Disorders - Psychosis Disorders
Thorup, Anne, Petersen, Lone, Jeppesen, Pia, Nordentoft, Merete
Background: Aim: Method: Results: From an 'objective' perspective, treatment of first-episode psychosis has improved in many ways with the development of specialised early and intensive team-based treatment like e.g. the 'OPUS' treatment. However, the patients' perspective is also important and was investigated in the 'OPUS' study by analysing data concerning quality of life.We aimed to investigate the 'quality of life from patients' perspective' among a cohort of young adults with a first-episode psychosis at the time of treatment initiation and after two years. Especially, we were interested in analysing if there were any significant effects on the subjective quality of life of receiving an intensive psychosocial assertive community treatment called 'OPUS' compared to standard treatment (ST).This study is part of the Danish 'OPUS' trial, a randomised controlled trial (RCT) comparing 'treatment as usual' (standard treatment, ST) with 'OPUS' treatment. The Lancashire Quality of Life Profile (LQoLP), which is a combined objective and subjective instrument, was administered at baseline and after two years of treatment, N=280.The intensive 'OPUS' treatment did not affect the quality of life measured by Lancashire QoLP in a significantly different way from the standard treatment (ST). There were no significant differences in quality of life between the ST group and the OPUS group concerning the 9 life domains. Quality of life correlated with psychopathology (both psychotic and negative symptoms) to a minor extent and more strongly with the affective balance and level of self-esteem.
Schizophrenia Research, 116(1) : 27-34
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
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Stage: First episode (psychosis only)
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Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions
vanVeelen, Nicoletta M. J., Grootens, Koen P., Peuskens, J., Sabbe, B. G. C., Salden, Miriam E., Verkes, R. J., Kahn, Rene S., Sitskoorn, Margriet M.
Background: Method: Results: Conclusion: Cognitive deficits are a core feature in schizophrenia. Cognitive deficits appear to be present at the onset of schizophrenia and persist after remission of psychotic symptoms. As cognitive deficits are associated with poor functional outcome, they form an important focus of treatment. There are relatively few head-to-head comparisons of the effects of second generation antipsychotics on cognition in recent onset schizophrenia. This is the first study to compare the effects of a short term treatment of olanzapine versus ziprasidone on cognitive functioning in recent onset schizophrenia. An earlier study conducted in chronic patients revealed an enhancement of cognition after treatment for both agents, but the extent of improvement was not significantly different between ziprasidone and olanzapine.Patients with recent onset schizophrenia with limited previous exposure to medical treatment underwent a double blind randomized controlled treatment trial. Fifty-six patients completed the neuropsychological testing procedure prior to randomization and after eight weeks of treatment and were included in the analysis. We tested cognitive functioning in general and verbal memory in particular. We calculated a single unweighted composite score based on nine cognitive tests to determine general cognitive functioning.Cognition appeared enhanced after treatment, but was not significantly different between treatment groups, neither for the verbal memory measures, nor for the neurocognitive composite score. Furthermore, cognitive enhancement did not correlate to clinical improvement.Cognitive deficits are not a reason for preferentially prescribing one of the two second generation antipsychotics tested over the other.
(c) 2010 Elsevier B.V. All rights reserved.
Schizophrenia Research, 120(1-3) : 191-198
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Preti, Antonio, Cella, Matteo
As an extension of the early intervention in psychosis paradigm, different focused treatments are now offered to individuals at ultra high risk of psychosis (UHR) to prevent transition to schizophrenia, however the effectiveness of these treatments is unclear. A systematic literature search in PubMed/Medline and PsycINFO was performed to derive information on randomized control trials (RCTs) in UHR samples. Seven reports were identified detailing results from five independent RCT studies. Two studies used antipsychotic drugs (one in combination with cognitive behavior therapy); one study employed cognitive therapy; one study used a two-year program of intensive community care with family psychoeducation; one study assessed the effectiveness of 3-months omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) supplementation. Intensive community care and the Omega-3 PUFAs supplementation were effective in reducing the transition to psychosis at 12 months. Overall, rates of transition to psychosis at 1 year were 11% for focused treatment groups (n=180) and 31.6% for control UHR groups (n=157). Receiving any of the focused treatment was associated with a lower risk of developing psychosis if compared with no treatment or treatment as usual (Relative Risk=0.36; 95%CI: 0.22-0.59). The available evidence at 2/3 years follow-up indicates that the effects of focused treatments are not stable after intervention cessation and when treatment is delivered over a restricted time (e.g. 6 months or less), it may achieve only a delay in psychosis onset. Due to the heterogeneity in the interventions considered, the current results do not allow recommendation for any specific treatment.
Copyright © 2010 Elsevier B.V. All rights reserved.
Schizophrenia Research, 123(1) : 30-36
- Year: 2010
- Problem: Psychosis Disorders
- Type: Systematic reviews
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Stage: At risk (indicated or selected prevention)
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Treatment and intervention: Biological Interventions (any)
, Psychological Interventions (any)
Nordentoft, M., Ohlenschlaeger, J., Thorup, A., Petersen, L., Jeppesen, P., Bertelsen, M.
BACKGROUND: The effects of hospital-based rehabilitation including weekly supportive psychodynamic therapy compared with specialized assertive intervention and standard treatment has not previously been investigated in first-episode psychosis. The aim of the study was to examine long-term effect on use of institutional care of different intensive interventions for patients with first-episode schizophrenia spectrum disorder on use of psychiatric bed days and days in supported housing. METHOD: A total of 94 severely ill patients with first-episode schizophrenia spectrum disorders were included in a special part of the Copenhagen OPUS trial and randomized to either the specialized assertive intervention program (OPUS), standard treatment or hospital-based rehabilitation. RESULTS: It was a stable pattern that patients randomized to hospital-based rehabilitation spent more days in psychiatric wards and in supported housing throughout the 5-year follow-up period compared with the two other groups. Patients in OPUS treatment spent significantly fewer days in psychiatric wards and supported housing in the first 3 years compared with patients in hospital-based rehabilitation. Due to attrition and small sample size, differences in level of psychotic and negative symptoms at 5-year follow-up could not be evaluated. CONCLUSIONS: The study indicates that hospital-based rehabilitation together with weekly supportive psychodynamic therapy was associated with a continued increased use of psychiatric bed days and days in supported housing. The data cannot justify using hospital-based rehabilitation in first-episode psychosis.
Psychological Medicine, 40(10) : 1-8
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
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Stage: First episode (psychosis only)
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Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions
Muller, Norbert, Krause, Daniela, Dehning, Sandra, Musil, Richard, Schennach-Wolff, Rebecca, Obermeier, Michael, Klauss, Volker, Schwarz, Markus J., Riedel, Michael
Recent trials support the hypothesis of the role of inflammation in the pathogenesis of schizophrenia. The overall therapeutic benefit of anti-inflammatory medication, in particular cyclo-oxygenase-2 (COX-2) inhibitors in schizophrenia, is still controversial. There are suggestions that therapy with COX-2 inhibitors may influence the early stages of the disease. Taking these findings into account, we conducted a double-blind, placebo-controlled, randomized trial of celecoxib augmentation to amisulpride treatment in patients with a first manifestation of schizophrenia. Forty-nine patients diagnosed with schizophrenia were randomly assigned. They were treated either with amisulpride (200-1000 mg) plus celecoxib (400 mg) or amisulpride (200-1000 mg) plus placebo. Inclusion criterion was the diagnosis of schizophrenia during the past two years according to DSM-IV. The trial lasted six weeks. At weekly intervals an assessment of the psychopathology was performed using the Positive and Negative Symptom Scale (PANSS) and the Global Clinical Impression Scale (CGI). A significantly better outcome was observed in the patient group treated with amisulpride plus celecoxib compared to the group with amisulpride plus placebo (PANSS negative: p=0.03; PANSS global; p=0.05 and PANSS total: p=0.02). In addition, ratings by the CGI scale during therapy with amisulpride and celecoxib showed a significantly better result (p< or =0.001). A significantly superior therapeutic effect could be observed in the celecoxib group compared to placebo in the treatment of early stage schizophrenia. This is the first time an improvement in patients' negative symptoms has been demonstrated with celecoxib. In future, further trials are needed to investigate the effect of COX-2 inhibitors on prodromal and negative symptoms of schizophrenia.
Copyright 2010 Elsevier B.V. All rights reserved.
Schizophrenia Research, 121(1-3) : 118-124
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Other biological interventions
Meltzer, Herbert Y., Bobo, William V., Lee, Myung A., Cola, Philip, Jayathilake, Karuna
Clozapine has been shown to be superior to typical neuroleptic drugs for treating positive symptoms in treatment-resistant (TR) schizophrenia. Long-term data from randomized clinical trials comparing clozapine with typical neuroleptics in non-TR schizophrenia are rare. We previously reported that clozapine was superior to typical neuroleptic drugs in some domains of cognition in recent onset non-TR schizophrenia. We now present data on psychopathology and quality of life from this randomized, flexibly dosed, 24-month study of clozapine vs. typical neuroleptics in non-TR schizophrenia patients. Both treatments produced significant improvement in measures of psychopathology, quality of life, and global function, with minor exceptions. There was no difference in extrapyramidal side effects between the patients treated with clozapine or typical neuroleptics. However, significantly more relapse/rehospitalization drop-outs occurred in the typical neuroleptic group. Two patients treated with typical neuroleptics, but none treated with clozapine, became non-responsive to treatment. Clozapine was associated with significantly greater weight gain. Clozapine and typical neuroleptic drugs appear to produce equivalent improvement in psychopathology in patients with non-TR schizophrenia. Clozapine may be more effective than typical neuroleptics for treatment retention and prevention of relapse, but it produces more severe metabolic side effects. These considerations should be taken into account in decisions of how best to utilize clozapine in the treatment of schizophrenia.
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Psychiatry Research, 177(3) : 286-293
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Levkovitz, Yechiel, Mendlovich, Shlomo, Riwkes, Sharon, Braw, Yoram, Levkovitch-Verbin, Hana, Gal, Gilad, Fennig, Shmuel, Treves, Ilan, Kron, Shmuel
Background: Objective: Method: Results: Conclusions: Trial Registration: Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia: negative symptoms and cognitive deficits. Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders. Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia. These findings may be linked to the effect of minocycline on the glutamatergic system, through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity. Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation.To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia.A longitudinal double-blind, randomized, placebo-controlled design was used, and patients were followed for 6 months from August 2003 to March 2007. Seventy early-phase schizophrenia patients (according to DSM-IV) were recruited and 54 were randomly allocated in a 2:1 ratio to minocycline 200 mg/d. All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry (risperidone, olanzapine, quetiapine, or clozapine; 200-600 mg/d chlorpromazine-equivalent doses). Clinical, cognitive, and functional assessments were conducted, with the Scale for the Assessment of Negative Symptoms (SANS) as the primary outcome measure.Minocycline was well tolerated, with few adverse events. It showed a beneficial effect on negative symptoms and general outcome (evident in SANS, Clinical Global Impressions scale). A similar pattern was found for cognitive functioning, mainly in executive functions (working memory, cognitive shifting, and cognitive planning).Minocycline treatment was associated with improvement in negative symptoms and executive functioning, both related to frontal-lobe activity. Overall, the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia.clinicaltrials.gov Identifier: NCT00733057.
Copyright 2010 Physicians Postgraduate Press, Inc.
Journal of Clinical Psychiatry, 71(2) : 138-149
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Other biological interventions
Grootens, K. P., van Veelen, N. M. J., Sitskoorn, M. M., Sabbe, B. G. C., Peuskens, J., Buitelaar, J. K., Verkes, R. J., Kahn, R. S.
Introduction: To enhance functional outcome in schizophrenia improvement of cognitive symptoms is crucial. Experimental procedures: Using a comprehensive test battery, this follow-up examines cognitive effects in patients with recent-onset schizophrenia after a change of medication following insufficient clinical response and intolerance. Results: After eight weeks cognitive outcomes had not improved in the patients having switched from olanzapine to ziprasidone (n=11; mean dose 136 mg) nor in those having switched from ziprasidone to olanzapine (n=10; mean 16 mg), while the symptoms of patients maintaining olanzapine (n=18; mean 10.9 mg) or ziprasidone (n=18; mean 88.9 mg) treatment had not improved further. Discussion: The findings suggest that also in early-stage schizophrenia the antipsychotics tested affect cognitive symptoms similarly. (copyright) 2010 Elsevier B.V. and ECNP.
European Neuropsychopharmacology, 20(12) : 907-912
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Gafoor, Rafael, Landau, Sabine, Craig, Tom K. J., Elanjithara, Thomas, Power, Paddy, McGuire, Philip
Objective: To compare the efficacy and adverse effect profiles of 2 widely used atypical antipsychotics in the short-term phase of first-episode schizophrenia in patients who were treatment-naive. A secondary objective was to establish the effective dose of these drugs in this context. Methods: A total of 72 patients with a first episode of schizophreniform psychosis (schizophrenia spectrum disorder) with less than 2 weeks of exposure to antipsychotic medication were randomized to quetiapine or risperidone in a single-blind 12-week controlled trial. Psychopathologic diagnoses and adverse effects were assessed by blinded raters at 4 weekly intervals. Medication was administered by a specialized clinical team following dosing guidelines. Data were analyzed using an intention-to-treat paradigm. Results: Both quetiapine and risperidone were associated with a reduction in immediate symptoms and relatively few adverse effects other than weight gain. There was no statistically significant difference between the 2 compounds in adverse effects, relative efficacies, or adherence to treatment. The median (SD) time to cessation for patients randomized to quetiapine was 65.3 (41.85) days and that for risperidone was 82.5 (44.88) days. There was no statistically significant difference between time to discontinuation for the 2 compounds. The mean daily doses prescribed were 375 mg of quetiapine and 2.72 mg of risperidone. Conclusions: Quetiapine and risperidone are both effective treatments in first-episode schizophrenia at doses lower than those used in patients with long-term schizophrenia and are similar in efficacy and the incidence of adverse effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved) (journal abstract)
Journal of Clinical Psychopharmacology, 30(5) : 600-606
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
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Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Gafoor, Rafael, Nitsch, Dorothea, McCrone, Paul, Craig, Tom K. J., Garety, Philippa A., Power, Paddy, McGuire, Philip
Background: Aims: Method: Results: Conclusions: Early specialised care may improve short-term outcome in first-episode non-affective psychosis, but it is unclear if these benefits endure.To assess the long-term effect of early intervention in psychosis.Individuals with first-episode psychosis were randomised to specialised care or care as usual (trial number: ISRCTN73679874). Outcome after 5 years was assessed by case-note review.There were no significant differences in the admission rate (coefficient 0.096, 95% CI -0.550 to 0.742, P = 0.770) or the mean number of bed days (coefficient 6.344, 95% CI -46 to 58.7, P = 0.810).These findings that specialist intervention did not markedly improved outcome at 5 years accord with those from a larger OPUS study. The sample size of this study was small and these results should be generalised with caution. More research is needed.
British Journal of Psychiatry, 196(5) : 372-376
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
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Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions
Josiassen, Richard C., Shaughnessy, Rita A., Filymer, Dawn M., Donohue, Ann Marie, Kacso, Margit, Finkel, Naomi, Curtis, Jessica, Audino, Brett, Skuban, Nina
Objective: Method: Results: Conclusions: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis.In a naturalistic, 'single-blind' design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly.The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged.Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms.
Early Intervention in Psychiatry, 4(1) : 57-63
- Year: 2010
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Findling, Robert L., Johnson, Jacqueline L., McClellan, Jon, Frazier, Jean A., Vitiello, Benedetto, Hamer, Robert M., Lieberman, Jeffrey A., Ritz, Louise, McNamara, Nora K., Lingler, Jacqui, Hlastala, Stefanie, Pierson, Leslie, Puglia, Madeline, Maloney, Ann E., Kaufman, Emily Michael, Noyes, Nancy, Sikich, Linmarie
Objective: Method: Results: Conclusions: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders.Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks.Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment.Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703.
2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Journal of the American Academy of Child & Adolescent Psychiatry, 49(6) : 583-594
- Year: 2010
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)