[Show abstract][Hide abstract] ABSTRACT: The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Dystrobrevin-binding protein 1 gene (dysbindin or DTNBP1) has been associated with schizophrenia and cognitive performance. Its expression in areas implicated in cognition such as the dorsolateral prefrontal cortex, as well as its role in dopaminergic and glutamatergic system, has been replicated by several studies. The main aim of this study was to examine the association between DTNBP1 variability and cognitive performance in a sample of 238 patients with a first episode of a non-affective psychosis.
Patients, and a comparison sample of 47 healthy subjects, completed an extensive neuropsychological battery. Five single nucleotide polymorphisms (SNPs) within DTNBP1 (rs2619528, rs2619538, rs3213207, rs2619539 and rs760761) and three haplotypes (GACAC, GAGAC and GTGAC) were analysed.
In the group of patients, we found a significant association between two of the DTNBP1 SNPs and one of the haplotypes (rs2619539, rs3213207 and GACAC) and a measure of premorbid IQ [Wechsler Adult Intelligence Scale-3rd Edition (WAIS-III) Vocabulary subtest]. Moreover, one of these SNPs, rs2619539, was also associated with our measure of working memory (WAIS-III Backward digits subtest) and two haplotypes, GAGAC and GTGAC, with our measure of verbal memory (Rey Auditory Verbal Learning Test), of visual memory (Rey Complex Figure Test) in the case of GAGAC, and of speed of processing (WAIS-III Digit Symbol-coding) in the case of GTGAC.
Our findings add further evidence suggesting an association between dysbindin gene variability and cognitive abnormalities in schizophrenia, providing preliminary evidence of this association since the time of illness onset among minimally medicated patients.
[Show abstract][Hide abstract] ABSTRACT: 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 3months 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 (1.2kg [SD=4.1] versus 4.3kg [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.
Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.045 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Lack of insight is recognized as a symptom that predisposes the individuals with psychosis to noncompliance with the treatment, leading to poorer course of illness. This study aimed to explore baseline predictors of disturbances on insight at follow-up.
Three insight dimensions (insight of: 'mental illness', 'need for treatment' and 'the social consequences of the disorder') were measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) in a cohort of 224 first-episode psychosis (FEP) patients at 3-year follow-up. Subgroups, good vs. poor insight, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics. Regression models tested baseline predictors for each insight dimension.
At 3-year follow-up a high percentage of patients, 45%, 36% and 33% for each dimension, were found to remain lacking insight. Poor insight into having an illness was predicted by a diagnosis of schizophrenia and poor baseline insight of the social consequences; insight into the need for treatment was predicted by adolescent adjustment and depression at baseline; and insight into the social consequences of the disorder was determined by late adolescent adjustment and baseline insight of mental illness.
Our findings support the hypothesis that long-term insight in psychosis seems to be, to some extent, determined from first presentation, showing trait-like properties. A subgroup of 'lacking insight' patients, which is characterized by a diagnosis of schizophrenia, lower levels of premorbid adjustment and less severe depressive symptoms at baseline might benefit from special interventions targeted at enhancing insight from their first contact with psychiatric services.
Schizophrenia Research 06/2014; 157(1-3). DOI:10.1016/j.schres.2014.05.011 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The course of cognitive function in first-episode psychosis (FEP) patients suggests that some individuals are normal or near normal whereas some cases present a marked decline. The goal of the present longitudinal study was to identify neuroanatomical differences between deficit and non-deficit patients.
Methods: Fifty nine FEP patients with neuroimage and neurocognitive information were studied at baseline and 3 year after illness onset. A global cognitive function score was used to classify deficit and non-deficit patients at baseline. Analysis of covariances and repeated-measures analysis were performed to evaluate differences in brain volumes. Age, premorbid IQ, and intracranial volume were used as covariates. We examined only volumes of whole brain, whole brain gray and white matter, cortical CSF and lateral ventricles, lobular volumes of gray and white matter, and subcortical (caudate nucleus and thalamus) regions.
Results: At illness onset 50.8% of patients presented global cognitive deficit. There were no significant differences between neuropsychological subgroups in any of the brain regions studied at baseline [all F(1, 54) ≤ 3.42; all p ≥ 0.07] and follow-up [all F(1, 54) ≤ 3.43; all p ≥ 0.07] time points. There was a significant time by group interaction for the parietal tissue volume [F(1, 54) = 4.97, p = 0.030] and the total gray matter volume [F(1, 54) = 4.31, p = 0.042], with the deficit group showing a greater volume decrease.
Conclusion: Our results did not confirm the presence of significant morphometric differences in the brain regions evaluated between cognitively impaired and cognitively preserved schizophrenia patients at the early stages of the illness. However, there were significant time by group interactions for the parietal tissue volume and the total gray matter volume during the 3-year follow-up period, which might indicate that cognitive deficit in schizophrenia would be associated with progressive brain volume loss.
Frontiers in Psychiatry 10/2013; 4(134):134. DOI:10.3389/fpsyt.2013.00134
[Show abstract][Hide abstract] ABSTRACT: 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.
The International Journal of Neuropsychopharmacology 10/2013; 17(01):1-11. DOI:10.1017/S1461145713001053 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a chronic brain disorder associated with structural brain abnormalities already present at the onset of the illness. Whether these brain abnormalities might progress over time is still under debate.
The aim of this study was to investigate likely progressive brain volume changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The study included 109 patients with a schizophrenia spectrum disorder and a control group of 76 healthy subjects. Subjects received detailed clinical and cognitive assessment and structural magnetic resonance imaging (MRI) at regular time points during a 3-year follow-up period. The effects of brain changes on cognitive and clinical variables were examined along with the impact of potential confounding factors.
Overall, patients and healthy controls exhibited a similar pattern of brain volume changes. However, patients showed a significant lower progressive decrease in the volume of the caudate nucleus than control subjects (F 1,307.2 = 2.12, p = 0.035), with healthy subjects showing a greater reduction than patients during the follow-up period. Clinical and cognitive outcomes were not associated with progressive brain volume changes during the early years of the illness.
Brain volume abnormalities that have been consistently observed at the onset of non-affective psychosis may not inevitably progress, at least over the first years of the illness. Taking together with clinical and cognitive longitudinal data, our findings, showing a lack of brain deterioration in a substantial number of individuals, suggest a less pessimistic and more reassuring perception of the illness.
Psychological Medicine 09/2013; 44(08):1-14. DOI:10.1017/S0033291713002365 · 5.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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 (3years) 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.
Schizophrenia Research 07/2013; 150(1). DOI:10.1016/j.schres.2013.06.042 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Differences among antipsychotics in terms of effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different second generation antipsychotics (SGAs) are scarce. We aimed to compare the clinical effectiveness in the short-term of Aripiprazole, Ziprasidone and Quetiapine in the treatment of first-episode schizophrenia-spectrum disorders.
From October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. 202 first-episode drug-naïve patients were randomly assigned to Aripiprazole (N = 78), Ziprasidone (N = 62), or Quetiapine (N = 62) and followed-up for 3 months. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat populations was conducted in the analysis for clinical efficacy.
The overall dropout rate at 3 months was small (13.86%). The treatment discontinuation rate differed significantly between treatment groups (Aripiprazole = 23.1%, Ziprasidone = 37.1% and Quetiapine = 61.3%) (χ(2) = 21.334; p < 0.001). Insufficient efficacy in the group of Quetiapine is the main reason for discontinuation rate differences (χ(2) = 20.223; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 23.467 p < 0.001). Aripiprazole and Quetiapine were associated with a greater depressive symptoms improvement (p = 0.043). The profile of side-effects varies between treatments. Patients on Quetiapine were less likely to be prescribed hypnotics.
Patients treated with Quetiapine had a higher risk of treatment discontinuation in the short-term after a first episode due to insufficient efficacy. Establishing differences between SGAs may help clinicians in prescribing decisions for the treatment of individuals presenting with first-episode schizophrenia.
Schizophrenia Research 05/2013; 147(2-3). DOI:10.1016/j.schres.2013.04.014 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 = 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.
[Show abstract][Hide abstract] ABSTRACT: Background:
Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data.
This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables.
Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension.
Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.
Psychological Medicine 03/2013; 44(1):1-14. DOI:10.1017/S0033291713000330 · 5.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Predicting response to antipsychotic treatment might optimize treatment strategies in early phases of schizophrenia. We aimed to investigate sociodemographic, premorbid and clinical predictors of response to antipsychotic treatment after a first episode of non-affective psychosis.
375 (216 males) patients with a diagnosis of non affective psychosis entered the study. The main outcome measure was clinical response at 6 weeks and variables at baseline were evaluated as predictors of response. ANOVA for continuous and chi-square for categorical data were used to compare responders and non-responders. Multivariate logistic regression was used to establish a prediction model.
53.3% of study subjects responded to antipsychotic treatment. The following variables were associated with an unfavorable response: 1.--lower severity of symptoms at baseline; 2.--diagnosis of schizophrenia; 3.--longer DUI and DUP; 4.--poorer premorbid adjustment during adolescence and adulthood; 5.--family history of psychosis, and 6.--hospitalization. Patients with a family history of psychosis, longer DUP, poor premorbid functioning and lower severity of psychotic symptoms at intake have a reduced likelihood of responding to antipsychotic treatment.
Helping clinicians to identify those first episode patients with a lower probability of having a favorable clinical response is meant as a first step to achieve a successful initial treatment.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2013; 44. DOI:10.1016/j.pnpbp.2013.02.009 · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Real-world functional deficits are common and persistent in individuals with psychosis. Cognitive deficits have been shown to compromise functioning. We aimed to study the predictive values of premorbid, sociodemographic, and baseline clinical and neurocognitive factors on long-term functional outcome for individuals with first episode non-affective psychosis. We failed to demonstrate a significant relationship between cognitive deficits at baseline and functional disability at 3year follow-up. Diagnosis of schizophrenia (OR=2.457, p=0.011), shorter education (OR=1.177, p=0.005) and poor premorbid social adjustment (OR=1.628, p=0.013) emerged as the strongest predictors for the 114 subjects (56%) that exhibited functional disability at 3-year follow-up. A considerable proportion of the variance in functioning (74% at 1year and 77% at 3year) remained unexplained by baseline variables. The set of variables that predicted functional outcome at medium- (1 year) and long-term (3 years) differed. In conclusion, the length of follow-up influenced the relationship between baseline variables and functional outcome. A substantial proportion of the variance in function was not explained by these variables and therefore the influence of other factors warrants further investigation. The data support the notion that premorbid social adjustment is an important aspect in functional outcome over the course of the illness.
[Show abstract][Hide abstract] ABSTRACT: Background:
Neurocognitive impairment is a core component of schizophrenia. However, patients show great variability in the level and course of deficits. The goal of the present longitudinal study was to identify predictors of neurocognitive impairment in first episode psychosis patients.
Neurocognitive performance was analyzed in a cohort of 146 patients 3 years after a first episode non-affective psychosis. Subgroups, impaired vs. unimpaired, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics.
Fifty-nine percent of participants presented general neurocognitive impairment and regression analyses demonstrated that clinical and sociodemographic characteristics were not predictive variables. A model composed of premorbid IQ, verbal memory and motor dexterity correctly classified 79.6% of the individuals.
The present study gives information on frequency and neurocognitive profile of subtypes of patients showing impairment. Our results suggest general neurocognitive impairment is a trait dimension of the disorder related to specific cognitive dysfunctions.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2012; 43. DOI:10.1016/j.pnpbp.2012.11.012 · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to identify predictors associated with a lower likelihood of achieving a clinical remission one year after the first break of the illness. Participants were 174 consecutive subjects included in a first episode programme with no prior treatment with antipsychotic medication. Patients were assigned to haloperidol, olanzapine or risperidone in a randomized, open-label, prospective clinical trial. The main outcome variable was the remission criteria developed by the Remission in Schizophrenia Working Group. Clinical variables were included in a logistic regression analysis in order to predict the remission state at one year. At one year, 31% of patients met criteria for remission. The logistic regression analysis revealed that the strongest predictors of achieving clinical remission one year away from a first episode of non-affective psychosis were the length of Duration of Untreated Psychosis (DUP), the severity of negative symptomatology and the educational level attained at baseline. The results suggest that: 1.-patients with a lengthy DUP, a greater severity of negative symptomatology at baseline and with a lower education level are in a higher risk of not achieving a clinical remission during the first year of treatment; and 2.-early intervention clinical programs should aim to reduce the length of DUP in order to provide a better outcome for patients.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.