Functional recovery in patients with schizophrenia: recommendations from a panel of experts

Functional recovery in patients with schizophrenia: recommendations from a panel of experts Background: The management of schizophrenia is evolving towards a more comprehensive model based on functional recovery. The concept of functional recovery goes beyond clinical remission and encompasses multiple aspects of the patient’s life, making it difficult to settle on a definition and to develop reliable assessment criteria. In this consensus process based on a panel of experts in schizophrenia, we aimed to provide useful insights on functional recovery and its involvement in clinical practice and clinical research. Methods: After a literature review of functional recovery in schizophrenia, a scientific committee of 8 members prepared a 75-item questionnaire, including 6 sections: (I) the concept of functional recovery (9 items), (II) assessment of functional recovery (23 items), (III) factors influencing functional recovery (16 items), (IV) psychosocial interventions and functional recovery (8 items), (V) pharmacological treatment and functional recovery (14 items), and (VI) the perspective of patients and their relatives on functional recovery (5 items). The questionnaire was sent to a panel of 53 experts, who rated each item on a 9-point Likert scale. Consensus was achieved in a 2-round Delphi dynamics, using the median (interquartile range) scores to consider consensus in either agreement (scores 7–9) or disagreement (scores 1–3). Items not achieving consensus in the first round were sent back to the experts for a second consideration. Results: After the two recursive rounds, consensus was achieved in 64 items (85.3%): 61 items (81.3%) in agreement and 3 (4.0%) in disagreement, all of them from section II (assessment of functional recovery). Items not reaching consensus were related to the concepts of functional recovery (1 item, 1.3%), functional assessment (5 items, 6.7%), factors influencing functional recovery (3 items, 4.0%), and psychosocial interventions (2 items, 5.6%). Conclusions: Despite the lack of a well-defined concept of functional recovery, we identified a trend towards a common archetype of the definition and factors associated with functional recovery, as well as its applicability in clinical practice and clinical research. Keywords: Schizophrenia, Functional recovery, Psychosocial therapy, Antipsychotic agents * Correspondence: mroca@uib.es Institut Universitari d’Investigació en Ciencies de la Salut (IUNIS), RedIAPP, Hospital Juan March, Universidad de las Islas Baleares, Cra. de Valldemossa, km 7.5., Palma de Mallorca, (Illes Balears), Spain Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lahera et al. BMC Psychiatry (2018) 18:176 Page 2 of 10 Background construct of functional recovery and to what extent The management of schizophrenia has traditionally these ideas meet the empirical evidence published in focused on the assessment of symptomatology and the literature. We present herein the results of a Del- neurocognitive functioning [1]. However, there is in- phi consensus process aimed to identify commonly creasing interest in developing more comprehensive accepted concepts regarding the definition and assess- models focusing on functional recovery [2–9]. Unlike ment of functional recovery, as well as the perceived clinical remission, which is well defined and can be impact of psychosocial and pharmacological interven- measured, the concept of recovery encompasses mul- tions on its attainment. tiple aspects of the patient’s life, making it difficult to settle on a definition and to develop reliable assess- Methods ment criteria. Liberman and colleagues [10]proposed Design of the consensus dynamics operational criteria for recovery from schizophrenia The aim of this consensus was to apprise various aspects that included symptom remission, improved voca- related to the assessment and functional intervention of tional functioning, independent living, and improved patients with schizophrenia and provide clinicians and peer relationships. In contrast, Anthony [11] investigators with insights into functional recovery in described functional recovery as a deeply personal, patients with schizophrenia. The consensus process was unique process of changing one’s attitudes, values, approached through two recursive rounds of Delphi feelings, goals, skills, and/or roles, even with limita- dynamics. The Delphi methodology is a structured, sys- tions caused by illness. On the other hand, some cli- tematic, and interactive forecasting method based on the nicians have warned that functional recovery can only individual judgments of a panel of experts [23, 24]. The be accepted when symptoms are mild and stable two Delphi rounds were held between May 5th 2016 and enough to not interfere with normal functioning in July 1st 2016. In each round, experts anonymously social activities and relationships [6, 12]. Regardless of acceded to an online questionnaire and rated each item the perspective of the various stakeholders, it is in the questionnaire on a 9-point Likert scale, where widely accepted that functional recovery is influenced lower scores meant disagreement and higher scores by theseverityofsymptomsaswellasby meant agreement. For each item, consensus was consid- disease-related aspects such as neurocognitive per- ered when at least two-thirds of the experts scored formance [7, 13–15]. Additionally, social and family either 1-to-3 (disagree) or 7-to-9 (agree) (Additional file 1: circumstances, opportunities, and lifetime events con- Table S1). Conversely, non-consensus was considered tribute to extending the list of environmental factors when the interquartile range (i.e. percentiles 25–75) was that may influence functional recovery beyond clinical greater than 4 or when one-third of the experts or more manifestations of schizophrenia [7, 15, 16]. scored either 1-to-3 or 7-to-9. In that case an indeter- Patients with schizophrenia now have access to a wide minate level was assigned to items not meeting the variety of pharmacological agents and psychosocial ther- criteria for either consensus or non-consensus. Items apies which may eventually meet the particular needs of not achieving consensus in the first round were sent each patient profile and, therefore, increase the chances back to the experts for a second assessment round. of positive therapeutic outcomes [17]. The lack of stan- Using bar graphs, a research assistance team, which dardized tools for the assessment of functional recovery did not interfere in the responses, assessed and pre- prevents from drawing strong conclusions regarding the sented the results from the first round to facilitate com- contribution of these interventions to functional recov- ments and clarifications from each participant. In the ery in patients with schizophrenia. Nevertheless, results second round, the expert panelists contrasted their per- of clinical studies – including randomized controlled tri- sonal opinion with the result of the first round and, if als – on various interventions for schizophrenia suggest necessary, reconsidered their initial opinion on those that the achievement of functional recovery is possible items in which consensus was not reached. The results in many cases [18–21]. of this second round were tabulated and presented de- Due to the heterogeneity of published information scriptively using the median and interquartile range and and the limited empirical evidence on functional re- the percentage of experts agreeing/disagreeing a particu- covery, this concept is not commonly considered an lar statement. assessment criterion and/or a therapeutic goal in At the end of the Delphi process, the scientific commit- most clinical practice guidelines [1]. In a tee discussed the final results during a group session, held non-standardized way, most clinicians are familiar on October 15th, 2016. A manuscript was drafted with with the concept of functional recovery and consider the conclusions drawn from the responses of the panel of it useful in their day-to-day practice [22]. Neverthe- experts and the literature review, which was revised and less, it is not clear whether clinicians have a common approved by all members of the scientific committee. Lahera et al. BMC Psychiatry (2018) 18:176 Page 3 of 10 Participants Table 1 Consensus rate in each section of the questionnaire The scientific committee consisted of eight psychiatrists No. % from Spanish hospitals. Each member of the scientific I. The concept of functional recovery (n =9) committee proposed and recruited psychiatrists from Agreement 8 88.9% Spanish hospitals, outpatient units, and academic set- Disagreement 0 – tings to participate in the panel of experts. To be No consensus 1 11.1% included in the panel, the expert must have at least II. Functional assessment (n = 22) 10 years of experience in a hospital setting. To prevent attrition bias between the two rounds, only experts who Agreement 15 68.2% completed the entire Delphi process were to be listed in Disagreement 3 13.6% the acknowledgement section of the publication [25]. No consensus 5 22.7% The research assistance team, led by BH, directed and III. Factors influencing functional recovery (n = 16) oversaw the entire process and was responsible for the Agreement 13 81.3% distribution and analysis of the questionnaires. Disagreement 0 – The questionnaire No consensus 3 18.8% After a literature review of the empirical evidence and ex- IV. Psychosocial interventions and functional recovery (n =8) pert opinions on functional recovery in patients with Agreement 6 75.0% schizophrenia, the members of the scientific committee Disagreement 0 – discussed the unmet needs regarding the definition of No consensus 2 25.0% functional recovery and its assessment, as well as the pos- V. Functioning and pharmacological treatment (n = 14) sible interventions to accomplish it. The items of interest were summarized in a questionnaire of 75 items, which Agreement 14 100% were grouped into six sections: (I) the concept of func- Disagreement 0 – tional recovery (9 items), (II) assessment of functional No consensus 0 – recovery (23 items), (III) factors influencing functional re- VI. the perspective of patients and their relatives on functional recovery covery (16 items), (IV) psychosocial interventions and (n =5) functional recovery (8 items), (V) pharmacological treat- Agreement 5 100% ment and functional recovery (14 items), and (VI) the per- Disagreement 0 – spective of patients and their relatives on functional No consensus 0 – recovery (5 items). The questionnaire was sent to the experts in the panel for their consideration. (i.e. not meeting criteria for either consensus or Results non-consensus) (Fig. 1). Most items not reaching con- Consensus overview sensus belonged to the functional assessment section Based on the criteria of the members of the scientific (5 items, 6.7%), followed by factors influencing func- committee, 80 experts were invited to participate in the tional recovery (3 items, 4.0%), psychosocial interven- Delphi process. Of them, 53 responded the first round tions and functional recovery (2 items, 5.6%), and the and 53 in the second one, indicating no drop out be- concept of functional recovery (1 item, 1.3%). tween the two recursive rounds of the Delphi process. In Additional file 1: Tables S2-S7 provide details on the the first round, consensus was achieved in 41 items median and interquartile range obtained on each (54.7%), all of them in agreement. Of the 34 items item. The median score in items meeting the consen- addressed in the second round, 23 met the consensus sus criteria ranged from 6.06 to 8.31. criteria (20 items in agreement and 3 in disagreement), yielding a final consensus list of64 items (85.3%): 61 The concept of functional recovery (81.3%) in agreement and 3 (4.0%) in disagreement. Additional file 1: Table S2 summarizes the median Table 1 shows the number and percentages of items in scores of the 9 items regarding the concept of functional each section on which the experts reached agreement recovery. The experts did not reach a consensus regard- (i.e. consensus on the score range 7-to-9), disagreement ing the existence of a standardized concept of functional (i.e. consensus on the score range 1-to-3), and lack of recovery in patients with schizophrenia (57.7% of agree- consensus. Of eleven items not meeting the consensus ment; median score 7.06; 95%CI 6.50–7.50). Neverthe- criteria, one resulted in non-consensus (i.e. more than less, the experts in the panel overall agreed on each one one-third of experts scoring 1-to-3 and more than of the multiple characteristics frequently included in the one-third scoring 7-to-9) and ten were indeterminate definition of functional recovery. For instance, most Lahera et al. BMC Psychiatry (2018) 18:176 Page 4 of 10 Fig. 1 Results of the items not meeting the consensus criteria. a functional recovery is a well-established concept. b The functional assessment is commonly included among the objectives of clinical trials on schizophrenia. c thepatient is themost reliablesourceof information for functional assessment. d: a proper functional assessment is not affordable in institutionalized patients. e I am familiar with the use of the Social and Occupational Functioning Assessment Scale (SOFAS) regarding the functional assessment of schizophrenic patients. f I am familiar with the use of the Health of the Nation Outcome Scales (HoNOS) regarding the functional assessment of schizophrenic patients. g living in an urban area is the environmental factor that has the greatest impact on functioning in patients with schizophrenia. h being an immigrant is the environmental factor that has the greatest impact on functioning in patients with schizophrenia. i: Public campaigns aimed at reducing stigma in patients with schizophrenia are effective. j cognitive-behavioral therapy is the most effective psychosocial intervention for functional recovery. k cognitive disorders should be the primary target of psychosocial interventions experts agreed that functional recovery overlaps with other Assessment of functional recovery concepts such as quality of life, cognition, and clinical remis- According to the experts, the assessment of functional re- sion. Furthermore, experts identified the influence of symp- covery is essential in both the clinical research and clinical tomatic remission, personal autonomy, professional activity, practice settings (96.2% of consensus). However, there was social relationships, and environmental factors on functional no consensus on whether the assessment of functional re- recovery. According to 86.5% of the experts, functional re- covery is commonly included among study objectives of covery is an achievable goal in patients with schizophrenia. clinical trials in schizophrenia (Additional file 1:Table S3). Lahera et al. BMC Psychiatry (2018) 18:176 Page 5 of 10 Regarding the source of information for the assessment of criteria determining the choice of pharmacological treat- functional recovery, there was strong agreement (98.1%) on ment (Additional file 1: Table S6). It was also agreed that the suitability of gathering information from three primary the various antipsychotic agents have different impacts sources: patients, their relatives (and/or caregivers), and cli- on functional recovery. Among the potential drawbacks nicians. The experts exhibited heterogeneous knowledge of of pharmacological treatment for achieving functional the functional assessment tools currently available for iden- recovery, cognitive impairment reached the highest tifying areas subject to improvement, and planning the agreement (100%); 94.3% of the experts agreed that management of patients with schizophrenia. Most of them second-generation are more useful than first-generation stated that they were familiar with the GAF scale, the (or atypical) antipsychotics for achieving functional Personal and Social Performance scale (PSP), and the sec- recovery. ond version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0). Conversely, the ma- The perspective of patients and their relatives on jority of experts were not familiar with the Social and functional recovery Occupational Functioning Assessment Scale (SOFAS) or The experts agreed that the perspective of clinicians on the Health of the Nation Outcome Scale (HoNOS). Beyond functional recovery differed significantly from that of the scales used, it was suggested that functional recovery is patients and their relatives (Additional file 1: Table S7). somehow assessed in routine practice, albeit without any According to this observation, psychiatrists are more standardized procedure. concerned with the clinical aspects of the disease, whereas patients and their relatives are more concerned Factors influencing functional recovery with subjective aspects of the lifetime project and factors The experts overall agreed that functional recovery is in- influencing activities of daily living. fluenced by various environmental factors, including stressful life events, substance abuse, socioeconomic Discussion conditions, and family dynamics (Additional file 1: Table Following a two-round Delphi dynamics approach, we S4). However, most of them (90%) acknowledged that found high homogeneity in the opinion of clinicians none of these factors predicts independently the regarding functional recovery in patients with schizo- non-achievement of functional recovery. Other environ- phrenia. Psychiatrists from different areas in Spain mental factors such as the type of origin (i.e. migrant/ achieved consensus in 85% of the concepts addressed local) and residence (i.e. urban/rural) were not consid- regarding various aspects of functional recovery. ered to influence functional recovery significantly. Both Functional recovery is a complex, multidimensional negative and cognitive symptoms were considered to concept to be considered not only by clinicians but also cause significant impact on functional recovery, with no researchers, patients and caregivers, as well mental superiority of either of the two symptom groups. Finally, health policy makers. Although the perspective of the the experts agreed that self-stigma (or internalized various stakeholders involved in the definition of func- stigma) has a greater impact on functional recovery than tional recovery may converge on many aspects, the lack social stigma. The idea that the negative image associ- of a common terminology and the pursuit of different ated with psychiatry compared to other medical special- goals has led to a wide repertoire of definitions, none of ties increases stigma in patients with schizophrenia also which stands out clearly over the rest [2, 6, 7, 16, 26]. reached a consensus in agreement. The result of our consensus regarding the concept of Psychosocial interventions and functional recovery functional recovery mirrored this scenario, resulting in a There was overall agreement that psychosocial interven- lack of consensus regarding a well-established concept tions are necessary to achieve functional recovery (92.3% of functional recovery. Nevertheless, the general agree- of agreement). Among all interventions proposed, family ment on specific factors influencing the concept of func- interventions and those aimed at developing social skills tional recovery suggests that despite the lack of a and improving employability were considered the most standardized definition of recovery, most clinicians share useful for functional recovery (Additional file 1: Table a common archetype of what functional recovery S5). Although the inclusion of cognitive rehabilitation in actually is. psychosocial interventions was considered useful, cogni- The feasibility of achieving functional recovery in tive disorders were not agreed to be the primary target patients with schizophrenia has been under discussion of these interventions. since the emergence of interest in this concept [2, 6, 22, 27]. Most experts in our panel (87%) agreed that Pharmacological treatment and functional recovery functional recovery is a realistic goal in the manage- The majority of experts in the panel (79.0%) considered ment of patients with schizophrenia. This is in line that functional recovery is one of the most important with the results of recent research on schizophrenia, Lahera et al. BMC Psychiatry (2018) 18:176 Page 6 of 10 which showed that psychological well-being and mental The experts exhibited heterogeneous knowledge of the health recovery can improve in individuals with functional assessment tools currently available for identi- first-episode psychosis [28]. The lack of a clear definition fying areas subject to improvement, and planning the and assessment tools prevents from drawing strong con- management of patients with schizophrenia. Beyond the clusions regarding the feasibility of a therapeutic model scales used, it was suggested that functional recovery is based on the concept of recovery. However, empirical evi- somehow assessed in routine practice, albeit without any dence on various therapeutic interventions suggests that standardized procedure. In this regard, treatments based many patients with schizophrenia can achieve goals on a recovery model should be consistent with related to functional recovery such as independent living evidence-based treatments [2]. and competitive employment and education in routine Functional recovery, may be influenced by multiple community settings [18–21, 29]. In line with the common factors. According to the experts, these factors are a perception regarding the definition of functional recovery, combination of environmental factors, stressful life M. Farkas proposed four key values commonly reflected events, substance abuse, socioeconomic conditions, in the recovery literature which should be considered in and family dynamics. Other environmental factors all recovery-oriented services: person orientation, person such as the type of origin (i.e. migrant/local) and resi- involvement, self-determination/choice, and growth dence (i.e. urban/rural) were not considered to influ- potential [30]. ence functional recovery significantly. Some authors The lack of a standardized definition is probably a have observed that patients living in rural areas tend bottleneck for the development of validated tools for the to show better functional outcomes, probably due to assessment of functional recovery. Other difficulties that greater family and social support as well as simpler may compromise an appropriate assessment of functional vocational roles [39]. However, in our consensus, the recovery include the limitations of some informants to experts’ opinion might be strongly influenced by the make accurate judgments [31], the limited capacity of area where they work. Thus, while some centers pro- some patients for self-assessment [32], and the heterogen- vide mental health care to patients from both rural eity in their clinical course, which may lead to inconsisten- and urban areas, most of them serve one or the other cies between the outcome of functioning scales and type, whereby the influence of this factor may be un- milestone achievement in some patients (e.g., in some noticed. Finally, there was 96% agreement that, des- patients, functioning scales may not capture milestone pite the different perspectives of clinicians and achievements in social, vocational, and residential patients (i.e. clinicians tend to focus on the clinical domains of patients with schizophrenia) [33]. Regarding aspects of recovery, whereas patients and their rela- the source of information for the assessment of functional tives attach importance to the activities of daily living recovery, there was strong agreement on the suitability of andlifeproject), theattitudeof the variousstake- gathering information from three primary sources: holders has an influence on functional recovery. patients, their relatives (and/or caregivers), and clinicians. In line with the results of clinical studies, which sug- Indeed, some authors have warned of the risk of bias asso- gest that both negative symptoms and cognitive deficits ciated with motivation-related negative symptoms (e.g. may be primary predictors of impaired social and voca- emotional withdrawal, passive-apathetic social withdrawal) tional performance [34, 40, 41], the experts in the panel [34]. Furthermore, patient-reported assessments of quality agreed that both negative and cognitive symptoms cause of life and everyday abilities have shown poor correlation a significant impact on functional recovery. Also, in with information about lifetime achievements in many agreement with recent recommendations to treat nega- patients with schizophrenia [35]. All these limitations are tive symptoms [42], the experts agreed that functional consistent with the lack of consensus on the concept that recovery should not be addressed only through symp- the patient is the most reliable source of information for toms but also considering the cognitive, emotional, and functional assessment. relationship difficulties. Due to the absence of a single tool for the assessment Stigma is another factor with potential influence on of functional recovery, clinicians and researchers use dif- functional recovery, and it is generally accepted that it ferent strategies to evaluate it. In an attempt to broaden has a major impact on self-esteem and hampers recovery functional assessment towards a comprehensive model in people with mental illnesses [7, 43]. The experts of functional recovery, researchers have combined com- agreed that the negative image associated with psych- monly used scales such as the Global Assessment Func- iatry compared to other medical specialties increases tioning (GAF) scale and Global Assessment Scale (GAS) stigma in patients with schizophrenia and that with the Social Functioning Rating Score – which self-stigma (or internalized stigma) has a greater impact includes both social skills and social roles – and other on functional recovery than social stigma. Although the objective indicators of lifetime achievements [36–38]. mechanisms of stigma are not clear, social (or public) Lahera et al. BMC Psychiatry (2018) 18:176 Page 7 of 10 stigma and self-stigma might work in different ways. In pharmacological treatments – particularly atypical anti- an interview-based study conducted on patients with psychotic agents – cause morphological changes in pa- major depression or schizophrenia, social stigma showed tients’ brains which could be associated with an a trend towards underestimating the importance of in- improvement in neurochemical functioning [55, 56]. formal caregivers (e.g. family and friends). Conversely, Despite the proven usefulness of some antipsychotic self-stigma had a negative impact on the perceived im- agents in achieving functional recovery [57, 58], the portance of seeking help provided by a general practi- experts identified potential drawbacks of pharmaco- tioner or a psychiatrist [44]. logical treatment for achieving functional recovery: The relevance of psychosocial interventions agreed in extrapyramidal symptoms, sedation, the worsening of this consensus are consistent with the positive results negative symptoms, and cognitive impairment. Of note, of these interventions reported in randomized clinical most of the adverse events limiting functional recovery trials conducted according to the gold standards of are more frequently associated with first-generation than clinical design [45–47]. Although the items regarding second-generation antipsychotics [59–61]. Combination the type of therapy with highest effectivity were written antipsychotic therapy was also considered to result in in an exclusive way, the experts achieved consensus in poorer functional recovery than monotherapy. the highest effectivity of social skills training, family therapy, cognitive rehabilitation, social cognitive train- Table 2 List of recommendations when addressing functional ing, and occupational programs. This result indicates recovery of patients with schizophrenia that, irrespective of the median score achieved in each The concept of functional recovery therapy, none of them stood out from the rest. Of note, Despite the lack of a unified definition of functional recovery, it is recovery-based interventions are not widespread in recommended to ponder quality of life, cognition and clinical clinical practice and some authors have stressed the remission when considering functional recovery in research and need to develop more interventions going beyond routine practice. symptom reduction [48]. Although the inclusion of Functional recovery should be considered a goal in the management of patients with schizophrenia. cognitive rehabilitation in psychosocial interventions was considered useful, cognitive disorders were not Functional recovery should be always included among endpoints of clinical trials assessing patients with schizophrenia. agreed to be the primary target of these interventions. The apparent inconsistency regarding the role of cogni- Assessment of functional recovery tive functioning in psychosocial interventions can be Irrespective of the tools used for assessing functional recovery, information for appraising it should be gathered from patients, their explained by the recent evolution of the concept of relatives (and/or caregivers), and the healthcare team. cognition. Thus, while the construct of cognitive im- Irrespective of the tools used for assessing functional recovery, the pairment has been traditionally built solely on basic patient’s socio-cultural background should be considered when neurocognition, it is now accepted that social cognition assessing functional recovery. differs from basic neurocognition and that it could be Factors influencing functional recovery the link between neurocognition and functional recov- When seeking for the achievement of functional recovery, the ery in psychosocial programming [5, 49]. combined influence of stressful life events, substance abuse, The positive impact of long-acting antipsychotics on socioeconomic conditions, and family relationships, should be considered. adherence and the closer relationship between patients and the healthcare team associated with the dosing of Although negative symptoms have a great impact on functioning, clinicians should not focus exclusively on symptom remission when these agents have been considered helpful for achieving considering functional recovery. functional recovery [38]. Some authors have questioned Psychosocial interventions and functional recovery the suitability of maintaining long-lasting treatment with Psychosocial interventions are necessary to achieve functional antipsychotics [50]. However, the impact of long-lasting recovery. A combination of various therapies (including social skills antipsychotic treatments on functional recovery is training, family therapy, cognitive rehabilitation, social cognitive unclear, and other authors have highlighted important training, and occupational programs) is likely to be most useful in achieving functional recovery. limitations of studies investigating early discontinuation of antipsychotic therapy [51]. Pharmacological treatment and functional recovery Although it is not clear whether medication alone can Functional recovery should be considered in decision-making on impact directly on functional performance, there is pharmacological treatments. long-time evidence on the synergistic effect of pharma- The perspective of patients and their relatives on functional recovery cological and psychosocial treatments, particularly The attitudes of all stakeholders (i.e., patients, their relatives, and pharmacological treatments with a significant impact on clinicians) influence functional recovery. Hence, when seeking for achieving functional recovery, all these perspectives should be taken positive symptoms [7, 52–54]. Besides attenuating into account. the symptomatology associated with schizophrenia, Lahera et al. BMC Psychiatry (2018) 18:176 Page 8 of 10 The scope of the results presented herein must be Funding This project was funded by Janssen. The funding body participated in study weighed considering some limitations of our work. First, the design and data interpretation. selection of experts was neither systematic nor randomized. Alternatively, we recruited specialists in the management of Availability of data and materials The datasets used and/or analyzed during the current study are available schizophrenia from various Spanish regions. Thus, although from the corresponding author on reasonable request. all experts must account at least 10 years of clinical practice, a selection bias cannot be ruled out. Second, some items ex- Authors’ contributions pressing mutually incompatible ideas yielded inconsistent GL, JLG, PS, MM, JVP, PG-P, BH, and MR have made substantial contributions to the conception and design of this consensus process, have revised all results. Items affected by this phenomenon were discussed manuscript drafts critically, and have approved the final version of the and eventually not considered for drawing the final conclu- manuscript. All co-authors agree to be accountable for all aspects of the sions. Finally, the resulting recommendations were not work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately addressed and resolved. drawn following a consensus process, but as an interpret- ation of the agreements and disagreements resulting from Ethics approval and consent to participate the Delphi process. Nevertheless, due to the expected Not applicable. heterogeneity on the concept, we deemed it more appropri- Competing interests ate to address the conclusions by weighing the scope of G. Lahera has received research grant support from the Ministry of Health each result carefully and addressing the inconsistencies that (Spain), CIBERSAM, Lilly, and Janssen, and has worked as an advisor board might arise from the responses of the panel of experts. member for Lundbeck, Otsuka, Janssen, and Pfizer. J. L. Gálvez has received grants from Janssen, Lundbeck, Pfizer and Servier. P. Sánchez has received research grant support from the Ministry of Health (Spain), has worked as an Conclusions advisor board member for Janssen and Ferrer, and has worked as a speaker for Janssen. M. Martínez has worked as a speaker and/or advisor and/or Despite the lack of a standardized definition of func- researcher in projects promoted by Esteve, GlaxoSmithKline, Janssen-Cilag, tional recovery in schizophrenia, clinicians are aware of Lilly, Lundbeck, Otsuka, Pfizer, Servier, Roche, and Rovi. J. V. Pérez has this approach, show a trend towards a common con- worked as a speaker for Janssen and Lundbeck. P. García-Portilla has been a consultant to and/or has received honoraria/grants from Alianza Otsuka- struct of this concept, and consider functional recovery Lundbeck, CIBERSAM, European Comission, Instituto de Salud Carlos III, in their day-to-day practice, albeit in a non-formal way. Janssen-Cilag, Lilly, Lundbeck, Otsuka, Pfizer, Servier, Roche, and Rovi. In our experience, 57 Spanish psychiatrists reached a B. Herrera is currently employed by Janssen-Cilag S. A. M. Roca has received research grant support from Health Institute Carlos III, Ministry of Economy consensus on 85% of items addressing various aspects of and Competitiveness, European Union ERDF as worked as a speaker and/or functional recovery in schizophrenia. Based on the advisorin project promoted by Janssen, Lundbeck and Pfizer. results of this consensus and their consistency with the information available in the literature, the experts of this Publisher’sNote panel provide a list of recommendations (Table 2). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Additional file Author details Departamento de Medicina y Especialidades Médicas, Facultad de Medicina, Universidad de Alcalá, Plaza de San Diego, s/n, 28801 Alcalá de Henares, Additional file 1: Results of the Delphi consensus. Score (median and Madrid, Spain. Centro de Investigación Biomédica en Red de Salud Mental interquartile range) of each item of the questionnaire. (PDF 397 kb) (CIBERSAM), Madrid, Spain. Unidad de Salud Mental Comunitaria del Hospital Universitario Virgen del Rocio, Av. Manuel Siurot, S/N, 41013 Sevilla, Abbreviations Spain. Unidad de Psicosis Refractaria, Hospital Psiquiátrico de GAF: Global Assessment Functioning; GAS: Global Assessment Scale; Álava-Osakidetza, C/ Álava, n°45, 01006 Vitoria – Gasteiz, Spain. Facultad de HoNOS: Health of the Nation Outcome Scale; PSP: Personal and Social Medicina, Universidad del País Vasco-Euskal Herriko Unibertsitatea, Leioa, Performance; SOFAS: Social and Occupational Functioning Assessment Scale; Spain. Hospital Royo Villanova, Avda. San Gregorio, s/n, 50015 Zaragoza, WHODAS: World Health Organization Disability Assessment Schedule Spain. Centro de Salud Mental Fuente San Luis, Hospital Universitario Doctor Peset, Av. de Gaspar Aguilar, 90, 46017 València, Spain. Área de Psiquiatría, Facultad de Medicina, Universidad de Oviedo, Av. Julián Clavería, Acknowledgements s/n, 33006 Oviedo, Asturias, Spain. Medical Affairs Department, Medical writing assistance was provided by Dr. Gerard Carot-Sans, PhD, and Janssen-Cilag, Avenida Partenón, 16 1 (Campo de las Naciones), S. A, 28042 Medical Writers 5.0 on behalf of Janssen. The authors gratefully acknowledge Madrid, Spain. Institut Universitari d’Investigació en Ciencies de la Salut the time and effort of the panel members: Adolfo Benito, Ainara Arnaiz, Ana (IUNIS), RedIAPP, Hospital Juan March, Universidad de las Islas Baleares, Cra. Catalán, Ana González-Pinto, Ana Landa, Celso Iglesias, Clemente García-Rizo, de Valldemossa, km 7.5., Palma de Mallorca, (Illes Balears), Spain. Consuelo Llinares, David Fraguas, Demetrio Mármol, Eduard Parellada, Fernando Montiano, Francisco Salido, Ignacio García, Ignacio Zarranz, Jesús Received: 2 October 2017 Accepted: 22 May 2018 Mesones, Jesús Morillas, José A. Alcalá, Jose L. Montero, José M. Montes, José M. Olivares, José R. Gutiérrez, Juan A. Martínez, Juan J. Fernández, Luis Docasar, Luis Gutiérrez, Luis San, M. Ángeles Escudero, Manuel Serrano, M. 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Functional recovery in patients with schizophrenia: recommendations from a panel of experts

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Medicine & Public Health; Psychiatry; Psychotherapy
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Abstract

Background: The management of schizophrenia is evolving towards a more comprehensive model based on functional recovery. The concept of functional recovery goes beyond clinical remission and encompasses multiple aspects of the patient’s life, making it difficult to settle on a definition and to develop reliable assessment criteria. In this consensus process based on a panel of experts in schizophrenia, we aimed to provide useful insights on functional recovery and its involvement in clinical practice and clinical research. Methods: After a literature review of functional recovery in schizophrenia, a scientific committee of 8 members prepared a 75-item questionnaire, including 6 sections: (I) the concept of functional recovery (9 items), (II) assessment of functional recovery (23 items), (III) factors influencing functional recovery (16 items), (IV) psychosocial interventions and functional recovery (8 items), (V) pharmacological treatment and functional recovery (14 items), and (VI) the perspective of patients and their relatives on functional recovery (5 items). The questionnaire was sent to a panel of 53 experts, who rated each item on a 9-point Likert scale. Consensus was achieved in a 2-round Delphi dynamics, using the median (interquartile range) scores to consider consensus in either agreement (scores 7–9) or disagreement (scores 1–3). Items not achieving consensus in the first round were sent back to the experts for a second consideration. Results: After the two recursive rounds, consensus was achieved in 64 items (85.3%): 61 items (81.3%) in agreement and 3 (4.0%) in disagreement, all of them from section II (assessment of functional recovery). Items not reaching consensus were related to the concepts of functional recovery (1 item, 1.3%), functional assessment (5 items, 6.7%), factors influencing functional recovery (3 items, 4.0%), and psychosocial interventions (2 items, 5.6%). Conclusions: Despite the lack of a well-defined concept of functional recovery, we identified a trend towards a common archetype of the definition and factors associated with functional recovery, as well as its applicability in clinical practice and clinical research. Keywords: Schizophrenia, Functional recovery, Psychosocial therapy, Antipsychotic agents * Correspondence: mroca@uib.es Institut Universitari d’Investigació en Ciencies de la Salut (IUNIS), RedIAPP, Hospital Juan March, Universidad de las Islas Baleares, Cra. de Valldemossa, km 7.5., Palma de Mallorca, (Illes Balears), Spain Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lahera et al. BMC Psychiatry (2018) 18:176 Page 2 of 10 Background construct of functional recovery and to what extent The management of schizophrenia has traditionally these ideas meet the empirical evidence published in focused on the assessment of symptomatology and the literature. We present herein the results of a Del- neurocognitive functioning [1]. However, there is in- phi consensus process aimed to identify commonly creasing interest in developing more comprehensive accepted concepts regarding the definition and assess- models focusing on functional recovery [2–9]. Unlike ment of functional recovery, as well as the perceived clinical remission, which is well defined and can be impact of psychosocial and pharmacological interven- measured, the concept of recovery encompasses mul- tions on its attainment. tiple aspects of the patient’s life, making it difficult to settle on a definition and to develop reliable assess- Methods ment criteria. Liberman and colleagues [10]proposed Design of the consensus dynamics operational criteria for recovery from schizophrenia The aim of this consensus was to apprise various aspects that included symptom remission, improved voca- related to the assessment and functional intervention of tional functioning, independent living, and improved patients with schizophrenia and provide clinicians and peer relationships. In contrast, Anthony [11] investigators with insights into functional recovery in described functional recovery as a deeply personal, patients with schizophrenia. The consensus process was unique process of changing one’s attitudes, values, approached through two recursive rounds of Delphi feelings, goals, skills, and/or roles, even with limita- dynamics. The Delphi methodology is a structured, sys- tions caused by illness. On the other hand, some cli- tematic, and interactive forecasting method based on the nicians have warned that functional recovery can only individual judgments of a panel of experts [23, 24]. The be accepted when symptoms are mild and stable two Delphi rounds were held between May 5th 2016 and enough to not interfere with normal functioning in July 1st 2016. In each round, experts anonymously social activities and relationships [6, 12]. Regardless of acceded to an online questionnaire and rated each item the perspective of the various stakeholders, it is in the questionnaire on a 9-point Likert scale, where widely accepted that functional recovery is influenced lower scores meant disagreement and higher scores by theseverityofsymptomsaswellasby meant agreement. For each item, consensus was consid- disease-related aspects such as neurocognitive per- ered when at least two-thirds of the experts scored formance [7, 13–15]. Additionally, social and family either 1-to-3 (disagree) or 7-to-9 (agree) (Additional file 1: circumstances, opportunities, and lifetime events con- Table S1). Conversely, non-consensus was considered tribute to extending the list of environmental factors when the interquartile range (i.e. percentiles 25–75) was that may influence functional recovery beyond clinical greater than 4 or when one-third of the experts or more manifestations of schizophrenia [7, 15, 16]. scored either 1-to-3 or 7-to-9. In that case an indeter- Patients with schizophrenia now have access to a wide minate level was assigned to items not meeting the variety of pharmacological agents and psychosocial ther- criteria for either consensus or non-consensus. Items apies which may eventually meet the particular needs of not achieving consensus in the first round were sent each patient profile and, therefore, increase the chances back to the experts for a second assessment round. of positive therapeutic outcomes [17]. The lack of stan- Using bar graphs, a research assistance team, which dardized tools for the assessment of functional recovery did not interfere in the responses, assessed and pre- prevents from drawing strong conclusions regarding the sented the results from the first round to facilitate com- contribution of these interventions to functional recov- ments and clarifications from each participant. In the ery in patients with schizophrenia. Nevertheless, results second round, the expert panelists contrasted their per- of clinical studies – including randomized controlled tri- sonal opinion with the result of the first round and, if als – on various interventions for schizophrenia suggest necessary, reconsidered their initial opinion on those that the achievement of functional recovery is possible items in which consensus was not reached. The results in many cases [18–21]. of this second round were tabulated and presented de- Due to the heterogeneity of published information scriptively using the median and interquartile range and and the limited empirical evidence on functional re- the percentage of experts agreeing/disagreeing a particu- covery, this concept is not commonly considered an lar statement. assessment criterion and/or a therapeutic goal in At the end of the Delphi process, the scientific commit- most clinical practice guidelines [1]. In a tee discussed the final results during a group session, held non-standardized way, most clinicians are familiar on October 15th, 2016. A manuscript was drafted with with the concept of functional recovery and consider the conclusions drawn from the responses of the panel of it useful in their day-to-day practice [22]. Neverthe- experts and the literature review, which was revised and less, it is not clear whether clinicians have a common approved by all members of the scientific committee. Lahera et al. BMC Psychiatry (2018) 18:176 Page 3 of 10 Participants Table 1 Consensus rate in each section of the questionnaire The scientific committee consisted of eight psychiatrists No. % from Spanish hospitals. Each member of the scientific I. The concept of functional recovery (n =9) committee proposed and recruited psychiatrists from Agreement 8 88.9% Spanish hospitals, outpatient units, and academic set- Disagreement 0 – tings to participate in the panel of experts. To be No consensus 1 11.1% included in the panel, the expert must have at least II. Functional assessment (n = 22) 10 years of experience in a hospital setting. To prevent attrition bias between the two rounds, only experts who Agreement 15 68.2% completed the entire Delphi process were to be listed in Disagreement 3 13.6% the acknowledgement section of the publication [25]. No consensus 5 22.7% The research assistance team, led by BH, directed and III. Factors influencing functional recovery (n = 16) oversaw the entire process and was responsible for the Agreement 13 81.3% distribution and analysis of the questionnaires. Disagreement 0 – The questionnaire No consensus 3 18.8% After a literature review of the empirical evidence and ex- IV. Psychosocial interventions and functional recovery (n =8) pert opinions on functional recovery in patients with Agreement 6 75.0% schizophrenia, the members of the scientific committee Disagreement 0 – discussed the unmet needs regarding the definition of No consensus 2 25.0% functional recovery and its assessment, as well as the pos- V. Functioning and pharmacological treatment (n = 14) sible interventions to accomplish it. The items of interest were summarized in a questionnaire of 75 items, which Agreement 14 100% were grouped into six sections: (I) the concept of func- Disagreement 0 – tional recovery (9 items), (II) assessment of functional No consensus 0 – recovery (23 items), (III) factors influencing functional re- VI. the perspective of patients and their relatives on functional recovery covery (16 items), (IV) psychosocial interventions and (n =5) functional recovery (8 items), (V) pharmacological treat- Agreement 5 100% ment and functional recovery (14 items), and (VI) the per- Disagreement 0 – spective of patients and their relatives on functional No consensus 0 – recovery (5 items). The questionnaire was sent to the experts in the panel for their consideration. (i.e. not meeting criteria for either consensus or Results non-consensus) (Fig. 1). Most items not reaching con- Consensus overview sensus belonged to the functional assessment section Based on the criteria of the members of the scientific (5 items, 6.7%), followed by factors influencing func- committee, 80 experts were invited to participate in the tional recovery (3 items, 4.0%), psychosocial interven- Delphi process. Of them, 53 responded the first round tions and functional recovery (2 items, 5.6%), and the and 53 in the second one, indicating no drop out be- concept of functional recovery (1 item, 1.3%). tween the two recursive rounds of the Delphi process. In Additional file 1: Tables S2-S7 provide details on the the first round, consensus was achieved in 41 items median and interquartile range obtained on each (54.7%), all of them in agreement. Of the 34 items item. The median score in items meeting the consen- addressed in the second round, 23 met the consensus sus criteria ranged from 6.06 to 8.31. criteria (20 items in agreement and 3 in disagreement), yielding a final consensus list of64 items (85.3%): 61 The concept of functional recovery (81.3%) in agreement and 3 (4.0%) in disagreement. Additional file 1: Table S2 summarizes the median Table 1 shows the number and percentages of items in scores of the 9 items regarding the concept of functional each section on which the experts reached agreement recovery. The experts did not reach a consensus regard- (i.e. consensus on the score range 7-to-9), disagreement ing the existence of a standardized concept of functional (i.e. consensus on the score range 1-to-3), and lack of recovery in patients with schizophrenia (57.7% of agree- consensus. Of eleven items not meeting the consensus ment; median score 7.06; 95%CI 6.50–7.50). Neverthe- criteria, one resulted in non-consensus (i.e. more than less, the experts in the panel overall agreed on each one one-third of experts scoring 1-to-3 and more than of the multiple characteristics frequently included in the one-third scoring 7-to-9) and ten were indeterminate definition of functional recovery. For instance, most Lahera et al. BMC Psychiatry (2018) 18:176 Page 4 of 10 Fig. 1 Results of the items not meeting the consensus criteria. a functional recovery is a well-established concept. b The functional assessment is commonly included among the objectives of clinical trials on schizophrenia. c thepatient is themost reliablesourceof information for functional assessment. d: a proper functional assessment is not affordable in institutionalized patients. e I am familiar with the use of the Social and Occupational Functioning Assessment Scale (SOFAS) regarding the functional assessment of schizophrenic patients. f I am familiar with the use of the Health of the Nation Outcome Scales (HoNOS) regarding the functional assessment of schizophrenic patients. g living in an urban area is the environmental factor that has the greatest impact on functioning in patients with schizophrenia. h being an immigrant is the environmental factor that has the greatest impact on functioning in patients with schizophrenia. i: Public campaigns aimed at reducing stigma in patients with schizophrenia are effective. j cognitive-behavioral therapy is the most effective psychosocial intervention for functional recovery. k cognitive disorders should be the primary target of psychosocial interventions experts agreed that functional recovery overlaps with other Assessment of functional recovery concepts such as quality of life, cognition, and clinical remis- According to the experts, the assessment of functional re- sion. Furthermore, experts identified the influence of symp- covery is essential in both the clinical research and clinical tomatic remission, personal autonomy, professional activity, practice settings (96.2% of consensus). However, there was social relationships, and environmental factors on functional no consensus on whether the assessment of functional re- recovery. According to 86.5% of the experts, functional re- covery is commonly included among study objectives of covery is an achievable goal in patients with schizophrenia. clinical trials in schizophrenia (Additional file 1:Table S3). Lahera et al. BMC Psychiatry (2018) 18:176 Page 5 of 10 Regarding the source of information for the assessment of criteria determining the choice of pharmacological treat- functional recovery, there was strong agreement (98.1%) on ment (Additional file 1: Table S6). It was also agreed that the suitability of gathering information from three primary the various antipsychotic agents have different impacts sources: patients, their relatives (and/or caregivers), and cli- on functional recovery. Among the potential drawbacks nicians. The experts exhibited heterogeneous knowledge of of pharmacological treatment for achieving functional the functional assessment tools currently available for iden- recovery, cognitive impairment reached the highest tifying areas subject to improvement, and planning the agreement (100%); 94.3% of the experts agreed that management of patients with schizophrenia. Most of them second-generation are more useful than first-generation stated that they were familiar with the GAF scale, the (or atypical) antipsychotics for achieving functional Personal and Social Performance scale (PSP), and the sec- recovery. ond version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0). Conversely, the ma- The perspective of patients and their relatives on jority of experts were not familiar with the Social and functional recovery Occupational Functioning Assessment Scale (SOFAS) or The experts agreed that the perspective of clinicians on the Health of the Nation Outcome Scale (HoNOS). Beyond functional recovery differed significantly from that of the scales used, it was suggested that functional recovery is patients and their relatives (Additional file 1: Table S7). somehow assessed in routine practice, albeit without any According to this observation, psychiatrists are more standardized procedure. concerned with the clinical aspects of the disease, whereas patients and their relatives are more concerned Factors influencing functional recovery with subjective aspects of the lifetime project and factors The experts overall agreed that functional recovery is in- influencing activities of daily living. fluenced by various environmental factors, including stressful life events, substance abuse, socioeconomic Discussion conditions, and family dynamics (Additional file 1: Table Following a two-round Delphi dynamics approach, we S4). However, most of them (90%) acknowledged that found high homogeneity in the opinion of clinicians none of these factors predicts independently the regarding functional recovery in patients with schizo- non-achievement of functional recovery. Other environ- phrenia. Psychiatrists from different areas in Spain mental factors such as the type of origin (i.e. migrant/ achieved consensus in 85% of the concepts addressed local) and residence (i.e. urban/rural) were not consid- regarding various aspects of functional recovery. ered to influence functional recovery significantly. Both Functional recovery is a complex, multidimensional negative and cognitive symptoms were considered to concept to be considered not only by clinicians but also cause significant impact on functional recovery, with no researchers, patients and caregivers, as well mental superiority of either of the two symptom groups. Finally, health policy makers. Although the perspective of the the experts agreed that self-stigma (or internalized various stakeholders involved in the definition of func- stigma) has a greater impact on functional recovery than tional recovery may converge on many aspects, the lack social stigma. The idea that the negative image associ- of a common terminology and the pursuit of different ated with psychiatry compared to other medical special- goals has led to a wide repertoire of definitions, none of ties increases stigma in patients with schizophrenia also which stands out clearly over the rest [2, 6, 7, 16, 26]. reached a consensus in agreement. The result of our consensus regarding the concept of Psychosocial interventions and functional recovery functional recovery mirrored this scenario, resulting in a There was overall agreement that psychosocial interven- lack of consensus regarding a well-established concept tions are necessary to achieve functional recovery (92.3% of functional recovery. Nevertheless, the general agree- of agreement). Among all interventions proposed, family ment on specific factors influencing the concept of func- interventions and those aimed at developing social skills tional recovery suggests that despite the lack of a and improving employability were considered the most standardized definition of recovery, most clinicians share useful for functional recovery (Additional file 1: Table a common archetype of what functional recovery S5). Although the inclusion of cognitive rehabilitation in actually is. psychosocial interventions was considered useful, cogni- The feasibility of achieving functional recovery in tive disorders were not agreed to be the primary target patients with schizophrenia has been under discussion of these interventions. since the emergence of interest in this concept [2, 6, 22, 27]. Most experts in our panel (87%) agreed that Pharmacological treatment and functional recovery functional recovery is a realistic goal in the manage- The majority of experts in the panel (79.0%) considered ment of patients with schizophrenia. This is in line that functional recovery is one of the most important with the results of recent research on schizophrenia, Lahera et al. BMC Psychiatry (2018) 18:176 Page 6 of 10 which showed that psychological well-being and mental The experts exhibited heterogeneous knowledge of the health recovery can improve in individuals with functional assessment tools currently available for identi- first-episode psychosis [28]. The lack of a clear definition fying areas subject to improvement, and planning the and assessment tools prevents from drawing strong con- management of patients with schizophrenia. Beyond the clusions regarding the feasibility of a therapeutic model scales used, it was suggested that functional recovery is based on the concept of recovery. However, empirical evi- somehow assessed in routine practice, albeit without any dence on various therapeutic interventions suggests that standardized procedure. In this regard, treatments based many patients with schizophrenia can achieve goals on a recovery model should be consistent with related to functional recovery such as independent living evidence-based treatments [2]. and competitive employment and education in routine Functional recovery, may be influenced by multiple community settings [18–21, 29]. In line with the common factors. According to the experts, these factors are a perception regarding the definition of functional recovery, combination of environmental factors, stressful life M. Farkas proposed four key values commonly reflected events, substance abuse, socioeconomic conditions, in the recovery literature which should be considered in and family dynamics. Other environmental factors all recovery-oriented services: person orientation, person such as the type of origin (i.e. migrant/local) and resi- involvement, self-determination/choice, and growth dence (i.e. urban/rural) were not considered to influ- potential [30]. ence functional recovery significantly. Some authors The lack of a standardized definition is probably a have observed that patients living in rural areas tend bottleneck for the development of validated tools for the to show better functional outcomes, probably due to assessment of functional recovery. Other difficulties that greater family and social support as well as simpler may compromise an appropriate assessment of functional vocational roles [39]. However, in our consensus, the recovery include the limitations of some informants to experts’ opinion might be strongly influenced by the make accurate judgments [31], the limited capacity of area where they work. Thus, while some centers pro- some patients for self-assessment [32], and the heterogen- vide mental health care to patients from both rural eity in their clinical course, which may lead to inconsisten- and urban areas, most of them serve one or the other cies between the outcome of functioning scales and type, whereby the influence of this factor may be un- milestone achievement in some patients (e.g., in some noticed. Finally, there was 96% agreement that, des- patients, functioning scales may not capture milestone pite the different perspectives of clinicians and achievements in social, vocational, and residential patients (i.e. clinicians tend to focus on the clinical domains of patients with schizophrenia) [33]. Regarding aspects of recovery, whereas patients and their rela- the source of information for the assessment of functional tives attach importance to the activities of daily living recovery, there was strong agreement on the suitability of andlifeproject), theattitudeof the variousstake- gathering information from three primary sources: holders has an influence on functional recovery. patients, their relatives (and/or caregivers), and clinicians. In line with the results of clinical studies, which sug- Indeed, some authors have warned of the risk of bias asso- gest that both negative symptoms and cognitive deficits ciated with motivation-related negative symptoms (e.g. may be primary predictors of impaired social and voca- emotional withdrawal, passive-apathetic social withdrawal) tional performance [34, 40, 41], the experts in the panel [34]. Furthermore, patient-reported assessments of quality agreed that both negative and cognitive symptoms cause of life and everyday abilities have shown poor correlation a significant impact on functional recovery. Also, in with information about lifetime achievements in many agreement with recent recommendations to treat nega- patients with schizophrenia [35]. All these limitations are tive symptoms [42], the experts agreed that functional consistent with the lack of consensus on the concept that recovery should not be addressed only through symp- the patient is the most reliable source of information for toms but also considering the cognitive, emotional, and functional assessment. relationship difficulties. Due to the absence of a single tool for the assessment Stigma is another factor with potential influence on of functional recovery, clinicians and researchers use dif- functional recovery, and it is generally accepted that it ferent strategies to evaluate it. In an attempt to broaden has a major impact on self-esteem and hampers recovery functional assessment towards a comprehensive model in people with mental illnesses [7, 43]. The experts of functional recovery, researchers have combined com- agreed that the negative image associated with psych- monly used scales such as the Global Assessment Func- iatry compared to other medical specialties increases tioning (GAF) scale and Global Assessment Scale (GAS) stigma in patients with schizophrenia and that with the Social Functioning Rating Score – which self-stigma (or internalized stigma) has a greater impact includes both social skills and social roles – and other on functional recovery than social stigma. Although the objective indicators of lifetime achievements [36–38]. mechanisms of stigma are not clear, social (or public) Lahera et al. BMC Psychiatry (2018) 18:176 Page 7 of 10 stigma and self-stigma might work in different ways. In pharmacological treatments – particularly atypical anti- an interview-based study conducted on patients with psychotic agents – cause morphological changes in pa- major depression or schizophrenia, social stigma showed tients’ brains which could be associated with an a trend towards underestimating the importance of in- improvement in neurochemical functioning [55, 56]. formal caregivers (e.g. family and friends). Conversely, Despite the proven usefulness of some antipsychotic self-stigma had a negative impact on the perceived im- agents in achieving functional recovery [57, 58], the portance of seeking help provided by a general practi- experts identified potential drawbacks of pharmaco- tioner or a psychiatrist [44]. logical treatment for achieving functional recovery: The relevance of psychosocial interventions agreed in extrapyramidal symptoms, sedation, the worsening of this consensus are consistent with the positive results negative symptoms, and cognitive impairment. Of note, of these interventions reported in randomized clinical most of the adverse events limiting functional recovery trials conducted according to the gold standards of are more frequently associated with first-generation than clinical design [45–47]. Although the items regarding second-generation antipsychotics [59–61]. Combination the type of therapy with highest effectivity were written antipsychotic therapy was also considered to result in in an exclusive way, the experts achieved consensus in poorer functional recovery than monotherapy. the highest effectivity of social skills training, family therapy, cognitive rehabilitation, social cognitive train- Table 2 List of recommendations when addressing functional ing, and occupational programs. This result indicates recovery of patients with schizophrenia that, irrespective of the median score achieved in each The concept of functional recovery therapy, none of them stood out from the rest. Of note, Despite the lack of a unified definition of functional recovery, it is recovery-based interventions are not widespread in recommended to ponder quality of life, cognition and clinical clinical practice and some authors have stressed the remission when considering functional recovery in research and need to develop more interventions going beyond routine practice. symptom reduction [48]. Although the inclusion of Functional recovery should be considered a goal in the management of patients with schizophrenia. cognitive rehabilitation in psychosocial interventions was considered useful, cognitive disorders were not Functional recovery should be always included among endpoints of clinical trials assessing patients with schizophrenia. agreed to be the primary target of these interventions. The apparent inconsistency regarding the role of cogni- Assessment of functional recovery tive functioning in psychosocial interventions can be Irrespective of the tools used for assessing functional recovery, information for appraising it should be gathered from patients, their explained by the recent evolution of the concept of relatives (and/or caregivers), and the healthcare team. cognition. Thus, while the construct of cognitive im- Irrespective of the tools used for assessing functional recovery, the pairment has been traditionally built solely on basic patient’s socio-cultural background should be considered when neurocognition, it is now accepted that social cognition assessing functional recovery. differs from basic neurocognition and that it could be Factors influencing functional recovery the link between neurocognition and functional recov- When seeking for the achievement of functional recovery, the ery in psychosocial programming [5, 49]. combined influence of stressful life events, substance abuse, The positive impact of long-acting antipsychotics on socioeconomic conditions, and family relationships, should be considered. adherence and the closer relationship between patients and the healthcare team associated with the dosing of Although negative symptoms have a great impact on functioning, clinicians should not focus exclusively on symptom remission when these agents have been considered helpful for achieving considering functional recovery. functional recovery [38]. Some authors have questioned Psychosocial interventions and functional recovery the suitability of maintaining long-lasting treatment with Psychosocial interventions are necessary to achieve functional antipsychotics [50]. However, the impact of long-lasting recovery. A combination of various therapies (including social skills antipsychotic treatments on functional recovery is training, family therapy, cognitive rehabilitation, social cognitive unclear, and other authors have highlighted important training, and occupational programs) is likely to be most useful in achieving functional recovery. limitations of studies investigating early discontinuation of antipsychotic therapy [51]. Pharmacological treatment and functional recovery Although it is not clear whether medication alone can Functional recovery should be considered in decision-making on impact directly on functional performance, there is pharmacological treatments. long-time evidence on the synergistic effect of pharma- The perspective of patients and their relatives on functional recovery cological and psychosocial treatments, particularly The attitudes of all stakeholders (i.e., patients, their relatives, and pharmacological treatments with a significant impact on clinicians) influence functional recovery. Hence, when seeking for achieving functional recovery, all these perspectives should be taken positive symptoms [7, 52–54]. Besides attenuating into account. the symptomatology associated with schizophrenia, Lahera et al. BMC Psychiatry (2018) 18:176 Page 8 of 10 The scope of the results presented herein must be Funding This project was funded by Janssen. The funding body participated in study weighed considering some limitations of our work. First, the design and data interpretation. selection of experts was neither systematic nor randomized. Alternatively, we recruited specialists in the management of Availability of data and materials The datasets used and/or analyzed during the current study are available schizophrenia from various Spanish regions. Thus, although from the corresponding author on reasonable request. all experts must account at least 10 years of clinical practice, a selection bias cannot be ruled out. Second, some items ex- Authors’ contributions pressing mutually incompatible ideas yielded inconsistent GL, JLG, PS, MM, JVP, PG-P, BH, and MR have made substantial contributions to the conception and design of this consensus process, have revised all results. Items affected by this phenomenon were discussed manuscript drafts critically, and have approved the final version of the and eventually not considered for drawing the final conclu- manuscript. All co-authors agree to be accountable for all aspects of the sions. Finally, the resulting recommendations were not work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately addressed and resolved. drawn following a consensus process, but as an interpret- ation of the agreements and disagreements resulting from Ethics approval and consent to participate the Delphi process. Nevertheless, due to the expected Not applicable. heterogeneity on the concept, we deemed it more appropri- Competing interests ate to address the conclusions by weighing the scope of G. Lahera has received research grant support from the Ministry of Health each result carefully and addressing the inconsistencies that (Spain), CIBERSAM, Lilly, and Janssen, and has worked as an advisor board might arise from the responses of the panel of experts. member for Lundbeck, Otsuka, Janssen, and Pfizer. J. L. Gálvez has received grants from Janssen, Lundbeck, Pfizer and Servier. P. Sánchez has received research grant support from the Ministry of Health (Spain), has worked as an Conclusions advisor board member for Janssen and Ferrer, and has worked as a speaker for Janssen. M. Martínez has worked as a speaker and/or advisor and/or Despite the lack of a standardized definition of func- researcher in projects promoted by Esteve, GlaxoSmithKline, Janssen-Cilag, tional recovery in schizophrenia, clinicians are aware of Lilly, Lundbeck, Otsuka, Pfizer, Servier, Roche, and Rovi. J. V. Pérez has this approach, show a trend towards a common con- worked as a speaker for Janssen and Lundbeck. P. García-Portilla has been a consultant to and/or has received honoraria/grants from Alianza Otsuka- struct of this concept, and consider functional recovery Lundbeck, CIBERSAM, European Comission, Instituto de Salud Carlos III, in their day-to-day practice, albeit in a non-formal way. Janssen-Cilag, Lilly, Lundbeck, Otsuka, Pfizer, Servier, Roche, and Rovi. In our experience, 57 Spanish psychiatrists reached a B. Herrera is currently employed by Janssen-Cilag S. A. M. Roca has received research grant support from Health Institute Carlos III, Ministry of Economy consensus on 85% of items addressing various aspects of and Competitiveness, European Union ERDF as worked as a speaker and/or functional recovery in schizophrenia. Based on the advisorin project promoted by Janssen, Lundbeck and Pfizer. results of this consensus and their consistency with the information available in the literature, the experts of this Publisher’sNote panel provide a list of recommendations (Table 2). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Additional file Author details Departamento de Medicina y Especialidades Médicas, Facultad de Medicina, Universidad de Alcalá, Plaza de San Diego, s/n, 28801 Alcalá de Henares, Additional file 1: Results of the Delphi consensus. Score (median and Madrid, Spain. Centro de Investigación Biomédica en Red de Salud Mental interquartile range) of each item of the questionnaire. (PDF 397 kb) (CIBERSAM), Madrid, Spain. Unidad de Salud Mental Comunitaria del Hospital Universitario Virgen del Rocio, Av. Manuel Siurot, S/N, 41013 Sevilla, Abbreviations Spain. Unidad de Psicosis Refractaria, Hospital Psiquiátrico de GAF: Global Assessment Functioning; GAS: Global Assessment Scale; Álava-Osakidetza, C/ Álava, n°45, 01006 Vitoria – Gasteiz, Spain. Facultad de HoNOS: Health of the Nation Outcome Scale; PSP: Personal and Social Medicina, Universidad del País Vasco-Euskal Herriko Unibertsitatea, Leioa, Performance; SOFAS: Social and Occupational Functioning Assessment Scale; Spain. Hospital Royo Villanova, Avda. San Gregorio, s/n, 50015 Zaragoza, WHODAS: World Health Organization Disability Assessment Schedule Spain. Centro de Salud Mental Fuente San Luis, Hospital Universitario Doctor Peset, Av. de Gaspar Aguilar, 90, 46017 València, Spain. Área de Psiquiatría, Facultad de Medicina, Universidad de Oviedo, Av. Julián Clavería, Acknowledgements s/n, 33006 Oviedo, Asturias, Spain. Medical Affairs Department, Medical writing assistance was provided by Dr. Gerard Carot-Sans, PhD, and Janssen-Cilag, Avenida Partenón, 16 1 (Campo de las Naciones), S. A, 28042 Medical Writers 5.0 on behalf of Janssen. The authors gratefully acknowledge Madrid, Spain. Institut Universitari d’Investigació en Ciencies de la Salut the time and effort of the panel members: Adolfo Benito, Ainara Arnaiz, Ana (IUNIS), RedIAPP, Hospital Juan March, Universidad de las Islas Baleares, Cra. Catalán, Ana González-Pinto, Ana Landa, Celso Iglesias, Clemente García-Rizo, de Valldemossa, km 7.5., Palma de Mallorca, (Illes Balears), Spain. Consuelo Llinares, David Fraguas, Demetrio Mármol, Eduard Parellada, Fernando Montiano, Francisco Salido, Ignacio García, Ignacio Zarranz, Jesús Received: 2 October 2017 Accepted: 22 May 2018 Mesones, Jesús Morillas, José A. Alcalá, Jose L. Montero, José M. Montes, José M. Olivares, José R. Gutiérrez, Juan A. Martínez, Juan J. Fernández, Luis Docasar, Luis Gutiérrez, Luis San, M. Ángeles Escudero, Manuel Serrano, M. 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