Devoe, D. J., Farris, M. S., Townes, P., Addington, J.

Interventions and social functioning in youth at risk of psychosis: A systematic review and meta- analysis

Aim: Youth at clinical high risk (CHR) for psychosis often exhibit difficulties in social functioning and poorer social functioning may be predictive of transition to a psychotic disorder. Therefore, the primary objective of this systematic review was to summarize the impact of all interventions on social functioning in CHR samples. Method(s): Electronic databases PsycINFO, CINAHL, Embase, EBM, and MEDLINE were searched from 1951 to June 2017. Studies were selected if they included any intervention that reported changes in social functioning in youth at CHR. Data were evaluated using random effects pairwise meta-analyses, stratified by time, and reported as the standardized mean difference (SMD). Result(s): Nineteen studies met our inclusion criteria, including a total of 1513 CHR participants. The mean age was 20.5 years and 47% were male. Cognitive behavioural therapy (4 studies) did not significantly improve social functioning at 6 months (SMD = 0.06; 95% confidence interval [CI] = -0.35, 0.46), 12 months (SMD = -0.15; 95% CI = -0.38, 0.08) and 18 months (SMD = 0.20; 95% CI = -0.10, 0.50). Omega-3 (2 studies) did not significantly improve social functioning at 6 months (SMD = 0.01; 95% CI = -0.21, 0.24) and 12 months (SMD = -0.08; 95% CI = -0.33, 0.17). Lastly, cognitive remediation (3 studies) did not significantly improve social functioning at 2- to 3-month follow-up (SMD = 0.13, 95% CI = -0.18, 0.43). Conclusion (s): This systematic review and meta-analysis demonstrated that no treatment significantly improved social functioning in youth at CHR. Future randomized control trials are required that are designed to target and improve social functioning in youth at CHR for psychosis. Copyright © 2018 John Wiley & Sons Australia, Ltd

Early Intervention in Psychiatry, 13(2) : 169-180

Vidarsdottir, O. G., Roberts, D. L., Twamley, E. W., Gudmundsdottir, B., Sigurdsson, E., Magnusdottir, B. B.

Integrative cognitive remediation for early psychosis: Results from a randomized controlled trial

Early application of cognitive remediation may help prevent the development of long-term functional impairments that characterize psychotic disorders. Interventions that encompass both neurocognitive and social-cognitive training may work synergistically to bridge the gap between cognitive gains and functional outcomes in early psychosis. We integrated three cognitive remediation approaches: Neuropsychological Educational Approach to Remediation (NEAR), Compensatory Cognitive Training (CCT), and Social Cognition and Interaction Training (SCIT), and evaluated the effects on cognition, clinical symptoms, self-assessed and informant- assessed social functioning in early psychosis. A total of 49 patients diagnosed with primary psychotic disorder seeking service at an early- intervention service in Iceland were randomized to either a waiting-list control group (n=24) or a 12-week group-based integrative cognitive remediation (n=25). Neurocognition, social cognition, community functioning and clinical symptoms were assessed at baseline and post-treatment. The intervention group showed significant improvements in verbal memory, cognitive flexibility, working memory, ToM and a significant reduction in hostile attributions, compared to those receiving standard treatment alone, but there were no differences between groups on measures of social functioning or clinical symptoms. The intervention was well tolerated and received high treatment satisfaction ratings. Findings indicate that integrated cognitive remediation has potential to improve neurocognition and social cognition in early psychosis.

Psychiatry Research, 273 : 690-698

Nuechterlein, K. H., Subotnik, K. L., Ventura, J., Turner, L. R., Gitlin, M. J., Gretchen-Doorly, D., Becker, D. R., Drake, R. E., Wallace, C. J., Liberman, R. P.

Enhancing return to work or school after a first episode of schizophrenia: the UCLA RCT of Individual Placement and Support and Workplace Fundamentals Module training

BACKGROUND: This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.\rMETHODS: Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.\rRESULTS: The IPS-WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS-WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS-WFM intervention (45 v. 26 weeks, p < 0.004).\rCONCLUSIONS: The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.

Psychological Medicine, : 1- 9

Killackey, E., Allott, K., Jackson, H. J., Scutella, R., Tseng, Y. P., Borland, J., Proffitt, T. M., Hunt, S., Kay-Lambkin, F., Chinnery, G., Baksheev, G., Alvarez-Jimenez, M., McGorry, P. D., Cotton, S. M.

Individual placement and support for vocational recovery in first-episode psychosis: Randomised controlled trial

Background High unemployment is a hallmark of psychotic illness. Individual placement and support (IPS) may be effective at assisting the vocational recoveries of young people with first-episode psychosis (FEP).Aims To examine the effectiveness of IPS at assisting young people with FEP to gain employment (Australian and Clinical Trials Registry ACTRN12608000094370).Method Young people with FEP (n = 146) who were interested in vocational recovery were randomised using computer-generated random permuted blocks on a 1:1 ratio to: (a) 6 months of IPS in addition to treatment as usual (TAU) or (b) TAU alone. Assessments were conducted at baseline, 6 months (end of intervention), 12 months and 18 months post-baseline by research assistants who were masked to the treatment allocations.Results At the end of the intervention the IPS group had a significantly higher rate of having been employed (71.2%) than the TAU group (48.0%), odds ratio 3.40 (95% CI 1.17- 9.91, z = 2.25, P = 0.025). However, this difference was not seen at 12-and 18-month follow-up points. There was no difference at any time point on educational outcomes.Conclusions This is the largest trial to our knowledge on the effectiveness of IPS in FEP. The IPS group achieved a very high employment rate during the 6 months of the intervention. However, the advantage of IPS was not maintained in the long term. This seems to be related more to an unusually high rate of employment being achieved in the control group rather than a gross reduction in employment among the IPS group.Declaration of interest None. Copyright © 2018 The Royal College of Psychiatrists.

British Journal of Psychiatry, 214(2) : 76- 82

Camacho-Gomez, M., Castellvi, P.

Effectiveness of Family Intervention for Preventing Relapse in First-Episode Psychosis Until 24 Months of Follow-up: A Systematic Review With Meta-analysis of Randomized Controlled Trials

BACKGROUND: Relapse risk during the early years of first-episode psychosis (FEP) considerably increases the risk of chronicity. The effectiveness of family intervention for psychosis (FIp) for preventing relapse after FEP remains unknown. We assessed the effectiveness of FIp until 24 months of follow-up for preventing relapse and other relapse-related outcomes in patients following FEP. METHOD(S): We searched the Cochrane, PubMed, PsycINFO, and ProQuest databases in June 2018. A systematic review with meta-analysis of randomized controlled trials (RCTs), sensitivity analyses, and publication bias were performed, comparing to treatment as usual (TAU) or TAU plus other psychosocial interventions. Outcomes assessed were relapse rates, duration of hospitalization, psychotic symptoms, and functionality. Risk ratios (RRs) and (standardized) mean differences (SMD; MD) were calculated. RESULT(S): Of the 2109 records retrieved, 14 (11 RCTs) were included. Pooled results showed that FIp was effective for preventing relapse (RR = 0.42; 95% CI = 0.29 to 0.61) compared to TAU and/or other psychosocial interventions. It also proved effective when compared to TAU alone (RR = 0.36) and TAU plus other psychosocial interventions (RR = 0.48). FIp showed benefits in reducing duration of hospitalization (TAU, MD = -3.31; other interventions, MD = -4.57) and psychotic symptoms (TAU, SMD = -0.68), and increased functionality (TAU, SMD = 1.36; other interventions, SMD = 1.41). CONCLUSION(S): These findings suggest that FIp is effective for reducing relapse rates, duration of hospitalization, and psychotic symptoms, and for increasing functionality in FEP patients up to 24 months. The study's main limitations were the inclusion of published research only; authors were not contacted for missing/additional data; and high heterogeneity regarding relapse definition was observed. Copyright © The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: [email protected].

Schizophrenia bulletin., :

Kishi, T., Ikuta, T., Matsui, Y., Inada, K., Matsuda, Y., Mishima, K., Iwata, N.

Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: a meta- analysis

BACKGROUND: Discontinuation of antipsychotics predisposes patients with remitted/stable first- episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance. METHOD(S): This meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18-24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model. RESULT(S): Ten RCTs were identified (n = 776; mean study duration, 18.6 +/- 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18-24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant). CONCLUSION(S): Maintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for 2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18-24 months) did not experience a relapse.

Psychological Medicine, 49(5) : 772-779

Grover, S., Sahoo, S., Rabha, A., Koirala, R.

ECT in schizophrenia: A review of the evidence

Electroconvulsive therapy (ECT) was initially used for the treatment of schizophrenia, but over the years with the advent of antipsychotics, its use in schizophrenia has been limited. Treatment guidelines vary in their recommendations for the use of ECT in schizophrenia. The usual indications of its use among patients with schizophrenia include treatment resistance, to augment pharmacotherapy, to manage catatonia, suicidal behaviour, severe agitation and clozapine-resistant schizophrenia. Available literature, including meta-analysis and systematic reviews, suggest that ECT is a safe and effective treatment in patients with schizophrenia. However, despite the available evidence, it is highly underutilised and is often used as one of the last resort among patients with schizophrenia. This review focuses on the indications of use of ECT in schizophrenia, studies evaluating its effectiveness, efficacy in certain special situations like first episode schizophrenia, adolescents, catatonia etc., predictors of response to ECT in schizophrenia and influence of various ECT-related parameters on efficacy/effectiveness among patients with schizophrenia. From the review, it can be concluded that ECT is not only is beneficial as an augmenting strategy in treatment-resistant schizophrenia but also can be used effectively in patients with schizophrenia in various other situations. Copyright © Scandinavian College of Neuropsychopharmacology 2018.

Acta Neuropsychiatrica, 31(3) : 115- 127

Chen, E. Y., Chang, W. C., Hui, C. L., Chan, S. K., Lee, E. H., Wong, G. H.

Duration of early intervention for psychosis: 2 years versus 3 years

Hong Kong medical journal = Xianggang yi xue za zhi, 25(Supplement 2) : 10-14

Pos, K., Franke, N., Smit, F., Wijnen, B. F. M., Staring, A. B. P., Van-Der-Gaag, M., Meijer, C., De-Haan, L., Velthorst, E., Schirmbeck, F.

Cognitive behavioral therapy for social activation in recent-onset psychosis: Randomized controlled trial

Objective: Negative symptoms largely account for poor outcome in psychotic disorders but remain difficult to treat. A cognitive- behavioral approach to these symptoms showed promise in chronic schizophrenia patients. We explored whether a combination of group and individual treatment focused on social activation (CBTsa) could benefit patients recently diagnosed with a psychotic disorder. Method(s): A single- blind randomized controlled trial enrolled 99 participants recently diagnosed with schizophrenia or a related disorder that received treatment as usual (TAU; n = 50), or TAU plus CBTsa (n = 49). Negative symptoms (Brief Negative Symptom Scale) and social withdrawal (Positive and Negative Syndrome Scale) were primary outcomes. Secondary outcome measures included dysfunctional beliefs (Dysfunctional Attitudes Scale-Defeatist Performance Attitude), stigma Internalized Stigma of Mental Illness Scale (ISMIS), and symptom severity and functioning as measured with the Global Assessment of Functioning (GAF). Outcomes were compared directly posttreatment and at follow-up (6 months posttreatment). Result(s): Intention-to-treat analyses showed significant improvement in GAF symptoms (p = .02, d = 0.36) and a decrease in negative symptoms on trend level (p = .08, d==0.29) in CBTsa compared to TAU at posttreatment. These group differences were no longer apparent at 6 months follow-up. Social withdrawal and negative symptoms improved over time in both conditions. Conclusion(s): The current trial showed small positive effects on symptom severity posttreatment but did not demonstrate maintenance of longer-term effects in favor of the CBTsa group. Findings suggest that the treatment duration may have been too short to change dysfunctional beliefs, a potentially important maintaining factor of negative symptom severity. Longer intervention periods in later, more stable stages of the illness when intensive standard treatment has tapered off may yield more beneficial effects. Copyright © 2019 American Psychological Association.

Journal of Consulting and Clinical Psychology, 87(2) : 151-160

Goff, D. C., Freudenreich, O., Cather, C., Holt, D., Bello, I., Diminich, E., Tang, Y., Ardekani, B. A., Worthington, M., Zeng, B., Wu, R., Fan, X., Li, C., Troxel, A., Wang, J., Zhao, J.

Citalopram in first episode schizophrenia: The DECIFER trial

Antidepressants are frequently prescribed in first episode schizophrenia (FES)patients for negative symptoms or for subsyndromal depressive symptoms, but therapeutic benefit has not been established, despite evidence of efficacy in later-stage schizophrenia. We conducted a 52 week, placebo-controlled add-on trial of citalopram in patients with FES who did not meet criteria for major depression to determine whether maintenance therapy with citalopram would improve outcomes by preventing or improving negative and depressive symptoms. Primary outcomes were negative symptoms measured by the Scale for Assessment of Negative Symptoms and depressive symptoms measured by the Calgary Depression Scale for Schizophrenia; both were analyzed by an intent-to-treat, mixed effects, area-under-the-curve analysis to assess the cumulative effects of symptom improvement and symptom prevention over a one-year period. Ninety-five patients were randomized and 52 (54%)completed the trial. Negative symptoms were reduced with citalopram compared to placebo (p =.04); the effect size of citalopram versus placebo was 0.32 for participants with a duration of untreated psychosis (DUP)of <18 weeks (median split)and 0.52 with a DUP >18 weeks. Rates of new-onset depression did not differ between groups; improvement in depressive symptoms was greater with placebo than citalopram (p =.02). Sexual side effects were more common with citalopram, but overall treatment-emergent side effects were not increased compared to placebo. In conclusion, citalopram may reduce levels of negative symptoms, particularly in patients with longer DUP, but we found no evidence of benefit for subsyndromal depressive symptoms. Copyright © 2019 The Authors

Schizophrenia Research, 208 : 331- 337

Marchira, C. R., Suprianto, I., Subandi, M. A., Good, M. J., Good, B. J.

Brief interactive psychoeducation for caregivers of patients with early phase psychosis in Yogyakarta, Indonesia

AIM: Brief psychoeducation for families of psychotic patients has been shown to significantly increase family members' knowledge of the disorder. This increase is associated with reductions in relapse and rehospitalization. The aim of this study was to assess the effectiveness of brief psychoeducation about schizophrenia to caregivers of patients in early phases of psychotic disorders in Yogyakarta, Indonesia.\rMETHODS: This study was a prospective, randomized trial with 2 parallel groups. Subjects were patients in the early phase of psychotic disorders and their respective caregivers. Inclusion criteria included a diagnosis of acute and transient psychotic disorders, schizophrenia, schizoaffective disorder or delusional disorder. Participants were randomly assigned to either control or intervention groups by means of paired simple randomization. A brief psychoeducation was conducted for both the patients and caregivers. The interventions were conducted in 4 interactive sessions, once per week. Effectiveness was measured using standardized instruments before the intervention, and at 1 and 6 months post-intervention. Assessment instruments included the Knowledge of Psychosis (KOP), the Compliance and Relapse Assessment, the Brief Psychiatric Rating Scale and the Positive and Negative Symptoms of Schizophrenia scale.\rRESULTS: Interventions improved KOP scores significantly in the intervention group. The intervention group had increased regularity of follow-up with health providers and improved compliance. No statistically significant difference in relapses/rehospitalization was observed.\rCONCLUSIONS: This study demonstrated that brief psychoeducation with caregivers of patients with early phase psychosis was feasible in our setting, significantly improved caregivers' knowledge, and resulted in improved regularity of contact with health providers and compliance with pharmacotherapy.

Early Intervention in Psychiatry, 13(3) : 469-476

Devoe, D. J., Farris, M. S., Townes, P., Addington, J.

Attenuated psychotic symptom interventions in youth at risk of psychosis: A systematic review and meta-analysis

Aim: Attenuated psychotic symptoms (APSs) have been the primary emphasis in youth at clinical high risk (CHR) for psychosis for assessing symptomology and determining subsequent transition to a psychotic disorder. Previous reviews primarily focused on the efficacy of cognitive behavioural therapy (CBT) on APS; however, a comprehensive assessment of other interventions to date is lacking. Therefore, we conducted a systematic review and meta-analysis of all intervention studies examining APS in CHR youth. Method(s): The authors searched Embase, CINAHL, PsycINFO, Medline and EBM from inception to May 2017. Studies were selected if they included any intervention that reported follow-up APS in youth at CHR. Interventions were evaluated and stratified by time using both pairwise and network meta-analyses (NMAs). Due to the differences in APS scales, effect sizes were calculated as Hedges g and reported as the standardized mean difference (SMD). Result(s): Forty-one studies met our inclusion criteria. In pairwise meta-analyses, CBT was associated with a trend towards reduction in APS compared to controls at 12-months. In the NMA, integrated psychological therapy, CBT, supportive therapy, family therapy, needs-based interventions, omega-3, risperidone plus CBT and olanzapine were not significantly more effective at reducing APS at 6 and 12 months relative to any other intervention. Conclusion(s): CBT demonstrated a slight trend at reducing APS at long-term follow-up compared to controls. No interventions were significantly more effective at reducing APS compared to all other interventions in the NMA. [Correction added on 4 June 2018, after first online publication: Some parts of the Abstract section particularly 'Results' and 'Conclusions' have been corrected.]. Copyright © 2018 John Wiley & Sons Australia, Ltd

Early Intervention in Psychiatry, 13(1) : 3- 17