 400 or PP1M therapy. These results suggest functional improvements with aLAIs are apparent not only in research but also real-world settings.Keywords: antipsychotic treatment, aripiprazole, aripiprazole once-monthly injectable, AOM, long-acting injectable, paliperidone palmitate once-monthly injectable

The aim of this study was to evaluate discontinuation and hospitalization rates in patients with schizophrenia spectrum disorder who were treated with long-acting injectable (LAI) antipsychotics. We recorded clinical data about the period before the LAI treatment, when LAI treatment was initiated, and during the LAI treatment. Variables related to early (

The objective here is to compare the effectiveness of long-acting injectable antipsychotics (LAI-APs) and oral ones (OAPs) in patients with severe (Global Clinical Impression-Severity ≥ 5) schizophrenia (N = 688). A 5-year follow-up study has been conducted in patients undergoing standard treatment in mental health units (MHUs) or on a severe mental illness program (SMIP). A total of 8.7% of the patients on the SMIP discontinued treatment, whereas 43.6% did so in MHUs (p < 0.0001). In both cases, treatment retention was significantly higher in patients on LAI-APs (p < 0.001). Also, hospital admissions were in both cases fewer among those on LAI-APs (p < 0.001). There was a significant link between suicide attempts and OAP treatment (p < 0.01). Given the relationship between the use of LAI-APs versus oral treatments in achieving higher adherence and less relapses and suicide attempts, the use of second-generation antipsychotics LAIs should be considered more suitable for people with severe schizophrenia.

Cell-free mitochondrial DNA (cf-mtDNA) is a damage-associated molecular pattern that boosts the release of cytokines and induces the immune response of the body; therefore, it is closely related to mental diseases. This study aims to evaluate a potential link between cf-mtDNA and clinical progression in first-episode patients with schizophrenia. In this study, plasma cf-mtDNA levels in 34 first-episode patients with schizophrenia before and after 8 weeks of antipsychotic treatment were examined. In addition, the clinical progression of first-episode schizophrenia was assessed using the Positive and Negative Syndrome Scale (PANSS). The copy number changes in the plasma cf-mtDNA (Δcf-mtDNA) were significantly correlated with changes in the PANSS scale scores (ΔPANSS) in first-episode patients with schizophrenia (ΔPANSS total score, P = 0.002; ΔPANSS positive score, P = 0.01). Plasma cf-mtDNA may represent a relevant tool in the future to assist in the assessment of clinical progression in first-episode patients with schizophrenia.

Aims: Non-compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first-episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group. Methods: We evaluated a large sample of patients with FEP for 2 years to compare the time to all-cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded. Results: A total of 310 FEP patients were assessed across seven early intervention teams (mean age = 30.2 years; SD = 11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non-compliance. There were no differences in the relapse rates between different APs. Patients treated with long-acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs. Conclusions: Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.

Background Brain dynamics abnormalities in the triple-network, which involves the salience network (SN), the default mode network (DMN) and the central executive network (CEN), have been reported in schizophrenia. However, it remains to be clarified how antipsychotics affect dynamic functional connectivity (DFC) within the triple-network and whether differences in clinical outcomes are associated with varying levels of network model dysfunction. Methods Resting-state functional magnetic resonance imaging scans were obtained from 64 first-episode schizophrenia patients (SZ) and 67 healthy controls (HC). All patients were scanned before and after 12-week antipsychotic treatment and the HC were scanned only at baseline. Results At baseline, SZ participants showed significantly reduced dynamic functional interactions across the triple-network compared to HC. The SZ group displayed a pattern of reduction in resting-state DFC among the triple-network compared with HC. After medication, the mean dynamic network interaction index (dNII) value was improved. A significant quadratic relation was observed between longitudinal change of mean dNII and the reduction ratio of PANSS total score within the SZ group. The DFC within inter-network (between DMN and SN, and between DMN and CEN) and intra-network connections of DMN were significantly higher relative to baseline. Intra-SN DFC, intra-DMN DFC and DFC between SN and DMN were found to be predictive of clinical features at baseline. Intra-CEN DFC and DFC between DMN and CEN were predictive of treatment response. Conclusions Aberrant brain dynamics in the triple-network could be regulated with medication. DFC organization in the triple network was found to predict the clinical outcome.