Disorders - Psychosis Disorders
Nieman, D. H., McGorry, P D.
The
at-risk mental state (ARMS) has been substantially researched and used as the basis for new clinical settings and strategies over the past two
decades. However, it has also caused controversy and intense debate. In this Review, we assess available evidence and propose future directions.
Accumulating research suggests that a blend of clinical staging and profiling, which naturally incorporates ARMS, might be a better guide for
treatment of patients in different stages of psychiatric illness than the categorical DSM and ICD systems. Furthermore, clinical staging, with its
emphasis on balancing risks and benefits, could help to prevent premature treatment or overtreatment with psychotropic drugs. Meta-analyses and
reviews show that treatment of ARMS leads to a significant reduction in transition rate to a first psychosis. The debate about stigma associated with
ARMS is based on scarce published work. The few studies that have been done suggest that stigma (including self-stigma) arises largely from negative
societal views on psychiatric disorders and, depending on the setting and approach, not from engagement in treatment for ARMS per se. The evidence
base suggests that definition of ARMS is an important step in implementation of clinical staging and profiling in psychiatry. However, more research
across traditional diagnostic boundaries is needed to refine these clinical phenotypes and link them to biomarkers with the goal of personalised
stepwise care. Health-system reform is overdue and a parallel process to support this approach is needed, which is similar to how physical forms of
non-communicable disease are treated. (PsycINFO Database Record (c) 2016 APA, all rights reserved) (journal abstract).
Lancet Psychiatry, 2(9) : 825-834
- Year: 2015
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Service Delivery & Improvement
Piskulic, D., Nelson, B., Alvarez-Jimenez, M., McGorry, P.
Background and Objectives: Schizophrenia is a progressive disorder that moves through
multiple stages starting from non-specific risk factors to at-risk mental state (ARMS) (also known as ultra-high risk of psychosis or UHR) to first
episode of psychosis (FEP) to chronic course marred by frequent relapses and varying degrees of disability. In order to prevent a deteriorating
course, treatments designed to address and possibly even correct the abnormal neuronal system functioning and psychosocial deficits need to be
implemented early before potentially irreversible and maladaptive changes take place.Methods: A literature search was conducted in the electronic
databases Pub-Med and MEDLINE for relevant empirical and review articles published in peer reviewed journals.Results: The review of literature
suggests that a range of pharmacological and psychosocial interventions are being used and trialled in treatment of early stages of schizophrenia
with varying degrees of success. Conclusions: There is a variety of therapies for schizophrenia ranging in scope from improving symptom profiles to
functional recovery and a good rationale for their use early in the course of illness. Treatments that focus on integrating pharmacological,
psychological and psychosocial interventions with a strong evidence base for effectiveness need to be integrated for the best chance to avert or
hinder schizophrenia. Schizophrenia research is moving towards a notion that early intervention can interact with existing and intact neuroplasticity
mechanisms that can be harnessed in an adaptive manner to promote healthier neural system functioning and increased stress resiliency, which will in
turn lead to symptom reduction and functional recovery.
European Journal of Psychiatry, 29(2) : 135-
143
- Year: 2015
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention), First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Psychological Interventions
(any)
Randall, J. R., Vokey, S., Loewen, H., Martens, P. J., Brownell, M., Katz, A., Nickel, N. C., Burland, E., Chateau, D.
Objectives: To review and synthesize the
currently available research on whether early intervention for psychosis programs reduce the use of inpatient services.; Methods: A systematic review
was conducted using keywords searches on PubMed, Embase (Ovid), PsycINFO (ProQuest), Scopus, CINAHL (EBSCO), Social Work Abstracts (EBSCO), Social
Science Citations Index (Web of Science), Sociological Abstracts (ProQuest), and Child Development & Adolescent Studies (EBSCO). To be included,
studies had to be peer-reviewed publications in English, examining early intervention programs using a variant of assertive community treatment, with
a control/comparison group, and reporting inpatient service use outcomes. The primary outcome extracted number hospitalized and total N. Secondary
outcome extracted means and standard deviations. Data were pooled using random effects models. Primary outcome was the occurrence of any
hospitalization during treatment. A secondary outcome was the average bed-days used during treatment period.; Results: Fifteen projects were
identified and included in the study. Results of meta-analysis supported the occurrence of a positive effect for intervention for both outcome
measures (any hospitalization OR: 0.33; 95% CI 0.18-0.63, bed-days usage SMD: -0.38, 95% CI -0.53 to -0.24). There was significant heterogeneity of
effect across the studies. This heterogeneity is due to a handful of studies with unusually positive responses.; Conclusion: These results suggest
that early intervention programs are superior to standard of care, with respect to reducing inpatient service usage. Wider use of these programs may
prevent the occurrence of admission for patients experiencing the onset of psychotic symptoms.; © The Author 2015. Published by Oxford University
Press on behalf of the Maryland Psychiatric Research Center.
Schizophrenia Bulletin, 41(6) : 1379-1386
- Year: 2015
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement
interventions
Revell, E. R., Neill, J. C., Harte, M., Khan, Z., Drake, R. J.
Neurocognitive impairment predicts disability in schizophrenia, making intervention theoretically attractive as
a means to minimise chronic disability. Many trials confirm that cognitive remediation (CR) produces meaningful, durable improvements in cognition
and functioning but fewer focus on the early stages. We systematically reviewed CR trials in early schizophrenia to determine its efficacy on global
cognition, functioning and symptoms. Two reviewers independently searched electronic databases to identify randomised controlled trials investigating
CR following a first episode of psychosis. Eleven trials with 615 participants were identified. Random effect models revealed a non-significant
effect of CR on global cognition (effect size=0.13, 95% CI -0.04, 0.31; p0.14), p<0.05 in sensitivity analysis (effect size 0.19; CI 0.00, 0.38). One
of seven neurocognitive domains showed a significant positive effect (verbal learning and memory) and five others showed borderline significant
benefits. There was a significant effect on functioning (0.18; CI 0.01, 0.36; p<0.05) and symptoms (0.19; CI 0.02, 0.36; p<0.05). CR's effect on
functioning and symptoms was larger in trials with adjunctive psychiatric rehabilitation and small group interventions. CR's effect sizes in early
illness were smaller than those in chronic schizophrenia, perhaps because of participants' reduced scope for improvement, though trials' small
number and size produces uncertain estimates of effect. However, significant benefits were seen in functioning and symptoms and moderator analyses
indicate factors that may increase CR's effect. Findings here, theoretical considerations and trials in chronic schizophrenia suggest that targeting
social cognition might also enhance its efficacy.; Copyright © 2015 Elsevier B.V. All rights reserved.
Schizophrenia
Research, 168(1-2) : 213-222
- Year: 2015
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive remediation
therapy
Srihari, V. H., Tek, C., Kucukgoncu, S., Phutane, V. H., Breitborde, N. J., Pollard, J., Ozkan,
B., Saksa, J., Walsh, B. C., Woods, S. W.
Objective: This study sought to determine the effectiveness of a comprehensive first-episode
service, the clinic for Specialized Treatment Early in Psychosis (STEP), in an urban U.S. community mental health center by comparing it with usual
treatment. Methods: This pragmatic randomized controlled trial enrolled 120 patients with first-episode psychosis within five years of illness onset
and 12 weeks of antipsychotic exposure. Referrals were mostly from inpatient psychiatric units, and enrollees were randomly allocated to STEP or
usual treatment. Main outcomes included hospital utilization (primary); the ability to work or attend age-appropriate schooling-or to actively seek
these opportunities (vocational engagement); and general functioning. Analysis was by modified intent to treat (excluding only three who withdrew
consent) for hospitalization; for other outcomes, only data for completers were analyzed. Results: After one year, STEP participants had less
inpatient utilization compared with those in usual treatment: no psychiatric hospitalizations, 77% versus 56% (risk ratio [RR] = 1.38, 95% confidence
interval [CI] = 1.08-1.58); mean hospitalizations, .33 +/- .70 versus .68 +/- .92 (p = .02); and mean bed-days, 5.34 +/- 13.53 versus 11.51 +/- 15.04
(p = .05). For every five patients allocated to STEP versus usual treatment, one additional patient avoided hospitalization over the first year
(number needed to treat = 5; CI = 2.7-26.5). STEP participants also demonstrated better vocational engagement (91.7% versus 66.7%; RR = 1.40, CI =
1.18-1.48) and showed salutary trends in global functioning measures. Conclusions: This trial demonstrated the feasibility and effectiveness of a
U.S. public-sector model of early intervention for psychotic illnesses. Such services can also support translational research and are a relevant
model for other serious mental illnesses. (PsycINFO Database Record (c) 2015 APA, all rights reserved) (journal abstract).
Psychiatric Services, 66(7) : 705-
712
- Year: 2015
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Service Delivery & Improvement, Psychological Interventions
(any), Cognitive & behavioural therapies (CBT), Psychoeducation, Case management
Subotnik, K. L., Casaus, L. R., Ventura, J., Luo, J. S., Hellemann, G. S., Gretchen-Doorly, D., Marder, S., Nuechterlein, K. H.
Importance: Long-acting,
injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However,
long-acting medications are rarely used following a first episode of schizophrenia.; Objective: To compare the clinical efficacy of the long-acting
injectable formulation of risperidone with the oral formulation in the early course of schizophrenia.; Design, Setting, and Participants: A
randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of
schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to
receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-
to-treat analysis was performed between October 4, 2012, and November 12, 2014.; Interventions: A 12-month trial comparing the long-acting injectable
vs oral risperidone and cognitive remediation vs healthy-behaviors training.; Main Outcomes and Measures: Psychotic relapse and control of
breakthrough psychotic symptoms.; Results: Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The
psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; ?21 = 11.1; P?
JAMA Psychiatry, 72(8) : 822-
829
- Year: 2015
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Psychological Interventions
(any), Cognitive remediation
therapy
Trampush, J.W., Lencz, T., DeRosse, P., John, M., Gallego, J. A., Petrides, G., Hassoun, Y., Zhang, J-P., Addington, J., Kellner, C. H., Tohen, M., Burdick, K.
E., Goldberg, T. E., Kane, J. M., Robinson, D. G., Malhotra,
A. K.
First-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains.
However, less is known about the course of cognitive functioning, following the first presentation of psychosis, and the relationship of cognition to
clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS
Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic
treatment with either aripiprazole or risperidone. At baseline, FES patients evidenced marked impairments in cognitive functioning. Notably,
performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom
remission during the first 12 weeks of the trial. Performance on indices of general cognitive function, working memory, and verbal learning improved
over time, but these improvements were mediated by improvements in both positive and negative symptoms. We did not detect any differential effects of
antipsychotic medication assignment (aripiprazole vs risperidone) on cognitive functioning. Our results suggest that a brief paper-and-pencil measure
reflecting planning/reasoning abilities may index responsivity to antipsychotic medication. However, improvements in cognitive functioning over time
were related to clinical symptom improvement, reflecting \"pseudospecificity.\"; © The Author 2015. Published by Oxford University Press on behalf of
the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected].
Schizophrenia Bulletin, 41(6) : 1237-
1247
- Year: 2015
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Robinson, D.G., Gallego, J. A., John, M., Petrides,
G., Hassoun, Y., Zhang, J-P., Lopez, L., Braga, R.
J., Sevy, S. M., Addington, J., Kellner, C. H., Tohen, M., Naraine, M., Bennett, N., Greenberg, J., Lencz, T., Correll, C. U., Kane, J.
M., Malhotra, A. K.,
Research findings are particularly important for medication choice for first-episode patients as individual prior
medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-
episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40
years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated
in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30 mg/d) or risperidone (1-6 mg/d)
and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated
participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but
advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc
analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used
in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations
based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications.; ©
The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions,
please email: [email protected].
Schizophrenia
Bulletin, 41(6) : 1227-1236
- Year: 2015
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Ruggeri, M., Bonetto, C., Lasalvia, A., Fioritti, A., deGirolamo,
G., Santonastaso, P., Pileggi, F., Neri, G., Ghigi, D., Giubilini, F., Miceli, M., Scarone, S., Cocchi, A., Torresani, S., Faravelli, C., Cremonese, C., Scocco, P., Leuci, E., Mazzi, F., Pratelli, M., Bellini, F., Tosato, S., DeSanti, K., Bissoli, S., Poli, S., Ira, E., Zoppei, S., Rucci, P., Bislenghi, L., Patelli, G., Cristofalo, D., Meneghelli, A.
Integrated multi-element psychosocial interventions have been suggested to improve
the outcomes of first-episode psychosis (FEP) patients, but they have been studied primarily in experimental settings and in nonepidemiologically
representative samples. Thus, we performed a cluster-randomized controlled trial, comparing an integrated multi-element psychosocial intervention,
comprising cognitive behavioral therapy, family intervention, and case management, with treatment as usual (TAU) for FEP patients in 117 community
mental health centers (CMHCs) in a large area of northern Italy (10 million inhabitants). The randomized units (clusters) were the CMHCs, and the
units of observation the patients (and, when available, their family members). The primary hypotheses were that add-on multicomponent intervention:
(1) results in greater improvements in symptoms, as assessed with positive and negative syndrome scale and (2) reduces in-hospital stay, based on
days of hospitalization over the 9-month follow-up. Four hundred and forty-four FEP patients received the intervention or TAU and were assessed at
baseline and 9 months. Based on the retention rates of patients (and families) in the experimental arm, multi-element psychosocial interventions can
be implemented in routine mental health services. Regarding primary outcomes, patients in the experimental arm showed greater reductions in overall
symptom severity, while no difference could be found for days of hospitalization. Among the secondary outcomes, greater improvements were detected in
the experimental arm for global functioning, emotional well-being, and subjective burden of delusions. No difference could be found for service
disengagement and subjective burden of auditory hallucinations. These findings support feasibility and effectiveness of early interventions for
psychosis in generalist mental health services.; © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric
Research Center.
Schizophrenia Bulletin, 41(5) : 1192-
1203
- Year: 2015
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Cognitive & behavioural therapies (CBT), Other Psychological Interventions, Case management
Sarpal, D.
K., Robinson, D. G., Lencz, T., Argyelan, M., Ikuta, T., Karlsgodt, K., Gallego, J. A., Kane, J. M., Szeszko, P. R., Malhotra, A. K.
Importance: Previous evidence has implicated
corticostriatal abnormalities in the pathophysiology of psychosis. Although the striatum is the primary target of all efficacious antipsychotics, the
relationship between its functional connectivity and symptomatic reduction remains unknown.; Objective: To explore the longitudinal effect of
treatment with second-generation antipsychotics on functional connectivity of the striatum during the resting state in patients experiencing a first
episode of psychosis.; Design, Setting, and Participants: This prospective controlled study took place at a clinical research center and included 24
patients with first-episode psychosis and 24 healthy participants matched for age, sex, education, and handedness. Medications were administered in a
double-blind randomized manner.; Interventions: Patients were scanned at baseline and after 12 weeks of treatment with either risperidone or
aripiprazole. Their symptoms were evaluated with the Brief Psychiatric Rating Scale at baseline and follow-up. Healthy participants were scanned
twice within a 12-week interval.; Main Outcomes and Measures: Functional connectivity of striatal regions was examined via functional magnetic
resonance imaging using a seed-based approach. Changes in functional connectivity of these seeds were compared with reductions in ratings of
psychotic symptoms.; Results: Patients had a median exposure of 1 day to antipsychotic medication prior to being scanned (mean [SD]?= 4.5 [6.1]).
Eleven patients were treated with aripiprazole and 13 patients were treated with risperidone. As psychosis improved, we observed an increase in
functional connectivity between striatal seed regions and the anterior cingulate, dorsolateral prefrontal cortex, and limbic regions such as the
hippocampus and anterior insula (P
JAMA
Psychiatry, 72(1) : 5-13
- Year: 2015
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Sanz-Fuentenebro, F. J., Taboada, D., Molina, V.
Background: Clozapine may be potentially valuable in first-episode
patients with psychosis, as an initial treatment seeking to limit early on clinical and cognitive deterioration. Nevertheless, until recently its
restricted use has limited the study of this possibility. Methods: Our research group is developing a multicentric and open label study, on the
differential efficacy between clozapine and risperidone in first-episode schizophrenia. Here we present clinical outcome results after one-year
follow-up. For clinical assessment, we employed the Positive and Negative Syndrome Scale (PANSS), and the Udvalg for KliniskeUndersøgelser (UKU) Side
Effects Rating Scale; applied at weeks 1, 2, 3, 4, 6, 8, 10 and 12, and months 6 and12. Results: Out of 33 patients included, 16 were randomized to
clozapine and 17 to risperidone; 7 patients dropped the study by their will, and three other patients due to lack of response Patients initially
assigned to clozapine remained on this treatment for a longer period than patients assigned to risperidone (71,31 vs 45,88, t 1,838, p=0,76). By last
observation carried forward (LOCF) analysis, patients on clozapine and risperidone displayed similar clinical improvements in Positive symptoms
(58,92 vs 50,60: t=1.02, p=0,31), although larger improvement in Total (44.64 vs 28,93: t=1,97, p=0.058), and Negative (18.72 vs -19,12, t 2.13,
p=0,041) symptoms scores were found in the clozapine group. At the 12-month point we observed a marginal improvement in negative symptom in patients
on clozapine (mean change -8.2, sd 10.3, z=-1.66, p=0.09), and marginal increase (mean change -0.4, sd 9.52, z=0.27, p=0.78) in this subscale in the
risperidone group. We found an inverse, significant association between Subjective secondary effects, as measured with the UKU scale, and negative
(Spearman's rho=-0.65, p=0.02) symptoms improvement in at 12 months. Discussion: Our data, although preliminary, suggest that clozapine may have a
slightly superior efficacy in the initial year of treatment of firstepisode treatment-naïve patients with schizophrenia. The worsening of negative
symptoms in the risperidone group seems attributable to secondary effects of the drug. Taken together with the larger attrition in this group, a
better tolerability is suggested for clozapine. The larger improvements in Total and Negative symptom scores with clozapine may point to a superior
efficacy in the earlier stages of illness, to be confirmed upon inclusion of a larger number of cases and follow-up completion.
Schizophrenia
Research, 153 : S117-S118
- Year: 2014
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Vinogradov, S., Fisher, M., Herman, A., Brown,
E., Nagarajan, S.
Background: Schizophrenia is characterized by dysfunction in
the distributed neural systems that subserve auditory processing and verbal memory. In patients with schizophrenia, we find that intensive
\"neuroplasticity-based\" computerized cognitive training of auditory and verbal learning processes drives significant improvement in verbal memory
and global cognition. We predicted that cognitive outcomes would be significantly related to evidence of target engagement during training. Methods:
We performed two double-blind randomized controlled trials of cognitive training: one in a sample of middle-aged adults with schizophrenia (average
age of 40 years); and one in a sample of young recent-onset individuals (average age of 20 years). In addition to neurocognitive and clinical outcome
measures, we assessed target engagement, defined as behavioral and magnetoencephalographic (MEG) evidence of plasticity in the fronto-temporal
networks targeted by this form of training. Results: Improvements in auditory processing speed after exposure to 20 hours of training were
significantly associated with better cognition after completion of training; faster auditory processing speed was also associated with gains in
quality of life 6 months later. Increases in prefrontal high-gamma band activation during an auditory working memory task were associated with better
cognition after training, and with fewer negative symptoms at 6 months. Conclusions: Our data indicate that it is possible to define specific
behavioral and neural system targets for neuroplasticity-based cognitive training; that it is possible to develop indices of target engagement during
exposure to the treatment; and that the degree of target engagement has predictive value for determining realworld outcomes after treatment.
Biological Psychiatry, 75(9) : 8S
- Year: 2014
- 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)