Dissecting the functional outcomes of first episode schizophrenia spectrum disorders: a 10-year follow-up study in the PAFIP cohort.

BACKGROUND: The aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach. METHOD: A large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored. RESULTS: The cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes. CONCLUSIONS: The current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.

Age of onset of Cannabis use and cognitive function in first-episode non-affective psychosis patients: Outcome at three-year follow-up.

BACKGROUND: In recent years, the effects of cannabis use on cognitive functions in patients with psychosis have been widely studied. Recently, special emphasis has been placed on the impact of age at the onset of consumption on cognition in these patients. METHOD: 349 patients with a first episode of non-affective psychosis were studied. Patients were classified as cannabis users and non-users. Users were divided, according to their age when they began using cannabis, into: early-onset (age < 16) and late-onset (age ≥ 16) users. Differences between groups at baseline were studied based on sociodemographic, clinical, and cognitive variables. The groups were longitudinally (3-year) compared on cognitive variables. RESULTS: Out of the 349 patients included in this study, 38.7% (N = 135) were cannabis users. Of them, 39.3% (N = 53) were early-onset and 60.7% (N = 82) were late-onset cannabis users. No baseline differences were found between the early-onset and late-onset groups on cognitive domains. Longitudinally, only patients who had withdrawn from cannabis use during follow-up showed a significant improvement in verbal memory. CONCLUSION: Our results did not show differences between the early-onset group and the other two groups in long-term cognitive performance, even if they kept consuming cannabis during the first three years of disease progression. Further studies are needed to elucidate the true relationship between early-onset cannabis use and cognitive function in patients with a first episode of psychosis.

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

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

The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals.

BACKGROUND: Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). OBJECTIVES: The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. METHODS: This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. RESULTS: In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1ß, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1ß, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. CONCLUSIONS: Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.

Incidence and risk factors of acute akathisia in 493 individuals with first episode non-affective psychosis: a 6-week randomised study of antipsychotic treatment.

INTRODUCTION: Acute akathisia is a neuropsychiatric syndrome with a negative effect on illness outcome. Its incidence in patients treated with antipsychotics has shown to be highly variable across studies. OBJECTIVES: Our goals were to investigate prevalence, risk factors for the development of acute akathisia, and differences in incidence between antipsychotics in a sample of 493 first episode non-affective psychosis patients. METHODS: This is a pooled analysis of three prospective, randomized, flexible-dose, and open-label clinical trials. Patients were randomized assigned to different arms of treatment (haloperidol, quetiapine, olanzapine, ziprasidone, risperidone, or aripiprazole). Akathisia was determined using the Barnes Akathisia Scale at 6 weeks after antipsychotic initialization. Univariate analyses were performed to identify demographic, biochemical, substance use, clinical, and treatment-related predictors of acute akathisia. Considering these results, a predictive model based of a subsample of 132 patients was constructed with akathisia as the dependent variable. RESULTS: The overall incidence of akathisia was 19.5%. No differences in demographic, biochemical, substance use, and clinical variables were found. Significant incidence differences between antipsychotics were observed (Χ 2 = 68.21, p = 0.000): haloperidol (57%), risperidone (20%), aripiprazole (18.2%), ziprasidone (17.2%), olanzapine (3.6%), and quetiapine (3.5%). The predictive model showed that the type of antipsychotic (OR = 21.3, p = 0.000), need for hospitalization (OR = 2.6, p = 0.05), and BPRS total score at baseline (OR = 1.05, p = 0.03) may help to predict akathisia emergence. CONCLUSIONS: Among second generation antipsychotics, only olanzapine and quetiapine should be considered as akathisia-sparing drugs. The type of antipsychotic, having been hospitalized, and a more severe symptomatology at intake seem to predict the development of acute akathisia.

Rates and predictors of relapse in first-episode non-affective psychosis: a 3-year longitudinal study in a specialized intervention program (PAFIP).

Relapses may represent a critical hazard in schizophrenia spectrum disorders as they are associated with an increased risk of a clinical and functional deterioration. Preventing relapse after recovering from a first psychotic episode has become a major challenge due to its critical impact on lifelong functionality. This study explored the rate of first and second relapses and the predictors associated with these relapses in a large cohort of non-affective psychosis patients during a period of 3 years after the first break of the illness. From February 2001 to May 2014, sociodemographic and clinical data from an epidemiological cohort of 341 non-affective first-episode psychosis patients at risk of relapse were analysed at a specialized early intervention service. Logistic regression, Cox regression, and Kaplan-Meier survival analyses were performed to compare non-relapsed and relapsed patients. One hundred and sixty-six (48.7%) individuals relapsed at least once. Median time to relapse was 17.0 months in non-adherent patients and 40.0 months in adherent patients (log-rankχ 2: 51.36; p < 0.001). Non-adherence to medication (odds ratio-OR 2.979; p < 0.001), schizophrenia diagnosis (OR 2.173; p = 0.002), and age of onset (OR 1.020; p = 0.033) were the main predictors of the first relapse. Fifty-six subjects experienced a second relapse (33.73%) predicted by diagnosis (OR 1.975; p = 0.074), age of onset (OR 1.078; p = 0.003), and positive symptoms (OR 0.863; p = 0.03), but not adherence. Non-adherence is the main predictive factor of first relapse after a first episode of psychosis. Second relapses were not often and not related to modifiable factors, suggesting that multiple relapsed patients may comprise a subgroup with a higher biological risk.

Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study.

RATIONALE: Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment. OBJECTIVES: Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients. RESULTS: A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (N = 83), risperidone (N = 12), quetiapine (N = 46), and ziprasidone (N = 50). At intake, 180 patients were antipsychotic naïve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score ≥60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score ≥60 and only 16.6 % who had a FLI score <30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score ≥60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score ≥ 60, 91.7 %; FLI < 60, 55.9 %; p < 0.001), increased triglyceride levels (FLI score ≥ 60, 54.2 %; FLI < 60, 5.6 %; p < 0.001), decreased HDL levels (FLI score ≥ 60, 41.7 %; FLI < 60, 17.5 %; p = 0.001), hypertension (FLI score ≥ 60, 19.5 %; FLI < 60, 4.5 %; p = 0.002), and waist circumference increase (steatosis 68.8 %; FLI < 60, 14.0 %; p < 0.001). CONCLUSIONS: Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.

Clinical outcome after antipsychotic treatment discontinuation in functionally recovered first-episode nonaffective psychosis individuals: a 3-year naturalistic follow-up study.

OBJECTIVE: The timing of antipsychotic discontinuation in patients who have fully recovered from their initial episode of psychosis is still open to discussion. We aimed to evaluate the risk of symptom recurrence during the 3 years after antipsychotic discontinuation in a sample of functionally recovered first-episode nonaffective psychosis (FEP) patients (DSM-IV criteria) with schizophrenia spectrum disorder. METHOD: Participants in this open-label, nonrandomized, prospective study were drawn from an ongoing longitudinal intervention program of FEP from a university hospital setting in Spain. From July 2004 to February 2011, functionally recovered FEP individuals were eligible if they met the inclusion criteria of (1) a minimum of 18 months on antipsychotic treatment, (2) clinical remission for at least 12 months, (3) functional recovery for at least 6 months, and (4) stabilization at the lowest effective doses for at least 3 months. Forty-six individuals who were willing to discontinue medication were included in the discontinuation group (target group). Twenty-two individuals opted to stay on the prescribed antipsychotic medication and therefore were included in the maintenance group (control group). Primary outcome measures were relapse rate at 18 and 36 months and time to relapse. RESULTS: The rates of relapse over the 3-year period were 67.4% (31 of 46) in the discontinuation group and 31.8% (7 of 22) in the maintenance group. The mean time to relapse was 209 (median = 122) days and 608 (median = 607) days, respectively (log rank = 10.106, P = .001). The resumption of antipsychotic medication after the relapse occurred was associated with clinical stability and lack of further relapses. When the overall group of relapsed individuals from the 2 conditions (N = 38) was compared to those who remained asymptomatic after 3 years (N = 30), there were significant differences (P < .05) in total scores on the Scale for the Assessment of Negative Symptoms, the Clinical Global Impressions scale, and the Disability Assessment Schedule. CONCLUSIONS: Antipsychotic treatment discontinuation in individuals who had accomplished a functional recovery after a single psychotic episode was associated with a high risk of symptom recurrence. Relapsed individuals had a greater severity of symptoms and lower functional status after 3 years. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02220504.

Comparison of metabolic effects of aripiprazole, quetiapine and ziprasidone after 12 weeks of treatment in first treated episode of psychosis.

This randomized open-label study compared the incidence of metabolic side effects of aripiprazole, ziprasidone and quetiapine in a population of medication-naïve first-episode psychosis patients. A total of 202 subjects were enrolled. Body weight, body mass index, leptin, fasting lipids and fasting glycaemic parameters were measured at baseline and at 3 months follow-up. A hundred and sixty-six patients completed the follow-up and were included in the analyses. A high proportion of patients experienced a significant weight increase (>7% of their baseline weight): 23% ziprasidone (n=12), 32% with quetiapine (n=16) and 45% with aripiprazole (n=31). Patients treated with aripiprazole gained significantly more weight than the patients in the ziprasidone group (1.2 kg [SD=4.1] versus 4.3 kg [SD=4.8], respectively). The increase in leptin levels was greater in women treated with aripiprazole than in those treated with ziprasidone (p=0.030). Mean prolactin levels significantly increased in patients treated with quetiapine and ziprasidone but not in those treated with aripiprazole. Patients treated with quetiapine and aripiprazole showed a significant increase in total cholesterol and LDL-cholesterol plasma levels. Quetiapine-treated patients resulted in a higher increase in LDL-cholesterol than patients treated with ziprasidone (p=0.021). No other significant differences between groups were found. No significant changes in glycaemic parameters were observed. Our results suggest that ziprasidone has a lower liability for inducing weight gain and lipid abnormalities than aripiprazole or quetiapine.

Differential associations of cognitive insight components with pretreatment characteristics in first-episode psychosis.

An increasing number of studies have focused on cognitive insight (i.e. awareness of one's own thinking) in psychotic disorders. However, little is known about the premorbid and pretreatment correlates of cognitive insight in the early course of psychosis. One hundred and three patients experiencing first-episode psychosis (FEP) were assessed shortly after treatment initiation for cognitive insight. Pretreatment and baseline clinical, functional and neurocognitive characteristics were examined. The self-reflectiveness dimension of cognitive insight was independently associated with clinical insight and executive functioning, whereas self-certainty was associated with premorbid IQ, premorbid academic adjustment and clinical insight. The amount of variance explained by the independent variables was small to moderate. Self-reflectiveness and self-certainty have differential pretreatment correlates in FEP and may reflect separate cognitive processes which require targeted interventions.

Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors.

Data on the long-term metabolic side-effects associated with antipsychotics are scarce. Prospective longitudinal studies in medication-naive patients with a first episode of psychosis are a valuable source of information as they provide an assessment prior to the antipsychotic exposure and minimize the effect of potential confounding factors. The aim of this study was to assess the course of weight gain and the incidence of metabolic abnormalities during the first 3 yr of antipsychotic treatment. Data were collected from a cohort of 170 first-episode psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine (32%) and risperidone (36%). The dose used was flexible. The initial antipsychotic treatment was changed when required, based on clinical response and tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the total mean weight gain) and then stabilized gradually over time. Total cholesterol, LDL-cholesterol and triglyceride levels followed a similar trajectory with a significant increase only during the first year. No significant changes were detected in the mean values of glycaemic parameters. Two patients with a family history of diabetes developed diabetes type II. At short-term the factors positively associated with weight gain were lower body mass index, male gender and olanzapine treatment. At long-term, functional status and clinical response were the main predictors. The results of our study indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic changes. Identification of weight gain patterns may help to inform studies that aim to prevent or mitigate the metabolic adverse events associated with antipsychotic therapy.

Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year.

RATIONALE: Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment. OBJECTIVES: The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year. METHOD: From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N = 78), ziprasidone (N = 62), or quetiapine (N = 62) and followed up for 1 year. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole = 43.6 %, ziprasidone = 66.1 % and quetiapine = 82.3 %) (χ 2 = 22.545; p < 0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ 2 = 19.436; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 30.732 p < 0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants. CONCLUSIONS: First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.

Course of cognitive deficits in first episode of non-affective psychosis: a 3-year follow-up study.

Cognitive dysfunctions are critical determinants of the quality of life and functionality in schizophrenia. Whether the cognitive deficits present at an early stage, are static or change across one's lifespan is still under debate. This study aims to investigate the long-term (3 years) course of cognitive deficits in a large and representative cohort of first episode schizophrenia spectrum patients (N=155),and evaluate their influence on disability. In addition, a healthy control sample (N=43) was also studied for comparison. This study evaluates the performance of patients and controls in a battery of cognitive assessments using baseline, 1-year and 3-year follow-up designs. The results show that, although cognitively outperformed by the controls at any time, the cognitive performance of the patients improved similar to the controls in all cognitive functions except verbal and visual memory. Even though the course of cognitive performance across the sample as a whole was stable, the subgroup of patients who experienced a cognitive decline had worse functionality and lesser amelioration of negative symptoms. Overall, there is no significant deterioration in the cognitive function in a group of first episode schizophrenia spectrum disorder patients, with the possible exception of tasks that were associated with episodic memory. However, patients whose cognitive performance demonstrated a declining trend may present with a poorer progression in terms of clinical and disability variables.

Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone.

INTRODUCTION: The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate. METHODS: A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis. RESULTS: Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis. CONCLUSIONS: The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.

Aripiprazole, ziprasidone, and quetiapine in the treatment of first-episode nonaffective psychosis: results of a 6-week, randomized, flexible-dose, open-label comparison.

Differences among antipsychotics in effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different second-generation antipsychotics are scarce. From October 2005 to March 2011, a prospective, randomized, open-label study comparing the effectiveness of aripiprazole, ziprasidone, and quetiapine in the short-term treatment of first-episode schizophrenia-spectrum disorders was undertaken. Two hundred two patients were randomly assigned to aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 6 weeks. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on per protocol populations was conducted in the analysis for clinical efficacy. The overall dropout rate at 6 weeks was small (6.4%). The treatment discontinuation rate differed significantly between treatment groups (aripiprazole, 15%; ziprasidone, 19%; and quetiapine, 35%; χ(2) = 8.529; P = 0.014). Insufficient efficacy in the group of quetiapine is the main reason for discontinuation rate differences (χ = 10.139; P = 0.006). The mean time to all-cause discontinuation was significantly different between the groups (log-rank, 12.783; P = 0.001). Quetiapine was associated with a greater depressive symptoms improvement than ziprasidone (P = 0.045). The rate of responders at 6 weeks differed between the groups (F = 6, 116; P = 0.047), with a higher rate of the responders with aripiprazole. The profile of adverse effects varies between the treatments. Patients on quetiapine were less likely to be prescribed concomitant medications. Treatment with quetiapine was associated with a higher risk of treatment discontinuation during treatment owing to insufficient efficacy. Differences in effectiveness between second-generation antipsychotics would determine their position in everyday clinical practice and could help physicians choose the more efficacious antipsychotics.

Long-term effect of haloperidol, olanzapine, and risperidone on plasma prolactin levels in patients with first-episode psychosis.

OBJECTIVE: The main goal of this study was to assess the long-term effect of haloperidol, olanzapine, and risperidone on serum prolactin levels in a naturalistically treated first-episode psychosis population. METHODS: Patients included in this study were drawn from a prospective, randomized, open-label clinical trial. Prolactin levels were measured in 110 patients with medication-naive first-episode psychosis at baseline, 3 months, and 1 year. RESULTS: A repeated-measures analysis of variance revealed a significant difference between treatments (F = 17.28, P < 0.001). At 1-year follow-up, most patients in the haloperidol and olanzapine arms had prolactin values that fell within the reference range. Patients treated with risperidone experienced a significant increase at 3 months resulting in prolactin levels above the reference range in 90% of men and 87% of women. The levels showed a tendency to decrease at 1 year, although still more than 70% of the values remained above the normative range. Sexual adverse drug reactions at 1 year assessed by the Udvalg for Kliniske Undersogelser scale showed that a higher percentage (39.3%) of patients had symptoms in the risperidone group compared to the olanzapine group (24%) or haloperidol group (20%), but the difference did not reach statistical significance (P = 0.281). CONCLUSION: Olanzapine and haloperidol treatments do not significantly affect serum prolactin levels at long term. After 1 year, elevated prolactin levels persist in most patients treated with risperidone.

Predicting relapse after a first episode of non-affective psychosis: a three-year follow-up study.

BACKGROUND: Preventing relapse during the first years of illness has a critical impact on lifelong outcomes in schizophrenia. A better understanding and improvement in factors which influence relapse should diminish the risk of relapse and consequently improve the outcome of the illness. OBJECTIVE: To identify factors associated with relapse after 3 years of a first episode in a sample of non-affective psychosis patients who are representative of clinical practice in an epidemiological catchment. METHOD: We analyzed socio-demographic and clinical data from a cohort of patients who were treated in a specialized early intervention service and who were at risk of relapse during a 3-year follow-up. Univariate analyses, logistic regression and survival analyses were performed. The analyzed variables included gender, age at onset, duration of untreated psychosis, clinical severity at baseline, insight at baseline, premorbid functioning, substance use, family history of psychosis and adherence to medication. RESULTS: Of the 140 patients considered to be at risk for relapse, 91 (65%) individuals relapsed at least once over the three-year period. The relapse rates at 1 year and 2 years were 20.7% and 40.7%, respectively. Adherence to medication was the only significant predictor of relapse after a three-year follow-up [hazard ratio (HR) 4.8, 95% confidence interval (CI) 2.9-7.7; p < 0.001]. Comparison of the mean time of relapse between adherent and non-adherent patients also revealed statistically significant differences (933 and 568 days, respectively). 50% of patients will relapse despite being categorized as treatment adherents. CONCLUSION: Non-adherence to medication is the biggest predictive factor of relapse after a first episode of psychosis.

Homocysteine and cognition in first-episode psychosis patients.

In the last years, there has been growing evidence linking elevated homocysteine levels with cognitive dysfunction in several neurological and neuropsychiatric diseases. The aim of the present study was to investigate the potential relationship between elevated homocysteine levels and cognitive deficits in first-episode psychosis patients. Plasma levels and cognitive performance of 139 patients and 99 healthy volunteers were compared. Patients were classified as elevated homocysteine (>90 percentile for controls) and normal and compared on 22 cognitive outcome measures grouped into cognitive domains known to be impaired in schizophrenia. Patients had a statistically significant increase in plasmatic homocysteine levels. In addition, they presented with significantly increased cognitive deficits. However, no relationship between homocysteine levels and cognitive impairment was detected. These results suggest the need for further studies to clarify the role of homocysteine in the etiology and prognosis of psychosis.

Long-term (3-year) effectiveness of haloperidol, risperidone and olanzapine: results of a randomized, flexible-dose, open-label comparison in first-episode nonaffective psychosis.

RATIONALE: To enhance the effectiveness of antipsychotics in first-episode psychosis is crucial in order to achieve the most favourable prognosis. Difference in effectiveness between antipsychotics is still under debate. OBJECTIVE: The purpose of this study is to determine the long-term (3-year) effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders. METHOD: This is a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention programme of first-episode psychosis. One hundred seventy-four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 3 years. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on per-protocol populations was conducted in the analysis for clinical efficacy. RESULTS: The treatment discontinuation rate for any cause differed significantly between treatment groups (χ (2) = 10.752; p = 0.005), with a higher rate in haloperidol than in risperidone and olanzapine. The difference in the discontinuation rate between risperidone and olanzapine showed a tendency towards significance (χ (2) = 3.022; p = 0.082). There was a significant difference in the mean time to all-cause discontinuation between groups (log-rank χ ( 2 ) = 12.657;df = 2; p = 0.002). There were no significant advantages to any of the three treatments in reducing the psychopathology severity. CONCLUSIONS: After 3 years of treatment, a lower effectiveness was observed in haloperidol compared to second-generation antipsychotics (SGAs). The use of SGAs for the treatment of early phases of nonaffective psychosis may enhance the effectiveness of antipsychotics.