Disorders - Psychosis Disorders
Berger, Gregor E., Proffitt, Tina-Marie, McConchie, Mirabel, Yuen, HokPan, Wood, Stephen J., Amminger, Paul, Brewer, Warrick, McGorry, Patrick D.
Objective: To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP). Method: We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures. Results: Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all time-points), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone. Conclusion: The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted. (PsycINFO Database Record (c) 2009 APA, all rights reserved) (journal abstract).
Journal of Clinical Psychiatry, 68(12) : 1867-1875
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Complementary & Alternative Interventions (CAM)
, Fish oil (Omega-3 fatty acids)
, Omega 3 fatty acids (e.g. fish oil, flax oil)
Bechdolf, Andreas, Wagner, Michael, Veith, Verena, Ruhrmann, Stephan, Pukrop, Ralf, Brockhaus-Dumke, Anke, Berning, Julia, et-al
Aim: Improvement of social adjustment is a major aim of indicated prevention in young people at risk of developing psychosis. The present study explores the effect of specific cognitive behaviour therapy (CBT) as compared with supportive counselling (SC) on social adjustment in people in a potential early initial prodromal state of psychosis (EIPS) primarily defined by self-experienced cognitive thought and perception deficits (basic symptoms). Methods: A total of 128 help-seeking outpatients in the EIPS were randomized to receive either specific CBT or SC for 12 months. Social adjustment was assessed with the Social Adjustment Scale II (SAS II) at baseline, time of transition or post treatment Results: From 113 patients, who completed the SAS II at intake, 67 (59.3%) completed the SAS assessments at time of transition or post treatment. Both specific CBT and SC resulted in improvements in scales of SAS II, with no significant between-group differences post treatment. Conclusions: Although treatment in specially designed early detection and intervention centres improves functioning of people in the EIPS, specific CBT was not superior to SC. One could hypothesize that additional vocational rehabilitation, case management and involvement of multidisciplinary teams are needed to further improve short-term outcome of specific interventions on this dimension. (PsycINFO Database Record (c) 2008 APA, all rights reserved) (journal abstract).
Early Intervention in Psychiatry, 1(1) : 71-78
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
, Supportive therapy
Harvey, P. O., Lepage, M., Malla, A.
Objective: To assess the effectiveness of enriched intervention (EI) on symptomatic and functional outcomes, compared with standard care (SC). Method: Studies were retrieved from search engines and, using a metaanalytic approach, we compared EI trials with SC trials. Eleven EI sample trials (1053 patients) and 6 SC sample trials (500 patients), totalling data from 1553 patients (69% male), were examined. We calculated the effect sizes (ESs) of both symptomatic and functional improvement over a follow-up period of about 1 year. Results: Significant differences between EI and SC were observed at follow-up for the improvement of both positive and negative symptoms, respectively: positive, EI = -1.54 (95%CI, -1.63 to -1.45 ) and SC = -1.07 (95%CI, -1.19 to -0.94 ) (Q between = 40.3, df 1, P < 0.001); negative, EI = -0.44 (95%CI, -0.53 to -0.35) and SC = -0.18 (95%CI, -0.31 to -0.05) (Qbetween = 10.6, df 1, P < 0.01). We also observed a significant difference between the EI and the SC groups for functional improvement over the follow-up period with mean EI = 1.11 (95%CI, 0.99 to 1.23) and SC = 0.63 (95%CI, 0.49 to 0.77) (Q between = 24.5, df 1, P < 0.001). Conclusions: There is now quantitative evidence across multiple studies and sites to indicate that EIs for patients with recent-onset psychosis are significantly more effective than SC for symptomatic and functional improvement over a period of about 1 year.
Canadian Journal of Psychiatry., 52(7) : 464-472
- Year: 2007
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
, First episode (psychosis only)
-
Treatment and intervention: Psychological Interventions (any)
Keefe, R. S. E., Sweeney, J. A., Gu, H., Hamer, R. M., Perkins, D. O., McEvoy, J. P., Lieberman, J. A.,
Objective: The authors sought to compare the effects of olanzapine, quetiapine, and risperidone on neurocognitive function in patients with early psychosis. Method: In a 52-week double-blind, multicenter study, 400 patients early in the course of psychotic illness (<5 years) were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day). The mean modal daily dose was 11.7 mg (SD=5.3) for olanzapine, 506 mg (SD=215) for quetiapine, and 2.4 mg (SD=1.0) for risperidone. A total of 224 patients completed neurocognitive assessments at baseline and at 12 weeks, and 81 patients also completed them at 52 weeks. Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and from the Brief Assessment of Cognition in Schizophrenia. Results: At week 12, there was significant improvement in neurocognition for each treatment (p<0.01), but no significant overall difference between treatments. Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine, 0.33 for quetiapine, and 0.32 for risperidone. Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine, 0.34 for quetiapine, and 0.22 for risperidone. Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52. Conclusions: Olanzapine, quetiapine, and risperidone all produced significant improvements in neurocognition in early-psychosis patients. Although cognitive improvements were modest, their clinical importance was suggested by relationships with improvements in functional outcome.
American Journal of Psychiatry., 164(7) : 1061-1071
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Gaebel, W., Riesbeck, M., Wolwer, W., Klimke, A., Eickhoff, M., Von Wilmsdorff, M., Jockers-Scherubl, M. C., et-al
Objective: Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested.
Method: Between November 2000 and May 2004, 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals. 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria. In the randomized controlled trial, double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for analysis. For 127 patients, this was a continuation trial after 8 weeks of randomized, double-blind, acute treatment with the same drugs; 24 patients were additionally randomly assigned after open acute treatment.
Results: With both antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved. Additionally, according to 2 post hoc defined measures of "marked clinical deterioration," significant differences occurred neither in the 2 respective deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time until deterioration. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Extrapyramidal symptoms were slightly higher with haloperidol. The overall dropout rate of 68%, however, was not significantly different between the 2 drug groups.
Conclusion: Against the background of an overall favorable outcome, the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with firstepisode schizophrenia. Possible design-related reasons for this finding are discussed. With regard to the high dropout rate, special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment.
Journal of Clinical Psychiatry, 68(11) : 1763-1774.
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
, Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
McEvoy, J. P., Lieberman, J. A., Perkins, D. O., Hamer, R. M., Gu, H., Lazarus, A., Sweitzer, D., Olexy, C., Weiden, P., Strakowski, S. D.
Objective: This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness. Method: Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%. Results: A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%). Conclusions: Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.
American Journal of Psychiatry., 164(7) : 1050-1060
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Morrison, A. P., French, P., Parker, S., Roberts, M., Stevens, H., Bentall, R. P., Lewis, S. W.
There have been recent advances in the ability to identify people at high risk of developing psychosis. This has led to interest in the possibility of preventing the development of psychosis. A randomized controlled trial compared cognitive therapy (CT) over 6 months with monthly monitoring in 58 patients meeting criteria for ultrahigh risk of developing a first episode of psychosis. Participants were followed up over a 3-year period. Logistic regression demonstrated that CT significantly reduced likelihood of being prescribed antipsychotic medication over a 3-year period, but it did not affect transition to psychosis defined using the Positive and Negative Syndrome Scale (PANSS) or probable Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis. However, exploratory analyses revealed that CT significantly reduced the likelihood of making progression to psychosis as defined on the PANSS over 3 years after controlling for baseline cognitive factors. Follow-up rate at 3 years was 47%. There appear to be enduring benefits of CT over the long term, suggesting that it is an efficacious intervention for people at high risk of developing psychosis. copyright The Author 2006. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
Schizophrenia Bulletin., 33(3) : 682-687
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
Ohlenschlaeger, J., Thorup, A., Petersen, L., Jeppesen, P., Koster, A., Munkner, R., Nordentoft, M.
Little evidence exists concerning the optimal treatment for patients with first-episode schizophrenia-spectrum disorders and the effect on traditional outcomes. The aim was to investigate whether optimal treatment models have an effect on the level of use of coercion and on traditional outcomes. Hospital-based Rehabilitation, an intensified inpatient treatment model, Integrated Treatment, an intensified model of Assertive Community Treatment, and standard treatment were compared for patients with first-episode schizophrenia-spectrum disorders. Ninety-four patients with first-episode schizophrenia-spectrum disorders estimated to benefit from long-term hospitalization were included consecutively from the Copenhagen OPUS-trial and randomized to the three treatment models. At 1-year follow-up, Hospital-based Rehabilitation and Integrated Treatment had better scores on symptoms in the negative dimension and on client satisfaction. Integrated Treatment had fewer bed-days, more patients living in non-supervised accommodation, and better score on quality of life. No differences were found as to the use of coercion. This study adds to the evidence that intensified treatment models are superior to standard treatment. A higher number of bed-days in Hospital-based Rehabilitation did not influence the effect on the outcomes measured.
Nordic Journal of Psychiatry., 61(5) : 369-378
- Year: 2007
- 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
Kennedy, E., Kumar, A., Datta, S. S.
Background: Childhood-onset schizophrenia is schizophrenia with onset prior to the age of 13 years. Although it is rare, people who suffer from schizophrenia at an early age appear to have a clinically severe form of the illness with poor long-term prognosis. Antipsychotic medication is one way of managing this rare but serious mental illness. Objectives: To examine the effects of antipsychotic medication for childhood-onset schizophrenia. Search strategy: We searched the Cochrane Schizophrenia Group Trials Register (November 2006 and February 2007), inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors of trials for additional information. Selection criteria: We included all randomised clinical trials involving children and young people with a diagnosis of childhood onset schizophrenia (i.e. with a diagnosis of schizophrenia before the age of 13) comparing any antipsychotic drug with another antipsychotic or placebo. Data collection and analysis: We reliably selected, quality assessed and extracted data fromtrials. We excluded data wheremore than 50% of participants in any group were lost to follow up. For homogenous dichotomous data we calculated random effects, relative risk (RR) and its 95% confidence interval (CI) and, where appropriate, number needed to treat (NNT) on an intention-to-treat basis. For normal continuous data we calculated the weighted mean difference (WMD). Main results: From a total of 2062 citations, we identified six relevant trials. We categorised trials into three comparisons: atypical versus typical, atypical versus atypical and typical versus typical antipsychotic drugs. The only comparison to find any differences between treatment groups was atypical versus typical antipsychotic drugs. A few results from one study favoured the atypical antipsychotic clozapine over haloperidol in treating treatment resistant childhood-onset schizophrenia (n=21, WMD CGAS 17.00 CI 7.74 to 26.26; n=21, WMD Bunney-Hamburg Psychosis Rating Scale -3.60 CI -6.64 to -0.56). Participants on clozapine, however, were three times more likely to have drowsiness (1 RCT, n=21, RR 3.30 CI 1.23 to 8.85, NNH 2 CI 2 to 17) and half of the children receiving clozapine had neutropenia (1 RCT, n=21, RR 12, CI 0.75 to192.86). Authors' conclusions: There are few relevant trials and, presently, there is little conclusive evidence regarding the effects of antipsychotic medication for those with early onset schizophrenia. Some benefits were identified in using the atypical antipsychotic clozapine compared with haloperidol but the benefits were offset by an increased risk of serious adverse effects. Larger, more robust, trials are required. Copyright (copyright) 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Database of Systematic Reviews, (4) :
- Year: 2007
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Phillips, L. J., McGorry, P. D., Yuen, H. P., Ward, J., Donovan, K., Kelly, D., Francey, S. M., Yung, A. R.
Valid criteria to identify young people who are believed to be at ultra high risk (UHR) of developing a psychotic episode were developed over the last decade. The first randomized controlled trial of treatment in a UHR cohort indicated that specific pharmacotherapy and psychotherapy delayed onset of disorder, and possibly reduced incidence. This paper reports results of follow-up of that trial. 41 of the 59 (69.5%) participants in the original study agreed to follow-up. No differences were found in transition rate, level of symptomatology or functioning between participants who received a combination of psychological treatment and anti-psychotic medication compared to those who received supportive therapy alone. A significant proportion of both treatment groups reported moderate levels of psychiatric morbidity and a continuing need and desire for care at this follow-up. Low levels of hospitalisation were noted for those who did progress to psychosis. Conclusions that can be drawn from this exploratory study are limited by the relatively small number of participants in the original study and the failure to follow-up the entire cohort. Although participants may have been treated too briefly to result in enduring positive effects, there appear to have been some cost savings in inpatient mental health treatment required after the end of the trial for individuals in both treatment groups who developed psychosis. copyright 2007 Elsevier B.V. All rights reserved.
Schizophrenia Research., 96(1-3) : 25-33
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Psychological Interventions (any)
, Supportive therapy, Other Psychological Interventions
Ruhrmann, S., Bechdolf, A., Kuhn, K. U., Wagner, M., Schultze-Lutter, F., Janssen, B., Maurer, K., Hafner, H., Gaebel, W., Moller, H. J., Maier, W., Klosterkotter, J.
BACKGROUND: People in a putatively late prodromal state not only have an enhanced risk for psychosis but already suffer from mental and functional disturbances. AIMS: To evaluate the acute effects of a combined supportive and antipsychotic treatment on prodromal symptoms. METHOD: Putatively prodromal individuals were randomly assigned to a needs-focused intervention without (n=59) or with amisulpride (n=65). Outcome measures at 12-weeks effects were prodromal symptoms, global functioning and extrapyramidal side-effects. RESULTS: Amisulpride plus the needs-focused intervention produced superior effects on attenuated and full-blown psychotic symptoms, basic, depressive and negative symptoms, and global functioning. Main side-effects were prolactin associated. CONCLUSIONS: Coadministration of amisulpride yielded a marked symptomatic benefit. Effects require confirmation by a placebo-controlled study.
British Journal of Psychiatry, 51 : s88-95
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Wykes, T., Newton, E., Landau, S., Rice, C., Thompson, N., Frangou, S.
Background: Schizophrenia with an onset in adolescence is known to be associated with a poorer outcome and cognitive difficulties. These impairments have an impact on quality of life and represent treatment targets. Cognitive remediation therapy (CRT) attempts to improve cognitive deficits by teaching information processing strategies through guided mental exercises. The objective of this study is to evaluate the efficacy of CRT in alleviating cognitive deficits compared to treatment as usual and explore the mediating and moderating effects of cognitive improvement. Method: Single-blind randomized controlled trial with two groups, one receiving CRT (N21) and the other standard care (N19) assessed at baseline, 3 months (post therapy) and follow-up (3 months post therapy). Participants were recruited from specialist inpatient and community mental health services and were young patients with recent onset schizophrenia (average age of 18) and evidence of cognitive and social behavioural difficulties. The intervention was individual cognitive remediation therapy delivered over a period of 3 months with at least three sessions per week. The main outcome measures were cognition (memory, cognitive flexibility and planning) and secondary outcomes (symptoms, social contacts and self-esteem). Results: Compared to standard care, CRT produced significant additional improvements in cognitive flexibility as measured by the Wisconsin Card Sort Test (WCST). Therapy moderated the effects of improved planning ability on symptoms such that improvements only had a beneficial effect when they were achieved in the context of CRT. Improvements in cognition in all domains had a direct effect on social functioning and improvements in WCST had a direct effect on overall symptom improvement. Conclusions: Cognitive remediation therapy can contribute to the improvement in WCST even in adolescents. The changes in cognitive outcomes also contributed to improvements in functioning either directly or solely in the context of CRT. Evidence of the mediator and moderator effects of cognitive changes should lead to more effective therapy development. copyright 2007 Elsevier B.V. All rights reserved.
Schizophrenia Research., 94(1-3) : 221-230
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive remediation therapy