improvement in negative symptoms and functional outcome ...improvement in negative symptoms and...
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Draft Manuscript for Review. Please review online at http://mc.manuscriptcentral.com/oup/szbltn
Improvement in negative symptoms and functional outcome
after a new generation cognitive remediation program: A randomized controlled trial
Journal: Schizophrenia Bulletin
Manuscript ID: Draft
Manuscript Type: Regular Article
Date Submitted by the Author: n/a
Complete List of Authors: Sanchez, Pedro; Hospital Psiquiátrico de Alava, Refractory Psychosis Unit; CIBERSAM, , Centro de Investigación Biomédica en Red de Salud Mental, ; University of the Basque Country, Department of Neuroscience Peña, Javier; University of Deusto, Bengoetxea, Eneritz; University of Deusto, Department Department of Foundations and Methods of Psychology Ojeda, Natalia; University of Deusto, Department Department of Foundations and Methods of Psychology Elizagarate, Edorta; Hospital Psiquiátrico de Alava, Refractory Psychosis Unit; CIBERSAM, , Centro de Investigación Biomédica en Red de Salud Mental, ; University of the Basque Country, Department of Neuroscience Ezcurra, Jesus; Hospital Psiquiátrico de Alava, Refractory Psychosis Unit Gutierrez, Miguel; Hospital Universitario Alava- Sede Santiago, Department of Psychiatry; University of the Basque Country, Department of Neuroscience; CIBERSAM, , Centro de Investigación Biomédica en Red de Salud Mental,
Keywords: schizophrenia, negative symptoms, functional outcome, cognitive rehabilitation, REHACOP
http://www.schizophreniabulletin.oupjournals.org
Schizophrenia Bulletin. For Peer Review Only
Cognitive rehabilitation in schizophrenia: A RCT
1
Improvement in negative symptoms and functional outcome after a new
generation cognitive remediation program: A randomized controlled trial
Pedro Sánchez a,b,c, Javier Peña d, Eneritz Bengoetxea d, Natalia Ojeda d *,
Edorta Elizagárate a,b,c, Jesus Ezcurra a, and Miguel Gutiérrez b,c,e
a Refractory Psychosis Unit, Hospital Psiquiátrico de Alava, C/ Alava, 43. 01006 Vitoria, Spain
b Department of Neuroscience, Psychiatry Section, School of Medicine and Odontology,
University of the Basque Country. Vizcaya, Spain.
c CIBERSAM, Centro de Investigación Biomédica en Red de Salud Mental
d Faculty of Psychology and Education, University of Deusto, Avda. Universidades, 24. 48007
Bilbao, Spain
e Department of Psychiatry, Hospital Universitario Alava- Sede Santiago, C/ Olaguibel, 29.
01006 Vitoria, Spain
* Corresponding author: Natalia Ojeda, Universidad de Deusto, Avda de las
Universidades 24, 48007 Bilbao (Spain). Phone: 34 944139000 (ext 2702).
Email: [email protected]
Word count of the abstract: 244
Word count of text body: 4,654
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Cognitive rehabilitation in schizophrenia: A RCT
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Abstract
Cognitive remediation improves cognition in schizophrenia, but its effectiveness
on other relevant factors such as negative symptoms and functional outcome
has not been studied to the same degree.
Eigthy-four inpatients with schizophrenia were recruited from Alava Hospital
(Spain). All subjects underwent a baseline and a 3 months assessment
including neurocognition, clinical symptoms, insight, functional outcome (Global
Asessment of Functioning (GAF) and Disability Assessment Schedule (DAS-
WHO). Patients were randomly assigned to either neuropsychological
rehabilitation (REHACOP) or control group for 3 months in addition to treatment
as usual. REHACOP is an integrative Spanish program that taps all basic
cognitive functions. It included experts´ last suggestions about positive
feedback and activities of daily living in patients´ enviroment.
REHACOP group showed significantly greater improvements at 3 months in
neurocognition, negative symptoms, disorganization and emotional distress
measures compared to the control group (Cohen´s effect size for these
changes ranged from d = .47 for emotional distress to d = .58 for
disorganization symptyoms). REHACOP group also improved significantly in
both GAF (d = .61) and DAS-WHO total score (d = .57). More specifically, they
showed significant improvement in vocational outcome (d = .47), family contact
(d = .50) and social competence (d = .56).
In conclusion, neuropsychological rehabilitation may be useful for the reduction
of negative symptoms and functional disability in schizophrenia. These findings
support the feasibility of integrating neuropsychological rehabilitation into
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Cognitive rehabilitation in schizophrenia: A RCT
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treatment as usual programs for patients with schizophrenia. Reasons for the
efficacy of this program are discussed.
Key Words: schizophrenia; negative symptoms; functional outcome; cognitive
rehabilitation; REHACOP.
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Cognitive rehabilitation in schizophrenia: A RCT
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Introduction
Negative symptoms and cognitive impairment are two of the most
common dimensions in schizophrenia. More than 50% of patients with
schizophrenia suffer from either negative and/or cognitive symptoms 1 in the
prodomal phase 2, during psychosis 3 and even after the remission of positive
symptoms 4. In addition, negative and cognitive symptoms are supposed to be
strong predictors of transition to psychosis in ultra high-risk samples 5 and of
poorer prognosis and functional outcome 6. More specifically, it has been
suggested that the presence of negative symptoms in early stages is
associated with a more adverse course, more psychotic episodes and greater
impairment in adaptative life skills 7.
The NIMH-MATRICS consensus statement on negative symptoms 6
suggested that persistent and clinically significant negative symptoms are a
distinct and important therapeutic target. Unfortunately, although proven as an
important factor in schizophrenia, negative symptoms have received less
attention in the literature than positive symptoms 1. Moreover, first and second
antipsychotic drugs have demonstrated limited efficacy on the improvement of
negative symptoms 8, although new promising glutamatergic agents are being
explored to target negative symptoms 9. Therefore, as a result new treatments
efforts should be placed on negative symptoms 6.
A recent meta-analysis carried out by Wykes et al. 10 reported data of the
effectiveness of cognitive remediation on clinical symptoms in general, but not
on negative symptoms in particular. A closer inspection at studies included in
this meta-analysis and studies published after it, offers inconsistent results. In
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spite of using different modalities of cognitive remediation, some authors have
found positive significant effects on negative symptoms 11-13. However, there are
also other studies published that have not found evidence of cognitive
remediation efficacy on negative symptoms 14-20. Most of the programs used in
these clinical trials were not specifically designed to target improvement in
negative symptoms but focused on the amilioration of cognitive deficits and
their impact in daily living.
On the other hand, most authors agree that the ultimate goal of any
treatment is to improve the functional capacity and quality of life of patients 10.
According to the meta-analysis previously mentioned 10, cognitive remediation is
effective for improving functioning, although effect sizes obtained were small to
medium. As previously stated with negative symptoms, functioning was
included as a single construct in this meta-analysis. Therefore, we cannot
conclude if cognitive remediation is equally effective for different functional
outcome domains, such as social functioning, vocational outcome, or self-care
management. A closer review of the literature including also recent studies
published in this topic indicates that the most studied functioning domains were
vocational and occupational outcome. Data showed mainly positive
improvement regarding occupational outcome 13,16,19,21. These results suggest
that cognitive remediation can be an effective tool for improving work or
vocational outcome in psychosis.
Social functioning has also been analysed, but studies have shown more
inconsistent results. Some studies reported that cognitive remediation improved
social functioning 12,13,22 whereas others have not 18,23. Less attention has been
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Cognitive rehabilitation in schizophrenia: A RCT
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paid to other outcome domains, such as self-care management or familly
contact. To the best of our knowledge, there is only one study that directly
addressed self-care management and has not informed of significant
improvements 17.
According to McGurk et al.´s meta-analysis and Roder´s research update
12,24, authors suggest that the use of a strategy learning method and transfer
techniques may increase the benefitial effect of the treatment. In addition, they
suggest that a combination of cognitive remediation with psychiatric
rehabilitation and social skills training might provide stronger effects, rather than
cognitive remediation programs alone. Spanish REHACOP is a new generation
multidimensional remediation program which includes these proposals with
specific emphasis on the implementation of learned skills into activities of daily
living. Besides the combination of strategy learning, drill and practice, the
patients are required to transfer obtained knowledge to a set of concrete
activities relevant in their lifes. In order to achieve this goal, patients combine
practice of activities of daily living in group, (during the rehabilitation program)
and homework activities at their real enviroment.
In the current study we aimed to evaluate the efficacy of cognitive
remediation with the REHACOP in schizophrenia. The primary targets of this
study were negative symptoms and functional outcome, including specific
domains such as self-care management, vocational outcome, family contact
and social competence.
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Methods
Participants
Eighty-four inpatients with schizophrenia were recruited from the Alava
Hospital. In order to be included in the study patients had to meet diagnostic
criteria for Schizophrenia according to American Psychiatric Association’s
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
Revision (DSM-IV-TR) 25. In addition, they had to show no evidence of alcohol
or drug abuse in the last 30 days, previous history of significant lack of
consciousness, mental retardation, and relevant neurological or medical
condition.
Ten days after admission, clinical, cognitive and functional evaluation
was carried out. Afterwards, they were randomly allocated to either the
REHACOP Group or the Control Group (see Figure 1). Assignment to the
program was conducted on the basis of a computer-generated randomization
list. Both groups received treatment as usual, consisted of individual case
management and medical review. All patients were voluntary and gave written
informed consent to participate in the study. The study protocol was approved
by the Ethics Committee at the Health Department of the Basque Mental Health
System in Spain.
Measures
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Clinical symptoms, neurocognitive performance and functional outcome
were assessed before and after treatment. Baseline assessments were carried
out when patients were stable in psychopathology and medication after intake
on the hospital. Post-treatment assessment was carried out within the first week
after completing the intervention. All raters were blind to treatment condition
and had no other role in the project that would undermine the blinding.
Clinical assessment
After admission, patients completed a psychiatric interview and
evaluation with the Spanish version 26 of Positive and Negative Syndrome Scale
(PANSS) 27, which was scored using a 5-factor model. The five components
were positive, negative, disorganization, excitement and emotional distress
(See 28 for details). The Premorbid Adjustment Scale (PAS) was administered to
obtain a measure of clinical premorbid adjustment. Insight was evaluated with
Schedule for the Assessment of Insight (SAI) 29. After the training period, inter-
rater reliability coefficients were obtained for the clinical scales (they ranged
from .83 for CGI to .91 for PANSS).
Cognitive Evaluation
Measures of cognitive functioning included tests to assess attention,
working memory, verbal learning and memory, verbal fluency, processing
speed and executive functioning. Our evaluation protocol consisted of the
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following tests: Digit Span, Symbol Search and Digit Symbol from the Wechsler
General Intelligence Scale (WAIS-III 30), Trail Making Test A and B 31, The
Hopkins Verbal Learning Test (form 2 & 4) 32, The Stroop Word and Color Test
33, and Verbal Fluency Subtest from Test Barcelona 34. We made a composite
score with the tests described above. All cognitive measures were converted
into Z-scores and the sign of some measures were adjusted so that higher
scores indicated better neurocognitive performance. The internal consistency of
these composite neurocognitive score was high (Cronbach´s alpha = .81). On
the other hand, the Accentuation Reading Test (TAP) 35, which is the Spanish
version of the National Adult Reading Test (NART), was also administered to
obtain an estimation of each patient´s premorbid abilities.
Functional Outcome
Functional disability was assessed with the Global Assessment of
Functioning (GAF) 36, The Clinical General Impression Scale (CGI) 37, and
Disability Assessment Schedule (DAS-WHO) 38 scales. The four functional
disability characteristic indicators offered by DAS-WHO were analyzed with the
aim of having a better understanding of functional disability and its
improvement: Self-Care Management, Social Competence, Vocational
Outcome and Family Contact.
Intervention
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Developed by Ojeda and Peña in 2007 39, the REHACOP program is the
first Spanish cognitive remediation program specifically designed for psychosis
and schizophrenia. REHACOP is a structured program based on paper-pencil
tasks, using the principles of restoration, compensation, and optimization with a
number of training procedures which gradually increased the level of cognitive
effort and demand. REHACOP trains patients in traditionally impaired cognitive
domains such as attention, memory, processing speed, language, and
executive functioning. Additionally, the program includes three units related to
functional outcome treatment: social skills training, activities of daily living and
psychoeducation. Patients´ relatives also take part in psychoeducation groups,
which provide them all with a better knowledge about the illness, ways to cope
with symptoms, early identifications of signs and relapse, and clinical and social
resources availability.
The REHACOP includes up to 150 different tasks (30 tasks per domain)
hierarchically organized in three levels of difficulty and subtypes of abilities to
be trained. Once a basic cognitive strategy has been trained and well acquired,
the therapist moves on to the next level. This characteristic enables patient´s
progression as performance feedback is provided in each session after tasks
are completed and the patient has access to the information about their level of
difficulty of the task. Each task includes fixed instructions for the therapist to be
read to the patients, verbal and visual materials, and the patient´s response
sheet for the answers. It also provides the therapist with a solution sheet for
tasks with non open responses to facilitate a fast correction and interpretation. It
also offers a graph representation about the patient´s progression that can be
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shown to the patient depending on the therapist´s criteria. In addition, patients
are required to put into practice obtained benefits with homework activities. The
format of the program allows both, the individual and the group administration
(between 5 and 8 patients per group), although for the purpose of this study, the
group administration was chosen.
In the present study, REHACOP´s group attended 90-minutes-long
sessions taking place at least three days per week. During three months,
patients are supposed to integrate the learning experience, to practice in real
life context and to bring to the sessions feedback about possible new difficulties
that must be faced. In this study, REHACOP groups were conducted by a
trained neuropsychologist, although the highly structured design, instructions
and materials could allow its administration by other trained professionals.
The Control Group consisted of treatment as usual along with group
activities including drawing, reading daily news, creating constructions using
different materials (such as paper or wood). These activities were accomplished
in group format and with the same frequency as the implementation of Rehacop
in the experimental group.
Data analysis
Normality of data was tested with Kolmogorov-Smirnov Test. All
variables resembled the normal distribution, with the exception of CGI which
was log-transformed for further analyses. Raw scores are presented for all
variables. χ2 test was used to analyse any differences between the two groups
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on gender, and ANOVA tests on sociodemographic and clinical variables at
baseline.
Repeated measures of multiple analysis of variance (MANOVA) was
performed for clinical, cognitive and functional variables with Group (REHACOP
vs Control Group) as the between subject factor and Time (pre-treatment and
post-treatment) as the within group factor. Main effects of Time (longitudinal
dimension), Group (cross-sectional dimension) and Time X Group (interaction
effect) were examined. Regression analyses were performed in order to
analyse predictors of functional changes. Significance level was set at .05. All
tests were two-tailed.
Results
Sociodemographic characteristics of the groups
The sociodemographic characteristics of the REHACOP group and
Control group are depicted in the Table 1. Differences between the groups were
analysed in order to control for the success of the randomization. There were
no significant differences between the groups in any of the sociodemographic
characteristics studied. Both groups were equivalent in term of age, gender
distribution, marital status, occupation, education, premorbid adjustment and
premorbid IQ. There were no significant differences in other clinical
characteristics such as age at onset, number of previous hospitalizations,
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schizophrenia diagnosis, alcohol and tobacco consumption or dose of
antipsychotic medication (mg/day chlorpromazine equivalents).
Clinical changes in REHACOP and Control groups after intervention.
As seen in table 2, both groups showed a similar pattern of clinical
symptom severity at baseline, as well as a general improvement in clinical
measures. However, REHACOP group improved significantly more than control
group, according to significant Group X Time interactions for negative
symptoms, disorganization symptoms and emotional distress, as well as
PANSS total score. Effect size of these changes fell mostly in the medium
range (negative symptoms d = .48, disorganization d = .58, emotional distress d
= .47 and PANSS total score d = .50). Group X Time interactions for CGI
scores, on the other hand, were not significant. Finally, although not significant,
there was a trend toward significance in insight.
As previously mentioned, we reported data for negative symptoms factor
according to Van der Gaag et al´s meta-analysis 28. However, in order to make
our results easier to compare to other studies that used the conventional
PANSS scores (positive, negative and general psychopathology) and possible
future meta-analyses, we decided to provide also results regarding this negative
symptoms scale (items N1 to N7). REHACOP group reduced negative
symptoms from 26.08 (SD=12.37) at baseline to 20.94 (SD=10.56) after
treatment, whereas control group reduced negative symptoms from 23.74
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(SD=9.57) to 21.63 (SD=10.24). Interaction effect was significant (F = 5.30, p <
.05), with Cohen´s effect size falling in the medium range (d = .51).
Functional outcome changes in REHACOP and Control groups after
intervention
As seen in table 3, both groups showed a similar pattern of functional
outcome at baseline, with a general pattern of improvement over the treatment
period. Repeated Measures of MANOVA revealed significant Group X Time
interactions in GAF and DAS-WHO, suggesting that REHACOP group showed
a significantly larger pre-post improvement than the control group. For
example, REHACOP group´s improvement in GAF was twice as much as the
improvement obtained by control group. The effect size for GAF was d = .61
and for DASWHO total score was d = .57.
A closer inspection at DAS-WHO´s specific domains showed significant
Group X Time interactions in vocational outcome (d = .47), family contact (d =
.50) and social competence (d = .56). On the other hand, self-care management
did not reach statistical significance.
Predictors of change in functional outcome
Changes in negative symptoms (B = -.58, p < .001) and cognition (B = -
.36, p < .05) predicted changes in GAF scores in REHACOP group, whereas
different predictors emerged from patients that received occoupational therapy.
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Only changes in negative symptoms (B = -.45, p < .001) predicted changes in
GAF scores among patients in control group. Changes in negative symtpoms (B
= .62, p < .001) predicted changes in CGI among patients in control group,
whereas changes in negative symptoms (B = .67, p < .001) and cognition (B =
.39, p < .01) predicted changes in CGI scores in REHACOP group.
Finally, negative symptoms (B = -.60, p < .001) and cognition (B = -.36, p
< .01) predicted changes in DAS-WHO scores in REHACOP group. Only
changes in negative symtpoms (B = -.45, p < .001) predicted changes in DAS-
WHO among patients in control group.
Discussion
The aim of the present study was to analyse the efficacy of a cognitive
remediation program which emphasizes the implementation of acquired skills
into activities of daily living, compared to other treatment options, in negative
symptoms and functional outcome.
In our study, patients attending cognitive remediation did not only
improve neurocognition, but also clinical symptoms and functional outcome.
Moreover, improvements in cognition and negative symptoms predicted the
changes in functional outcome in REHACOP group, but not in the Control
group. This general improvement cannot be justified by receiving more
professional attention, differences in medication, or by other sample
characteristics. The improvement can be neither attributed to the effect of the
number of hours of exposure to treatment, since both groups received
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equivalent ones, nor to group vs individual interventions as both formats were
alike.
Regarding clinical symptomatology mayor finding of this study is that
REHACOP significantly reduced patients´ negative symptoms. Those results
support previous studies that indicated improvements in negative symptoms
12,13,40-42 but not all 14-20. It is difficult to find a clear reason for these inconsistent
results since cognitive remediation has been administrated in the same
hetereogeneous way trough studies that found significant improvements in
negative symptoms and those who have not. Moreover, the specific
assessment tools used across these studies were similar too. McGurk et al. 43
indicated that only cognitive remediation programs that provide positive learning
experiences that boslter self-esteem and perceived self-efficacy have benefitial
effects on symptom improvement. Grant supported this idea by showing that
cognitive impairment imposes discouraging life experiences in patients 44.
Those experiences may lead them to perceive negative expectancies and
develop defeatist believes, especially among patients with schizophrenia.
Consequently, it is possible to suggest that the way cognitive rehabilitation is
provided has an important role in the improvement of negative symptoms. The
implementation of the REHACOP training in this study emphasized the
relevance of these variables.
This cognitive remediation program has several characteristics that can
provide patients with positive learning experiences. These characteristics
include exercises hierarchically organized depending on their difficulty. Based
on patients´ performance and degree of impairment, the therapist starts
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providing exercises and strategies that can be achieved in an adecuate way by
patients. Once that level is reinforced, the patient is challenged with new tasks
with progressively higher levels of difficulty. Therefore, activities´ difficulty only
increases once they are able to use learned strategies properly. Owing to
gradual learning, positive feedback, and the transfer of learned strategies to
their daily life activities (with homework), patients may feel themselves more
capable of overcoming daily problems caused by cognitive impairments. As a
result, they may be more encouraged to take part in activities that they tended
to avoid before.
Unexpectedly, the intervention with the REHACOP turned out to be an
effective tool for improving other clinical symptoms, namely emotional distress
and disorganization symptoms. Very few studies have previously found
significant improvement in disorganization symptoms 16,19,42. On the other hand,
opposite to previous studies that reported data on emotional distress 16,17, we
found significant improvement in emotional distress symptoms. Group support,
positive feedback, involvement of family members in patient´s treatment and the
improvement on other areas (such as neurocognitive performance and negative
symptoms) may have accounted for these positive results in emotional distress.
However, REHACOP did not produce significant improvements on
positive symptoms, excitement or insight. These results are consistent with
most similar studies 14-16,19,20,45. Therefore, it might be worth examining potential
variables relevant to these clinical symptoms to aim additional benefits in future
trials and overcome limitations of this intervention. For example, a future goal
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could include analyzing the benefit of adding specific relaxation training
techniques and determine its possible relation to excitement symptoms.
The other main purpose of this kind of intervention is usually to improve
patients´ functional outcome. Consistent with previous articles 10, the
improvement in the experimental group in functional outcome was significantly
greater than in the control group. Likewise, the intervention with the REHACOP
program enabled our sample to obtain unexpected higher rates in some used
assessment scales. In fact, far from other studies 22, participants in this trial
improved twice as much as control group in general functioning (GAF). The
benefit of the cognitive remediation intervention in this study could be reinforced
by the inclusion of strategy learning, transfer techniques and the combination
with treatment as usual. On the other hand, patients learned strategies related
to cognitive functioning. These strategies must be used by the patients again
during the social skills training and homework exercises. Thus, patients
achieved the generalization of acquired knowledge and obtained higher benefits
into their ordinary life activities.
Since functional outcome consists of many different domains, it is useful
to discriminate in greater detail the obtained information about functional
disability. Observed improvements in vocational outcome in our study match up
with most of the previous studies published in this field 13,16,19,21. Contrary to the
methodology of our study, however, most other groups have combined
cognitive remediation with various types of vocational rehabilitation in the
experimental group. Despite the absence of vocational rehabilitation,
REHACOP turned out to be effective as well. Only one of the mentioned studies
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13 did not combine cognitive remediation with vocational rehabilitation and
showed also positive results. In a similar way to us, Eack et al. 13 trained their
patients in various cognitive domains and social skills. In both studies, learned
strategies were generalized to patients´ daily living using homeworks and
therapists provided them with positive feedback. According to this fact, we may
hypothesize that mentioned characteristics can play an important role in the
improvement of vocational outcome.
However, the efficacy of cognitive remediation in social competence
improvement has been inconsistent. REHACOP improved patients´ social
competence as previous studies have done 13,22. Studies that have not found
positive changes in social competence 14,17,18,20 have some features in common,
including that most of them were administered individually, and none included
social skills or daily life activities. Therefore, the inclusion of social skills training
and working with other patients simultaneously with feed back from both, the
therapist and colleagues is shown as a key factor for improving social
competence.
Consistent with previous findings 17, REHACOP group did not
significantly improved self-care management when compared to control group.
However, the degree of improvement was reduced and the baseline status of
the groups in self-care (good enough) could have introduced a ceiling effect.
Unfortunately, none of the reviewed studies have reported data on family
contact, so very little is known about this functional domain. However, the family
involvement in rehabilitation process benefits the patients´ recovery and it
seems reasonable to think that a good management of the family intervention
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can contribute to the general patient´s status. Our cognitive remediation
program encourages relatives to take part in some group activities, so that,
family members improve their knowledge of the relative´s feelings and improve
their management, including fears and worries.
Despite its promising findings, this study has several limitations. Firstly,
we did not assess social cognition. At the beginning of the study, REHACOP
had not included yet a social cognition training unit. Social cognition unit has
just been recently included in REHACOP and we hope to show our results in
future studies. Secondly, the study lacks measures of subjective quality of life
and it is important to know if REHACOP has a significant influence on patients´
self-steem or self-efficacy. Finally, a longitudinal follow up must be carried out in
order to know if the effects of the treatments are maintained in the long-term.
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Conflict of Interest
The Authors declare that there are no conflicts of interest in relation to
the subject of this study.
Funding
This work was supported by Health Department of Basque Government
(grant number 2010111136) and Educational and Science Department of the
Basque Goverment (Researcher Training Program, grant number BFI09.123).
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Table 1. Sociodemographic and Diagnostic Differences of Participants by
Treatment Group (REHACOP; Control Group).
REHACOP Control Group Group
differences p
Age (years) 33.60 (9.4) 36.92 (10.5) F = 2.50 0.118
Years of education (years) 9.23 (2.7) 10.24 (2.8) F = 2.17 0.146
Gender: n (%)
Males
Females
27 (75.0%)
9 (25.0%)
37 (77.1%)
11 (22.9%)
χ2 = 0.05
0.824
Age at onset 22.28 (6.1) 22.04 (6.1) F = 0.03 0.863
Number of previous hospitalizations 7.11 (6.6) 8.98 (10.3) F = 0.89 0.349
Accentuation Reading Test (TAP) 18.50 (4.5) 19.56 (6.3) F = 0.67 0.414
Premorbid Adjustment (Cannon-Spor) 49.64 (25.5) 46.75 (22.2) F = 0.30 0.582
Dose of antipsychotic medication
(converted to mg/day chlorpromazine) 695.09 (362.6) 911.88 (922.9) F = 1.77 0.186
DSM-IV-TR: n (%)
Paranoid
Disorganized
Residual
Non specified
29 (80.6%)
4 (11.1%)
2 (5.6%)
1 (2.8)
40 (77.9%)
3 (6.3%)
3 (6.3%)
2 (4.2%)
χ2 = 0.73 0.866
Occupation: n (%)
Employed
Unemployed
Disabled
3 (8.3%)
9 (25.0%)
24 (66.7%)
2 (4.2%)
7 (14.6%)
39 (81.3%)
χ2 = 2.35 0.308
Marital Status: n (%)
Single
Married
Separated or divorced
33 (91.7%)
1 (2.1%)
2 (5.6%)
45 (93.8%)
1 (2.8%)
2 (4.2%)
χ2 = 0.13 0.935
Alcohol consumption (g/day) 0.92 (1.5) 0.96 (1.5) F = 0.06 0.809
Tobacco Smoking (cigarettes /day) 20.56 (11.2) 18.04 (12.4) F = 0.90 0.345
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Note. DSM-IV-TR = The Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text
Revised.
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Table 2. Changes in Clinical Symptoms and Cognitive Functioning from Baseline to Postreatment by Treatment Group (REHACOP;
Control Group)
Mean (SD) Main Effect Group Main Effect Time Main Effect Group X Time
REHACOP Control Group F P F P F P
Positive Symptoms Pre 18.47 (1.2) 16.47 (1.1) 0.54 0.464 46.15 <0.001 2.10 0.151
Post 12.72 (1.1) 12.75 (0.9)
Negative Symptoms Pre 27.23 (1.7) 24.85 (1.5) 0.10 0.749 23.54 <0.001 4.89 0.030
Post 21.91 (1.6) 22.84 (1.4)
Disorganization Pre 17.03 (1.0) 14.13 (0.9) 1.58 0.212 32.27 <0.001 7.32 0.008
Post 12.91 (0.9) 12.67 (0.8)
Excitement Pre 12.61 (0.8) 9.56 (0.7) 7.45 0.008 27.72 <0.001 1.64 0.204
Post 9.36 (0.6) 7.58 (0.6)
Emotional Distress Pre 10.97 (0.9) 7.95 (0.8) 5.32 0.024 38.01 <0.001 4.42 0.039
Post 7.66 (0.6) 6.33 (0.6)
Insight Pre 6.09 (0.7) 6.31 (0.6) 0.15 0.694 41.81 <0.001 2.98 0.088
Post 8.64 (0.6) 7.79 (0.5)
PANSS-Total Pre 99.39 (4.9) 84.56 (4.28) 2.77 0.100 48.13 <0.001 4.71 0.033
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Post 74.83 (4.1) 71.70 (3.6)
Neurocognition Pre -0.11 (0.59) 0.13 (0.71) 0.90 0.769 0.12 0.734 13.15 <0.001
Post 0.09 (0.48) -0.09 (0.54)
Note. SD = Standard Deviation; PANSS = Positive and Negative Syndrome Scale; Neurocognition = composite score of previously described
neurocognitive tests.
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Table 3. Functional outcome from Baseline to Post-treatment by Treatment Group (REHACOP; Control Group).
Mean (SD) Main Effect Group Main Effect Time Main Effect Group X Time
REHACOP Control Group F P F P F P
GAF Pre 38.88 (2.5) 43.33 (2.2) 0.00 0.983 64.42 <0.001 5.64 0.020
Post 58.06 (3.1) 53.75 (2.8)
DAS-WHO Pre 14.50 (0.6) 13.70 (0.6) 0.03 0.855 63.08 <0.001 6.26 0.014
Post 10.50 (0.8) 11.63 (0.7)
CGI Pre 5.08 (0.3) 4.64 (0.2) 0.48 0.490 66.04 <0.001 2.74 0.102
Post 3.66 (0.2) 3.71 (0.2)
Self-Care Pre 2.70 (0.2) 2.40 (0.2) 0.04 0.851 16.44 <0.001 1.22 0.272
Post 2.11 (0.2) 2.07 (0.2)
Social Competence Pre 3.78 (0.2) 3.71 (0.2) 1.99 0.164 54.57 <0.001 5.90 0.017
Post 2.72 (0.2) 3.18 (0.2)
Vocational Outcome Pre 4.00 (0.2) 3.97 (0.2) 2.41 0.127 48.01 <0.001 4.28 0.042
Post 2.88 (0.2) 3.38 (0.2)
Family Contact Pre 3.72 (0.2) 3.46 (0.2) 0.11 0.746 64.64 <0.001 4.88 0.030
Post 2.47 (0.2) 2.76 (0.2)
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Note.SD = Standard Deviation; GAF = Global Assessment of Fucntioning; DAS-WHO = Disability Assessment Schedule from WHO; CGI = Clinical
General Impression Scale.
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Figure 1. Recruitment procedure and study profile/Participants´ flow card
N= 92
Baseline assessment
and randomization
N= 38 subjects assigned to the
REHACOP Group.
2 patients did not complete
treatment (One of them had a
diagnosis change and the
other suffered from a health
N= 54 subjects assigned to
the Control Group.
6 patients did not complete
treatment (2 were
discharged, 4 declined to
collaborate in the time 2
Final N= 36 Final N= 48
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