Search

Abstract Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia. Trial Registration Clincaltrials.gov Identifier: NCT00395915

The present study aims at exploring the relationship between content-related aspects of delusions and hallucinations in schizophrenia and the basic domains of cognition, controlling for the other clinical and demographic variables that could produce bias in the interpretation of the results. Seventy stable schizophrenic patients were evaluated through psychiatric assessment and a neuropsychological battery including tests on attention, memory, perceptual-motor speed and executive functions. We found that the severity of negative symptoms was strongly correlated with poor performance in almost all domains of cognitive functions, while only the attentional deficit was correlated with positive symptoms. The relationships between different cognitive domains and specific types of delusions and hallucinations showed that thought insertion, guilt, grandiose, religious and somatic delusions were associated with impairment in different cognitive functions (verbal and visual memory, attention and executive functions). Voices arguing and tactile hallucinations were correlated to delay-recall memory function. Our results suggest that no specific cognitive pattern is associated with typical-content delusions and hallucinations. On the basis of our findings, cognitive impairments associated with delusions and hallucinations, as measured by our battery, seem not to play a central role in the genesis and the maintenance of these symptoms, suggesting a more complex model of pathogenesis.

Objective: Data in the literature comparing second-generation antipsychotics (SGAs) and depot neuroleptics are scarce. The aim of this retrospective, naturalistic study is to examine the relative effectiveness of SGAs and depot neuroleptics in 2 matched groups of patients affected by schizophrenia., Method: Between July 2004 and September 2004, we collected data from 2 groups of 30 DSM-IV-TR schizophrenia outpatients, matched for a number of demographic and clinical characteristics, who received a 2-year treatment with depot neuroleptics or SGAs. Treatments were compared through the Clinical Global Impressions-Severity of Illness scale (CGI-S), performed on several symptom domains of schizophrenia. Other outcomes included 1-and 2-year readmission rates, the number of self-injuries during the treatment period, and anticholinergic drug prescription, considered as an index of extrapyramidal symptoms., Results: Treatment with both drug classes produced broadly comparable clinical effects. Clinician-assessed effectiveness was similar for SGA and depot recipients, with significant decreases over baseline in all CGI-S symptom domain scores. The percentages of patients readmitted during the follow-up period were similar among drug groups. After 1 year, 6 SGA patients (20%) were readmitted compared with 7 depot patients (23%); after 2 years, 9 SGA patients (30%) were rehospitalized compared with 11 depot patients (37%). Also, no between-group differences were detected with respect to the number of self-injuries. Anticholinergic drug prescription was significantly less common in SGA patients compared with depot recipients (p = .0112)., Conclusion: These findings confirm at least equal long-term effectiveness of depot neuroleptics and SGAs, but a possible advantage for SGAs in decreased use of anticholinergic drugs.

Objective: The primary aim of this study was to investigate whether depressive symptoms were significantly associated with functional outcome measures in a clinically stable group of outpatients with schizophrenia. We also analyzed whether depressive and negative symptoms presented different patterns of predictors., Method: Seventy-eight consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for schizophrenia in the stable period were enrolled in this cross-sectional study. Assessment were performed using the Calgary Depression Scale for Schizophrenia, Positive and Negative Syndromes Scale (PANSS), Clinical Global Impression Scale-severity, Social and Occupational Functioning Assessment Scale, Sheehan Disability Scale, and Quality of Life Scale. A neuropsychologic battery including the vocabulary and block design subtests of the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale, Wisconsin Card Sorting Test, and Continuous Performance Test was also administered to the patients. Two multiple regressions were performed testing demographic and clinical factors, rating scales, and cognitive measures as independent variables and Calgary Depression Scale for Schizophrenia and PANSS-negative subscale scores as dependent variables., Results: Four variables were predictors of depressive symptoms in our sample of schizophrenic patients: 2 outcome measures (Sheehan Disability Scale and Quality of Life Scale), gender, and Continuous Performance Test reaction time. Predictors of negative symptoms were the measures of severity of psychopathology (Clinical Global Impression Scale-severity and PANSS-general psychopathology subscale) and the cognitive tests Wechsler Adult Intelligence Scale-Revised block design and Wechsler Memory Scale., Conclusion: We found that depressive symptoms in schizophrenia are mainly a function of the level of social adjustment and quality of life, whereas negative symptoms constitute an indicator of severity of schizophrenia. The 2 symptom dimensions showed also distinct cognitive correlates.

Objective: The aim of this study was to compare over 1 year the effect of sertraline and citalopram on depressive symptoms and cognitive functions of nondemented elderly patients with minor depressive disorder and subsyndromal depressive symptomatology., Method: We recruited 138 consecutive non-demented outpatients of either sex, aged > or =65 years, who were classified as meeting research criteria for minor depressive disorder or sub-syndromal depressive symptomatology using the Structured Clinical Interview for DSM-IV. Subjects were assigned to receive citalopram 20 mg/day (66 patients) or sertraline 50 mg/day (72 patients) orally for 1 year. Patients were assessed at baseline and after 1, 2, 3, and 6 months and at 1 year by raters masked with regard to patients' treatment assignments. The Hamilton Rating Scale for Depression, the Geriatric Depression Scale, and the Global Assessment of Functioning were administered to assess the course of depressive symptoms and social functioning during the study. Cognitive measures included Trail Making Test-Parts A and B, Wechsler Memory Scale, Mini-Mental State Examination, and a verbal fluency test. Data were collected from March 2000 to March 2003., Results: The overall completion rate was 72%. Both treatments induced a significant, sustained, and comparable improvement in depressive symptoms and in social functioning. Nearly half of the subjects in the 2 groups achieved remitter status at study endpoint. Significant within-group improvements also were observed in all cognitive measures. Both drugs were well tolerated during the whole study period., Conclusion: Our results suggest that sertraline and citalopram can improve depressive symptoms and cognitive functions of minor depressive disorder and subsyndromal depressive symptomatology in elderly nondemented patients.

Background: A number of studies investigated the relationships of age at onset with clinical presentation and cognitive performance of schizophrenic patients. The aim of the present study was to assess demographic and clinical characteristics; psychopathologic, social functioning, and quality-of-life ratings; and neuropsychological measures in a sample of patients with stabilized schizophrenia and to identify which factors independently contributed to a multiple regression model with age at onset as the dependent variable., Method: Ninety-six consecutive outpatients with schizophrenia (DSM-IV-TR criteria) were included in the study. Assessment instruments were as follows: a semistructured interview, the Clinical Global Impressions scale, the Comprehensive Psychopathological Rating Scale, and the Positive and Negative Syndrome Scale (PANSS) for psycho-pathology of schizophrenia; the Calgary Depression Scale for Schizophrenia (CDSS) for depression; the Social and Occupational Functioning Assessment Scale and the Sheehan Disability Scale for social functioning; the Quality of Life Scale; and a neuro-psychological battery including the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test. Two models of multiple regression were tested: the first included clinical features and psychopathologic, social functioning, and quality-of-life scales; the second also considered neuro-psychological variables. Data were collected from October 2001 to November 2002., Results: The first multiple regression showed that age at onset was significantly related to scores on the PANSS subscale for negative symptoms (p =.042) and the CDSS (p =.041); the second regression found a relation of age at onset with PANSS score for negative symptoms (p =.002) and 2 neuropsychological measures, number of preservative errors on the WCST and Continuous Performance Test reaction time (p =.0005 for both)., Conclusion: Our data indicate that, when results of neuropsychological tests are considered, early age at onset of schizophrenia is associated with severity of negative symptoms and compromised cognitive measures of executive functioning and sustained attention.

Dysthymic disorder is a chronic depressive condition with considerable psychosocial impairment. Even if DD patients respond to various antidepressant medications, there has been little systematic study on antidepressant-refractory DD. Only a few trials have evaluated the effects of treatment on psychosocial functioning of dysthymic patients. In this 3-month, open-label study, 60 outpatients with DSM-IV criteria for dysthymic disorder who failed to respond to 3-month treatment with paroxetine 20 mg/day were randomly assigned to treatment with paroxetine 40 mg/day or paroxetine 20 mg/day plus amisulpride 50 mg/day. The effects of the two treatments were assessed for both mood symptoms (21-item Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression, severity and improvement) and psychosocial outcomes (DSM-IV Global Assessment of Functioning, Social Adaptation Self-evaluation Scale). Analysis of variance on all rating scales showed that both treatments were effective over this observation period. Response and remission rates did not differ in the treatment groups. A significantly greater psychosocial improvement was observed in the group receiving combined treatment compared with patients receiving paroxetine alone. Both treatments appeared to be effective in our sample of dysthymic subjects. Combined treatment with paroxetine and amisulpride resulted in a better outcome in terms of social functioning.

Objectives: The evaluation of the possible role of dopamine in psychiatric disorders has been limited by the relative inadequacy of tools. A tempting approach to examine alterations of dopaminergic system in major depression is to examine the expression of dopamine receptors in peripheral blood mononuclear cells (PBMC)., Methods: D4 dopamine receptor (D4DR) messenger RNA (mRNA) expression in PBMC from 12 patients with major depressive disorder was examined before and after an 8-week treatment with paroxetine at 20-50 mg/day. Ten healthy subjects were analyzed in parallel. The relative content of D4DR mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). using beta-actin as internal standard., Results: D4DR mRNA levels were significantly decreased in untreated depressed patients as compared to controls. D4DR mRNA expression returned to control levels after paroxetine treatment, when patients achieved a significant improvement of depressive symptoms., Conclusions: Results of our study suggest the role of PBMC D4DR mRNA expression as a peripheral marker of the central dopaminergic function in major depression.

Background: Of the various Axis II disorders, borderline personality disorder (BPD) is among the more critical to treat. There are at present few results in terms of clinical outcome with the psychotropic agents available. Possible targets for pharmacotherapy are affective symptoms, cognitive disturbances, and impulsive, self-injurious behaviors. In previous studies, atypical antipsychotics at low-to-moderate doses provided symptom reduction with good tolerability. Our purpose was to assess the efficacy of risperidone in BPD, focusing on its effects on impulsive-aggressive behavior., Method: Fifteen BPD outpatients (DSM-IV diagnosis) with prominent histories of aggressive behavior were included in an 8-week open-label study with risperidone at low-to-moderate doses. Axis II codiagnoses included antisocial personality disorder (N = 4). Exclusion criteria included current Axis I diagnosis or any major medical or neurologic illness. Efficacy measures were the 21-item Hamilton Rating Scale for Depression, the Brief Psychiatric Rating Scale, the DSM-IV Global Assessment of Functioning, and the self-rated Aggression Questionnaire. Evaluations were carried out at baseline and at the end of the treatment., Results: Thirteen patients completed the trial; 2 patients dropped out because of lack of compliance. Final mean dose of risperidone was 3.27 mg/day. There was a significant (p = .0057) reduction in aggression based on Aggression Questionnaire scores. This amelioration was coupled with an overall improvement, including a reduction in depressive symptoms and an increase in energy and global functioning., Conclusion: Risperidone at low-to-moderate doses can improve BPD symptomatology. Further studies are needed to explore the efficacy of risperidone versus placebo as well as in comparison to other potential treatments for BPD.

Objectives: The aim of this study was to evaluate the long-term efficacy, safety and tolerability of donepezil in the treatment of Alzheimer's disease (AD)., Methods: Twenty-five patients (15 females and 10 males) with mild to moderate AD, according to DSM IV criteria, were recruited in the study. The principal efficacy measures were Alzheimer Disease Assessment Scale-cognitive subscale score (ADAS-cog), Mini Mental State Examination (MMSE) and Physical Self-Maintenance Scale (PSMS). Patients were treated with donepezil 5 mg/day for 1 month, after which an increase to 10 mg/day was encouraged. Evaluations were carried out prior to the start of the treatment and every 3 months for a period of 1 year., Results: A significant improvement from baseline score of cognitive performances was seen through Week 24. Beginning with Week 36, performances declined relative to baseline, indicating continued disease progression., Conclusions: Donepezil improved cognition and global functioning and was well tolerated especially considered the long duration of the observation period.