- Email: [email protected]
Psychoeducational Group Intervention for Adolescents With Psychosis and Their Families: A Two-Year Follow-Up
Accepted Manuscript Psychoeducational Group Intervention for Adolescents With Psychosis and Their Families: A Two-Year Follow-Up Ana Calvo, PhD, Miguel Moreno, MD, PhD, Ana Ruiz-Sancho, MD, Marta RapadoCastro, PhD, Carmen Moreno, MD, PhD, Teresa Sánchez-Gutiérrez, PhD, Celso Arango, MD, PhD, María Mayoral, PhD PII:
S0890-8567(15)00649-8
DOI:
10.1016/j.jaac.2015.09.018
Reference:
JAAC 1311
To appear in:
Journal of the American Academy of Child & Adolescent Psychiatry
Received Date: 13 July 2015 Revised Date:
25 September 2015
Accepted Date: 26 September 2015
Please cite this article as: Calvo A, Moreno M, Ruiz-Sancho A, Rapado-Castro M, Moreno C, SánchezGutiérrez T, Arango C, Mayoral M, Psychoeducational Group Intervention for Adolescents With Psychosis and Their Families: A Two-Year Follow-Up, Journal of the American Academy of Child & Adolescent Psychiatry (2015), doi: 10.1016/j.jaac.2015.09.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Psychoeducational Group Intervention for Adolescents With Psychosis and Their Families: A TwoYear Follow-Up RH = The PIENSA Trial Ana Calvo, PhD; Miguel Moreno, MD, PhD; Ana Ruiz-Sancho, MD; Marta Rapado-Castro, PhD; Carmen Moreno, MD, PhD; Teresa Sánchez-Gutiérrez, PhD; Celso Arango, MD, PhD; María Mayoral,
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PhD Accepted October 5, 2015
Drs. Calvo, Rapado-Castro, C. Moreno, Sánchez-Gutiérrez, Arango, and Mayoral are with Hospital
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General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid. Dr. Rapado-Castro is also with Melbourne Neuropsychiatry Centre, the University of Melbourne and Melbourne Health, Carlton South, Australia. Dr. M. Moreno is with Gipuzkoako
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Osasun Mentaleko Sarea, Red de Salud Mental de Guipuzcoa, Biodonostia, San Sebastian, Spain. Dr. Ruiz-Sancho is with VocAcción Director-Group Processes and Institutional Consulting, Madrid. This study was supported by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, CIBERSAM, the Madrid Regional Government (S2010/BMD-2422 AGES), and the European Union Structural Funds and European Union Seventh Framework Program under grant agreements FP7-
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HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7-HEALTH-2009-2.2.1-3-242114 (Project OPTiMISE), FP7-HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN), and FP7-HEALTH-2013-2.2.12-602478 (Project METSY). The study was also supported by Fundación Alicia Koplowitz and
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Fundación Mutua Madrileña.
M.M., A.R.S., and M.M. designed the present study. A.C., M.M., and C.M. undertook the statistical
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analysis. A.C. wrote the first draft of the manuscript, which was subsequently edited by all authors, who contributed to the interpretation of the findings and approved the final version. The authors thank all those who participated in this study, namely, the adolescents, their families, and the team members of the PIENSA program. Disclosure: Dr. Calvo has received a predoctoral fellowship award from Gobierno de La Rioja, an IiSGM Fellowship Award for Short-term Placements from the Health Research Institute of Hospital Gregorio Marañón (IiSGM) (Madrid, Spain), and a 2015 Alicia Koplowitz Grant for Short-Term Placements from the Alicia Koplowitz Foundation. Dr. M. Moreno has received grant or research support from Fundación Alicia Koplowitz, Instituto de Salud Carlos III, the Spanish Ministry of Economy and Competitiveness,
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ACCEPTED MANUSCRIPT and Janssen-Cilag, and has served as a consultant for Fundación Alicia Koplowitz and the Spanish Ministry of Economy and Competitiveness. Dr. Rapado-Castro has received a Health Research Sara Borrell Fellowship from the Spanish Ministry of Economy and Competitiveness (SCO/523/2008), an Alicia Koplowitz Grant for Short-Term Placements from the Alicia Koplowitz Foundation, and a 2014 IiSGM Fellowship Award for Short-term Placements from the Health Research Institute of Hospital
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Gregorio Marañón (IiSGM) (Madrid, Spain). She has also received grant support from Fundación Alicia Koplowitz. Dr. C. Moreno has received grant or research support from European Union Funds, Fundación Alicia Koplowitz, Instituto de Salud Carlos III, and Spanish Ministry of Economy and Competitiveness,
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and has served as a consultant for Fundación Alicia Koplowitz, Instituto de Salud Carlos III, the Spanish Ministry of Economy and Competitiveness, and Janssen-Cilag. Dr. Arango has served as a consultant to or has received honoraria or grants from Abbot, AMGEN, AstraZeneca, Bristol-Myers Squibb, Caja
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Navarra, CIBERSAM, Fundación Alicia Koplowitz, Instituto de Salud Carlos III, Janssen Cilag, Lundbeck, Merck, Ministerio de Ciencia e Innovación, Ministerio de Sanidad, Ministerio de Economía y Competitividad, Mutua Madrileña, Otsuka, Pfizer, Roche, Servier, Shire, Schering Plough, and Takeda. Dr. Mayoral has received grant or research support from Comunidad de Madrid (predoctoral fellowship award), Instituto de Salud Carlos III, and the Spanish Ministry of Economy and Competitiveness. Drs.
interest.
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Ruiz-Sancho and Sánchez-Gutiérrez report no biomedical financial interests or potential conflicts of
Correspondence to Ana Calvo, PhD, Child and Adolescent Psychiatry Department, Instituto de
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Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón,
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CIBERSAM, C/ Ibiza 43, 28009 Madrid, Spain; email: [email protected].
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ACCEPTED MANUSCRIPT ABSTRACT Objective: To investigate whether the beneficial effects of a structured psychoeducational parallel group program for adolescents with early-onset psychosis and their families observed immediately after the intervention were maintained two years later. Method: The present study examines the longitudinal efficacy of a randomized controlled trial based on a
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psychoeducational, problem-solving, structured group intervention for adolescents with early-onset psychosis and their families (PE) and compares it with that of a non-structured group intervention (NS) after a two-year follow-up. We analyzed whether the differences between PE and NS found after the intervention persisted two
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years later. Inter-group differences in number and duration of hospitalizations, symptoms, and functioning were also assessed.
Results: After two years of follow-up, we were able to reassess 89% of patients. In the PE group, 13% of
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patients had visited the emergency department, compared with 50% in the NS group (p=.019). However, no statistically significant differences were found between the groups for negative symptoms or number and duration of hospitalizations. A significant improvement in Positive and Negative Syndrome Scale (PANSS) general symptoms was observed in the PE group.
Conclusion: Our psychoeducational group intervention showed sustained effects by diminishing the number of
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visits to emergency department two years after the intervention. Our findings indicate that this psychoeducational intervention could provide patients with long-lasting resources to manage crises more effectively.
NCT02101372.
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Clinical trial registration information: Intervention Module AGES (AGES-CM); http://clinicaltrials.gov/;
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Key Words: Psychosis, Adolescents, Families, Group Therapy, Psychoeducation
INTRODUCTION
Psychotic disorders typically emerge in adolescence and young adulthood. While some patients recover
fully, many experience persistent difficulties or remain vulnerable to future episodes. The prognosis for children and adolescents is usually worse than for adults, although it could be improved by early intervention.1 The duration of early interventions necessary to prevent relapse is unknown. Several studies show that the benefits of interventions are not maintained in the long term2-4. Available approaches usually take the form of assertive outreach programs (e.g., cognitive-behavioral therapy [CBT], medication, family support), which include a
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ACCEPTED MANUSCRIPT combination of psychoeducational interventions aimed at family groups. Studies in adults with bipolar disorder have shown that group psychoeducational intervention combined with drug therapy is the approach of choice and that it maintains its efficacy over time.5, 6 The PIENSA intervention program for adolescents with psychosis (Programa de Intervención en Psicosis Adolescente [PIENSA, which in Spanish means “think”]), developed at the Child and Adolescent
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Psychiatry Department, Hospital General Universitario Gregorio Marañón, Madrid, provides appropriate treatment and monitoring for adolescents with psychosis (http://www.ua.hggm.es). The PIENSA trial is the first randomized clinical trial to longitudinally assess the effectiveness of a parallel, structured, and specific
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psychoeducational group intervention (PE) for adolescent patients and their families and to compare the intervention with a non-structured group intervention (NS). Significant positive effects on clinical outcomes were observed in the PE group at the end of the group intervention. In particular, the number of visits to the
compared with patients from the NS group7.
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emergency department had decreased and negative symptoms in adolescents with psychosis had improved
The aim of the present study was to investigate whether our early intervention (PE) sustained its positive effects 2 years after the intensive group phase.
Based on our previous results7, we tested two hypotheses. Hypothesis 1 was that patients in the PE
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group would have made fewer visits to the emergency department than those in the NS group after two years of follow-up. Hypothesis 2 was that patients in the PE group would have fewer negative symptoms after two years
functioning. METHOD
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of follow-up. We also investigated variables such as number and duration of hospitalizations, symptoms, and
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The present study examines the two-year longitudinal efficacy of a randomized controlled trial based on a structured psychoeducational parallel group intervention for adolescents with early-onset psychosis and their families. The study methodology has been described in detail elsewhere7. Participants
Participation was offered to 90 adolescent outpatients diagnosed with early-onset psychosis and accompanied by one or both parents (Figure 1). The inclusion criteria were as follows: 1) one or more positive psychotic symptoms (delusions or hallucinations) before age 18; 2) diagnosis of a psychotic disorder according to DSM-IV-TR; 3) age between 14 and 18 years; and 4) cohabitation with one or both parents, caregivers, or legal guardians.
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ACCEPTED MANUSCRIPT The exclusion criteria were as follows: 1) drug abuse or dependence at the time of the intervention (drug use was not an exclusion criterion); 2) any neurological developmental disorder; and 3) inability to engage in conversation or read in Spanish that could have interfered with the progress of group treatment. Of the 55 patients finally enrolled in the trial, 48 had a first episode of psychosis (6 had never been
hospitalizations [n = 3]). INSERT Figure 1 HERE. Assessment and Measuring Instruments
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admitted to hospital) and 7 had had previous episodes (1 hospitalization [n = 1], 2 hospitalizations [n = 3], and 3
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The raters were all psychiatrists with clinical and research experience in child and adolescent psychiatry and carried out the assessments blind. Participants and their families were assessed before treatment, after treatment (the intervention lasted 9 months), and 2 years after treatment finished (2-year follow-up
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posttreatment).
Diagnoses were made at baseline and confirmed after a 2-year follow-up according to DSM-IV-TR criteria using the Spanish version of a semi-structured interview for children and parents, namely, the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime version (K-SADSPL)8, 9. Symptoms of psychosis were assessed using the Spanish version of the Positive and Negative Syndrome
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Scale (PANSS)10, 11. We used the positive, negative, and general subscales and total PANSS scores. The level of functioning was measured using the Children’s Global Assessment Scale (C-GAS)12, 13. Interrater reliability for the PANSS was determined using the intraclass correlation coefficient, which was superior to 0.80. Finally, the
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number of hospital admissions, the total number of days of psychiatric hospitalization, and the number of visits to the emergency department were obtained using a custom-designed questionnaire that was administered to
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both parents and adolescents. Psychiatric hospitalizations and emergency room visits for psychiatric reasons were recorded, but we did not include other medical emergency visits or medical hospitalizations. In order to verify our findings, data were independently corroborated by a blinded rater using medical records. Interventions
The same therapists delivered both group interventions depending on whether the groups were comprised of patients or parents/family members. Therefore, there were two therapists for both patient groups (intervention and control) and two different therapists for both parent groups. Given the age of the participants and the fact that one of the developmental challenges that adolescents have to face as they mature is differentiation from their parents, we decided to run two simultaneous and parallel groups: one group for parents, and the other for
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ACCEPTED MANUSCRIPT adolescents in each of our two proposed clinical interventions. (For a detailed description of the program, please see Ruiz-Sancho, Calvo et al 2012.14) The characteristics of the PIENSA trial have been comprehensively described elsewhere. 7 -
Psychoeducational group intervention
The PE consisted of two consecutive treatment phases adapted from W. McFarlane15: the initiation/alliance
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phase and the group phase (following the Multifamily Therapy [MFT] format). The initiation phase consisted of three individual sessions of 50 minutes each conducted for families and adolescents separately. The group phase consisted of two separate group interventions of twelve biweekly, 90-minute structured sessions, one for
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patients and the other for parents. Groups focused specifically on problem-solving strategies to manage difficulties with daily living associated with the disease to mitigate crises and to prevent relapses. Patients and
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Non-structured group intervention
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their families received written PE material within this treatment modality 7, 14.
The NS also has an initiation phase (three individual sessions for parents and adolescents) and twelve biweekly support group sessions. No written material was provided in this modality.
Both the PE and NS group interventions were complementary to current individual psychiatric
Data Analysis
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management and psychopharmacological treatment.
Data were analyzed on an intention-to-treat basis. The baseline characteristics of the sample were
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compared using the Pearson χ2 test for categorical variables such as gender, race, and diagnosis. Quantitative variables were analyzed using parametric tests (2-sample t tests).
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We followed a likelihood-based mixed-effects model repeated measures (MMRM) approach to study the group x time interaction between treatment groups for symptoms and function during the two-year followup.
We compared visits to the emergency department (number of hospitalizations and days of
hospitalization) between PE and NS two years after treatment using the Pearson χ2 test for categorical variables and the two-sample t test for quantitative variables. The time to hospitalization after treatment curve was plotted using the Kaplan-Meier method. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp, Armonk, New York, USA).
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ACCEPTED MANUSCRIPT RESULTS Sociodemographic and Clinical Variables We found no statistically significant differences between the PE and NS groups for sociodemographic, diagnostic, or clinical variables at baseline (Table 1). After two years of follow-up, there were no statistically significant differences between the PE and NS
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groups for diagnostic types of psychoses: PE=11 (40%) vs NS=16 (54.2%) for schizophrenia spectrum psychosis, PE=8 (32%) vs NS=6 (20.8%) for affective psychosis, and PE=8 (28%) vs NS=6 (25%) for other types of psychosis.
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INSERT TABLE 1. HERE Symptoms and Functional Outcomes
PANSS total scores improved significantly in the PE and NS groups during the two years of follow-up after
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treatment. However, the PANSS general symptom scores only improved significantly in the PE group (Table 2). No statistically significant differences were found between the two groups when we analyzed time x group interactions (MMRM approach) for symptoms in the different PANSS scores evaluated or for functional outcome from the end of the intervention to two years after the group treatment (Table 2). Effects on Relapse
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Patients in the PE group had made fewer visits to the emergency department at the end of follow-up. Figure 3 shows that 14.8% of patients in the PE group and 39.3% of patients in the NS group had visited the emergency department immediately after the end of the intervention (p=.039). At the end of follow-up, 13% of
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patients from the PE group and 50% from the NS group had visited the emergency department (p=.019; Table 3). No differences were observed in the number of hospitalizations or in the number of days of hospitalization
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between the two groups at the end of follow-up (Table 3). After treatment, 11.1% of patients in the PE group and 32.1% in the NS group had been hospitalized. At the end of follow-up, 30.4% of patients in the PE group and 40% in the NS group were hospitalized (Figure 2). Survival analysis showed that there were no differences in time to hospitalization between the PE and
NS groups (Mantel-Cox = 0.334, p=.563). DISCUSSION The results presented here support one of our hypotheses, namely, that patients in the PE group would have fewer visits to the emergency department than those in the NS group after two years of follow-up. However, we
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ACCEPTED MANUSCRIPT were not able to find a maintained beneficial effect on negative symptoms, although we did detect an improvement in the PANSS general symptoms in the PE group. The fact that the reduction in the visits to the emergency department persisted over time in the PE group compared with the NS group could be relevant for prevention of relapse. The PE might reduce the number of contacts with the emergency services as a result of the implementation of improved problem-solving
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strategies within the family, as this kind of PE intervention was specifically designed to empower families in conflict resolution in order to manage crises more efficiently. The reduction could be associated with the problem solving–based methodology, which aims to improve the ability to balance the needs of the individual to
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adapt to a given situation, while emphasizing that all solutions have both positive and negative implications and empowering adolescents through the idea that they can manage problems using their own resources and with the help of their family and friends.
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We did not find statistically significant differences between the PE and NS groups for hospitalizations. Less than 50% of the patients who received treatment within the two modalities were hospitalized during follow-up. Although a trend toward significance was observed regarding differences between the groups for the number of posttreatment hospital admissions, it is important to highlight that the number of patients hospitalized was a little over a third of that of the NS group (11.1% vs 32.1%). We observed that this trend of significance
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was not maintained during follow-up. The absence of statistically significant differences between the PE and NS groups during follow-up could be due to the small sample size and the fact that the NS group also received a psychological intervention. It is also possible that the number of hospitalizations was not necessarily associated
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with differences between the groups. Furthermore, the outcome of hospitalization was very variable and depended on external factors not associated with the disorder, as was the case in the RAISE study, where
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patients in the intervention arm functioned better than, but did not differ in number of hospitalizations from, the treatment-as-usual (TAU) group 16, 17 Another possible explanation is that our intervention was not long enough. Thus, it would be interesting to increase the duration of the intervention to cover the critical period of the illness, as in other intervention programs, by expanding the group treatment to two years and including booster sessions or extending the duration of the current intervention18-20. It would also be interesting to assess whether this period translates into significant differences between groups. We previously showed that negative symptoms improved in adolescents in the PE group at the end of treatment7. After the two-year follow-up, no statistically significant differences were observed between groups in terms of negative symptoms. We observed that negative symptoms had also improved in the NS group. This
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ACCEPTED MANUSCRIPT could account for the absence of statistically significant differences. Consequently, the PE modality could be more effective in the short term, whereas the NS seems to be effective in the long term. In any case, effectiveness did not worsen in either group in the long term. As negative symptoms are the best predictors of functioning in individuals with early psychosis
21,1, 22
, faster improvement might increase the possibility of
recovery in the PE group. Negative symptoms are the target of most of the therapies used in psychosis owing to
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the suffering they cause patients and the low efficacy of available treatment modalities, whether pharmacotherapy or psychotherapy. Therefore, we think it is important to maintain intensive treatment during the early stages of the disease in order to obtain a global improvement that can be maintained over time,
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possibly with booster sessions, a longer group phase, or an adjustment of the contents so that patients can focus on those aspects of therapy that have a greater effect on negative symptoms (e.g., group attendance, promotion
activities within the therapy setting).23
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of leisure activities with people outside the therapeutic context, and inclusion of organized physical group
Our pilot study is subject to a series of limitations. The sample size may have been insufficient to obtain significant results, and the indicators used to assess prevention of relapse (e.g., number of admissions or quantitative symptom scales) might not be as comprehensive as the global impact on psychosocial functioning that a group intervention can produce.
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We performed a randomized controlled trial to test a structured psychoeducational group intervention for adolescents with early-onset psychosis and their families. The intervention was implemented early to improve the course of the disease. Effectiveness was evaluated at two years of follow-up, when we were able to
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reassess 89% of patients. The fact that the study assessments were made at the site where patients receive treatment could be important in that it improves recruitment, subsequent engagement, and global adherence to
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treatment.
Psychosocial interventions in individuals with first-episode psychosis (FEP) aim to reduce relapse
rates24. Naturalistic long-term follow-up studies have shown that the early course of psychosis is characterized by relapses. Up to 80% of patients with FEP experience a relapse within the five years of remission following the initial episode25, 26. Therefore, psychotherapy is especially important for FEP patients within specialized early intervention services (including assertiveness community treatment and antipsychotic medication), and family intervention in particular is very effective for the prevention of relapses 24. However, the intensive early-intervention program has been shown to improve clinical outcome after treatment,19 although the effects were not maintained.2-4 We were unable to replicate some of our findings after
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ACCEPTED MANUSCRIPT two years of follow-up, very likely because of the duration of our group intervention. In other words, the results obtained with our adaptation of McFarlane’s MFT approach may not be sufficient in the long term, thus suggesting that intensification of the intervention might make it possible to test whether symptoms and functioning could also be improved, as we have previously shown 7. The PIENSA PE group intervention seemed to be effective after treatment with respect to negative
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symptoms and visits to the emergency department; however, after two years of follow-up, it was only effective at reducing visits to the emergency department. Although its effectiveness in improving other variables (e.g., symptoms) was not as expected, it is important to note that unlike other comprehensive programs consisting of
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several integrated psychotherapeutic interventions (e.g., cognitive social skills, vocational counselling, and CBT), our study is based on a single psychoeducational intervention over a very short period (9 months). We now propose to test the effectiveness of a new approach in the PIENSA program. Our intention is
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that this approach will consist of an extended and more intensive intervention (weekly groups for 18 months, similar to the MFT approach) and include new therapeutic components. Monthly booster sessions would be implemented during the year following the group intervention phase to maintain generalization of the positive outcomes. Developing and implementing an online intervention with that purpose has also been considered. Such an approach might provide easy, timely, and cost-effective access to treatment and serve as a tool for the
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implementation of complementary psychotherapeutic approaches (i.e. CBT) that may enhance the generalization and extension of the clinical gains observed. Figures
intervention.
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Figure 1. Progress of patients during the trial. Note: NS = non-structured intervention; PE = psychoeducational
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Figure 2. Group differences in percentage of hospitalizations over time. NS = non-structured intervention; PE = psychoeducational intervention.
Figure 3. Group differences over time (visits to emergency department). Note: NS = non-structured intervention; PE = psychoeducational intervention. *p ≤ .05.
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26.
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ACCEPTED MANUSCRIPT Table 1. Sociodemographic, Diagnostic, and Clinical Variables at Baseline
NS
16.4 (1.34)
16.5 (1.45)
.88
Male gender
16 (59.3)
18 (64.3)
.70
White race
25 (92.6)
24 (85.7)
.14
Schizophrenia spectrum psychosis
9. (33.3)
12. (42.9)
.46
Affective psychosis
7. (25.9)
9. (32.1)
Other psychosis
11. (40.7)
7. (25.0)
Age, mean (SD)
p Value
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Diagnosis
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PE
.52
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.21
14.77 (8.22)
16.92 (9.10)
.35
PANSS Negative, mean (SD)
16.55 (7.27)
17.03 (7.42)
.87
PANSS General, mean (SD)
30.51 (11.16)
34.55 (14.67) .40
PANSS Total, mean (SD)
61.85 (23.37)
69.00 (27.71) .50
C-GAS, mean (SD)
64.37 (18.79)
58.46 (19.02) .35
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PANSS Positive, mean (SD)
Note: Values are expressed as n (%) unless otherwise indicated. None of the p values were statistically significant. C-GAS = Children’s Global Assessment Scale; NS = non-structured intervention; PANSS = Positive
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and Negative Syndrome Scale; PE = psychoeducational intervention.
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ACCEPTED MANUSCRIPT Table 2. Differences Between the Groups: End of Treatment and After 2 Years of Follow-Up Posttreatment
2 Years Follow-
Intra group (p)
Time x Group interaction (p)a
Up PANSS Positive, mean (SD) 10.72 (14.33)
9.78 (14.33)
p=0.288
NS
11.77 (3.93)
10.63 (3.56)
p=0.293
PANSS Negative, mean (SD) 12.84 (7.87)
12.39 (5.66)
p=0.837
NS
15.81 (6.37)
14.47 (5.87)
p=0.690
p=0.037
PANSS General, mean (SD) 26.20 (8.42)
23.17 (6.96)
NS
27.69 (8.66)
27.95 (9.42)
p=0.421
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PE
PANSS Total, mean (SD) PE
50.29 (19.28)
45.35 (14.65)
p=0.008
NS
55.35 (17.39)
53.58 (18.23)
p=0.015
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C-GAS, mean (SD)
p=0.258
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PE
p=0.859
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PE
PE
73.92 (14.33)
74.05 (16.28)
p=0.891
NS
66.31 (15.23)
70.67 (13.06)
p=0.991
p=0.709
p=0.981
p=0.905
Note: Boldface text represents p values statistically significant at p ≤ .05. C-GAS = Children’s Global
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Assessment Scale; PANSS = Positive and Negative Syndrome Scale; PE = psychoeducational intervention; NS = non-structured intervention
Likelihood-based mixed-effects model, repeated measures approach (MMRM).
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a
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Table 3. Outcome of Relapse Posttreatment and at 2 Year Follow-Up Posttreatment
2 Year Follow-Up
PE (n = 25)
NS (n = 26)
p Value
PE (n = 25)
NS (n=24)
p Value
Patients hospitalized, n (%)
3 (11.1)
9 (32.1)
.057a
7 (30.4)
8 (40)
.686a
No. of days hospitalized,
4.08 (13.03)
7.42 (13.64)
.142b
6.09 (12.84)
7.9 (16.56)
.661b
4 (14.8)
11 (39.3)
.039a
3 (13)
10 (50)
.019a
mean (SD)
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Patients who visited the ED,
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Relapse
No. (%)
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Note: Boldface text represents p values statistically significant at p ≤ .05. ED = emergency department; NS = non-structured intervention; PE = psychoeducational intervention. χ test.
a 2
b
t-test.
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*p≤.05
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Assessed for eligibility (n = 90)
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Excluded (n = 35) -Did not meet inclusion criteria (n = 3)
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-Declined to participate (n = 32)
Randomized (N = 55)
Allocated to PE intervention (n = 27)
Allocated to NS intervention (n = 28)
Discontinued intervention but attended assessments (n = 10)
Discontinued intervention but attended assessments (n = 17)
Analysis
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Received allocated intervention (n = 28)
Analyzed at baseline (n = 27)
Analyzed at baseline (n = 28)
Analyzed at end of treatment (n = 25)
Analyzed at end of treatment (n = 26)
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Allocation
Received allocated intervention (n = 27)
Analyzed at 2-year follow-up (n = 25)
Analyzed at 2-year follow-up (n = 24)
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% of Hospitalizations
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Pretreatment
Posttreatment
2-Year Follow-Up
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% Visits to Emergency Department
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Pretreatment
Posttreatment 2-Year Follow-Up*
S0890-8567(15)00649-8
DOI:
10.1016/j.jaac.2015.09.018
Reference:
JAAC 1311
To appear in:
Journal of the American Academy of Child & Adolescent Psychiatry
Received Date: 13 July 2015 Revised Date:
25 September 2015
Accepted Date: 26 September 2015
Please cite this article as: Calvo A, Moreno M, Ruiz-Sancho A, Rapado-Castro M, Moreno C, SánchezGutiérrez T, Arango C, Mayoral M, Psychoeducational Group Intervention for Adolescents With Psychosis and Their Families: A Two-Year Follow-Up, Journal of the American Academy of Child & Adolescent Psychiatry (2015), doi: 10.1016/j.jaac.2015.09.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Psychoeducational Group Intervention for Adolescents With Psychosis and Their Families: A TwoYear Follow-Up RH = The PIENSA Trial Ana Calvo, PhD; Miguel Moreno, MD, PhD; Ana Ruiz-Sancho, MD; Marta Rapado-Castro, PhD; Carmen Moreno, MD, PhD; Teresa Sánchez-Gutiérrez, PhD; Celso Arango, MD, PhD; María Mayoral,
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PhD Accepted October 5, 2015
Drs. Calvo, Rapado-Castro, C. Moreno, Sánchez-Gutiérrez, Arango, and Mayoral are with Hospital
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General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid. Dr. Rapado-Castro is also with Melbourne Neuropsychiatry Centre, the University of Melbourne and Melbourne Health, Carlton South, Australia. Dr. M. Moreno is with Gipuzkoako
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Osasun Mentaleko Sarea, Red de Salud Mental de Guipuzcoa, Biodonostia, San Sebastian, Spain. Dr. Ruiz-Sancho is with VocAcción Director-Group Processes and Institutional Consulting, Madrid. This study was supported by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, CIBERSAM, the Madrid Regional Government (S2010/BMD-2422 AGES), and the European Union Structural Funds and European Union Seventh Framework Program under grant agreements FP7-
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HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7-HEALTH-2009-2.2.1-3-242114 (Project OPTiMISE), FP7-HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN), and FP7-HEALTH-2013-2.2.12-602478 (Project METSY). The study was also supported by Fundación Alicia Koplowitz and
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Fundación Mutua Madrileña.
M.M., A.R.S., and M.M. designed the present study. A.C., M.M., and C.M. undertook the statistical
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analysis. A.C. wrote the first draft of the manuscript, which was subsequently edited by all authors, who contributed to the interpretation of the findings and approved the final version. The authors thank all those who participated in this study, namely, the adolescents, their families, and the team members of the PIENSA program. Disclosure: Dr. Calvo has received a predoctoral fellowship award from Gobierno de La Rioja, an IiSGM Fellowship Award for Short-term Placements from the Health Research Institute of Hospital Gregorio Marañón (IiSGM) (Madrid, Spain), and a 2015 Alicia Koplowitz Grant for Short-Term Placements from the Alicia Koplowitz Foundation. Dr. M. Moreno has received grant or research support from Fundación Alicia Koplowitz, Instituto de Salud Carlos III, the Spanish Ministry of Economy and Competitiveness,
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ACCEPTED MANUSCRIPT and Janssen-Cilag, and has served as a consultant for Fundación Alicia Koplowitz and the Spanish Ministry of Economy and Competitiveness. Dr. Rapado-Castro has received a Health Research Sara Borrell Fellowship from the Spanish Ministry of Economy and Competitiveness (SCO/523/2008), an Alicia Koplowitz Grant for Short-Term Placements from the Alicia Koplowitz Foundation, and a 2014 IiSGM Fellowship Award for Short-term Placements from the Health Research Institute of Hospital
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Gregorio Marañón (IiSGM) (Madrid, Spain). She has also received grant support from Fundación Alicia Koplowitz. Dr. C. Moreno has received grant or research support from European Union Funds, Fundación Alicia Koplowitz, Instituto de Salud Carlos III, and Spanish Ministry of Economy and Competitiveness,
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and has served as a consultant for Fundación Alicia Koplowitz, Instituto de Salud Carlos III, the Spanish Ministry of Economy and Competitiveness, and Janssen-Cilag. Dr. Arango has served as a consultant to or has received honoraria or grants from Abbot, AMGEN, AstraZeneca, Bristol-Myers Squibb, Caja
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Navarra, CIBERSAM, Fundación Alicia Koplowitz, Instituto de Salud Carlos III, Janssen Cilag, Lundbeck, Merck, Ministerio de Ciencia e Innovación, Ministerio de Sanidad, Ministerio de Economía y Competitividad, Mutua Madrileña, Otsuka, Pfizer, Roche, Servier, Shire, Schering Plough, and Takeda. Dr. Mayoral has received grant or research support from Comunidad de Madrid (predoctoral fellowship award), Instituto de Salud Carlos III, and the Spanish Ministry of Economy and Competitiveness. Drs.
interest.
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Ruiz-Sancho and Sánchez-Gutiérrez report no biomedical financial interests or potential conflicts of
Correspondence to Ana Calvo, PhD, Child and Adolescent Psychiatry Department, Instituto de
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Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón,
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CIBERSAM, C/ Ibiza 43, 28009 Madrid, Spain; email: [email protected].
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ACCEPTED MANUSCRIPT ABSTRACT Objective: To investigate whether the beneficial effects of a structured psychoeducational parallel group program for adolescents with early-onset psychosis and their families observed immediately after the intervention were maintained two years later. Method: The present study examines the longitudinal efficacy of a randomized controlled trial based on a
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psychoeducational, problem-solving, structured group intervention for adolescents with early-onset psychosis and their families (PE) and compares it with that of a non-structured group intervention (NS) after a two-year follow-up. We analyzed whether the differences between PE and NS found after the intervention persisted two
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years later. Inter-group differences in number and duration of hospitalizations, symptoms, and functioning were also assessed.
Results: After two years of follow-up, we were able to reassess 89% of patients. In the PE group, 13% of
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patients had visited the emergency department, compared with 50% in the NS group (p=.019). However, no statistically significant differences were found between the groups for negative symptoms or number and duration of hospitalizations. A significant improvement in Positive and Negative Syndrome Scale (PANSS) general symptoms was observed in the PE group.
Conclusion: Our psychoeducational group intervention showed sustained effects by diminishing the number of
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visits to emergency department two years after the intervention. Our findings indicate that this psychoeducational intervention could provide patients with long-lasting resources to manage crises more effectively.
NCT02101372.
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Clinical trial registration information: Intervention Module AGES (AGES-CM); http://clinicaltrials.gov/;
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Key Words: Psychosis, Adolescents, Families, Group Therapy, Psychoeducation
INTRODUCTION
Psychotic disorders typically emerge in adolescence and young adulthood. While some patients recover
fully, many experience persistent difficulties or remain vulnerable to future episodes. The prognosis for children and adolescents is usually worse than for adults, although it could be improved by early intervention.1 The duration of early interventions necessary to prevent relapse is unknown. Several studies show that the benefits of interventions are not maintained in the long term2-4. Available approaches usually take the form of assertive outreach programs (e.g., cognitive-behavioral therapy [CBT], medication, family support), which include a
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ACCEPTED MANUSCRIPT combination of psychoeducational interventions aimed at family groups. Studies in adults with bipolar disorder have shown that group psychoeducational intervention combined with drug therapy is the approach of choice and that it maintains its efficacy over time.5, 6 The PIENSA intervention program for adolescents with psychosis (Programa de Intervención en Psicosis Adolescente [PIENSA, which in Spanish means “think”]), developed at the Child and Adolescent
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Psychiatry Department, Hospital General Universitario Gregorio Marañón, Madrid, provides appropriate treatment and monitoring for adolescents with psychosis (http://www.ua.hggm.es). The PIENSA trial is the first randomized clinical trial to longitudinally assess the effectiveness of a parallel, structured, and specific
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psychoeducational group intervention (PE) for adolescent patients and their families and to compare the intervention with a non-structured group intervention (NS). Significant positive effects on clinical outcomes were observed in the PE group at the end of the group intervention. In particular, the number of visits to the
compared with patients from the NS group7.
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emergency department had decreased and negative symptoms in adolescents with psychosis had improved
The aim of the present study was to investigate whether our early intervention (PE) sustained its positive effects 2 years after the intensive group phase.
Based on our previous results7, we tested two hypotheses. Hypothesis 1 was that patients in the PE
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group would have made fewer visits to the emergency department than those in the NS group after two years of follow-up. Hypothesis 2 was that patients in the PE group would have fewer negative symptoms after two years
functioning. METHOD
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of follow-up. We also investigated variables such as number and duration of hospitalizations, symptoms, and
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The present study examines the two-year longitudinal efficacy of a randomized controlled trial based on a structured psychoeducational parallel group intervention for adolescents with early-onset psychosis and their families. The study methodology has been described in detail elsewhere7. Participants
Participation was offered to 90 adolescent outpatients diagnosed with early-onset psychosis and accompanied by one or both parents (Figure 1). The inclusion criteria were as follows: 1) one or more positive psychotic symptoms (delusions or hallucinations) before age 18; 2) diagnosis of a psychotic disorder according to DSM-IV-TR; 3) age between 14 and 18 years; and 4) cohabitation with one or both parents, caregivers, or legal guardians.
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ACCEPTED MANUSCRIPT The exclusion criteria were as follows: 1) drug abuse or dependence at the time of the intervention (drug use was not an exclusion criterion); 2) any neurological developmental disorder; and 3) inability to engage in conversation or read in Spanish that could have interfered with the progress of group treatment. Of the 55 patients finally enrolled in the trial, 48 had a first episode of psychosis (6 had never been
hospitalizations [n = 3]). INSERT Figure 1 HERE. Assessment and Measuring Instruments
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admitted to hospital) and 7 had had previous episodes (1 hospitalization [n = 1], 2 hospitalizations [n = 3], and 3
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The raters were all psychiatrists with clinical and research experience in child and adolescent psychiatry and carried out the assessments blind. Participants and their families were assessed before treatment, after treatment (the intervention lasted 9 months), and 2 years after treatment finished (2-year follow-up
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posttreatment).
Diagnoses were made at baseline and confirmed after a 2-year follow-up according to DSM-IV-TR criteria using the Spanish version of a semi-structured interview for children and parents, namely, the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime version (K-SADSPL)8, 9. Symptoms of psychosis were assessed using the Spanish version of the Positive and Negative Syndrome
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Scale (PANSS)10, 11. We used the positive, negative, and general subscales and total PANSS scores. The level of functioning was measured using the Children’s Global Assessment Scale (C-GAS)12, 13. Interrater reliability for the PANSS was determined using the intraclass correlation coefficient, which was superior to 0.80. Finally, the
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number of hospital admissions, the total number of days of psychiatric hospitalization, and the number of visits to the emergency department were obtained using a custom-designed questionnaire that was administered to
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both parents and adolescents. Psychiatric hospitalizations and emergency room visits for psychiatric reasons were recorded, but we did not include other medical emergency visits or medical hospitalizations. In order to verify our findings, data were independently corroborated by a blinded rater using medical records. Interventions
The same therapists delivered both group interventions depending on whether the groups were comprised of patients or parents/family members. Therefore, there were two therapists for both patient groups (intervention and control) and two different therapists for both parent groups. Given the age of the participants and the fact that one of the developmental challenges that adolescents have to face as they mature is differentiation from their parents, we decided to run two simultaneous and parallel groups: one group for parents, and the other for
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ACCEPTED MANUSCRIPT adolescents in each of our two proposed clinical interventions. (For a detailed description of the program, please see Ruiz-Sancho, Calvo et al 2012.14) The characteristics of the PIENSA trial have been comprehensively described elsewhere. 7 -
Psychoeducational group intervention
The PE consisted of two consecutive treatment phases adapted from W. McFarlane15: the initiation/alliance
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phase and the group phase (following the Multifamily Therapy [MFT] format). The initiation phase consisted of three individual sessions of 50 minutes each conducted for families and adolescents separately. The group phase consisted of two separate group interventions of twelve biweekly, 90-minute structured sessions, one for
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patients and the other for parents. Groups focused specifically on problem-solving strategies to manage difficulties with daily living associated with the disease to mitigate crises and to prevent relapses. Patients and
-
Non-structured group intervention
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their families received written PE material within this treatment modality 7, 14.
The NS also has an initiation phase (three individual sessions for parents and adolescents) and twelve biweekly support group sessions. No written material was provided in this modality.
Both the PE and NS group interventions were complementary to current individual psychiatric
Data Analysis
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management and psychopharmacological treatment.
Data were analyzed on an intention-to-treat basis. The baseline characteristics of the sample were
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compared using the Pearson χ2 test for categorical variables such as gender, race, and diagnosis. Quantitative variables were analyzed using parametric tests (2-sample t tests).
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We followed a likelihood-based mixed-effects model repeated measures (MMRM) approach to study the group x time interaction between treatment groups for symptoms and function during the two-year followup.
We compared visits to the emergency department (number of hospitalizations and days of
hospitalization) between PE and NS two years after treatment using the Pearson χ2 test for categorical variables and the two-sample t test for quantitative variables. The time to hospitalization after treatment curve was plotted using the Kaplan-Meier method. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp, Armonk, New York, USA).
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ACCEPTED MANUSCRIPT RESULTS Sociodemographic and Clinical Variables We found no statistically significant differences between the PE and NS groups for sociodemographic, diagnostic, or clinical variables at baseline (Table 1). After two years of follow-up, there were no statistically significant differences between the PE and NS
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groups for diagnostic types of psychoses: PE=11 (40%) vs NS=16 (54.2%) for schizophrenia spectrum psychosis, PE=8 (32%) vs NS=6 (20.8%) for affective psychosis, and PE=8 (28%) vs NS=6 (25%) for other types of psychosis.
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INSERT TABLE 1. HERE Symptoms and Functional Outcomes
PANSS total scores improved significantly in the PE and NS groups during the two years of follow-up after
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treatment. However, the PANSS general symptom scores only improved significantly in the PE group (Table 2). No statistically significant differences were found between the two groups when we analyzed time x group interactions (MMRM approach) for symptoms in the different PANSS scores evaluated or for functional outcome from the end of the intervention to two years after the group treatment (Table 2). Effects on Relapse
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Patients in the PE group had made fewer visits to the emergency department at the end of follow-up. Figure 3 shows that 14.8% of patients in the PE group and 39.3% of patients in the NS group had visited the emergency department immediately after the end of the intervention (p=.039). At the end of follow-up, 13% of
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patients from the PE group and 50% from the NS group had visited the emergency department (p=.019; Table 3). No differences were observed in the number of hospitalizations or in the number of days of hospitalization
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between the two groups at the end of follow-up (Table 3). After treatment, 11.1% of patients in the PE group and 32.1% in the NS group had been hospitalized. At the end of follow-up, 30.4% of patients in the PE group and 40% in the NS group were hospitalized (Figure 2). Survival analysis showed that there were no differences in time to hospitalization between the PE and
NS groups (Mantel-Cox = 0.334, p=.563). DISCUSSION The results presented here support one of our hypotheses, namely, that patients in the PE group would have fewer visits to the emergency department than those in the NS group after two years of follow-up. However, we
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ACCEPTED MANUSCRIPT were not able to find a maintained beneficial effect on negative symptoms, although we did detect an improvement in the PANSS general symptoms in the PE group. The fact that the reduction in the visits to the emergency department persisted over time in the PE group compared with the NS group could be relevant for prevention of relapse. The PE might reduce the number of contacts with the emergency services as a result of the implementation of improved problem-solving
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strategies within the family, as this kind of PE intervention was specifically designed to empower families in conflict resolution in order to manage crises more efficiently. The reduction could be associated with the problem solving–based methodology, which aims to improve the ability to balance the needs of the individual to
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adapt to a given situation, while emphasizing that all solutions have both positive and negative implications and empowering adolescents through the idea that they can manage problems using their own resources and with the help of their family and friends.
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We did not find statistically significant differences between the PE and NS groups for hospitalizations. Less than 50% of the patients who received treatment within the two modalities were hospitalized during follow-up. Although a trend toward significance was observed regarding differences between the groups for the number of posttreatment hospital admissions, it is important to highlight that the number of patients hospitalized was a little over a third of that of the NS group (11.1% vs 32.1%). We observed that this trend of significance
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was not maintained during follow-up. The absence of statistically significant differences between the PE and NS groups during follow-up could be due to the small sample size and the fact that the NS group also received a psychological intervention. It is also possible that the number of hospitalizations was not necessarily associated
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with differences between the groups. Furthermore, the outcome of hospitalization was very variable and depended on external factors not associated with the disorder, as was the case in the RAISE study, where
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patients in the intervention arm functioned better than, but did not differ in number of hospitalizations from, the treatment-as-usual (TAU) group 16, 17 Another possible explanation is that our intervention was not long enough. Thus, it would be interesting to increase the duration of the intervention to cover the critical period of the illness, as in other intervention programs, by expanding the group treatment to two years and including booster sessions or extending the duration of the current intervention18-20. It would also be interesting to assess whether this period translates into significant differences between groups. We previously showed that negative symptoms improved in adolescents in the PE group at the end of treatment7. After the two-year follow-up, no statistically significant differences were observed between groups in terms of negative symptoms. We observed that negative symptoms had also improved in the NS group. This
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ACCEPTED MANUSCRIPT could account for the absence of statistically significant differences. Consequently, the PE modality could be more effective in the short term, whereas the NS seems to be effective in the long term. In any case, effectiveness did not worsen in either group in the long term. As negative symptoms are the best predictors of functioning in individuals with early psychosis
21,1, 22
, faster improvement might increase the possibility of
recovery in the PE group. Negative symptoms are the target of most of the therapies used in psychosis owing to
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the suffering they cause patients and the low efficacy of available treatment modalities, whether pharmacotherapy or psychotherapy. Therefore, we think it is important to maintain intensive treatment during the early stages of the disease in order to obtain a global improvement that can be maintained over time,
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possibly with booster sessions, a longer group phase, or an adjustment of the contents so that patients can focus on those aspects of therapy that have a greater effect on negative symptoms (e.g., group attendance, promotion
activities within the therapy setting).23
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of leisure activities with people outside the therapeutic context, and inclusion of organized physical group
Our pilot study is subject to a series of limitations. The sample size may have been insufficient to obtain significant results, and the indicators used to assess prevention of relapse (e.g., number of admissions or quantitative symptom scales) might not be as comprehensive as the global impact on psychosocial functioning that a group intervention can produce.
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We performed a randomized controlled trial to test a structured psychoeducational group intervention for adolescents with early-onset psychosis and their families. The intervention was implemented early to improve the course of the disease. Effectiveness was evaluated at two years of follow-up, when we were able to
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reassess 89% of patients. The fact that the study assessments were made at the site where patients receive treatment could be important in that it improves recruitment, subsequent engagement, and global adherence to
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treatment.
Psychosocial interventions in individuals with first-episode psychosis (FEP) aim to reduce relapse
rates24. Naturalistic long-term follow-up studies have shown that the early course of psychosis is characterized by relapses. Up to 80% of patients with FEP experience a relapse within the five years of remission following the initial episode25, 26. Therefore, psychotherapy is especially important for FEP patients within specialized early intervention services (including assertiveness community treatment and antipsychotic medication), and family intervention in particular is very effective for the prevention of relapses 24. However, the intensive early-intervention program has been shown to improve clinical outcome after treatment,19 although the effects were not maintained.2-4 We were unable to replicate some of our findings after
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ACCEPTED MANUSCRIPT two years of follow-up, very likely because of the duration of our group intervention. In other words, the results obtained with our adaptation of McFarlane’s MFT approach may not be sufficient in the long term, thus suggesting that intensification of the intervention might make it possible to test whether symptoms and functioning could also be improved, as we have previously shown 7. The PIENSA PE group intervention seemed to be effective after treatment with respect to negative
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symptoms and visits to the emergency department; however, after two years of follow-up, it was only effective at reducing visits to the emergency department. Although its effectiveness in improving other variables (e.g., symptoms) was not as expected, it is important to note that unlike other comprehensive programs consisting of
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several integrated psychotherapeutic interventions (e.g., cognitive social skills, vocational counselling, and CBT), our study is based on a single psychoeducational intervention over a very short period (9 months). We now propose to test the effectiveness of a new approach in the PIENSA program. Our intention is
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that this approach will consist of an extended and more intensive intervention (weekly groups for 18 months, similar to the MFT approach) and include new therapeutic components. Monthly booster sessions would be implemented during the year following the group intervention phase to maintain generalization of the positive outcomes. Developing and implementing an online intervention with that purpose has also been considered. Such an approach might provide easy, timely, and cost-effective access to treatment and serve as a tool for the
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implementation of complementary psychotherapeutic approaches (i.e. CBT) that may enhance the generalization and extension of the clinical gains observed. Figures
intervention.
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Figure 1. Progress of patients during the trial. Note: NS = non-structured intervention; PE = psychoeducational
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Figure 2. Group differences in percentage of hospitalizations over time. NS = non-structured intervention; PE = psychoeducational intervention.
Figure 3. Group differences over time (visits to emergency department). Note: NS = non-structured intervention; PE = psychoeducational intervention. *p ≤ .05.
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episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. Mar 1999;56(3):241-247.
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26.
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ACCEPTED MANUSCRIPT Table 1. Sociodemographic, Diagnostic, and Clinical Variables at Baseline
NS
16.4 (1.34)
16.5 (1.45)
.88
Male gender
16 (59.3)
18 (64.3)
.70
White race
25 (92.6)
24 (85.7)
.14
Schizophrenia spectrum psychosis
9. (33.3)
12. (42.9)
.46
Affective psychosis
7. (25.9)
9. (32.1)
Other psychosis
11. (40.7)
7. (25.0)
Age, mean (SD)
p Value
SC
Diagnosis
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PE
.52
M AN U
.21
14.77 (8.22)
16.92 (9.10)
.35
PANSS Negative, mean (SD)
16.55 (7.27)
17.03 (7.42)
.87
PANSS General, mean (SD)
30.51 (11.16)
34.55 (14.67) .40
PANSS Total, mean (SD)
61.85 (23.37)
69.00 (27.71) .50
C-GAS, mean (SD)
64.37 (18.79)
58.46 (19.02) .35
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PANSS Positive, mean (SD)
Note: Values are expressed as n (%) unless otherwise indicated. None of the p values were statistically significant. C-GAS = Children’s Global Assessment Scale; NS = non-structured intervention; PANSS = Positive
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and Negative Syndrome Scale; PE = psychoeducational intervention.
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ACCEPTED MANUSCRIPT Table 2. Differences Between the Groups: End of Treatment and After 2 Years of Follow-Up Posttreatment
2 Years Follow-
Intra group (p)
Time x Group interaction (p)a
Up PANSS Positive, mean (SD) 10.72 (14.33)
9.78 (14.33)
p=0.288
NS
11.77 (3.93)
10.63 (3.56)
p=0.293
PANSS Negative, mean (SD) 12.84 (7.87)
12.39 (5.66)
p=0.837
NS
15.81 (6.37)
14.47 (5.87)
p=0.690
p=0.037
PANSS General, mean (SD) 26.20 (8.42)
23.17 (6.96)
NS
27.69 (8.66)
27.95 (9.42)
p=0.421
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PE
PANSS Total, mean (SD) PE
50.29 (19.28)
45.35 (14.65)
p=0.008
NS
55.35 (17.39)
53.58 (18.23)
p=0.015
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C-GAS, mean (SD)
p=0.258
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PE
p=0.859
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PE
PE
73.92 (14.33)
74.05 (16.28)
p=0.891
NS
66.31 (15.23)
70.67 (13.06)
p=0.991
p=0.709
p=0.981
p=0.905
Note: Boldface text represents p values statistically significant at p ≤ .05. C-GAS = Children’s Global
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Assessment Scale; PANSS = Positive and Negative Syndrome Scale; PE = psychoeducational intervention; NS = non-structured intervention
Likelihood-based mixed-effects model, repeated measures approach (MMRM).
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a
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Table 3. Outcome of Relapse Posttreatment and at 2 Year Follow-Up Posttreatment
2 Year Follow-Up
PE (n = 25)
NS (n = 26)
p Value
PE (n = 25)
NS (n=24)
p Value
Patients hospitalized, n (%)
3 (11.1)
9 (32.1)
.057a
7 (30.4)
8 (40)
.686a
No. of days hospitalized,
4.08 (13.03)
7.42 (13.64)
.142b
6.09 (12.84)
7.9 (16.56)
.661b
4 (14.8)
11 (39.3)
.039a
3 (13)
10 (50)
.019a
mean (SD)
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Patients who visited the ED,
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Relapse
No. (%)
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Note: Boldface text represents p values statistically significant at p ≤ .05. ED = emergency department; NS = non-structured intervention; PE = psychoeducational intervention. χ test.
a 2
b
t-test.
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*p≤.05
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Assessed for eligibility (n = 90)
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Excluded (n = 35) -Did not meet inclusion criteria (n = 3)
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-Declined to participate (n = 32)
Randomized (N = 55)
Allocated to PE intervention (n = 27)
Allocated to NS intervention (n = 28)
Discontinued intervention but attended assessments (n = 10)
Discontinued intervention but attended assessments (n = 17)
Analysis
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Received allocated intervention (n = 28)
Analyzed at baseline (n = 27)
Analyzed at baseline (n = 28)
Analyzed at end of treatment (n = 25)
Analyzed at end of treatment (n = 26)
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Allocation
Received allocated intervention (n = 27)
Analyzed at 2-year follow-up (n = 25)
Analyzed at 2-year follow-up (n = 24)
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M AN U
% of Hospitalizations
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Pretreatment
Posttreatment
2-Year Follow-Up
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% Visits to Emergency Department
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Pretreatment
Posttreatment 2-Year Follow-Up*