Disorders - Psychosis Disorders
Nuechterlein, K. H., Ventura, J., Subotnik, K. L., Gretchen-Doorly, D., Turner, L., Casaus, L. R., Luo, J. S., Medalia, A., Bell, M. D.
Background: Cognitive deficits are already evident at a first episode of schizophrenia and are strongly predictive of functional outcome. Work/ school functioning tends to be the most common domain of continuing functional impairment and is known to be linked to continuing cognitive deficit. Thus, intervention to improve cognitive functioning early in the course of schizophrenia is critical if we hope to prevent or limit long-term disability in this disorder. Methods: We recently completed a 12-month randomized controlled trial of cognitive remediation in patients with a recent first episode of schizophrenia, using healthy behavior training as an active comparison group. A broad spectrum approach to cognitive remediation was employed, using programs emphasizing repeated practice with basic cognitive processes (processing speed, attention, immediate memory) and more complex, life-like situations (higher-order memory and problem solving). In addition to 2 hours/week of computerized cognitive training, cognitive remediation patients participated in a bridging group to encourage transfer to work and school situations. Patients in both treatment groups were provided supported employment/ education to encourage return to competitive work or schooling. Results: Consistent antipsychotic medication adherence was found to impact cognitive improvement in this period after a first psychotic episode, so medication adherence and protocol completion were covaried to examine cognitive remediation effects. Cognitive remediation produced significant improvement in the overall composite score and the attention/ vigilance domain from the MATRI CS Consensus Cognitive Battery, compared to healthy behavior training. Cognitive remediation also led to significantly greater improvement in work/school functioning. Cognitive improvement was significantly correlated with the degree of work/school functional improvement. Conclusion: These results indicate that cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/ education, cognitive remediation shows an impact on work/school functioning that goes beyond the facilitating effect of that compensatory work rehabilitation approach. Additional research will be needed to understand the conditions under which cognitive training can produce an impact on more individual cognitive domains and to examine ways to increase the magnitude of its effects on cognition and functional outcome.
Schizophrenia Bulletin, 39 : S347
- Year: 2013
- 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, Psychological Interventions (any)
, Cognitive remediation therapy, Technology, interventions delivered using technology (e.g. online, SMS)
Ou, Jian-Jun, Xu, Yi, Chen, Hong-Hui, Fan, Xiaoduo, Gao, Keming, Wang, Juan, Guo, Xiao-Feng, Wu, Ren-Rong, Zhao, Jing-Ping
Objective: The objective of the study was to compare metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia.; Methods: In this 6-week, multicenter, open-label trial, 260 patients were randomly assigned to receive ziprasidone or olanzapine treatment (130 per group). Primary metabolic measures were changes in weight and body mass index (BMI). Secondary metabolic measures were changes in glucose, insulin, lipids, and blood pressure. Efficacy and safety were also measured additionally.; Results: A total number of 230 patients completed the study. The mean daily dosages were 138.2(28.6) mg for ziprasidone and 19.0(2.3) mg for olanzapine. After 6-week treatment, there were significant between-group differences in change scores on weight [4.22(3.49) kg versus -0.84(2.04) kg, p < 0.001] and BMI [1.59(1.37) versus -0.30(0.74), p < 0.001]. In addition, there were significant between-group differences in change scores on fasting plasma glucose, insulin, homeostasis model assessment 2-insulin resistance, low-density lipoprotein, total cholesterol, and triglycerides (p < 0.001); all the changes were clinically in favor of ziprasidone treatment. Both medications were effective in improving schizophrenia symptoms, but the decreases in Positive and Negative Syndrome Scale total scores of the olanzapine group were significantly greater than that of the ziprasidone group (p < 0.05). Compared with olanzapine, ziprasidone also induced more prolonging of corrected QT interval and extrapyramidal side effects (p < 0.05). Both medications were well tolerated, and no serious adverse events were observed in either group.; Conclusions: Compared with olanzapine, ziprasidone treatment was associated with less adverse effects on glucose and lipid metabolism in patients with first-episode schizophrenia.;
Psychopharmacology, 225(3) : 627-635
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
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Stage: First episode (psychosis only)
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Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Puig, O., Penades, R., Baeza, I., De La Serna, E., Sanchez-Gistau, V., Bernardo, M., Castro-Fornieles, J.
Early-onset schizophrenia (EOS) is a severe form of schizophrenia associated with significant decline or arrest in several cognitive domains. Cognitive Remediation Therapy (CRT) is a behavioral intervention that aims to improve cognitive processes with the goal of durability and generalization to patients' community functioning. Large body of data supports the efficacy of CRT in adults with schizophrenia but few studies have analyzed its effects in young people. Objective: To examine the efficacy of CRT to improve cognition and functional outcome in adolescents with EOS. Methods: Randomized controlled trial of CRT plus treatment as usual (CRT) compared to treatment-as-usual as control group (TAU) (NCT01701609). CRT was implemented on an individual basis following the Frontal/Executive program procedure. Fifty adolescents (aged 12-18 years) with EOS (DSM-IV schizophrenia or schizoaffective disorder, onset before 18) were randomized to the groups (25 and 25). Patients had to be clinically and pharmacologically stabilized during the last 6 weeks before the baseline assessment and had to be cognitively impaired. Exclusion criteria were current IQ<70, active misuse disorder, organic brain syndromes and having received electroconvulsive therapy in the previous 6 months. Assessment: Symptoms (PANSS, Calgary Depression Scale), cognitive domains (tests in Spanish similar to those included in the MATRICS consensus battery) and functional measures (Life Skills Profile - LSP-, Vineland Adaptive Behavior Scales - VABS-, C-GAS, Rosenberg Self-Esteem Scale and Caregiver Burden Inventory - CBI). Intention-to-treat analyses were used. Repeated measures ANOVA design was employed, between conditions (CRT vs. TAU), and baseline and post-treatment as the time points. ANCOVAs were performed to control for potential confounders. Results: There were no significance baseline differences between groups on demographic measures, IQ, mean chlorpromazine equivalent for antipsychotic medication dosage (CPZE), depressive and positive symptoms, emotional discomfort and hostility. CRT group had more negative symptoms (t = 2.16, p = 0.036) and total PANSS scores (t = 2.63, p = 0.012). The groups were comparable in all cognitive domains and functional measures, excepting for C-GAS (CRT group scored lower, t = 2.19, p = 0.034). The groups did not differ in symptoms changes and in CPZE adjustments during the trial. Results showed a beneficial effect of CRT overt TAU on global cognition (F = 7.48, p = 0.009), verbal memory (F = 10.12, p = 0.003), working memory (F = 4.43, p = 0.041) and executive functions (F = 5.85, p = 0.019). Results did not change when controlling for baseline cognition, excepting in working memory domain (F = 3.85, p = 0.056). The addition of symptoms baseline differences between groups as a covariate did not affect the results. CRT group had also greater improvements in LSP (F = 4.52, p = 0.039) and VABS (F = 5.08, p = 0.031), with baseline symptoms differences between groups adjusted for. No significant differences were found in C-GAS or self-esteem. Parents of patients in the CRT group reported greater improvement of their self-perceived burden after treatment (F = 7.44, p = 0.011). Conclusions: The findings are consistent with previous studies of CRT and add evidence for its efficacy in ameliorating cognitive impairments and improving functional outcome in adolescents with EOS.
European Neuropsychopharmacology, 23 : S611
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Psychological Interventions (any)
, Cognitive remediation therapy
Ventura, J., Gretchen-Doorly, D., Subotnik, K. L., Vinogradov, S., Nahum, M., Nuechterlein, K. H.
Background: Cognitive remediation and physical exercise have separately been shown to have promise for improving cognitive deficits in schizophrenia. Their combined use in schizophrenia may yield even more robust effects. Engaging in regular aerobic exercise might provide a mechanism which allows neuroplasticity-based cognitive training to impact cognition to a greater degree than is usually observed with cognitive training alone. Further, targeting cognition in the initial period of illness may lead to greater generalization to functional outcome compared to periods in which illness factors are well established. Methods: First-episode schizophrenia patients (n = 15 mean age = 21) were assessed at baseline and at the conclusion of a 10-week intervention. Patients in the combined Cognitive Training and Exercise program (CT&E) participated in computerized brain plasticity- based training focused on auditory discrimination and then switched to computerized social cognition training (4 hours per week, total of 40 hours). These same patients exercised for 30 minutes twice a week at the clinic and for 30 minutes at home (total of 20 hours). CT&E patients were compared to an Aftercare Treatment as Usual (ATAU ) control group involving a healthy lifestyle psychoeducational group (3 hours per week, total of 30 hours). Results: Attendance at the in-clinic CT&E sessions was highly consistent for the cognitive training (100%) and the exercise training (95%) sessions. The CT&E patients' cognitive functioning compared to ATAU improved as shown in Group X Time effects for the MATRI CS Cognitive Consensus Battery (MCCB) Overall Composite Score (Cohen's d = 0.43) and the Attention/Vigilance score (d = 0.67). Patients showed large improvements in domains of social cognition such as Facial Emotion Identification (d = 1.48), Managing Emotions (d = 1.54), and Emotional Prosody (d = 0.87). Group X Time analyses for patients in CT&E compared to ATAU indicated improvement in school or work functioning (d = 0.73), in independent living skills (d = 1.26), and in family relationships (d = 0.93). Conclusion: We conclude that treatment adherence was excellent despite the demands of a combined cognitive training and exercise program. Considering the brief duration of this pilot study, the magnitude of neurocognitive and social cognitive performance gains and the broad functional outcome improvements compared to ATAU , support an intervention approach combining cognitive training and exercise in the early course of schizophrenia.
Schizophrenia Bulletin, 39 : S309-S310
- Year: 2013
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
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Stage: First episode (psychosis only)
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Treatment and intervention: Complementary & Alternative Interventions (CAM)
, Service Delivery & Improvement, Psychological Interventions (any)
, Cognitive remediation therapy, Physical activity, exercise, Technology, interventions delivered using technology (e.g. online, SMS)
Rauch, Anna-Sophia, Fleischhacker, W. Wolfgang
Antipsychotics are the mainstay of the long-term treatment of patients with schizophrenia. In this context, the evidence also supports the effectiveness of long-acting injections (LAIs) or depots of antipsychotics regarding their relapse-preventing properties. When a LAI formulation of risperidone was launched as the first second-generation depot, there was a renaissance of interest in these formulations. In the meantime, olanzapine, paliperidone, and aripiprazole have been approved by regulatory authorities as LAIs in various countries. All studies using the new-generation depots have shown a clear advantage over placebo regarding relapse prevention and symptom reduction. Safety profiles of the long-acting compounds are comparable to their oral formulations with the exception of olanzapine pamoate injections, which can sometimes lead to a post-injection delirium. Despite the fact that many treatment guidelines recommend LAI antipsychotics as an important treatment option for the long-term management of schizophrenia, they are still most frequently used in chronically ill patients with considerable compliance problems. It is imperative to overcome this indication bias in order to be able to utilize all available treatment options in the long-term management of schizophrenia. There is little evidence on comparisons between LAIs and their oral mother compounds, and even less concerning effectiveness comparisons between different depots. The purpose of this manuscript is to review the recent clinical evidence on new-generation depot antipsychotics. ;
CNS Drugs, 27(8) : 637-652
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
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Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Service Delivery & Improvement, Other service delivery and improvement interventions
Nitta, M., Kishimoto, T., Muller, N., Weiser, M., Davidson, M., Kane, J. M., Correll, C. U.
Objective: To meta-analytically assess the efficacy and tolerability of nonsteroidal anti-inflammatory drugs (NSAIDs) vs placebo in schizophrenia. Method: Searching PubMed, PsycINFO, ISI Web of Science, and the US National Institute of Mental Health clinical trials registry from database inception to December 31, 2012, we conducted a systematic review/meta-analysis of randomized placebo-controlled studies assessing the efficacy of adjunctive NSAIDs. Primary outcome was the change in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included change in PANSS positive and negative subscores, all-cause discontinuation, and tolerability outcomes. Random effects, pooled, standardized mean changes (Hedges' g) and risk ratios were calculated. Results: Across 8 studies, including 3 unpublished reports (n = 774), the mean effect size for PANSS total score was -0.236 (95% CI: -0.484 to 0.012, P =. 063, I2 = 60.6%), showing only trend-level superiority for NSAIDs over placebo. The mean effect sizes for the PANSS positive and negative scores were -0.189 (95% CI: -0.373 to -0.005, P =. 044) and -0.026 (95% CI: -0.169 to 0.117, P =. 72), respectively. The relative risk for all-cause discontinuation was 1.13 (95% CI: 0.794 to 1.599, P =. 503). Significant superiority of NSAIDs over placebo regarding PANSS total scores was moderated by aspirin treatment (N = 2, P =. 017), inpatient status (N = 4, P =. 029), first-episode status (N = 2, P =. 048), and (in meta-regression analyses) lower PANSS negative subscores (N = 6, P =. 026). Interpretation: These results indicate that adjunctive NSAIDs for schizophrenia may not benefit patients treated with first-line antipsychotics judged by PANSS total score change. NSAIDs may have benefits for positive symptoms, but the effect was minimal/small. However, due to a limited database, further controlled studies are needed, especially in first-episode patients. (copyright) 2013 The Author 2013.
Schizophrenia Bulletin, 39(6) : 1230-1241
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Other biological interventions
O'Connor, K.
Background: The past 15 years have seen a growing interest in early intervention and detection of psychosis before the onset of the first episode. Recent proposals to include a psychosis risk syndrome (PRS) in DSM 5 have focused attention on the evidence base achieved to date in this field. Aims: This article aims to (1) review the underlying principles of early identification and intervention during the pre-psychotic phase, (2) summarise the naturalistic follow-up studies conducted to date in this 'at-risk' population, (3) discuss the identified clinical risk factors for transition to psychosis, (4) summarise the interventional studies both psychological and pharmacological completed to date and (5) briefly discuss the controversy around the proposed inclusion of the PRS in DSM 5. Methods: Electronic databases EmBase, MedLine and PsycINFO were searched using the keywords ultra-high risk/at-risk mental state/risk syndrome/pre-psychotic/prodrome/prodromal and psychosis/schizophrenia. Results: The evidence suggests that it is possible to identify individuals who may be at risk of developing psychosis. Results from intervention studies, mostly involving second-generation antipsychotics and cognitive behavioural therapy, are currently insufficient to make treatment recommendations for this group. The emerging research with regard to possible neuroprotective factors such as omega fatty acids is promising, but will require replication in larger cohorts before it can be recommended. (PsycINFO Database Record (c) 2014 APA, all rights reserved) (journal abstract)
Irish Journal of Psychological Medicine, 30(1) : 77-89
- Year: 2013
- 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)
Mokhtari, M., Rajarethinam, R.
Objective. Strategies for preventing the development of schizophrenia are in their infancy but are associated with much hope and potential. The relatively long prodrome in schizophrenia allows for indicated prevention as an effective intervention. "High-risk" individuals have subtle symptoms and, without intervention, a third would develop psychosis within 1 year, and many will have poor functional outcomes, even in the absence of psychosis. Research in this area is preliminary but encouraging. Methods. A literature search was performed using databases including PubMed, PsychInfo, and Cochrane, as well as a search of individual journals through cross-referencing. The search used the following key words: schizophrenia, psychosis, psychotic disorders, first episode, early, prodrome, prodromal, prevention, ultra high risk, at risk, and intervention. Results. Strategies for preventing the development of schizophrenia are divided into universal, selective, and indicated levels of prevention. The common preventive methods include treatment with antipsychotic medications and psychotherapy. Early intervention helps at risk individuals with symptom reduction and appears to delay conversion to full blown psychosis. However, the criteria for identifying at risk individuals have low predictive value, which raises concerns about unnecessary and potentially harmful interventions. Conclusion. Although a range of interventions appear to be effective in reducing rates of transition to psychosis, they are inadequately differentiated and require further study. Current data suggest that clinicians take an individualized approach to intervention, considering the risk-benefit ratio on a case-by-case basis. Copyright (copyright) Lippincott Williams & Wilkins.
Journal of Psychiatric Practice, 19(5) : 375-385
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
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Treatment and intervention: Biological Interventions (any)
, Psychological Interventions (any)
Vesterager, L., Christensen, T., Olsen, B., Melau, M., Krarup, G., Nordentoft, M.
Background: Inasmuch as the cognitive and functional decline associated with onset of schizophrenia can be reduced or prevented, it seems timely to consider cognitive remediation in the early stages of the illness. The study was an investigation of the effects of cognitive remediation (CR) combined with a comprehensive psychosocial program (OPUS) for patients with first episode schizophrenia compared with the comprehensive psychosocial program alone. Methods: A total of 117 outpatients (aged 19-34) with a first episode schizophrenia spectrum disorder were randomly assigned to CR combined with OPUS treatment or OPUS treatment alone. The CR program used a hybrid approach that incorporated both restorative and compensatory learning for 2-3 hours a week for 16 weeks. Statistical analysis of effect was based on the intentionto- treat principle. Results: At post-training 98 patients were available for assessments: The CR group had improved significantly on self-esteem, general psychopathology symptoms, and verbal learning. At follow-up assessment, 92 patients were available for assessments: The CR group retained the significant improvements on verbal learning. Significant improvements were also observed on working memory and positive symptoms, while improvement on the composite cognitive score was marginally significant. Overall, functional capacity did not improve, however, a subgroup analysis to circumvent ceiling effects on the functional capacity measure showed a trend in favor of the CR group. An additional analysis of the impact of CR attendance showed that 'high-attenders' gained significant improvements on self-esteem, psychopathology, and cognition compared to 'low-attenders'. Conclusion: The results correspond to meta-analytic evidence of durable improvements of cognitive remediation with small to medium effect sizes.
Schizophrenia Bulletin, 39 : S356
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
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Treatment and intervention: Psychological Interventions (any)
, Cognitive remediation therapy, Other Psychological Interventions
Vinogradov, S.
Background: The cognitive deficits of schizophrenia are present in the prodrome, worsen as the illness progresses, and predict functional outcome. Cognitive dysfunction thus must be a primary target for aggressive early intervention. Further, we must develop methods of delivering the intervention that are scalable, engaging, and convenient for young individuals. Methods: We performed a two-site randomized controlled trial to test the effects of neuroplasticity-based cognitive training of auditory/verbal processing in 80 subjects with recent onset schizophrenia (mean age of 21 years). Subjects were given laptop computers to take home and performed either 40 hours of auditory training or 40 hours of commercial computer games over an 8 week period. We examined MATRICS neurocognitive outcome measures, symptoms, and functioning. We also investigated psychophysical improvement in auditory processing and its association with cognitive gains. Results: Auditory training subjects demonstrated significant improvements in global cognition, verbal learning and memory, and problem solving compared to computer games control subjects. Both groups showed a slight but significant decrease in symptoms, likely as a result of receiving adjunctive standard treatment. Subjects in the training group showed significant psychophysical improvement in early auditory processing that correlated with gains in cognition. Conclusions: nullNeuroplasticity-basednull cognitive training of auditory/verbal learning processes via a portable computing device thus represents a highly promising and scalable treatment approach to target key aspects of cognitive dysfunction in early psychosis. Future studies must investigate whether it improves long-term outcome and community functioning and how best to integrate it into critical psychosocial interventions.
Biological Psychiatry, 73(9) : 134S
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions (any)
, Cognitive remediation therapy, Technology, interventions delivered using technology (e.g. online, SMS)
VanDerGaag, M., Nieman, D. H., Rietdijk, J., Dragt, S., Ising, H. K., Klaassen, R. M., Koeter, M., Cuijpers, P., Wunderink, L., Linszen, D. H.
Background: A newly developed cognitive behavioural intervention specifically targeted at cognitive biases (CBTuhr) was compared with treatment as usual in a group of young help-seeking ultrahigh risk (UHR) subjects. Methods: A total of 201 patients were recruited at four sites and randomised. In most cases CBTuhr was an add-on therapy as most people were seeking help for a comorbid disorder. The CBT was provided for 6 months and the follow-up period was 18 months. Results: In the CBTuhr condition, 10 patients transitioned to psychosis compared to 22 in the TAU condition ((chi)2(1) = 5.575, p = 0.03). The number needed to treat (NNT) was 9 (95% CI: 4.7 to 89.9). At 18-months follow-up the CBTuhr group was significantly more often remitted from an at-risk mental state, with a NNT of 7 (95% CI: 3.7 to 71.2). Conclusion: Compared to TAU , this new CBT (focusing on normalisation and awareness of cognitive biases) showed a favourable effect on the transition to psychosis and reduction of subclinical psychotic symptoms in subjects at UHR to develop psychosis.
Schizophrenia Bulletin, 39 : S356
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
Stevens, H., Agerbo, E., Dean, K., Mortensen, P. B., Nordentoft, M.
Objective: Violence and criminality are adverse outcomes for some persons who develop psychotic illnesses. The extent to which treatment can reduce offending has rarely been studied. The aim of this study was to evaluate whether assertive specialized treatment would reduce the rate of crime in patients with a first episode of psychotic illness. Method: From January 1998 to December 2000, a total of 547 patients aged 18-45 years with a first episode of schizophrenia spectrum disorder (ICD-10 diagnostic code within F2) were randomized to assertive specialized treatment or standard treatment in an outpatient setting. In the current secondary analysis of the data, levels of criminality during the 2-year treatment period and the 3 years following were assessed using official records from Danish registers. Main outcome measures were any offending and violent offending. Results: No significant reduction in violent offending or any offending was found in the assertive specialized treatment group (adjusted hazard ratio = 1.06; 95% CI, 0.72-1.56) compared with the control group. Prevalence of offending was low and had often commenced prior to inclusion in the trial. Conclusions: While assertive specialized treatment has shown good treatment effects, it had no impact on rates of offending, thereby calling into question the potential efficacy of universally applied improvements in outpatient services with respect to reducing crime and violence. More specific interventions that address criminogenic needs in a more narrowly defined group of high-risk patients may be considered. (copyright) Copyright 2013 Physicians Postgraduate Press, Inc.
Journal of Clinical Psychiatry, 74(5) : e439-e444
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions