Multiple-episode Patients Research Articles

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Background-Cognitive deficits are known to be one of the core features of schizophrenia. Study shows that cognitive impairment was present in up to 75% of patients with schizophrenia. Deficits have been noted in attention/vigilance, processing speed, working memory, verbal learning and memory, visual learning and memory, problem solving and verbal comprehension.Aim-To study neurocognitive status and disability status between first episode and multiple episode schizophrenia patients.Methodology- 120 patients diagnosed with Schizophrenia were included after due consent and divided into two groups (first episode and multiple episode). Neurocognitive status was assessed by Addenbrooke’s cognitive examination III (ACE-III) and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS). Disability status was assessed using Indian Disability and Assessment Scale (IDEAS). Statistical analysis was done using MS Excel and SPSS software V. 20. Pearson’s correlation and Mann Whitney U test was used for analysis. P value < 0.05 was considered significant.Result-It was found that memory score was significantly impaired in multiple episode patients as compared to first episode patients (U=300.5, p = 0.03) in (ACE-III). (SSTICS) score was better in first episode as compared to multiple episode which was statistically significant (U=979.5, p<0.01). The IDEAS score was significantly more in patients with first episode as compared to multiple episode (U=985.0, p <0.01).Conclusions –It is concluded that greater neuro-cognitive impairment reported in patients with multiple episodes compared with first-episode patients. Hence, Exercises targeting all domains of neurocognition and insight building to be practiced regularly especially in chronic patients.

T87. TOWARD DEVELOPING CLINICAL CUTOFF VALUES FOR THE BECK COGNITIVE INSIGHT SCALE

BackgroundCognitive insight represents the ability to question and criticize the validity of one’s beliefs, to recognize when beliefs may be faulty, and to then rely on external feedback to make correct assessments of a situation. Cognitive insight is characteristically impaired in persons with schizophrenia and related psychoses. The Beck Cognitive Insight Scale (BCIS) is the most widely used tool to assess cognitive insight, yet there is no consensus regarding clinical cutoff values. Cognitive insight is predictive of better response to psychosocial treatment and the ability to accept critical feedback from treatment teams, thus cutoffs are an important next step needed to facilitate the clinical interpretation of the BCIS. Some studies have attempted to develop diagnostic cutoffs, yet no study has proposed clinical cutoffs to differentiate levels of cognitive insight between patients with schizophrenia.MethodsThree hundred and eighty-five English or French-speaking patients with a schizophrenia spectrum disorder (203 first-episode and 182 multiple-episode psychosis patients) and 185 healthy controls completed a battery of clinical and neuropsychological tests, including the BCIS. Patients and controls were matched on age, sex, level of education, and socio-economic-status. Correlations were calculated between the composite index and previously identified correlates of cognitive insight. Variables significantly correlating with the BCIS composite index were then included in a clustering analysis to classify patients according to their clinical profile. Two clinical profiles representing low and high cognitive insight were identified, and were based on global functioning and IQ. Composite index scores at the 33rd percentile in the low cognitive insight cluster and the 66th percentile in the high cognitive insight cluster were calculated.ResultsFunctioning and IQ significantly correlated with the BCIS composite index and were included in a clustering analysis, using a pre-determined number of two clusters. Independent samples t-tests revealed that the 2 clusters differed significantly on the BCIS self-reflectiveness score (t(372) = -3.93, p < .001) and on the composite index (t(372) = -3.17, p = .002). There was no difference between clusters on self-certainty (t(372) = .31, p = .76). Patients in cluster A had a mean SR, SC, and composite index of 12.65 (SD = 4.3, Range = 2 to 26), 7.78 (SD = 3.3, Range = 0 to 18) and 4.87 (SD = 5.8, Range = -11 to 20), respectively, while mean scores for patients in cluster B were 15.11 (SD = 4.1, Range = 3 to 25), 7.64 (SD = 2.9, Range = 1 to 15) and 7.47 (SD = 4.8, Range = -3 to 22). In cluster A, the values of the 33rd and 66th percentiles were 2.6 and 7 respectfully. In cluster B, these values were 5 and 9. We are proposing that 33% of patients with the lowest composite index scores in cluster A represent those with low cognitive insight. Accordingly, 33% of patients with the highest composite index scores classified in cluster B represent those with high cognitive insight. Low cognitive insight is thus represented by a score of 3 or below, borderline scores range from 4 to 9, and high cognitive insight is represented by a score of 10 or above.DiscussionWe proposed clinical cutoffs for the BCIS with a theoretical basis anchored in patient clinical profiles (functioning and IQ). Clinical cutoffs will facilitate and better orient treatment teams in the clinical interpretation of the BCIS and ergo to patients’ level of cognitive insight. The development of such cutoffs will help to reduce heterogeneity in psychosocial group intervention, will facilitate interventions aimed at increasing cognitive insight, and improve communication between patients and their treatment teams.

Individual differences in schizophrenia.

BackgroundWhether there are distinct subtypes of schizophrenia is an important issue to advance understanding and treatment of schizophrenia.AimsTo understand and treat individuals with schizophrenia, the aim was to advance understanding of differences between individuals, whether there are discrete subtypes, and how first-episode patients (FEP) may differ from multiple episode patients (MEP).MethodThese issues were analysed in 687 FEP and 1880 MEP with schizophrenia using the Positive and Negative Syndrome Scale for (PANSS) schizophrenia before and after antipsychotic medication for 6 weeks.ResultsThe seven Negative Symptoms were correlated with each other and with P2 (conceptual disorganisation), G13 (disturbance of volition), and G7 (motor retardation). The main difference between individuals was in the cluster of seven negative symptoms, which had a continuous unimodal distribution. Medication decreased the PANSS scores for all the symptoms, which were similar in the FEP and MEP groups.ConclusionsThe negative symptoms are a major source of individual differences, and there are potential implications for treatment.Declaration of interestsL.P. received speaker fees from Otsuka Canada and educational grant from Janssen Canada in 2017.Copyright and usage© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Serum 25-OH vitamin D level in patients with schizophrenia spectrum disorders

Introduction25-OH vitamin D level is an immediate precursor metabolite of the active form of vitamin D that leads to expression of more than 200 genes.AimsThe aim of our study was to examine 25-OH vitamin D deficiency (&lt;50nmol/L) and its relationship to demographic factors in recently hospitalised patients with schizophrenia spectrum disorders (SSD).MethodsWe assessed 25-OH vitamin D serum level in 41 SSD patients (54% of males, 46% with first episode, 63% during sunny season [May to October]), mean age 30 ± 10.4 years, within first days of hospitalization. The serum 25-OH vitamin D level was analysed with electrochemiluminiscence, using imunoanalysators Elecsys Roche.ResultsThe serum level was significantly higher in sunny season (41.3 ± 27.2 nmol/L) than in November to April (28.4 ± 11.2 nmol/L): t-test, P &lt; .05. Sixty-nine percent of patients suffered from 25-OH vitamin D deficiency (&lt; 50nmol/L) in May to October and 100% during November to April. The 25-OH vitamin D serum levels were not different between males and females, or between first-episode and multiple-episode patients. No significant correlation between age and 25-OH vitamin D level was found.ConclusionsThe high prevalence of 25-OH vitamin D deficiency (&lt; 50nmol/L) suggests that some patients with SSD may benefit from vitamin D supplementation.FundingThis study is a result of the research funded by the project Nr. LO1611 with a financial support from the MEYS under the NPU I program.Disclosure of interestThe authors have not supplied their declaration of competing interest.

New evidence in support of staging approaches in schizophrenia: Differences in clinical profiles between first episode, early stage, and late stage

Few studies have examined the progression of symptom dimensions in schizophrenia patients over the course of the illness. The objective of this study was to investigate whether clinical and psychopathological differences exist between first-episode schizophrenia (FES) and multiple-episode patients in an inpatient setting. Patients (N=203) were evaluated using the Positive and Negative Syndrome Scale (PANSS) over time. Five different generalized estimating equations were built for the PANSS factors using the following as covariates: sex, patient's age, assessment time point (i.e., moment of patient's evaluation, with a minimum of two and a maximum of four assessments throughout the study timeframe). The FES group was used as the reference to which the groups with up to five years of illness and more than five years of illness were compared. Remission rates and treatment resistance (TRS) rates were also compared. Generalized estimating equations were used to allow for different numbers of assessments over the study period. Patients with FES showed significantly milder severity in positive, disorganized, and hostility factors. Also, FES patients were more likely to achieve remission (P=0.002) and had lower rates of TRS (P=0.001). First-episode schizophrenia seems to be the critical period to improve outcome, as multiple-episode patients were similar in clinical characteristics regardless of illness duration.

Gesture Performance in First- and Multiple-Episode Patients with Schizophrenia Spectrum Disorders

Background/Aim: Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. Methods: In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. Results: Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. Conclusions: Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course.

Impact of pretreatment with antidepressants on the efficacy of duloxetine in terms of mood symptoms and functioning: an analysis of 15 pooled major depressive disorder studies.

This post hoc analysis aimed to determine whether patients with major depressive disorder (MDD) in duloxetine trials who were antidepressant naive or who were previously exposed to antidepressants exhibited differences in efficacy and functioning. Data were pooled from 15 double-blind, placebo- and/or active-controlled duloxetine trials of adult patients with MDD conducted by Eli Lilly and Company. The individual studies took place between March 2000 and November 2009. Data were analyzed using 4 pretreatment subgroups: first-episode never treated, multiple-episode never treated, treated previously only with selective serotonin reuptake inhibitors (SSRIs), and previously treated with antidepressants other than just SSRIs. Measures included the 17-item Hamilton Depression Rating Scale (HDRS-17) total and somatic symptom subscale scores, Montgomery-Asberg Depression Rating Scale (MADRS) total score, and Sheehan Disability Scale total score. Response rates (50% and 30%) were based on the HDRS-17 total score and remission rates on either the HDRS-17 or MADRS total score. Response and remission rates were significantly greater (P < .05 in 11 of 12 comparisons) for duloxetine versus placebo in the 4 subgroups. A trend of greater response and remission occurred for first-episode versus multiple-episode patients; both groups were generally higher than the antidepressant-treated groups. Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores. Duloxetine was generally superior to placebo on response and remission rates and in mean change on efficacy measures. Response and remission rates were numerically greater for first-episode versus multiple-episode and drug-treated patients. Mean change differences on efficacy measures among the 4 subgroups were inconsistent. Duloxetine showed a similar therapeutic effect independent of episode frequency and antidepressant pretreatment.

Reward, memory and prediction of treatment response in affective disorders

The reward system has been reported to be affected in patients with major depression or anhedonia and has been viewed as a symptom expressed by deficits in experiencing proper reward. In a sample of first-episode and multipleepisode patients with major depression plus healthy controls, Hall et al. [1] for the first time compared functional magnetic resonance imaging (fMRI) during performance of a contingency reversal reward paradigm. They detected group differences in orbitofrontal and medial prefrontal regions. Additionally, nucleus accumbens, anterior cingulate and ventral prefrontal cortices were most activated in healthy controls, less in patients with one-episode and least in multiple-episode patients. Those brain areas may be sensitive to neurobiological alterations during repeated episodes of depression. While impaired cognition and decreased volumes of the hippocampus repeatedly have been reported for patients with major depression, bipolar patients present inconsistent structural imaging data possibly due to lithium therapy. Using a transitive inference (TI) paradigm suitable for assessing relational memory performance and fMRI, Avery et al. [2] examined hippocampal activity and hippocampal volumes via manual segmentation in patients with bipolar disorder compared to healthy controls. They found no differences in any of these parameters between both groups but very well a positive correlation between hippocampal volume and relational memory performance. These results possibly distinguish bipolar disorder from schizophrenia without consulting a common neurogenetic background, which confirms recent genome-wide association studies. Low-resolution brain electromagnetic tomography is a neuroelectric brain imaging technique based on electroencephalography (EEG), which Rentzsch et al. [3] used in combination with assessing symptoms improvement after 4 weeks of antidepressant therapy in patients with major depression to predict treatment response. Responders showed more slow-frequency power in the right anterior cingulate cortex compared to non-responders which the authors attribute to antidepressant treatment response. In a

Remission in Schizophrenia: Critical and Systematic Review

In 2005, the Remission in Schizophrenia Working Group published consensus criteria to define remission. These criteria have been widely accepted and utilized and have provided further insights about schizophrenia management and prognosis. We systematically reviewed studies that utilized these criteria, with the aim of assessing the remission rate in follow-up studies and the variables predicting or associated with remission. Remission has a reported rate of 17% to 78% (weighted mean = 35.6%) in first-episode schizophrenia and 16% to 62% (weighted mean = 37%) in multiple-episode patients, with no statistical difference between the two weighted means (p = .79). Patients who were treated with long-acting injectable risperidone showed high maintenance of remission status. Studies comparing second-generation antipsychotics versus haloperidol showed higher remission rates for the former. The variables most frequently associated with remission were better premorbid function, milder symptoms at baseline (especially negative symptoms), early response to treatment, and shorter duration of untreated psychosis. Variability in the length and frequency of follow-ups, as well as differences in dropout rates, could partially explain the differences in reported rates. Rates of symptomatic remission exceeded reported rates for functional recovery. Moreover, the majority of studies used Remission in Schizophrenia Working Group severity criteria only, neglecting duration. To enhance comparison between future research findings, we suggest further specifiers of the working group's criteria, to better define frequency and duration of follow-up, and proxy measures of remission.

Neurocognitive functioning in patients recently diagnosed with bipolar disorder

Cognitive dysfunction in bipolar disorder (BD) is well established in the literature; however, there are few studies of neurocognition in patients early in the course of the illness. In this study we compare neurocognitive function in a cohort of first-contact mania patients with a healthy control group matched for age, gender, and education. Patients with a first manic episode (FM) (n = 34) or previous untreated manic episodes (PM) (n = 21) were neuropsychologically tested following their first treated manic episode. A total of 110 matched healthy control comparison subjects were also tested. The following cognitive domains were evaluated: verbal and visual learning and memory, attention, processing speed, executive functioning, and IQ. Results were corrected for speed of processing differences and were compared with previously reported results for multiple-episode BD patients. BD patients early in their disease course showed impairments in psychomotor speed, attention, learning and memory, executive functioning, and IQ. When controlling for speed of processing, measures of visuoconstructive reasoning and motor dexterity remained statistically significant. Eighteen percent of FM and 16% of PM patients were found to have clinically significant neurocognitive impairment. No significant relationship between clinical symptoms and neurocognition was found. The first-contact mania patients studied were found to have smaller neurocognitive deficits compared to multiple-episode patients in previous studies. Neurocognitive dysfunction is present in early BD and is clinically significant for a proportion of patients. Our findings also suggest that neurocognitive dysfunction may increase with illness progression.

Cost-Effectiveness of 12-Month Therapeutic Assertive Community Treatment as Part of Integrated Care Versus Standard Care in Patients With Schizophrenia Treated With Quetiapine Immediate Release (ACCESS Trial)

To compare the 1-year cost-effectiveness of therapeutic assertive community treatment (ACT) with standard care in schizophrenia. ACT was specifically developed for patients with schizophrenia, delivered by psychosis experts highly trained in respective psychotherapies, and embedded into an integrated care system. Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT (n = 64) or standard care (n = 56) to 120 first- and multiple-episode patients with schizophrenia spectrum disorders (DSM-IV), the latter with a history of relapse due to medication nonadherence. Primary outcome was the incremental cost-effectiveness ratio (ICER) based on mental health care costs from a payer perspective and quality-adjusted life-years (QALYs) as a measure of health effects during the 12-month follow-up period (2006-2007). ACT was associated with significantly lower inpatient but higher outpatient costs than standard care, resulting in nonsignificantly lower total costs (P = .27). Incremental QALYs in the ACT group were 0.1 (P < .001). Thus, the point estimate for the ICER showed dominance of ACT. The probability of an ICER below €50,000 per QALY gained was 99.5%. The implementation of a psychotherapeutically oriented schizophrenia-specific and -experienced ACT team led to an improved patient outcome with reduced need of inpatient care. Despite the introduction of such a rather "costly" ACT team, treatment in ACT was cost-effective with regard to improved quality of life at comparable yearly costs. ClinicalTrials.gov identifier: NCT01081418.

Subjective Disturbance of Perception Is Related to Facial Affect Recognition in Schizophrenia

To examine the relationship between facial affect recognition (FAR) and subjective perceptual disturbances (SPDs), we assessed SPDs in 82 patients with DSM-IV schizophrenia (44 with first-episode psychosis [FEP] and 38 with multiple episodes [ME]) using two subscales of the Frankfurt Complaint Questionnaire (FCQ), WAS (simple perception) and WAK (complex perception). Emotional judgment ability was assessed using Ekman and Friesen's FAR task. Impaired recognition of emotion correlated with scores on the WAS but not on the WAK. The association was significant in the entire group and in the ME group. FAR was more impaired in the ME than in the FEP group. Our findings suggest that there is a relationship between SPDs and FAR impairment in schizophrenia, particularly in multiple-episode patients.

Prevalence, Predictors, and Consequences of Long-Term Refusal of Antipsychotic Treatment in First-Episode Psychosis

Studies investigating medication adherence in psychosis are limited by the need of a certain degree of medication adherence and the inclusion of mostly multiple-episode patients. By contrast, noninformed consent, epidemiological studies in first-episode psychosis (FEP) allow the assessment of an important subgroup of patients who persistently refuse antipsychotic medication and thereby never receive an adequate antipsychotic trial. The present study aims to assess the prevalence and predictors of such a "medication refusal" subgroup and its association with illness outcome. The present file audit study assessed medication adherence in an epidemiological cohort of 605 FEP patients who were treated within the Early Psychosis Prevention and Intervention Centre for up to 18 months. Medication adherence was categorized into full adherence, nonadherence, and persistent medication refusal. Predictors were analyzed using logistic regression models. During the 18-month treatment period, 204 patients (33.7%) were fully adherent, 287 (47.4%) displayed at least 1 phase of nonadherence, and 114 patients (18.8%) were persistent medication refusers. Poor premorbid functioning, comorbid substance use, and poor insight predicted both medication refusal and nonadherence; a forensic history and no previous contact to psychiatric care were specifically predictive of medication refusal. With respect to illness outcome, nonadherent patients were worse off when compared with fully adherent patients, and medication refusers were even worse off compared with nonadherent patients. Within a nonselected epidemiological FEP cohort, almost 20% of patients are persistent medication refusers. The found predictors may help to identify the individual risk of persistent medication refusal and may enable an early (preventive) treatment adaptation.

Relapse Prevention in First-Episode Schizophrenia—Maintenance vs Intermittent Drug Treatment With Prodrome-Based Early Intervention

After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia. A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits). Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects. Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases. clinicaltrials.gov Identifier: NCT00159120.

Assertive Community Treatment as Part of Integrated Care Versus Standard Care

The ACCESS trial examined the 12-month effectiveness of continuous therapeutic assertive community treatment (ACT) as part of integrated care compared to standard care in a catchment area comparison design in patients with schizophrenia spectrum disorders treated with quetiapine immediate release. Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT as part of integrated care (n = 64) or standard care (n = 56) to 120 patients with first- or multiple-episode schizophrenia spectrum disorders (Structured Clinical Interview for DSM-IV Axis I Disorders criteria); multiple-episode patients were restricted to those with a history of relapse due to medication nonadherence. The primary outcome was time to service disengagement. Secondary outcomes comprised medication nonadherence, improvements of symptoms, functioning, quality of life, satisfaction with care from patients' and relatives' perspectives, and service use data. The study was conducted from April 2005 to December 2008. 17 of 120 patients (14.2%) disengaged with service, 4 patients (6.3%) in the ACT and 13 patients (23.2%) in the standard care group. The mean Kaplan-Meier estimated time in service was 50.7 weeks in the ACT group (95% CI, 49.1-52.0) and 44.1 weeks in the standard care group (95% CI, 40.1-48.1). This difference was statistically significant (P = .0035). Mixed models repeated measures indicated larger improvements for ACT compared to standard care regarding symptoms (P < . 01), illness severity (P < . 001), global functioning (P < . 05), quality of life (P < . 05), and client satisfaction as perceived by patients and family (both P < . 05). Logistic regression analyses revealed that ACT was associated with a higher likelihood of being employed/occupied (P = .001), of living independently (P = .007), and of being adherent with medication (P < . 001) and a lower likelihood of persistent substance misuse (P = .027). Compared to standard care, intensive therapeutic ACT as part of integrated care could improve 1-year outcome. Future studies need to address in which settings these improvements can be sustained. clinicaltrials.gov Identifier: NCT01081418.

Baseline Characteristics and Outcomes in Patients With First Episode or Multiple Episodes of Acute Mania

Previous studies have reported differential responses to therapeutic interventions depending on the patient's history with bipolar disorder, which highlights the importance of understanding the longitudinal nature of the disorder. The goal of the present analyses was to describe and compare the baseline characteristics, response to treatment, and medication patterns in adult patients experiencing a first episode versus multiple episodes of mania. The European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study was a 2-year prospective, observational study to evaluate outcomes in patients experiencing a DSM-IV- or ICD-10-diagnosed manic or mixed episode. The study was conducted from December 2002 to June 2004. Among 3,115 patients, 256 (8.2%) enrolled with a first manic or mixed episode. Relative to multiple-episode patients, first-episode patients were younger and had a lower body mass index (BMI), a higher incidence of past or current cannabis abuse, significantly higher baseline Young Mania Rating Scale total and Clinical Global Impressions-Bipolar Disorder (CGI-BP) mania scores, and lower CGI-BP depression and Hamilton Depression Rating Scale (5-item version) total scores. At the 12-week endpoint, rates of recovery and remission were greater for first-episode patients, and times to recovery and remission were shorter. Limitations of the study were that entry of patients into this study with an acute manic or mixed episode was determined by clinical interview but not confirmed with a structured diagnostic interview. That information on the course of illness prior to entry into the study was obtained retrospectively. First-episode patients presented with different baseline illness characteristics and achieved recovery and remission more rapidly than multiple-episode patients.

Maintenance Treatment With Risperidone or Low-Dose Haloperidol in First-Episode Schizophrenia

Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested. Between November 2000 and May 2004, 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals. 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria. In the randomized controlled trial, double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for analysis. For 127 patients, this was a continuation trial after 8 weeks of randomized, double-blind, acute treatment with the same drugs; 24 patients were additionally randomly assigned after open acute treatment. With both antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved. Additionally, according to 2 post hoc defined measures of "marked clinical deterioration," significant differences occurred neither in the 2 respective deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time until deterioration. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Extrapyramidal symptoms were slightly higher with haloperidol. The overall dropout rate of 68%, however, was not significantly different between the 2 drug groups. Against the background of an overall favorable outcome, the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia. Possible design-related reasons for this finding are discussed. With regard to the high dropout rate, special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment. ClinicalTrials.gov identifier: NCT00159081.

Neurocognitive Functioning in Subjects at Risk for a First Episode of Psychosis Compared with First- and Multiple-episode Schizophrenia

Evidence from neurobiological studies suggests that schizophrenia arises from an early abnormality in brain development and possibly further progressive developmental mechanisms. Despite a delay between the acquisition of neuropathology and the triggering of psychosis, neurobiological susceptibility is likely to be expressed subclinically by biobehavioral markers in the premorbid stage. The exploratory study aims at identifying potential neurocognitive risk factors and investigating the unfolding of the illness within a cross-sectional design by comparing neurocognitive profiles in 179 healthy controls, 38 clinically identified subjects in an early initial prodromal state (EIPS) for psychosis, 90 subjects in a late initial prodromal state (LIPS), 86 first-episode patients with schizophrenia, and 88 multiple-episode patients. Subjects at risk were substantially impaired in verbal executive and verbal memory functions. Compared to EIPS subjects, LIPS subjects demonstrated additional attentional deficits. Both EIPS and LIPS subjects were superior to first-episode patients who presented a generalized neuropsychological deficit profile, and to multiple-episode patients who showed evidence for further decline. Although results were influenced by general intellectual abilities and demographic and clinical characteristics, they could not account for total group differences. Results support a neurodevelopmental model of psychosis with further progressive mechanisms and are consistent with a primary involvement of left frontotemporal networks in the prodromal phase.

Psychopathological characteristics and treatment response of first episode compared with multiple episode schizophrenic disorders

ObjectiveThe aim was to investigate the hypothesis that patients with first episode schizophrenic disorders have a more favorable treatment response than those with multiple episodes.MethodA total of 400 inpatients from an ongoing multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic disorders (F2) were assessed at admission to and discharge from hospital using the Positive and Negative Syndrome Scale (PANSS).ResultsAt admission, first episode patients (n = 121) showed higher levels of positive symptoms (PANSS positive subscore) and lower ones of negative symptoms (PANSS negative subscore) than multiple episode patients (n = 279), whereas the global disease severity (PANSS total score) was comparable. Analyses of covariance revealed that treatment response (adjusted symptom levels at discharge) was more favorable in first-episode patients, with respect to both positive and negative symptoms.ConclusionThe results are compatible with the hypothesis that treatment response becomes less favorable during the course of schizophrenic illness. This finding might be associated with progressive neurobiological alterations.

Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients

In this longitudinal study we compared brain volume changes in first- and multiple-episode patients with schizophrenia to normal aging changes observed in healthy control subjects scanned at comparable times. Two to four years after an initial examination including MRI volumetry, we followed up 21 first episode patients, 17 patients after multiple episodes of schizophrenia, and 20 healthy controls. Volumetric measurements of left and right hemispheres, total brain volume, lateral ventricles, hippocampus and amygdala as well as a clinical evaluation were performed. Patients with schizophrenia showed significant ventricular enlargement and volume reduction of the hippocampus–amygdala complex compared with healthy control subjects both at baseline and follow-up. While there were no differences between patients and controls with respect to mean annual volume changes in the measured regions, patients with schizophrenia showed higher between-subject variability in ventricular volume change. These data are consistent with cross-sectional studies demonstrating ventricular enlargement and hippocampal volume deficits in schizophrenia. However, we were not able to demonstrate a difference in the rate of volume changes over time that distinguished patients with schizophrenia from healthy controls for any of the brain structures measured. Drawbacks of the study are that the follow-up was done after a relatively short interval and that there was a difference in time to follow-up and age between patients and controls. Our results do not support the hypothesis that schizophrenia leads to progressive volume reduction in these areas, although there may be a subset of patients with morphologically visible disease progression.