Background: Treatment during first-episode psychosis (FEP) or early schizophrenia may affect the rates of relapse and remission, as well as cognitive functioning, over time. Prolonged duration of psychosis is associated with a poor prognosis, but the effects of treatment in patients with FEP or early schizophrenia on the long-term outcomes are not well defined.Objective: To understand the long-term effects of treatment with antipsychotic agents on remission, relapse, and cognition in patients with FEP or early schizophrenia.Methods: Using PubMed and Scopus databases, a systematic review was undertaken of articles published between January 1, 2000, and May 20, 2015, that reported randomized and nonrandomized prospective clinical trials on the long-term effects of oral or long-acting injectable antipsychotics on measures of relapse, remission, or cognition in patients with FEP or early schizophrenia. For comparative purposes, trials reporting the effects of later intervention with antipsychotics in patients with longer disease history were also evaluated. Titles, abstracts, and full-text articles were independently screened for eligibility by all the authors based on the predefined criteria.Results: Nineteen studies met inclusion criteria: 13 reported long-term outcomes of relapse, remission, or cognition following antipsychotic treatment in patients with FEP and six reported on patients with a longer disease history. Antipsychotic treatment in patients with FEP produced high rates of remission in the year following treatment initiation, and untreated FEP reduced the odds of later achieving remission. Maintenance therapy was more effective than treatment discontinuation or intermittent/guided discontinuation in preventing relapse. Initiating antipsychotic treatment in patients with FEP also produced sustained cognitive improvement for up to 2 years. Antipsychotic therapy also reduced the risk or rate of relapse in patients with a longer disease history, with outcomes in one study favoring a long-acting injectable formulation over an oral antipsychotic.Conclusion: Treatment of patients with FEP is associated with benefits in the long-term outcomes of remission, relapse, and cognition. More long-term studies of treatment in patients with FEP are needed to confirm these findings.

OBJECTIVE This study analyzed hospital readmission rates of patients with schizophrenia who were treated with long-acting injectable antipsychotics (LAIs) or with oral antipsychotics after being discharged from a hospitalization. METHODS Medical claims of patients with schizophrenia who were ages 18-64 and had a first hospitalization for a serious mental illness (index hospitalization, October 2007 through September 2012) and at least one prescription for a first- or second-generation antipsychotic were analyzed from the Truven Health MarketScan Multi-State Medicaid Database. Analyses were conducted for patients with a sole diagnosis of schizophrenia (N=1,450) and for all patients with schizophrenia (N=15,556), which added patients with a codiagnosis of bipolar disorder or major depressive disorder. Probability of rehospitalization for any cause at 30 and 60 days after the initial hospitalization was assessed with multivariate logistic regression and propensity score matching (PSM) methods. The PSM model matched age, preindex use of LAIs or short-acting injectables, and select comorbidities between the LAI and the oral antipsychotics groups. RESULTS LAIs were associated with significantly lower probability of rehospitalization compared with oral antipsychotics at 60 days for schizophrenia-only patients (adjusted odds ratio [AOR]=.60, 95% confidence interval [CI]=.41-.90) and for all patients (AOR=.70, CI=.52-.95). The absolute difference in probability of rehospitalization for all patients was significantly lower by 5.0% at 60 days in the LAI group compared with the oral antipsychotics group. CONCLUSIONS Compared with use of oral antipsychotics, use of LAIs was associated with fewer readmissions of Medicaid patients with schizophrenia within 60 days after an index hospitalization.

BACKGROUND:Database analyses have indicated that medical treatment for schizophrenia varies among racial groups. This study assessed antipsychotic use and healthcare utilization across races in Medicaid-insured patients with schizophrenia. METHODS:A Medicaid database of inpatient/outpatient medical claims and outpatient prescription claims for more than 28 million enrollees in 11 geographically diverse states was analyzed. The primary outcome, racial differences in antipsychotic use in 2012, was examined in 5 multivariable logistic regression models: (1) any antipsychotic, (2) first-generation (FG) long-acting injectables (LAIs), (3) FG oral antipsychotics, (4) second-generation (SG) LAIs, and (5) SG oral antipsychotics. RESULTS:Odds ratios and adjusted predicted probabilities were comparable for any antipsychotic use between black and white patients. Black patients were less likely to receive SG oral antipsychotics (P < .001) and more likely to receive SG or FG LAIs (P = .001 and P < .001, respectively) and FG oral antipsychotics (P = .003) vs white patients. Further, black patients had a higher mean number of emergency room visits (P < .001) and a lower mean number of hospitalizations (P < .05) vs white patients; the mean number of physician visits was comparable. CONCLUSIONS:Disparities in antipsychotic use and healthcare utilization across races in patients with schizophrenia warrant further investigation and elimination of these disparities should be a national goal.

This study evaluated the impact of using long-acting injectable (LAI) antipsychotics for a longer treatment duration versus a short duration on health care resource utilization among Medicaid-insured schizophrenia patients. Schizophrenia patients 13 years or older initiating LAI antipsychotics were identified from the Truven Health Analytics MarketScan Research Medicaid database between July 1, 2005, and June 30, 2010. The study population was grouped into 2 study cohorts (longer-usage-duration cohort: ≥ 180 days of supply and short-usage-duration cohort: <180 days of supply). Hospitalization-related resource utilization and costs were determined during a variable follow-up period and compared at the unadjusted and adjusted levels. Of the 5694 patients identified, 2838 patients were treated with LAI antipsychotics for a mean duration of 604 (SD, 432) days (mean age, 38.91 years), and 2856 were treated for 86 (SD, 43) days (mean age, 39.96 days). Total hospital lengths of stay, all cause (6.56 [SD, 18.63] vs 4.93 [SD, 13.40] days, P < 0.001) and schizophrenia related (5.18 [SD, 14.96] vs 4.16 [SD, 11.94] days, P = 0.005), and the mean number of hospitalizations, all cause (0.79 [SD, 1.78] vs 0.61 [SD, 1.41], P < 0.001) and schizophrenia related (0.63 [SD, 1.55] vs 0.51 [SD, 1.26], P = 0.001), were lower for the longer-usage-duration cohort. Cox regression results showed that using LAI antipsychotics for a longer duration was correlated with longer time to the first hospitalization for any cause and for schizophrenia. After multivariate regression, longer usage duration of LAI antipsychotics was associated with a decreased number of hospitalizations (-0.15 per year, P < 0.001), a decreased hospital length of stay (-1.50 days, P < 0.001), and reduced hospital payment (-26%, P < 0.001). Patients who are treated with LAI antipsychotics for a longer versus shorter duration use hospital resources less.

Abstract Objective: This study compared healthcare resource usage and costs before and after initiating LAI antipsychotics among Medicaid-insured schizophrenia patients. Methods: Schizophrenia patients ≥13 years of age initiating LAI antipsychotics were identified from the Thomson Reuters MarketScan® Research Medicaid database between 7/1/2005 and 6/30/2010. Patients were required to have 6 months of continuous medical/prescription drug coverage prior to LAI initiation (baseline period) and during a variable follow-up period. Annualized healthcare resource usage and costs for the baseline and follow-up periods were determined and compared. Results: Among 5694 eligible patients, 55% were male and 45% were female, and the majority of the population was between the ages of 18–55 (86%). The study population had low general comorbidity, as assessed by the Charlson Comorbidity Index (CCI). Diabetes (17%) and chronic pulmonary disease (14%) were the most prevalent comorbidities. In comparison to the baseline period, during the follow-up period (mean duration = 25.7 months) the mean number of hospitalizations, all cause (1.52 ± 2.41 vs 0.70 ± 1.61, p < 0.001) and schizophrenia-related (1.21 ± 2.04 vs 0.57 ± 1.41, p < 0.001) declined as well as hospital lengths of stay (all cause: 14.77 ± 28.61 vs 5.75 ± 16.26 days, p < 0.001; schizophrenia-related: 12.39 ± 25.86 vs 4.67 ± 13.54 days, p < 0.001). As a result, annualized hospital payments were much lower (all cause: $16,249 ± $36,404 vs $7380 ± $21,087, p < 0.001; schizophrenia-related: $13,388 ± $31,614 vs $5645 ± $15,767, p < 0.001). Limitations: This study attempted to minimize the impact of differences in patient characteristics by having patients serve as their own controls in the before vs after comparison, however one still may not be able to account for all confounders in this non-randomized study population. Conclusion: For patients with schizophrenia who initiate LAI antipsychotic therapy, there is an improvement in disease management based on fewer hospitalizations for relapses, which is also associated with a marked reduction in healthcare costs.

Objective: Evaluate utilization of inpatient healthcare resources and associated costs after 12 months of treatment using long-acting injectable (LAI) antipsychotic medications among a large sample of Medicaid-insured patients categorized by different age groups. Method: Adult patients with schizophrenia were identified from the Thomson Reuters MarketScan Research database (1/1/2006–12/31/2010) before initiation of treatment using LAI antipsychotic agents. Utilization of inpatient healthcare resources and associated direct medical costs were compared for 12-month baseline and 12-month follow-up periods. Results: Among 3,094 Medicaid-insured patients with schizophrenia initiating treatment with LAIs, the mean number of all-cause hospitalizations and hospitalization days were reduced by 24% and 31% (p<0.0001) compared with baseline, respectively, with similar significant reductions among all age groups (18–30, 31–40, 41–50, and 51–60 years). During 12-month follow-up with LAIs, mean reductions in all-cause costs were $4,369 (18–30 years, p<0.0001), $3,681 (31–40 years, p<0.0001), $2,051 (41–50 years, p=0.1332), and $4,492 (51–60 years, p=0.0107). Subanalyses separating first-generation and second-generation medication groups resulted in mean reduction in all-cause costs of $3,561 and $3,645, respectively. Conclusions: Results from this large cohort study provide naturalistic real-world evidence of the utility of LAIs in patients with schizophrenia and suggest that these agents may help to reduce the risk of relapse across all age groups (especially among younger patients). Given that relapse prevention is the ultimate goal of antipsychotic treatment, results from this large Medicaid patient population establish the value of LAIs for the management of schizophrenia.

OBJECTIVE:Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U.S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures.METHOD:In this four-site validation study, schizophrenia patients were assessed at baseline (N=166) and 4 weeks later (N=144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performance-based measures were evaluated.RESULTS:All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data.CONCLUSIONS:Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance.

It has been hypothesized that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) composition and metabolism. We have used high resolution, in vitro 31P nuclear magnetic resonance (NMR) to characterize the PLs in left frontal cortex (gray matter) of postmortem brain from four schizophrenics and five controls. High resolution 31P NMR spectra were obtained in an organic-solvent system to resolve PL classes (headgroups) and in a sodium-cholate, aqueous dispersion system to resolve phosphatidylcholine (PC) molecular species. Multivariate analysis which included the major PC molecular species and phosphatidylinositol (PI) showed a significant difference between schizophrenics and controls. Analysis of specific interactions showed that the PI was significantly higher in the schizophrenic group than in the control group. There were no differences between the two groups for other individual PL classes, or for individual PL subclasses determined by the linkage type at the sn-1 position on glycerol. There was a trend for total PL content to be higher in schizophrenics than in controls. There was no evidence for elevated lysophosphatidylcholine or lysophosphatidylethanolamine in schizophrenia. The intensity of the PC peak representing molecular species with one saturated and one unsaturated (one or two double bonds) acyl chain was higher for the schizophrenic group than for the control group. Although these results are not in complete agreement with previous studies, they support the idea that PL abnormalities occur in the brain in schizophrenia and that fatty acid metabolism may be abnormal.

We have previously demonstrated elevation of the extracellular signal-regulated kinase (ERK) pathway in the cerebellum from patients with schizophrenia, an illness that may involve dysfunction of the N-methyl-D-aspartate (NMDA) receptor. Since the NMDA antagonist, phencyclidine (PCP), produces schizophrenic-like symptoms in humans, and abnormal behavior in animals, we examined the effects of chronic PCP administration in time- and dose-dependent manner on ERK and two other members of mitogen-activated protein kinase family, c-Jun N-terminal protein kinase (JNK) and p38, in rat brain. Osmotic pumps for PCP (18 mg/kg/day) and saline (controls) were implanted subcutaneously in rats for three, 10, and 20 days. Using Western blot analysis, we found no change at three days, but a significant increase in the phosphorylation of ERK1, ERK2 and MEK in the cerebellum at 10- and 20-days of continuous PCP infusion. For the experiments involving various doses of PCP, rats were infused with PCP at concentrations of 2.5, 10, 18, or 25 mg/kg/day, or saline for 10 days. We observed a dose-dependent elevation in the phosphorylation of ERK1 and ERK2 only in the cerebellum but not in brainstem, frontal cortex or hippocampus. The activities of JNK and p38 were unchanged in all investigated brain regions including cerebellum. These results demonstrate that chronic infusion of PCP in rats produces a differential and brain region-specific activation of MAP kinases, suggesting a role for the ERK signaling pathway in PCP abuse and perhaps in schizophrenia.

The metabolites of the antipsychotic drug trifluoperazine (TFP) were investigated with on-line coupling of high-performance liquid chromatography (HPLC) and NMR spectroscopy. A chromatographic method was developed using a reversed-phase C-30 silica gel column. Rats were given a cumulative dose of 90 mg kg(-1) TFP dihydrochloride and samples of brain and muscle tissues were extracted after 29 h. The peaks obtained on chromatographic separation were assigned to trifluoperazine and its metabolites. With the help of chromatograms obtained from test mixtures, 1D and 2D HPLC-NMR were used to identify the peaks found for these mixtures. Copyright (C) 2000 John Wiley & Sons, Ltd.

Localized in vivo proton magnetic resonance spectroscopy at 4.7 T was used to examine the brains of rats that were given the antipsychotic drugs haloperidol, clozapine, or olanzapine for 1 week. Spectra were collected before and during treatment. The ratios of N-acetylaspartate (NAA) to creatine (Cr) and choline to Cr were determined from the spectra. No significant differences in these ratios were seen among the rats given the various antipsychotic medications or between the control rats and the treated rats. No significant time-dependent changes were seen in most cases, except for a small reduction of NAA/Cr after 7 days of olanzapine administration. These results suggest that differences in brain metabolite ratios in vivo in schizophrenics relative to controls, at least for short-term treatment, arise from the disease, and not as a metabolic effect of the medication. (C) 2000 Wiley-Liss, Inc.

The current study used a paired stimulus paradigm to investigate the P1 midlatency auditory evoked potential in Vietnam combat veterans with posttraumatic stress disorder (PTSD) and three comparison groups: alcohol dependents, combat-exposed normals, and combat-unexposed normals. Compared to each comparison group, PTSD subjects exhibited significantly diminished habituation of the P1 potential. P1 potential habituation within the PTSD group, correlated significantly with intensity of PTSD reexperiencing symptoms, such as trauma-related nightmares and flashbacks. These findings are discussed as consistent with a sensory gating defect at the brainstem level in PTSD, and are further discussed in the context of other psychophysiological measures in PTSD and of P1 potential findings in psychiatric disorders other than PTSD.

A high proportion of neurons in the cerebellum and in cholinergic brainstem nuclei stain positive for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd), which is a nitric oxide synthase (NOS). Recent evidence suggests that schizophrenia may involve increased numbers of NADPHd-stained neurons in different areas of the subcortex. This led us to examine the actual concentration of NOS in postmortem brain specimens of cerebellum, and the relevant regions of brainstem tegmentum, to see if NOS concentrations were also increased in schizophrenia. Postmortem rain tissue was obtained at autopsy from schizophrenics and controls who did not have other brain disease. In patients with schizophrenia, NOS concentration was increased in the cerebellum (0.62±0.31 vs 0.32±0.27 absorption intensity or AI,p<0.05), but not in mesopontine tegmentum or temporal pole. Increased vermal NOS concentration in schizophrenia may signify a developmentally based alteration in subcortical neuronal systems whose early development may be promoted by basic fibroblast growth factor, rather than nerve growth factor.

The objective was to replicate a reported decrease of choline acetyltransferase (ChAT) in the mesopontine tegmentum of deceased schizophrenics and to see if such a decrease is related to their cognitive status as measured during life. Rigorous antemortem psychiatric evaluations were performed on our large population of schizophrenic patients. Mesopontine tissue was collected promptly following death from eight of these patients, from an additional five schizophrenics without systematic premortem psychiatric evaluation, and from control subjects. ChAT content of this brain tissue was determined using Western immunoblot analysis. There were 13 schizophrenic patients and 8 control subjects. The mean age of subjects in the two groups was similar (64±9 yr vs 63±10 yr). Even in the face of reduced post mortem intervals in the patients with schizophrenia, mesopontine tegmental ChAT concentrations were depressed by 70% in schizophrenic patients (1.28±1.74 vs 4.39±3.20 ng ChAT/μg tissue protein,P<0.01), and correlated with orientation and reasoning (r s=0.90 and 0.98, respectively) in those subjects assessed antemortem. Mesopontine ChAT concentrations are depressed in schizophrenia and correlate significantly with measures of cognitive performance in patients with this disorder.

Back to table of contents Previous article Next article ArticleNo AccessHandbook of Schizophrenia, vol. 5: Neuropsychology Psychophysiology and Information ProcessingCRAIG N. KARSONCRAIG N. KARSONSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.151.4.612AboutSections ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Handbook of Schizophrenia, vol. 5: Neuropsychology Psychophysiology and Information Processing." American Journal of Psychiatry, 151(4), p. 612 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byNone Volume 151Issue 4 April 1994Pages 612-612 Metrics History Published online 1 April 2006 Published in print 1 April 1994

1. Patterns of fluid intake and urine output was examined in schizophrenia and normal controls. 2. Fluid intake and urine output were significantly higher in schizophrenic patients. 3. Bouts of drinking correlated significantly with fluid intake but did not differ significantly between schizophrenic patients and normal controls. 4. Schizophrenic patients drink more per bout compared to normal controls.

Being effective readers provide university students the onset to follow through their academic pursuit successfully. Nonetheless, reading academic materials pose challenges to many tertiary level students, particularly to the second-language speaker of English. Unfamiliarity with the text content and lack of vocabulary to tackle a variety of text types may impede students’ understanding of materials read. Thus, the role of the instructor is to arrange and design suitable pedagogical instruction to facilitate the students to become effective readers. This paper explores a pedagogical approach which comprises both the cognitive and human science approach in facilitating students to become effective readers. The approach focuses on understanding students’ comprehension of texts by listening to their voices as well as activating their cognitive ability in tackling the nuances of academic reading materials. Data was gathered qualitatively. Discussion will centre on the hows and whys of the approach, as well as the feedback component in terms of instructor's as well as students’ responses. Implications for policy, curriculum development and practice will be drawn.