Disorders - Psychosis Disorders
Mossaheb,
N., Schafer, M. R., Schlogelhofer, M., Klier, C. M., Cotton, S. M., McGorry, P. D., Amminger, G. P.
The results of a recent
double-blind, randomized, placebo-controlled trial performed in 81 young patients at ultra-high risk for psychosis indicated that a 12-week
intervention of 1.2. g/day of (omega)-3 polyunsaturated fatty acids (PUFA) significantly reduced the risk of transition to psychosis and improved
positive, negative and general symptoms as well as functioning. The aim of this post-hoc analysis was to determine at which time point (omega)-3
PUFAs start to significantly differ from placebo in improving psychopathology and functioning in young people at risk of developing psychosis.
Analyses were performed using the mixed model repeated-measures analysis of variance. Compared to placebo, (omega)-3 PUFAs' significant effects on
the amplitude of the reduction in General and Total PANSS scores are evident after the first four weeks of treatment; a reduction of positive
symptoms and a lower mean PANSS positive score were apparent after eight weeks, whereas the significant drop in negative symptoms and the significant
change and higher mean scores in global functioning occur later at 12. weeks. The delay of onset of (omega) -3 PUFAs seems comparable to that of
antipsychotics and antidepressants. (copyright) 2013 Elsevier B.V..
Schizophrenia Research, 148(1-3) : 163-
167
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Complementary & Alternative
Interventions (CAM), Fish oil (Omega-3 fatty acids), Omega 3 fatty
acids (e.g. fish oil, flax oil)
McClellan, J., Stock, S.
This Practice Parameter reviews the literature on the assessment and treatment of children and adolescents with schizophrenia.
Early-onset schizophrenia is diagnosed using the same criteria as in adults and appears to be continuous with the adult form of the disorder.
Clinical standards suggest that effective treatment includes antipsychotic medications combined with psychoeducational, psychotherapeutic, and
educational interventions. Since this Practice Parameter was last published in 2001, several controlled trials of atypical antipsychotic agents for
early-onset schizophrenia have been conducted. However, studies suggest that many youth with early-onset schizophrenia do not respond adequately to
available agents and are vulnerable to adverse events, particularly metabolic side effects. Further research is needed to develop more effective and
safer treatments.
Journal of the
American Academy of Child & Adolescent Psychiatry, 52(9) : 976-990
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Psychological Interventions
(any)
Nuechterlein, K. H., Subotnik, K. L., Ventura, J., Gretchen-Doorly, D., Casaus, L. R., Luo, J. S., Turner,
L., Kurtz, A. S., DeTore, N. R.
Background: Medication adherence after an initial psychotic episode is particularly poor, as awareness of having an illness is
typically limited. Yet long-acting injectable antipsychotic medication is rarely used, so we know relatively little about its effects in the early
course of schizophrenia. Furthermore, while we know that cognitive deficits are present at the first episode and are strongly predictive of everyday
functioning, we have little systematic data on the impact of long-acting injectable antipsychotic medication on cognition and functional outcome
after a first psychotic episode. Methods: We conducted an open-label, randomized controlled trial of long-acting injectable risperidone (RLAI) vs.
oral risperidone (RisO) to determine the impact of medication adherence after an initial episode of schizophrenia. To optimize the opportunity for
improvement beyond psychotic symptoms, all participants in these analyses were provided supported employment/education (Individual Placement and
Support (IPS)). Sixty patients were randomized to RLAI vs. oral risperidone and provided supported employment/education for at least 6 months, with
all completing the MATRI CS Consensus Cognitive Battery (MCCB) at baseline and 6 months. Results: RLAI was found to significantly improve verbal
learning (p < .03) and tended to improve working memory (p = .08) and the MCCB overall cognitive composite score (p = .09). The impact of consistent
medication was also evident when a medication adherence rating for all patients, across the RLAI and RisO medication conditions, was examined. High
medication adherence was significantly predictive of cognitive improvement from baseline to 6 months on the overall composite score (p < .03) and in
the cognitive domain of working memory (p < .03). RLAI also led to enhanced work/school functioning (p < .02) compared to RisO. Conclusion: These
data indicate that consistent use of a second-generation antipsychotic medication improves cognition and work functioning in the initial course of
schizophrenia more than has been appreciated. The provision of IPS to all patients appears to have facilitated the translation of gains in cognition
to real-world improvement in work and school functioning. Although longacting injectable antipsychotic medication has typically not been used with
first-episode schizophrenia patients, it may have notable advantages for a range of key outcomes.
Schizophrenia
Bulletin, 39 : S347
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Service Delivery & Improvement, Other service delivery and improvement
interventions
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
-
Stage: First episode (psychosis only)
-
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
-
Stage: First episode (psychosis only)
-
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)
-
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
-
Stage: First episode (psychosis only)
-
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
-
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)
-
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
-
Stage: At risk (indicated or selected prevention)
-
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)
-
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)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive remediation
therapy, Other Psychological Interventions