[Show abstract][Hide abstract] ABSTRACT: DISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis.
[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. METHOD: 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 3months. 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. RESULTS: The overall dropout rate at 3months 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. CONCLUSIONS: 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; · 4.59 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.
Journal of clinical psychopharmacology 04/2013; 33(2):215-20. · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[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. METHOD: 375 (216 males) patients with a diagnosis of non affective psychosis entered the study. The main outcome measure was clinical response at 6weeks 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. RESULTS: 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. CONCLUSION: 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; · 3.55 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: The 'early intervention' model has been applied with good results to the care of a range of serious medical conditions. The key rationale for this model is to guarantee early identification and treatment for the illness, thus preventing its progression to a more advanced and severe stage. It would also provide a framework for optimal treatment according to the stage of the disorders. Although in the field of psychiatry this model has mainly been implemented in nonaffective psychosis, research evidence supports its application in other mental disorders. To promote this initiative, the chapter explores the available evidence demonstrating the feasibility of adopting the key elements of the model in the care of the whole spectrum of anxiety disorders. In addition, the chapter describes the different stages that are possible to identify in the process of developing an illness, and also the phase-specific interventions that could be applied. Finally, the service repercussions of implementing an early intervention model in anxiety disorders are discussed.
Anxiety Disorders. Modern Trends in Psychopharmacoloy., Edited by D.S. Baldwin, B.E. Leonard, 01/2013: chapter The Early Phases of Anxiety Disorders: From Prevention to Treatment: pages 98-110; Karger., ISBN: 978-3-318-02463-0
Improving Mental Health Care, Edited by G. Thornicroft, M. Ruggeri, D. Goldberg, 01/2013: chapter The feasibility of applying the clinical staging paradigm to the care of people with mental disorders: pages 145-162; Wiley-Blackwell., ISBN: 978-1-118-33797-4
[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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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; · 3.55 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. 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.
Journal of clinical psychopharmacology 11/2012; · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives. Community psychiatry has mainly relied upon intermediate long term care services while there is a large gap between patient’s needs and availability of acute care services. Taking this into consideration, the main aim of this paper is to review the evidence supporting the efficacy and feasibility of implementing the new models of care developed to fulfil the gap in the provision of community and hospital care for acute and severely ill patients. Finally the paper will propose a “care balanced approach” to integrate the key elements of the new alternatives of acute community and hospital care in the mental health system. Material and Method. A review of the current literature was used to identify the key components of acute care for psychiatric illness. For this purpose Medline (1966-2010), EMBASE (1980-2010), and PsycINFO (1985-2010) databases were reviewed using key terms relating to assertive outreach, home treatment/crisis resolution, psychiatric acute day care, deinstitutionalization, Mental Health Service Models. Results. Three main types of acute care have been identified: Acute Continuous Day Care (ACDC) –day hospitals -, Assertive Outreach Care (AOC) –Assertive Community and Assertive Outreach teams-, and Home Acute Care (HAC) -Crisis resolution, Home treatment teams-. The feasibility of these alternatives is supported by available evidence. Although these acute care alternatives may be complementary and could be combined for achieving a greater positive impact on the clinical and social recovery of the patients, there are usually implemented independently. Conclusions. An integrative acute care subsystem combining these three strategies in a balanced care system should be formally incorporated to the advanced community model in mental health care. Key words: Community Mental Health Care, Mental Health Service Models, Balanced Care Model, Assertive Outreach, Home Acute Care, Crisis resolution/Home treatment, Acute Day Hospital, Acute Day Care.
Actas espanolas de psiquiatria 11/2012; 40(6):323-32. · 0.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Imaging evidence indicates that brain alterations are primary to the full-blown onset of schizophrenia and seem to progress across time. The potential effects of antipsychotic medication on brain structure represent a key factor in understanding brain changes in psychosis. We aimed to investigate the effects of low doses of haloperidol, risperidone and olanzapine on cortical thickness.
We investigated the effects of risperidone (N=16), olanzapine (N=18) and low doses of haloperidol (N=18) in cortical thickness changes during 1-year follow-up period in a large and heterogeneous sample of schizophrenia spectrum patients. The relationship between cortical thickness changes and clinical and cognitive outcome was also assessed. A group of 45 healthy volunteers was also longitudinally evaluated. Magnetic resonance imaging brain scans (1.5T) were obtained and images were analyzed by using BRAINS2.
There were no significant effects of time (F(1,47)<1.66; P>0.204), treatment group (F(2,47)<1.47; P>0.242) or group-by-time interaction (F(2,47)<1.82; P>0.174) for any of the cortical thickness variables. When the group of healthy controls was included in the analyses, it is of note that group-by-time interaction showed a significant result for the frontal lobe at trend level (F(3,81)=2.686; P=0.052). After the Bonferroni adjustment for multiple comparisons, there were no significant associations between changes in cortical thickness and clinical and cognitive outcome.
Low doses of haloperidol, risperidone, and olanzapine seem to equally affect gray matter cortical thickness, overall and lobes, at the medium-term (1year). The clinical effectiveness of treatments was not significantly related to changes in cortical thickness.
Schizophrenia Research 08/2012; 141(1):22-8. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Non-adherence to medication is the biggest predictive factor of relapse after a first episode of psychosis.
Journal of Psychiatric Research 06/2012; 46(8):1099-105. · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to use a region-of-interest approach with magnetic resonance imaging to examine the volume of the straight gyrus volume change in first-episode schizophrenia-spectrum patients compared with healthy subjects over a 1-year follow-up period. We did not find a differential pattern of volumetric change between the two groups.
Psychiatry Research 05/2012; 202(1):80-3. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
European Archives of Psychiatry and Clinical Neuroscience 03/2012; 262(7):557-64. · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to improve relapse and recurrence prevention in bipolar disorder, the purposes of this paper are: (i) to summarize the evidence published on treatments for this disorder, particularly on psychological interventions in its early phases; (ii) to provide a description of the Jano Intervention and Research Program on the Early Phases of Bipolar Disorder, which is being developed at Valdecilla Hospital (Santander, Spain). Firstly, we review the data from randomized controlled trials and systematic reviews regarding four psychotherapies proven to be effective in the treatment of bipolar disorder: psychoeducation, cognitive-behavioral therapy, family therapy and interpersonal and social rhythm therapy. Secondly, we display a systematic review on the effectiveness of psychological therapies during the early stage of bipolar disorder. Out of 456 studies, all were excluded due to not meeting the inclusion criteria. Finally, we outline the Jano Program, which provides psychiatric management, psychoeducation, psychotherapy and family therapy for patients in the early stage of bipolar disorder. Several standardized clinical, social and neuropsychological tests are administered to the patients at the beginning of the program, and also at 2, 4, 6 and 8 weeks, 3 and 6 months, 1, 2, 3 and 5 years later. CONCLUSIONS: It's necessary to enlarge the sample and finish our data collection in order to determine the effectiveness and efficiency of this kind of program, and specially of its psychological components. Early intervention for bipolar disorder may need to be adapted in some way from usual treatments to better reach our goals.
Actas espanolas de psiquiatria 03/2012; 40(2):51-6. · 0.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to examine the correspondence between clinical ratings of inattention problems in the early course of a psychotic disorder and concurrent neuropsychological data for sustained attention and speed of processing/executive functioning (SP/EF) derived from a comprehensive neuropsychological test battery.
A sample of 131 patients with first-episode psychosis (FEP) was clinically rated after clinical stabilization with the attention subscale of the Scale for the Assessment of Negative Symptoms (SANS) and a completed neuropsychological test battery, which included measurements of sustained attention and SP/EF. To test the associations of the clinical ratings and objective data, correlations and regression analyses were conducted.
Clinical ratings of inattention showed only weak correlations with the global score of SP/EF and with the clinical ratings of negative symptoms (ρ < 0.25). None of the independent variables entered in the logistic regression model were significant (all P values > .05). Percentages of agreement between clinical judgment and neuropsychological measures were unacceptably low (ranged from 53% to 68%). κ values indicate only slight agreement (κ < 0.2).
Clinical ratings based on the SANS attention subscale do not reliably match neuropsychological test measures of attention or other related cognitive processes in FEP. Even for those cognitive domains more pronouncedly impaired, mental health professionals will likely need to rely on psychometric testing or, alternatively, specific guidelines and also, probably, to collect data from different sources to adequately identify cognitive impairments.
[Show abstract][Hide abstract] ABSTRACT: Some antipsychotics probably increase the risk of metabolic syndrome. Antipsychotics may differentially influence some elements of metabolic syndrome (obesity, hyperlipidemia, hyperglycemia or hypertension) through various pharmacological mechanisms. In a published study of all first psychotic episodes in a Spanish hospital's catchment area population in Cantabria (Spain), patients were randomly assigned to receive haloperidol (3-9 mg/day), olanzapine (5-20mg/day) or risperidone (3-6 mg/day). In this article, a structural-equation modeling approach tested the mechanistic hypothesis that olanzapine directly (without the mediation of weight gain) increases triglyceride levels, whereas risperidone and haloperidol do not have these effects. A structural equation model was built using the 110 patients whose assigned antipsychotic was not changed during the first 3 months of treatment, and who provided both triglyceride and body mass index (BMI) measurements at baseline and at the end of the 3rd month of treatment. A second structural equation included 72 patients whose antipsychotic was not changed during the first year. After 3 months and controlling for confounders, olanzapine patients had triglyceride levels that were 29.2mg/dL higher [95% confidence interval, (10.9, 47.5)] than those of risperidone patients with comparable baseline triglyceride levels. After 12 months, they were 63.1mg/dL higher (18.6, 107.6) than those of patients with a comparable history of triglyceride values during the first 3 months. Haloperidol effects on triglyceride levels and BMI were no different from those of risperidone. In conclusion, olanzapine increased triglyceride levels without the mediation of weight gain during a one-year study in naïve patients.
Schizophrenia Research 09/2011; 131(1-3):82-9. · 4.59 Impact Factor