Initiation Of Antipsychotic Medication Research Articles

The risk of diabetes and HbA1c deterioration during antipsychotic drug treatment: A Danish two-cohort study among patients with first-episode schizophrenia.

Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c). We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before. In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication. This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES.

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery

BackgroundThe effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults.MethodsA total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP−). Therefore, the four groups were defined as Adolescent-AP−, Adolescent-AP+, Adult-AP−, and Adult-AP+.ResultsDuring the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP− group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP− group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP− group. The Adolescent-AP− group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults.ConclusionsEarly use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

Suicide in Schizophrenia: A literature review

IntroductionMore than 90 percent of patients who attempt suicide have a psychiatric disorder. The diagnosis of schizophrenia is associated with a decrease in life expectancy of about 10 years, with suicide being the most important related factor. Literature suggests that the risk of suicide death in this population has been found to be 10 to 20 times higher than that in the general populationObjectivesTo present a case report of a patient with a first psychotic episode and suicide attempt focusing on clinical features and risk factors.MethodsPresentation of a clinical case supported by a non-systematic review of literature containing the key-words “suicide”, “Suicidal ideation”, “psychosis” and “schizophrenia”.ResultsThis is a case report of a male 28-year-old patient, with no known psychiatric history, admitted to our inpatient service after a suicide attempt by precipitation. In a first evaluation, the patient presented psychotic symptoms consisting of paranoid delusions, auditory hallucinations, tendency to social isolation and the appearance of self-harming ideation in the days prior to the episode. After initiation of antipsychotic medication, a significant improvement in positive symptoms was observed. The patient has since had no delusions or hallucinations and is living independently at home.Contemporary research studies indicate that the lifetime rate of completed suicide in individuals with schizophrenia is between 4% and 13%. Several specific risk factors have been described in the schizophrenia population, such as early stage of the illness, lack of adherence to treatment, recurrent relapses, comorbid depression and the paranoid subtype. The antipsychotic treatments with the most scientific evidence are clozapine, risperidone, olanzapine and quetiapine. Within psychotherapy, cognitive behavioral therapy appears to be the most effective.Conclusions-It is important to know the risk factors that are associated with an increased risk of suicide in patients diagnosed with schizophrenia.-An early intervention and specific treatment can improve prognosis of this population.Disclosure of InterestNone Declared

Florida Medicaid Children's Receipt of First-Line Psychosocial Care Prior to Antipsychotic Initiation.

First-line, nonpharmacological therapy is recommended for many pediatric mental health (MH) conditions prior to initiating antipsychotic prescription therapies. Many children do not receive these recommended services, despite the known association between antipsychotic medications and metabolic dysfunction. The main objective of this study was to quantify the association among children's MH diagnosis categories, sociodemographic characteristics and receipt of first-line psychosocial care among children in Florida Medicaid METHODS: Florida Medicaid enrollment, healthcare and pharmacy claims were used for this multivariate analysis. Children were assigned to condition clusters wherein related diagnoses were grouped into clinically relevant categories. A total of 7704 children were included in the final analysis. Twenty-four percent of children in Florida Medicaid do not receive first-line, nonpharmacological psychosocial care. Age was significantly associated with not receiving psychosocial services, with older children less likely to receive. Non-Hispanic White children as well as those living in rural areas had lower odds of receiving behavioral intervention prior to initiating antipsychotics. Children with mood-disorders, behavior problems, anxiety and stress related disorders were more likely to receive first-line psychosocial care. This study provides an important understanding of the variability in receipt of first-line psychosocial care before antipsychotic medication initiation among children in Medicaid based on sociodemographic and MH health characteristics. These analyses can be used to develop quality improvement initiatives targeted toward children that are most vulnerable for not receiving recommended care.

A-8 Developmental Cognitive Phenotypes in First-Episode Psychosis and Longitudinal Cognitive Change Following Antipsychotic Treatment

Abstract Objective The present study applied a developmentally based subgrouping procedure previously examined in chronic psychosis patients to a sample of first-episode psychosis (FEP) and examined change in cognition following treatment with antipsychotic medication. Method Medication naïve FEP patients (n = 119; age = 27.96; 63.9% male; 62.2% White, 32.8% Black, 5.0% Other) recruited during initial hospitalization were categorized into groups based on 1) estimated premorbid intellectual ability and 2) the discrepancy between predicted (modeled on 151 healthy controls) and current cognitive ability. Consistent with findings from chronic psychosis samples, groups were characterized as Preserved (n = 46; average premorbid, no discrepancy), Deteriorated (n = 44; average premorbid, significant discrepancy), and Compromised (n = 29, low premorbid and current cognitive ability). A mixed analysis of variance was used to examine change in a composite cognitive score derived from a comprehensive neuropsychological battery at baseline, 6 weeks, and 12 months. Results There was a significant group by time interaction [Figure 1; F(5.4142.4) = 2.81, p = 0.02] in which the Preserved group performed similar to healthy controls across all time points, the Compromised group demonstrated stable deficits after treatment, and the Deteriorated group diverged from the Compromised group at 6 weeks and 12 months. Discussion There is considerable cognitive heterogeneity in FEP at baseline and after initiation of antipsychotic medication. Findings of cognitive improvement in the Deteriorated group after treatment initiation suggests a differential response to antipsychotic medications that was not found in the Compromised or Preserved groups. Future work may benefit from examining medication and symptom severity as potential factors contributing to the unique change observed in the Deteriorated group.

Active psychosis and pro-inflammatory cytokines in first-episode of psychosis

Higher levels of pro-inflammatory cytokines are consistently found in the serum of first episode psychosis (FEP) patients and this immune dysfunction could contribute to neural harm. On the other hand, lengthy periods of active psychosis during the early phases of the illness appear to be associated to worst functional outcome. We aim to explore the possible relationship between lengthy periods of active psychosis during early phases of the illness and the levels of pro-inflammatory cytokines. This is a prospective clinical study consisting of a 3-year clinical follow-up. We assessed the relation between the duration of active psychosis in patients with FEP and the serum levels of 21 cytokines at baseline and 3 months after initiating antipsychotic medication. We used the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. The sample consisted of 59 patients with a FEP. The percentage of variation of the serum levels of the chemokine MIP-3α during the first 3 months of antipsychotic treatment and the score in negative psychotic symptoms 3 months after the initiation of antipsychotic medication, acted as predictors of the initial time to remission of positive psychotic symptoms. Our findings open the possibility to investigating the potential use of the variation in chemokine MIP-3α serum levels during the first months of antipsychotic treatment to identify a subtype of FEP patients that could benefit from an add-on treatment with immune modulators. Clinicaltrials.gov idNCT02897167. Date of first registrationSeptember 13, 2016.“Study of the Activation of Proinflammatory Pathways of Toll-like Receptors in Schizophrenia Patients (PAFIP_TLR)”.https://clinicaltrials.gov/ct2/show/NCT02897167.

Immune and Neuroendocrine Trait and State Markers in Psychotic Illness: Decreased Kynurenines Marking Psychotic Exacerbations.

Objective: Different patterns of immune system upregulation are present in the acute vs. post-treatment states of psychotic illness. We explored the existence of state and trait markers in the peripheral immune system and two immune-associated neuroendocrine pathways (IDO and GTP-CH1 pathway) in a longitudinal sample of psychosis patients. We also evaluated the association of these markers with neuropsychiatric symptomatology.Method: Plasma concentrations of peripheral blood markers were measured in a transdiagnostic group of 49 inpatients with acute psychosis and 52 matched healthy control subjects. Samples were obtained in patients within 48 h after hospital admission for an acute psychotic episode (before initiation of antipsychotics), after 1–2 weeks and again after 8 weeks of treatment. Kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), phenylalanine, tyrosine, nitrite, and neopterin were measured using HPLC and LC-MS/MS analysis. Concentrations of CRP, CCL2 (MCP1) and cytokines were determined with multiplex immunoassay. PANSS interviews and cognitive tests were performed at baseline and follow-up. Mixed model analyses were used to identify trait and state markers.Results: Patients had significantly higher plasma concentrations of CRP, CCL2, IL1RA, and lower concentrations of KA and KA/Kyn at all time points (F7.5–17.5, all p < 0.001). Increased concentrations of IL6, IL8, IL1RA, TNFα, and CCL2 and decreased QA and 3-HK (F8.7–21.0, all p < 0.005) were found in the acute psychotic state and normalized after treatment. Low nitrite concentrations at admission rose sharply after initiation of antipsychotic medication (F42.4, p < 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers (r ≥ |0.5|), while negative scale scores correlated inversely with IDO pathway markers (r ≥ |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms (r = 0.5, p < 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels (r = 0.5, p < 0.010).Conclusion: The acute psychotic state is marked by state-specific increases of immune markers and decreases in peripheral IDO pathway markers. Increased CRP, CCL2, and IL1RA, and decreased KA and KA/Kyn are trait markers of psychotic illness.

Impact of antipsychotic medication on IL-6/STAT3 signaling axis in peripheral blood mononuclear cells of drug-naive schizophrenia patients.

Immunopathogenesis remains a widely appreciated etiopathological model of schizophrenia. Persistent efforts have aimed to identify schizophrenia biomarkers indexing immune system abnormalities and also immuno-dampening effects of antipsychotic medications. Although data arising from published reports are encouraging, such studies are limited to a few immune parameters and not focused on a specific pathway. Th17 cells-mediated immuno-inflammatory responses have emerged as a potential mechanism in various neuropsychiatric conditions, including schizophrenia. The Th17 pathway is distinctly regulated through a coordinated action of multiple cytokines and transcription factors. In this study, we explored whether antipsychotic medication has any effect on the cytokines and transcription factors of the Th17 pathway. A total of 27 drug-naive schizophrenia patients were recruited and followed up for 3 months after initiation of antipsychotic medication. Lymphocyte gene expression levels of two transcription factors (STAT3 and RORC) and one of their upstream regulators, IL6, were quantified before and after treatment. Plasma levels of cytokines, such as interleukin (IL)-1β, IL-6, IL-17A, IL-23, and IL-33, were also analyzed before and after treatment. Treatment with antipsychotic medication for 3 months resulted in significant downregulation of STAT3 gene expression as well as reduction in plasma levels of IL-1β, IL-6, and IL-17A. Significant reduction in total scores for the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms was also observed in schizophrenia patients after 3 months of antipsychotic treatment. Our findings suggest possible immuno-modulatory effects of antipsychotic medication on the critical regulators, such as IL-6 and STAT3, of the Th17 pathway in schizophrenia patients. The IL-6/STAT3 signaling axis involved in the transcriptional regulation of Th17 cells might appear as an important target of antipsychotic treatment in schizophrenia patients. Alternatively, irrespective of the effect of antipsychotic drugs, the IL-6/STAT3 signaling axis might be crucially involved in ameliorating psychotic symptoms.

Comparison of the anti-inflammatory effect of aripiprazole and risperidone in 75 drug-naïve first episode psychosis individuals: A 3 months randomized study

IntroductionEvidence about the anti-inflammatory properties of antipsychotics has grown. However, no previous studies have compared the immunomodulatory effect of risperidone and aripiprazole. ObjectivesThe main aim of the present work is to compare the anti-inflammatory effect of risperidone and aripiprazole on a large array of serum cytokines at 3 months following the onset of treatment. MethodsThis is a prospective, randomized, open-label study. Patients were randomly assigned to risperidone or aripiprazole. From this randomization, 75 patients and 75 healthy volunteers that matched with the selected patients were picked for entry in this study. Serum concentrations of 21 cytokines/chemokines were measured at baseline and 3 months following the initiation of antipsychotic medication. ResultsThose patients who were randomly assigned to risperidone had higher levels of IL-8 (p = 0.000) and MIP-1β (p = 0.007) than healthy volunteers at baseline, whereas no differences were found between patients initially assigned to aripiprazole and healthy volunteers. Three months following the onset of medication several cytokines decreased significantly: IL-8, MIP-1β, Fractalkine, TNF-α, IL-7, IL-13, IL-17α, IL-23, IL-21 (all ps < 0.01). No differences were found in the percentages of change between both treatments. The effect size of the two antipsychotics was similar, except for TNF-α, IL-13, IL-17α and Fractalkine, in which aripiprazole seems to have a greater effect size than risperidone, whereas risperidone seems to have a greater effect size than aripiprazole on MIP-1β. ConclusionsThis is the first study that has compared the immunomodulatory effect of risperidone and aripiprazole, finding that the anti-inflammatory effect of both treatments was similar.

Changes in the cytokine profile in first episode, drug-naïve patients with psychosis after short-term antipsychotic treatment

IntroductionAn increasing body of evidence suggests that antipsychotic medication can cause immunological changes that could be attributed to the amelioration of psychotic symptoms or the metabolic side effects of the drugs. So far, the results of the studies remain controversial.ObjectiveOur aim was to compare the levels of interleukin (IL) IL-2, IL-6 and transforming growth factor-β2 (TGF-β2) in drug-naïve, first-episode patients with psychosis before and after six weeks of antipsychotic medication.MethodsThirty-nine first episode patients with psychosis were enrolled in the study. Serum levels of IL-2, IL-6 and TGF-β2 were measured by enzyme linked immunosorbent assay (ELISA) before and six weeks after the initiation of antipsychotic medication. In addition, clinical psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS) before and after treatment.ResultsSerum levels of IL-2 were significantly higher in the study group six weeks after the initiation of antipsychotic treatment (P &lt; 0.001) while TGF-β2 levels were decreased (P &lt; 0.001) and IL-6 levels were slightly reduced (P &lt; 0.004).ConclusionThe changes in cytokine levels may be attributed to the action of antipsychotic medication and the remission of psychopathology. The reduction in TGF-β2 levels is observed in all patients and with all antipsychotic medications used. TGF-β2 may be a marker of clinical efficacy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment

BackgroundWhile reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of “treatment initiation” on the predictive value of DUP on outcome in an early psychosis sample. Methods221 early psychosis patients aged 18–35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). Results10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. ConclusionsThe limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies.

Monitoring of Physical and Mental Health in Secondary Care Services Following Initiation of Antipsychotic Medications.

Aim To assess the monitoring of antipsychotic medication in secondary care services in accordance with The National Institute for Health and Care Excellence (NICE) guidelines1. Background Recent NICE guidelines on Psychosis and schizophrenia in adults1state that the secondary care team should monitor patients' physical health and the effects of antipsychotic medication for at least 12 months or until the person's condition has stabilised, and thereafter consider shared care with Primary care. Methods The electronic database generated a sample of 30 new service users attending a local community team in Solihull, UK who were initiated on antipsychotics between January 2012 and March 2013. We analysed electronic documentation according to an audit tool developed by our Trust Clinical Pharmacist, based on NICE guidelines. Results Results showed that 83% of patients were monitored for over 12 months or until stabilised. Other documentations included response to treatment and side effects of treatment (96.7%), emergence of movement disorders (36.7%), adherence to treatment (86.7%) and physical health (90%). Conclusions Most patients were followed up for their mental health. Documentation and/or specific monitoring of physical health parameters as detailed in the guidelines remained less than 30%. Similarly, the emergence of movement disorders was infrequently recorded. Training is required to improve the understanding of the importance of monitoring of physical health in individuals with psychosis or schizophrenia, especially those taking antipsychotics. Re-audit to follow. [1] NICE. NICE guideline on Psychosis and schizophrenia in adults: treatment and management, CG178: February 2014. http://www.nice.org.uk/guidance/CG178/chapter/1-Recommendations .

First-episode affective psychosis and lipid monitoring: survival analysis of the first abnormal lipid test.

This study aimed to assess the probability of developing a lipid test abnormality over time, among first-time users of antipsychotic medications with affective psychosis. Survival analysis was used to analyse data from an early intervention in psychosis programme for the first 53 consecutive and eligible cases of patients between the ages of 14 and 40 years who had a diagnosis of affective psychosis. Data on initiation of antipsychotic medications and lipid laboratory test results were abstracted from chart reviews. Within the first 18 months of receiving antipsychotic medications, the probability of surviving without an abnormal lipid test was only 25% (confidence interval 95%: 13.1%, 40.4%). The median time to the development of an abnormal test was 8 months for males and 12 months for females (P < 0.001). Additional studies are needed to document the incidence over time of abnormal lipid tests to inform clinicians about the optimal frequency of monitoring.

Fracture Risk in Nursing Home Residents Initiating Antipsychotic Medications

To determine whether antipsychotic medication initiation is associated with subsequent fracture in nursing home residents, whether fracture rates differ between users of first- and second-generation antipsychotics, and whether fracture rates differ between users of haloperidol, risperidone, olanzapine, and quetiapine. Time-to-event analyses were conducted in a retrospective cohort using linked Medicaid; Medicare; Minimum Data Set; and Online Survey, Certification, and Reporting data sets. Nursing homes in California, Florida, Missouri, New Jersey, and Pennsylvania. Nursing home residents aged ≥ 65. Fracture outcomes (any fracture; hip fracture) in users of first- and second-generation anti-psychotic and specifically users of haloperidol, risperidone, olanzapine, and quetiapine. Comparisons incorporated propensity scores that included individual- (demographic characteristics, comorbidity, diagnoses, weight, fall history, concomitant medications, cognitive performance, physical function, aggressive behavior) and facility- (nursing home size, ownership factors, staffing levels) level variables. Of 8,262 subjects (in 4,131 pairs), 4.3% suffered any fracture during observation, with 1% having a hip fracture during an average follow-up period of 93 ± 71 days (range 1-293 days). Antipsychotic initiation was associated with any fracture (hazard ratio (HR) = 1.39, P = .004) and hip fracture (HR = 1.76, P = .02). The highest risk was found for hip fracture when antipsychotic use was adjusted for dose (HR = 2.96, P = .008), but no differences in time to fracture were found between first- and second-generation agents or between individual drugs. Antipsychotic initiation is associated with fracture in nursing home residents, but risk does not differ between commonly used antipsychotics.

Bridging the gap from evidence to policy and practice: Reducing the progression to metabolic syndrome for children and adolescents on antipsychotic medication

For children and adolescents, the adverse effects from antipsychotic medicines exaggerate the already considerable burden of having a serious mental illness. Many of these young people face a future not only limited by stigmatizing psychiatric illness but also a life restricted and shortened by physical ill-health, particularly cardiovascular disease and type-2 diabetes. This review focuses on bridging the current gap between available evidence and practice guidelines and policies. Following an extensive literature search, key papers focusing on the evidence of the nature and occurrence of metabolic morbidity in children and adolescents following the use of antipsychotic medication were included. There is growing evidence to suggest that some of the key antecedents of metabolic syndrome occur soon after diagnosis and initiation of antipsychotic medication, and they accumulate over time. While guidelines and policies around the monitoring of metabolic syndrome in children and adolescents with mental illness receiving antipsychotic medication are limited, an opportunity lies in altering the trajectory towards cardiovascular disease and type-2 diabetes by early recognition and intervention to reduce cardiometabolic risk rather than waiting until disease end-points are reached later in life.

Duration of untreated psychosis: a proposition regarding treatment definition

Duration of untreated psychosis (DUP) refers to the time elapsing between psychosis onset and treatment initiation. Despite a certain degree of consensus regarding the definition of psychosis onset, the definition of treatment commencement varies greatly between studies and DUP may be underestimated due to lack of agreement. In the present study, three sets of criteria to define the end of the untreated period were applied in a first-episode psychosis cohort to assess the impact of the choice of definition on DUP estimation. The DUP of 117 patients admitted in the Treatment and Early Intervention in Psychosis Program Psychosis in Lausanne was measured using the following sets of criteria to define treatment onset: (i) initiation of antipsychotic medication; (ii) entry into a specialized programme; and (iii) entry into a specialized programme and adequate medication with a good compliance. DUP varied greatly according to definitions, the most restrictive criteria leading to the longest DUP (median DUP1=2.2 months, DUP2=7.4 months and DUP3=13.6 months). A percentage of 19.7 of the patients who did not meet these restrictive criteria had poorer premorbid functioning and were more likely to use cannabis. Longer DUP3 was associated with poorer premorbid functioning and with younger age at onset of psychosis. These results underline the need for a unique and standardized definition of the end of DUP. We suggest that the most restrictive definition of treatment should be used when using the DUP concept in future research.

Targeted Intervention to Improve Monitoring of Antipsychotic-Induced Weight Gain and Metabolic Disturbance in First Episode Psychosis

International guidelines recommend monitoring for weight gain and metabolic disturbance in patients prescribed second generation antipsychotics. We aimed to investigate whether a targeted intervention could improve levels of monitoring in a first episode psychosis clinic. A pre-intervention audit of both metabolic screening rates and specific monitoring of weight and metabolic indices following the initiation of antipsychotic medication was performed in our first episode psychosis clinic. This was repeated 18 months later, following an intervention that included a number of targeted improvement strategies based on an analysis of barriers and enablers to performing monitoring within the clinic. The intervention included provision of monitoring equipment, interactive educational events, reminders and prompts and embedding processes for monitoring within team structure. There were significant improvements in both the screening of metabolic indices and the monitoring of indices following initiation of antipsychotic medications. There were also improvements in the number of active interventions offered to clients by clinicians. However, the level of guideline concordant monitoring remains low within our service. A comprehensive programme of implementation strategies can improve both screening and monitoring of the metabolic side-effects of antipsychotic medications. Further focused strategies are necessary to continue to improve monitoring to guideline concordant levels.

Effects of antipsychotics on D3 receptors: A clinical PET study in first episode antipsychotic naive patients with schizophrenia using [ 11C]-(+)-PHNO

Most antipsychotics are thought to have an effect on D 2 and D 3 receptors, although their D 3, versus D 2 binding has not been clearly established in vivo in humans. However, the development of [ 11C]-(+)-PHNO now permits the differentiation of antipsychotic activity on these two receptor subtypes. In this study we examined the effects of antipsychotics on D 2 and D 3 receptors by comparing [ 11C]-(+)-PHNO in D 2-rich (caudate, CAU and putamen, PUT), mixed (ventral striatum) and D 3-rich (globus-pallidus, GP and substantia nigra, SN) regions before and after the initiation of antipsychotic medication. The investigation therefore represents a longitudinal within-subject follow-up design wherein antipsychotic-naive patients with schizophrenia spectrum disorders were first scanned in a drug-naïve state and then again after ~ 2.5 weeks of antipsychotic treatment (risperidone or olanzapine). Binding potential (non displaceable or BP ND) was obtained to derive estimates of drug occupancy in the identified brain regions. Antipsychotic treatment was associated with the expected occupancies in the D 2-rich regions; unexpectedly though, patients showed a higher, rather than the expected lower, [ 11C]-(+)-PHNO BP ND in the GP and SN despite simultaneous evidence for ongoing D 2 blockade in the other regions (CAU and PUT). In conclusion, patients treated with atypical antipsychotics demonstrated no evidence of D 3 receptor occupancy, but instead possible D 3 up-regulation following short-term treatment. The present findings add to a very limited body of evidence related to D 3 binding in vivo. [ 11C]-(+)-PHNO offer new opportunities for exploring the potential therapeutic significance of the D 3 receptor in schizophrenia and the action of antipsychotics.

MTHFR and risk of metabolic syndrome in patients with schizophrenia

Objective Meta-analyses have implicated polymorphisms in MTHFR, encoding a critical enzyme in folate and homocysteine metabolism, in both schizophrenia and CVD. Method A possible association between the C677T and A1298C polymorphisms of the MTHFR gene on the one hand, and metabolic syndrome on the other, was examined in a naturalistic cohort of 518 patients with a schizophrenia spectrum disorder screened for metabolic disturbances at the Catholic University of Louvain, Belgium. Results MTHFR A1298C, but not C677T, was associated with the metabolic syndrome, C/C genotypes having a 2.4 times higher risk compared to A/A genotypes (95% CI 1.25–4.76, p = 0.009). Haplotype analysis revealed similar findings, showing greater risk for metabolic syndrome associated with the 677C/1298C haplotype compared to the reference 677C/1298A haplotype (OR 1.72, 95% CI 1.24–2.39, p = 0.001). These associations were not explained by circulating folate levels. Differences between A1298C genotype groups were considerably greater in the subsample treated with clozapine or olanzapine (OR C/C versus A/A 3.87, 95% CI 1.51–9.96) than in subsample treated with any of the other antipsychotics (OR C/C versus A/A 1.30, 95% CI 0.47–3.74), although this did not formally reach statistical significance in the current cross-sectional study (gene-by-group interaction χ 2 = 3.0, df = 1, p = 0.08). Conclusion These data provide evidence supporting an association between MTHFR and risk of metabolic syndrome in patients with schizophrenia. Prospective studies evaluating the course of metabolic outcomes after initiation of antipsychotic medication are needed to evaluate possible gene-by-treatment interaction more specifically.

Predictors of poor adherence to medication among patients with first‐episode schizophrenia‐spectrum disorder

This study sought to identify predictors for poor adherence to medication among patients with first-episode schizophrenia-spectrum disorder. Medication adherence was measured 1 and 2 years after initiation of antipsychotic medication in a follow-up study of 547 patients. Relevant variables were systematically assessed at baseline, 1- and 2-year follow up. Most patients have difficulties with medication adherence over time. Negative attitudes towards medication and lack of consistent family support are the strongest predictors for poor adherence to medication for first-episode psychotic patients in the first 2 years. After 1 year of treatment, unawareness of the effect of medication, lack of positive attitudes towards medication, substance abuse, young age and high global functioning also predict poor adherence to medication. A number of variables were independently associated with poor adherence. Rating of insight and attitudes towards medication makes it possible to predict poor adherence in incident cases with schizophrenia.