Disorders - Psychosis Disorders
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
Subotnik, K. L., Ventura, J., Gretchen-Doorly,
D., Casaus, L. R., Luo, J. S., Turner, L., DeTore, N. R., Hellemann, G. S., Marder, S. R., Amano, J. E., Kaiser, S. K., Nuechterlein, K. H.
Background:
Long-acting injectable antipsychotic medication is typically reserved for periods of schizophrenia in which adherence with oral medication has been
repeatedly poor. In addition, the use of higher cost long-acting injectable second-generation antipsychotic medication needs to be justified by
research demonstrating clear clinical advantages for the long-acting medications over daily oral medication. Methods: At the UCLA Aftercare Research
Program, we compared the clinical efficacy of the long-acting injectable formulation of risperidone (RLAI) to the oral form (RisO) in a 12-month
randomized controlled trial in schizophrenia patients with a recent first psychotic episode. Analyses were conducted with 82 recent-onset
schizophrenia patients who were randomized to RLAI vs. RisO. Each patient's adherence was rated on a 1-5 scale based on timeliness of injections for
RLAI, and on pill counts, plasma levels, patient reports, and psychiatrist judgments for oral medication. Frequency of breakthrough positive
psychotic symptoms and psychotic relapse during follow up were the outcome variables. Results: To date, only 3 patients (7%) have refused to continue
treatment at the time of randomization to RLAI. There were clear clinical advantages of RLAI. The rate of psychotic relapse was lower (5% versus 33%)
for the RLAI group compared to the RisO group, and breakthrough psychotic symptoms were rarer for the patients treated with RLAI. In general, the
occurrence of side effects did not differ between medication conditions. Discontinuations on RisO were more common due to inadequate clinical
response than for RLAI, but the rate of discontinuation due to intolerable side effects was similar for both medications. Adherence with RisO did not
differ prior to randomization, but adherence was much better for injectable compared to oral medication during the randomized treatment (p < .001).
The rating of medication adherence across both medication conditions was significantly associated with both prevention of relapse and control of
breakthrough positive psychotic symptoms. Conclusion: These data document that long-acting RLAI has very clear advantages for the promotion of
adherence and the consistent administration over time in the initial period of schizophrenia. The clinical advantages of RLAI appear to be more
pronounced in this first-episode schizophrenia sample than in prior studies of chronically ill patients, supporting the increased use of RLAI in the
early course of schizophrenia.
Schizophrenia Bulletin, 39 : S353-
S354
- 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
VanDerGaag, M., Smit, F., Bechdolf, A., French, P., Linszen, D. H., Yung, A. R., McGorry, P., Cuijpers, P.
Over the last decade many studies were conducted to
assess the feasibility of early detection of people at risk of developing psychosis and intervention to prevent or delay a first psychotic episode.
Most of these studies were small and underpowered. A meta-analysis can demonstrate the effectiveness of the efforts to prevent or postpone a first
episode of psychosis.A search conducted according the PRISMA guideline identified 10 studies reporting 12-month follow-up data on transition to
psychosis, and 5 studies with follow-ups varying from 24 to 48. months. Both random and fixed effects meta-analyses were conducted.The quality of the
studies varied from poor to excellent. Overall the risk reduction at 12. months was 54% (RR. = 0.463; 95% CI. = 0.33-0.64) with a Number Needed to
Treat (NNT) of 9 (95% CI. = 6-15). Although the interventions differed, there was only mild heterogeneity and publication bias was small. All sub-
analyses demonstrated effectiveness. Also 24 to 48-month follow-ups were associated with a risk reduction of 37% (RR. = .635; 95% CI. = 0.44-0.92)
and a NNT of 12 (95% CI. = 7-59). Sensitivity analysis excluding the methodologically weakest study showed that the findings were robust.Early
detection and intervention in people at ultra-high risk of developing psychosis can be successful to prevent or delay a first psychosis.
Antipsychotic medication showed efficacy, but more trials are needed. Omega-3 fatty acid needs replication. Integrated psychological interventions
need replication with more methodologically sound studies. The findings regarding CBT appear robust, but the 95% confidence interval is still wide.
(copyright) 2013 Elsevier B.V.
Schizophrenia Research, 149(1
-3) : 56-62
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Complementary & Alternative
Interventions (CAM), Psychological Interventions
(any)
Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., Nienhuis, F. J.
IMPORTANCE: Short-term outcome studies of
antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no
other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. OBJECTIVE: To compare
rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT)
trial. DESIGN: Seven-year follow-up of a 2-year open randomized clinical trial comparingMT and DR. SETTING: One hundred twenty-eight patients
participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care
services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission.
PARTICIPANTS: After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up
assessment. INTERVENTION: After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment
was at the discretion of the clinician. MAIN OUTCOMES AND MEASURES: Primary outcomewas rate of recovery, defined as meeting the criteria of
symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR)
was controlled for baseline parameters. RESULTS: The DR patients experienced twice the recovery rate of the MT patients (40.4%vs 17.6%). Logistic
regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but
were not related to symptomatic remission rates. CONCLUSIONS AND RELEVANCE: Dose reduction/discontinuation of antipsychotics during the early stages
of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing
long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated
into general practice. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16228411.
JAMA Psychiatry, 70(9) : 913-
920
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only), Relapse prevention
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation), Medication dose
reduction/discontinuation, Service Delivery & Improvement, Other service delivery and improvement
interventions
Stafford, M. R., Jackson, H., Mayo-Wilson, E., Morrison, A. P., Kendall, T.
Objective To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay
transition to psychotic disorders for people at high risk. Design Systematic review and meta-analysis. Data sources Embase, Medline, PreMedline,
PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status. Review methods Randomised trials comparing any
psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal
diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising
the results. Results 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range
51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and
discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at
12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference -0.07 (-0.14 to -0.01). Very low quality evidence for omega-3
fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions
in transition to psychosis at 12 months. Conclusions Although evidence of benefits for any specific intervention is not conclusive, these findings
suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the
potential for benefit of psychological interventions in the treatment of people at high risk of psychosis. (copyright) BMJ Publishing Group Ltd
2013.
British Journal of Psychiatry, 346(7892) :
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Complementary & Alternative
Interventions (CAM), Psychological Interventions
(any), Fish oil (Omega-3 fatty acids), Omega 3 fatty
acids (e.g. fish oil, flax oil)
Taylor, M., Ng, K. Y. B.
Background: The relapse rate after a first episode of schizophrenia is high, often due to non-adherence with medication. Long-acting
injections of antipsychotics (LAI) are used to promote adherence to medication. Objective: To review the literature on the use of LAIs in first-
episode and early schizophrenia. Method: A systematic electronic search of all original data containing peer-reviewed studies published in English
using EMBASE, MEDLINE, Cochrane and PsychINFO from the onset of records. Reference lists from retrieved articles were examined for further relevant
studies. Results: Ten studies were identified: two cohort studies; three randomised controlled trials; and five open studies. These studies, although
limited, demonstrated the effectiveness of LAI in early schizophrenia. Seven of the 10 studies had risperidone long-acting injection as the only LAI.
Conclusion: LAIs may be useful in the treatment of early schizophrenia in terms of symptom control and relapse reduction, particularly if chosen by
the patient or when medication adherence is a priority. There is a need for a large-scale, randomised controlled trial comparing oral and LAI
antipsychotics to assess long-term outcomes. (copyright) The Royal Australian and New Zealand College of Psychiatrists 2012.
Australian & New Zealand Journal of Psychiatry, 47(7) : 624-
630
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only), Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation), Service Delivery & Improvement, Other service delivery and improvement
interventions
Sanz-Fuentenebro, J., Taboada, D., Palomo, T., Aragues, M., Ovejero, S., Del-Alamo, C., Molina, V.
In first-episode patients with psychosis, clozapine may be potentially valuable 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. Our research group is developing a non-commercial, multicentric and open label study on the differential efficacy between clozapine
and risperidone in first-episode schizophrenia. In this paper, we present the results related to clinical variables after a one-year follow-up. So
far, we have recruited 30 patients diagnosed with schizophrenia or schizophreniform disorder with illness duration of less than two years. The
patients had not received any previous treatment and they were randomized to treatment with clozapine or risperidone. Our results indicate that on
average, patients on clozapine adhered to their original treatment for a longer time period than patients on risperidone. By last observation carried
forward (LOCF) analysis, patients on clozapine and risperidone displayed similar clinical improvements, although marginally greater improvements in
positive and total symptoms scores were found in the clozapine group. At the 12-month point we observed a marginal improvement in negative symptom
scores in patients on clozapine. Subjective secondary effects, as measured with the Udvalg for KliniskeUndersogelser (UKU) scale, correlated
negatively with negative symptoms at follow-up. Our data, although preliminary, suggest that clozapine may have a slightly superior efficacy in the
initial year of treatment of first-episode treatment-naive patients with schizophrenia, and this can be explained for the most part by greater
adherence to this treatment. (copyright) 2013 Elsevier B.V.
Schizophrenia Research, 149(1-3) : 156-161
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Sigrunarson, V., Grawe, R. W., Morken, G.
Background: The aim of this study is to compare the 12-year follow-up effects on in- and outpatient services of 2 years of integrated treatment
for recent-onset schizophrenia versus treatment as usual in a randomized controlled trial. Methods: 50 patients aged 18-35 years were randomized to
Integrated Treatment (IT) (N = 30) or Treatment-as-Usual (TAU) (N = 20) for two years. TAU comprised optimal pharmacotherapy and outreach assertive
treatment, while IT also included cognitive-behavioural family treatment, skills training, strategies for residual psychotic and non-psychotic
problems and home-based crisis management. Results: There were no differences in number of days in hospital, time to readmission, number of
admittances to psychiatric wards, number of involuntarily psychiatric admissions or number of outpatient contacts over a period of 12 years following
the initial 2-year treatment trial. Fewer patients in the IT group were, however, involuntary admitted to hospital in the period. Conclusions: The
intensive two-year psychosocial intervention seemed to have little long-term effects on use of in- and outpatient services. Trial registration:
Current Controlled Trials: NCT00184509. (copyright) 2013 Sigrunarson et al.; licensee BioMed Central Ltd.
BMC Psychiatry, 13 :
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Cognitive & behavioural therapies (CBT), Skills training, Other Psychological Interventions, Case management, Other service delivery and improvement
interventions
Scoriels, Linda, Barnett, Jennifer
H., Soma, Praveen K., Sahakian, Barbara J., Jones, Peter B.
Rationale: Cognitive impairments are important determinants of functional outcome in psychosis, which are inadequately treated by
antipsychotic medication. Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy
population and in patients with schizophrenia.; Objectives: We aimed to establish modafinil's role in the adjunctive treatment of cognitive
impairments in the first episode of psychosis, a time when symptoms may be more malleable than at chronic stages of the disease.; Methods: Forty
patients with a first episode of psychosis participated in a randomised, double-blind, placebo-controlled crossover design study assessing the
effects of a single dose of 200 mg modafinil on measures of executive functioning, memory, learning, impulsivity and attention.; Results: Modafinil
improved verbal working memory (d?=?0.24, p?=?0.04), spatial working memory errors (d?=?0.30, p?=?0.0004) and strategy use (d?=?0.23, p?=?0.03). It
also reduced discrimination errors in a task testing impulsivity. Modafinil showed no effect on impulsivity measures, sustained attention,
attentional set-shifting, learning or fluency.; Conclusions: Modafinil selectively enhances working memory in first episode psychosis patients, which
could have downstream effects on patients' social and occupational functioning.;
Psychopharmacology, 220(2) : 249-258
- Year: 2012
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Other biological interventions
Secher, R. G., Nordentoft,
M., Austin, S., Mors, O.
In the OPUS trial, 547 people
with a first diagnose within the schizophrenic spectrum were randomized to either two years of intensive, early, psychosocial intervention (OPUS
treatment) or treatment as usual (TAU). OPUS treatment included social skills training, multi family groups, own case manager, optional house calls
and more. TAU generally offered none of the treatment elements mentioned above. After the intervention the OPUS patients showed significantly lower
psychopathology, rates of hospitalization and improved social functioning as compared to the TAU patients. After 5 years, the only significant
difference between the two interventions was that the former OPUS patients had significantly fewer days in supported housing. Study Focus: The 10-
year follow-up compares clinical, psychological and social outcomes in the OPUS-group with the TAU-group. Methods and Materials: All the original
participants were invited to complete a series of interviews and questionnaires measuring levels of psychopathology, quality of life, social
functioning, meta-cognitive beliefs, perceived ability to cope with everyday life and symptoms and cognitive functioning. Results: A total of 347
participants were interviewed, giving a follow-up rate of over 70%, of those of the former patients who were not emigrated or dead. Results comparing
the OPUS-treatment and the TAU will be presented. Perspectives: The OPUS trial is the worlds' largest randomized controlled trial comparing
intensive, early, psychosocial intervention with TAU for schizophrenia spectrum disorders. Data gathered 10 years after the commencement of the
interventions will inform us about the long term effects of psychosocial treatments for this group of patients.
Early Intervention in Psychiatry, 6 : 21
- Year: 2012
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Skills training, Other Psychological Interventions, Case management