Months Of Antipsychotic Treatment Research Articles

Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

Short-term Medication Effects on Brain Functional Activity and Network Architecture in First-Episode psychosis: a longitudinal fMRI study.

The effect of antipsychotic medications is critical for the long-term outcome of symptoms and functions during first-episode psychosis (FEP). However, how brain functions respond to the antipsychotic treatment in the early stage of psychosis and its underlying neural mechanisms remain unclear. In this study, we explored the cross-sectional and longitudinal changes of regional homogeneity (ReHo), whole-brain functional connectivity, and network topological properties via resting-state functional magnetic resonance images. Thirty-two drug-naïve FEP patients and 30 matched healthy volunteers (HV) were included, where 23 patients were re-visited with effective responses after two months of antipsychotic treatment. Compared to HV, drug-naive patients demonstrated significantly different patterns of functional connectivity involving the right thalamus. These functional alterations mainly involved decreased ReHo, increased nodal efficiency in the right thalamus, and increased thalamic-sensorimotor-frontoparietal connectivity. In the follow-up analysis, patients after treatment showed reduced ReHo and nodal clustering in visual networks, as well as disturbances of visual-somatomotor and hippocampus-superior frontal gyrus connectivity. The longitudinal changes of ReHo in the visual cortex were associated with an improvement in general psychotic symptoms. This study provides new evidence regarding alterations in brain function linked to schizophrenia onset and affected by antipsychotic medications. Moreover, our results demonstrated that the functional alterations at baseline were not fully modulated by antipsychotic medications, suggesting that antipsychotic medications may reduce psychotic symptoms but limit the effects in regions involved in disease pathophysiology.

Worth the Weight? Olanzapine Prescribing in Schizophrenia. A Review of Weight Gain and Other Cardiometabolic Side Effects of Olanzapine.

About 80% of patients who experience a first episode of psychosis (FEP) will have another within 5 years (1). In a large meta-analysis of randomized controlled trials (RCTs), 12 months of antipsychotic treatment reduced the rate of relapse from 61 to 26% in FEP, and from 64 to 27% in chronic cases (2). Long-term antipsychotic treatment has been associated with a decrease in mortality rates, compared to untreated cases (3). However, compared to the general population, those with schizophrenia still die, on average, 14.5 years earlier (3, 4). Most life years lost relate to poor physical health outcomes—specifically mortality related to cardiovascular disease (CVD) (4). Adverse cardiometabolic side effects of antipsychotics, particularly second-generation antipsychotics (SGA), represent an undeniable contributor to the burden of cardiovascular morbidity and mortality amongst this cohort (5). Olanzapine, a SGA with one of the most significant cardiometabolic side effect profiles (5, 6), continues to be one of the most popular antipsychotics prescribed in schizophrenia (7–9). This commentary will consider some of the most pertinent research assessing the efficacy of olanzapine in schizophrenia management; suggest potential reasons for incongruence observed between guideline recommendations and prescribing practices; and finally, make suggestions as to how olanzapine-induced weight gain—a side effect that often represents the beginning of a series of escalating cardiometabolic derangements–can be recognized and its effects ameliorated. Olanzapine and Weight Gain Amongst those prescribed olanzapine early in psychosis management, 80% experience an increase of ≥7% of their baseline body weight (10, 11). With the exception of clozapine, whether short- or long-term anthropometric outcomes are being assessed, olanzapine is invariably listed as causing the most significant increases amongst users (6). This is not new information–the first review that aggregated data on weight changes following SGA use was published in 1999 (12). In a 2019 meta-analysis of 402 RCTs including data from 53,463 participants with multi-episode schizophrenia, olanzapine remained the antipsychotic most likely to induce clinically significant weight gain after clozapine and zotepine, the latter of which is not licensed in many countries (6). Antipsychotic-induced weight gain (AIWG) is a particularly important side effect, as it mediates cardiometabolic outcomes, including development of type 2 diabetes mellitus (T2DM) and subsequent CVD–the latter being responsible for approximately 60% of the excess mortality amongst those with schizophrenia previously highlighted (13). Aside from drastically reducing life expectancy, such high rates of physical comorbidity increases the personal, social and economic burden on mental illness across the lifespan. Significant weight gain may also influence outcomes related to mental health. AIWG is consistently listed as one of the most distressing side effects of antipsychotic treatment, frequently resulting in partial or complete antipsychotic non-adherence, and future reluctance to engage with treatment (14, 15). Furthermore, research is now emerging suggesting that obesity and metabolic syndrome may be independent predictors of relapse and re-hospitalization amongst those with a Severe Mental Illness (SMI) (16). Due to its significant association with weight gain and other cardiometabolic abnormalities, since 2009 several international guidelines in Europe, the United States, Australia and New Zealand have advised against olanzapine's use as part of first-line psychosis management (17). However, today olanzapine continues to be one of the most popular antipsychotics, extensively prescribed in both FEP and chronic cases, across the spectrum of illness severity and in many jurisdictions (7–9). Considering the cardiometabolic adverse effects of olanzapine are well-documented, what might be the reasons underlying its popularity? Does its prevalent use reflect poor translation of evidence and subsequent guideline recommendations into clinical practice? Or does its popularity reflect an “availability bias”, whereby clinicians ascribe greater efficacy to olanzapine compared to other antipsychotics, simply based on their more familiar and frequent use of olanzapine? It is worth first assessing efficacy data supporting olanzapine, both in symptom reduction and relapse prevention.

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.

Longitudinal study of inflammatory markers and psychopathology in schizophrenia

ObjectiveSchizophrenia is associated with abnormal levels of blood inflammatory markers, which may be correlated with levels of psychopathology. Few previous studies have explored whether baseline inflammatory marker levels predict longitudinal changes in psychopathology. In the present study, we explored this association in a cohort of patients with schizophrenia. MethodWe investigated inflammatory markers and psychopathology after 3, 6, and 12 months of antipsychotic treatment for subjects with baseline and follow-up data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Linear regression models, controlling for multiple potential confounding factors, were used to investigate these associations. ResultsThere was a significant decrease in monocyte, ICAM, and adiponectin levels between baseline and 12 months. Higher baseline blood interleukin-6 (IL-6) predicted greater reduction in PANSS total and general subscale scores at 3 and 6 months, and PANSS negative subscale scores at 3 months (β = −0.10 to −0.16, p < 0.05 for each). Higher baseline blood leptin levels predicted greater reduction in PANSS total, negative and general subscale scores at 6 months (β = −0.09 to −0.11, p < 0.05 for each). In post-hoc analyses, associations between baseline IL-6 levels and symptom reduction were strongest in patients treated with either ziprasidone or quetiapine. Changes in blood inflammatory markers were generally not associated with changes in psychopathology. ConclusionsOur findings provide additional support that measuring blood inflammatory markers may be relevant to the clinical care of patients with schizophrenia. Specifically, these markers may help guide selection of antipsychotic treatment towards more personalized medicine approaches for patients with schizophrenia.

The Predictive Value of Endothelial Inflammatory Markers in the Onset of Schizophrenia.

PurposeThis study aimed to assess the serum levels of intracellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1), in the first psychotic episode schizophrenia (SZ) patients, before and after six months of antipsychotic treatment.Patients and MethodsThe study included 50 patients with a first hospitalization for SZ and 50 healthy control subjects that were patient-matched regarding age, gender, body mass index and smoking status. The evaluation included the presence of cardiovascular risk factors, measurements of systolic and diastolic blood pressure, body mass index, smoking status, ankle-brachial index, carotid intima-media thickness, and echocardiography. The Brief Psychiatric Rating Scale (BPRS) score was calculated for the patients. The plasma levels of fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, sICAM-1 and sVCAM-1 were determined at baseline in all subjects and after six months of antipsychotic treatment. Thirty patients (60%) were treated with olanzapine and 20 (40%) with risperidone.ResultsThe average age of patients experiencing their first episode of SZ was 29.7±6.6 years, and 23 (46%) were men. The initial sICAM-1 levels of the patients were lower than those of the control group (P<0.0001), and increased after treatment (P=0.02), but remained lower than in the healthy controls (P=0.026). The initial levels of sVCAM-1 levels were higher in the patients (P<0.0001) and decreased after treatment (P<0.0001) to values that were similar to those of the control group (P=0.39). The only independent predictor of a baseline BPRS over 120 was the baseline sVCAM-1 level (P<0.0001). Antipsychotic treatment induced significant decreases in BPRS score (P<0.0001), in systolic (P=0.005) and diastolic (P<0.0001) blood pressure, in HDL-c (P=0.02), as well as significant increases in blood glucose (P<0.01) and LDL-c (P<0.001), with no differences between olanzapine and risperidone.ConclusionIn the patients experiencing an FEP of SZ, the levels of sICAM-1 were lower, while the levels of sVCAM-1 were higher than in the healthy control subjects. The antipsychotics used in the treatment of schizophrenia increased sICAM-1 and decreased sVCAM. The baseline level of sVCAM-1 was an independent predictor of a BPRS score >120 at baseline.

P.382 Circadian rhythm of hallucinatory experiences in patients with schizophrenia

The metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia.For subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations.39% of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95% CI 1.01–1.24, p = 0.031) and leptin (HR = 1.12, 95% CI 1.01–1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95% CI 1.00–1.19, p = 0.059).Our findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify—prior to treatment—patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted.

P.739 Use of cannabis, alcohol and other substances in mentally ill offenders-data from Northern Greece

Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients.In a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N = 119, consisting of N = 88 patients with persisting SUD at baseline and N = 31 patients with previous SUD) and without SUD (FE-non-SUD, N = 204) were compared at baseline and 6 months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding.In total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p = 0.033, Cohen's d = 0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p = 0.008, Cohen's d = 0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16 years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption.FE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6 months of antipsychotic treatment.

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.

Total and differential white blood cell counts, inflammatory markers, adipokines, and incident metabolic syndrome in phase 1 of the clinical antipsychotic trials of intervention effectiveness study

ObjectiveThe metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia. MethodFor subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations. Results39% of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95% CI 1.01–1.24, p = 0.031) and leptin (HR = 1.12, 95% CI 1.01–1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95% CI 1.00–1.19, p = 0.059). ConclusionsOur findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify—prior to treatment—patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted.

Cognitive impairment and its improvement after six months in adolescents with schizophrenia

Studies evaluating the cognitive impairment in schizophrenic adolescents reported a variable course following antipsychotic treatment, with improvement being associated to patients' demographic or clinical characteristics. ObjectivesTo examine the cognitive impairments of a Mexican sample of adolescents with schizophrenia using the MATRICS Consensus Cognitive Battery (MCCB) before and after six months of antipsychotic treatment and to determine which demographic or clinical characteristics could be associated to cognitive improvement. MethodsA sample of 87 Mexican patients was evaluated with the MCCB. Domain scores for three age groups (12–13, 14–15 and 16–17 y.o.) were obtained at baseline, and after 3 and 6 months of treatment. The groups were compared for demographic and clinical variables (sex, school attendance, years of education, being on their first psychotic episode, duration of illness and mean dose of antipsychotic), and a logistic regression analysis was performed to determine which variables predicted larger improvement. ResultsThe baseline performance showed scores below the standardized mean, with improvement in all domains except for social cognition; female adolescents showed a larger improvement in attention/vigilance and visual learning domains. ConclusionsWe observed cognitive impairments on schizophrenic adolescents, which improved after six months of treatment in almost all domains.

Antipsychotic-Associated Symptoms of Tourette Syndrome: A Systematic Review.

Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxical induction of tics by first- and second-generation antipsychotics. The objective of this systematic review was to better characterize tics as the potential adverse effect of antipsychotics. A literature search was performed, with no language restriction, using the MEDLINE, EMBASE, and PsycINFO databases for all publications up to January 2018. To be included, studies utilizing any study design had to meet the following criteria: (1) a temporal association of tics with antipsychotic use where tics emerged during treatment or after discontinuation and (2) no diagnosis of Tourette syndrome before tic emergence. More stringent criteria were used for individuals under 18years of age that included (1) no personal or family history of primary tic disorder and either (2) tics occurring during antipsychotic treatment improved significantly upon discontinuation or dose reduction or (3) tics emerged after discontinuation of at least 3months of antipsychotic treatment. Data were extracted according to: age, sex, diagnosis, personal history of motor symptoms or family history of tics, antipsychotic type and dose, treatment duration, types of symptoms emerged, treatment strategies, and follow-up. A Fisher's exact test was used to compare the occurrence of symptoms between first- and second-generation antipsychotic users. The search identified 1290 articles, of which 92 full-text articles were assessed leading to the inclusion of 50 articles. Most of the included articles were case reports or series, involving a total of 60 cases. Thirty cases were associated with treatment with first-generation antipsychotics, 27 with second-generation antipsychotics, and three with a combination of first- and second-generation antipsychotics. Antipsychotics were being used to treat schizophrenia in 60% of the cases and other indications included developmental, behavioral, and mood or anxiety disorders. Tics occurred during treatment (n = 44) or following treatment discontinuation (n = 16). The occurrence of vocal tics with or without motor tics was significantly higher in the first- vs. second-generation antipsychotic users (p < 0.0001). Significantly higher occurrences were also noted in the first- vs. second-generation antipsychotic users for specific types of vocal tics (i.e., barking and coprolalia) and other concurrent motor symptoms (i.e., tardive dyskinesia). In the cases identified, antipsychotic-associated tics were treated by (1) discontinuing the offending antipsychotic, reducing its dose, or switching to different antipsychotics for tics occurring during treatment, (2) reinitiating antipsychotic treatment for tics occurring following discontinuation, or (3) using non-antipsychotic agents. It should be noted that symptoms were not always fully reversible and recurred at times. Tics can be a disturbing adverse effect of antipsychotics. Clinicians need to be particularly vigilant when initiating and modifying antipsychotic regimens.

F166. LOW-GRADE INFLAMMATION IN FIRST-EPISODE PSYCHOSIS IS DETERMINED BY WAIST CIRCUMFERENCE INCREASE

BackgroundThere is evidence of low-grade inflammation in psychosis, as measured by the high-sensitivity C-reactive protein (hs-CRP). Significant weight gain is common during the first months of antipsychotic treatment. In the general population, overweight and obesity often lead to systemic low-grade inflammation. Lifestyle factors, such as smoking, can contribute to the pro-inflammatory changes. The metabolic changes in people with first-episode psychosis (FEP) taking place after the onset of psychosis can be especially harmful as these individuals are typically young and without major somatic illnesses. We aimed to study how the low-grade inflammation, measured by hs-CRP, develops in FEP and to clarify the effect of waist circumference increase in the inflammation.MethodsThe Helsinki Early Psychosis Study recruited FEP patients (age 18 to 40 years) attaining their first treatment for psychosis from the catchment area of the Helsinki University Hospital. We recruited 95 FEP patients and 62 controls. The inclusion criterion for the study was receiving a score of at least 4 in Unusual thought content or Hallucinations in the Brief Psychiatric Rating Scale - Extended (BPRS-E). Diagnoses of psychotic disorders according to the DSM-IV criteria were later verified using the Structured Diagnostic Interview for DSM-IV and reviewing all medical records. Substance-induced psychotic disorders and psychotic disorders due to a general medical condition were excluded. We measured the changes in hs-CRP, weight, waist circumference, glucose metabolism and lipids at baseline and at follow-ups of 2 and 12 months. We used linear mixed effects models to analyze the relationship between hs-CRP and waist circumference. In the model, we included a random intercept for each patient and, as fixed effects, we entered sex, time (days from baseline measurement), waist circumference and antipsychotic use at each assessment point, and baseline cigarette smoking.ResultsAt baseline, FEP patients (mean age 26.1 years) had higher insulin resistance, total and LDL cholesterol, apolipoprotein B and triglyceride levels than controls. However, baseline weight and waist circumference, hs-CRP, fasting glucose and HDL cholesterol were similar between patients and controls. A robust change in anthropometric measures and inflammation was evident among patients by 12 months. Hs-CRP was significantly higher in patients at 12-month follow up than at baseline (baseline hs-CRP 0.67 mg/l, IQR 0.33–2.54; 12-month 1.73 mg/l, IQR 0.49–4.21; Wilcoxon signed-rank p = 0.007). When at the baseline the prevalence of overweight or obesity was 30% (28/94) in patients with FEP, by 12 months the prevalence was 59% (35/59) (McNemar′s test p < 0.001). The proportion of patients gaining ≥ 7 % of baseline weight was 68 % (40/59). The median weight gain among patients was 9.6 kg (IQR 1.5–13.6 kg), and the waist circumference increase 6.0 cm (IQR 2.0–13.0 cm). In the mixed effects model waist circumference (p < 0.0001) and sex (p = 0.014) were significantly associated with hs-CRP level.DiscussionWe detected a significant elevation in hs-CRP in people with FEP during the first treatment year. The rise in hs-CRP was determined by waist circumference increase. Patients with FEP are in a marked risk of developing abdominal obesity and subsequent low-grade inflammation during the first year of treatment. Prevention of the early metabolic changes in first-episode psychosis is important, as abdominal obesity and inflammation are associated with increased risk of cardiovascular events and mortality.

SU19. Effects of N-Acetyl-Cysteine as an Add-on to Standard Treatment on Neurocognition in Early Psychosis

Abstract Background: Schizophrenia is associated with neurocognitive dysfunction already in the early phase of the disease.1 However, cognitive impairments are actually poorly treated by pharmacological interventions, leaving severe problems in functioning.2 Increasing evidence suggest oxidative stress and redox dysregulation play a role in the emergence of psychosis.3 In particular, levels of glutathione (GSH) are lower in chronic schizophrenia.4 In addition, a previous trial with the antioxidant N-acetyl-cysteine (NAC) led to negative symptoms reduction in chronic patients.5 Therefore, we explored if NAC had also an impact on neurocognition in early psychosis (EP) patients. Methods: The study was a 6-month, double-blind, randomized, placebo-controlled trial of NAC supplementation (2700 mg/d) to standard medications. Neurocognition was assessed at baseline and at the end of treatment with the MATRICS Consensus Cognitive Battery (MCCB),6 excluding the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Sixty-one patients (31 NAC, 30 placebo) with a diagnostic of psychotic disorder and less than 12 months of antipsychotic treatment were enrolled. Results: We found significant interaction Time × Treatment in favor of NAC on the MCCB processing speed factor and for 2 of 3 processing speed’s tasks (Trail Making A and Verbal Fluency). The improvement in processing speed within the NAC group was correlated with a decrease in negative symptoms. In addition, it was possible to identify a subgroup of patients who responded to NAC treatment considering their biological variables. Indeed, patients having a low peroxidase (GPx) activity at baseline benefited more than others from NAC supplementation in terms of processing speed’s scores. Moreover, in those individuals only, the improvement in processing speed was related to a decrease of the GSH reductase (GR) activity and to a regulation of the balance GPx – GR. Conclusion: Addition of NAC improved processing speed in EP patients, in particular in those who displayed a low basal level of redox dysregulation. Further, larger studies on antioxidant interventions are needed to replicate these findings. This work was supported by the National Center of Competence in Research (NCCR) “SYNAPSY – The Synaptic Bases of Mental Diseases” financed by the Swiss National Science Foundation, Damm-Etienne Foundation, Alamaya Foundation, the Commonwealth of Massachusetts Center of Excellence in Clinical Neuroscience and Psychopharmacological Research (SCDMH82101008006, LJS), and the Weisman family (LJS).

Acute psychosis owing to recurrence of craniopharyngioma in an elderly woman

A 63-year-old woman, after 5 years of resection of craniopharyngioma, developed recurrence of tumor with acute onset of psychotic symptoms. After 4 years of resection of craniopharyngioma, the patient presented with psychotic symptoms of varied delusion of reference, persecution, black magic and occasional auditory hallucinations. On physical examination, she showed no neurological deficit. Her blood investigations were at normal levels. Her recent magnetic resonance imaging brain scan showed large cystic lesion supposed to be a recurrent mass in sellar and suprasellar regions. After 2 months of antipsychotic treatment, her delusions and hallucinations were much decreased to extent that now she can do some household work. Her psychosis was controlled while she awaits neurosurgical intervention for recurrent craniopharyngioma. Acute psychosis is rarely found in elderly people and after few years of craniotomy for craniopharyngioma resection. So, the psychosis can be associated with the recurrence of craniopharyngioma. Such psychosis needs surgical intervention for primary cause.

Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program

The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life. Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities. The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups. Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.

Relationship between symptomatic improvement and overall illness severity in patients with schizophrenia.

Whether improvement on ratings of global illness severity is differentially associated with improvement in specific symptom domains in patients with schizophrenia is not well understood. The present study examined the independent relationships between improvement in specific symptom clusters and change in global impressions of illness severity. This study included 589 patients with chronic schizophrenia who were assessed at baseline and after 6 months of antipsychotic treatment. Both clinicians and patients completed the Clinical Global Impressions-Severity of Illness Scale (CGI-S). Symptom severity was assessed using factor scores derived from the Positive and Negative Syndrome Scale. Change in illness severity ratings made by the clinician and those made by the patient demonstrated moderate overlap. Nearly half of the patients were evaluated as clinically improved during the 6-month period, as rated by the clinician, with less than a third of patients experiencing a reduction in illness severity as determined by both the clinician and themselves. Improvements in clinician-rated CGI-S scores were most strongly associated with reduction in positive symptom severity. In contrast, change in patient-rated CGI-S scores was not linked to reduction in positive symptoms but rather to improvement in depressive and anxiety symptoms. This latter finding remained in a subsample of patients with relatively preserved insight into illness, suggesting that lack of insight cannot account for these findings. Finally, reduction in positive symptoms beyond 2 to 3 points was found to be clinically meaningful. In conclusion, change in overall illness severity, as determined by clinicians, is not necessarily interchangeable with patients' view of improvement of their own clinical status. Moreover, changes in the 2 evaluations of illness severity are associated with changes in different symptom domains.

Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: Findings from the NIMH CATIE study

The field of schizophrenia is redefining optimal outcome, moving beyond clinical remission to a more comprehensive model including functional recovery and improved subjective well-being. Although numerous studies have evaluated subjective outcomes within the domain of subjective quality of life in patients with schizophrenia, less is known about global evaluations of subjective well-being. This study examined the effects of antipsychotic medication on overall life satisfaction in patients with chronic schizophrenia. Data were drawn from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, where participants with a DSM-IV diagnosis of schizophrenia were randomized to receive olanzapine, perphenazine, quetiapine, risperidone or ziprasidone under double-blind conditions (N=753). The primary outcome measure was prospective change in subjectively evaluated overall life satisfaction scores following 12 months of antipsychotic treatment. Psychopathology, medication side effects and functional status were also evaluated, among other variables. Patients experienced modest improvements in overall life satisfaction (d=0.22, p<0.001), with no differences between antipsychotic medications (all tests, p>0.05). Change in severity of positive, negative, and depressive symptoms as well as functional status each demonstrated a small, albeit statistically significant, association with change in life satisfaction (r=0.10–0.21, p׳s<0.01). In a multivariate regression model, change in clinical symptoms and functional status had limited independent predictive value for change in life satisfaction scores (explained variance <3%). These data suggest that despite antipsychotic medications being effective for symptom-based psychopathology, such clinical effectiveness does not necessarily translate to improved general satisfaction with life. Clinicians should be aware that these two domains are not inextricably linked.

Twenty-Four Months of Antipsychotic Treatment in Children and Adolescents With First Psychotic Episode

The Child and Adolescent First-Episode Psychosis Study is a longitudinal study of early-onset first psychotic episodes. This report describes the naturalistic psychopharmacological treatment administered during a 24-month follow-up period, as well as discontinuation rates, reasons for discontinuation, and adverse effects. The sample comprised 110 patients, aged 9 to 17 years, with a first psychotic episode. Pharmacological treatment, changes, reasons for discontinuation, and the UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale were registered at 6, 12, and 24 months of follow-up. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, were the most commonly used. The discontinuation rate was 44.5% at 6 months, 59.1% at 12 months, and 70.9% at 24 months. Discontinuation rates or reasons for discontinuation (adverse reaction, insufficient response, and other) did not differ significantly between antipsychotics. At 6 months, significant differences were found in body mass index increase and body mass index z score increase, which were higher with olanzapine, and in neurological effects, which were higher with risperidone; at 12 and 24 months, these differences were no longer significant. High maintenance rates were found in the clozapine group, although they had higher scores on the autonomic subscale of the UKU. A long follow-up period reveals high discontinuation rates similar to those observed in adults, particularly during the first year. No differences were found between antipsychotics. Differences in adverse effects were found at 6 months but not subsequently after changes in treatment. Clozapine had a high maintenance rate, and its tolerability was comparable to that of other antipsychotics.

Comorbid substance abuse in first-episode schizophrenia: Effects on cognition and psychopathology in the EUFEST study

Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients. MethodIn a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N=119, consisting of N=88 patients with persisting SUD at baseline and N=31 patients with previous SUD) and without SUD (FE-non-SUD, N=204) were compared at baseline and 6months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding. ResultsIn total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p=0.033, Cohen's d=0.26) in patients with SUD at 6months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p=0.008, Cohen's d=0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption. ConclusionsFE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6months of antipsychotic treatment.