Functional outcome assessment in bipolar disorder: A systematic literature review

Abstract Objectives Functional impairment is an important driver of disability in patients with bipolar disorder (BD) and can persist even when symptomatic remission has been achieved. The objectives of this systematic literature review were to identify studies that assessed functioning in patients with BD and describe the functional scales used and their implementation. Methods A systematic literature review of English‐language articles published between 2000 and 2017 reporting peer‐reviewed, original research related to functional assessment in patients with BD was conducted. Results A total of 40 articles met inclusion criteria. Twenty‐four different functional scales were identified, including 13 clinician‐rated scales, 7 self‐reported scales, and 4 indices based on residential and vocational data. The Global Assessment of Functioning (GAF) and the Functional Assessment Short Test (FAST) were the most commonly used global and domain‐specific scales, respectively. All other scales were used in ≤2 studies. Most studies used ≥1 domain‐specific scale. The most common applications of functional scales in these studies were evaluations of the relationships between global or domain‐specific psychosocial functioning and cognitive functioning (eg, executive function, attention, language, learning, memory) or clinical variables (eg, symptoms, duration of illness, number of hospitalizations, number of episodes). Conclusions The results of this review show growing interest in the assessment of functioning in patients with BD, with an emphasis on specific domains such as work/educational, social, family, and cognitive functioning and high utilization of the GAF and FAST scales in published literature.

individuals with bipolar disorder (BD) may experience continued disability, due in part to lack of treatment intervention, which could potentially limit their functioning and productivity and also decrease overall quality of life for them and their families.
The World Health Organization (WHO) has ranked BD as the 12th leading cause of disability worldwide, and the worldwide prevalence of moderate or severe disability for BD is estimated at approximately 22 million individuals. 4 Poor functioning is considered a key driver of disability in patients with BD. 5 The WHO International Classification of Functioning, Disability, and Health describes functioning and disability as multidimensional concepts involving the ability to control physical functions; perform activities related to domains such as self-care and domestic, occupational, social, and civic life; engage in all aspects of life; and manage aspects of the environment that help or hinder these experiences. 6,7 Patients with BD report a variety problems in work functioning, 8 with severe work impairment during a considerable portion of their long-term course of illness, 9 and high unemployment rates. 10 They have decreased social engagement, 11 weaker family relationships, 12 and an increased likelihood of being separated, divorced, or widowed. 13 For many patients with BD, these functional impairments persist into symptomatic remission, leading to difficulties in many aspects of their lives. 14, 15 The negative effects of BD extend to caregivers, who report substantial burden and distress involving relationships and day-to-day activities. 16 Thus, for many patients with BD and their families, functional outcome, measured as the ability to fulfill role expectations in all aspects of life and maintain interpersonal relationships, is at times more important than syndromal outcome. 17 Although most interventional studies in patients with BD have focused on symptoms, recurrences, and mood states as the primary outcome variable, increasingly, studies are also assessing functioning as a key outcome. 17 In addition, numerous studies have sought to identify determinants of functional outcome in patients with BD.
A variety of correlates of poor functional outcome have been identified, including clinical factors such as lack of treatment adherence, comorbid substance abuse or anxiety disorder, and subsyndromal symptoms; demographic variables such as older age, male sex, and low socioeconomic status; and cognitive dysfunction, particularly verbal memory impairment and executive dysfunction. 5 The growing interest in the relationship between cognitive and psychosocial function in BD is reflected in several recent reviews on this topic 6,[17][18][19] and compels a better understanding of the tools used for functional assessment in this population. The purpose of this systematic literature review was to identify and describe scales that are used to assess functioning in studies of patients with BD and to gain an understanding of the domains of function that clinicians are measuring.

| Information sources and eligibility criteria
This systematic literature review was conducted according to the recommendations outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. 20 A search was performed in BIOSIS Previews, Embase, and MEDLINE for English-language articles published in peer-reviewed journals between 1 January 2000 and 6 November 2017. The following search string was applied using the abstract and title as search fields: ("functional impairment" OR "psychosocial outcome" OR "psychosocial functioning" OR "psychosocial treatment" OR "psychosocial impairment" OR "occupational function" OR "occupational impairment" OR "occupational" or "functional disability" OR "psychosocial disability" OR "disability or work" OR "cognition" OR "social cognition" OR "stress" OR "functional remediation" OR "cognitive remediation") AND ("functional recovery" OR "functional outcome" OR "outcome n/1 [patient or recovery]" AND ("bipolar disorder" OR "bipolar I disorder" OR "bipolar II disorder" OR mania OR manic OR "bipolar mania" OR "bipolar depression" OR "bipolar I disorder" OR "manic psychosis" OR "bipolar disorder" OR "affective disorders, psychotic") AND (scale* OR measure*). Conference publications (ie, posters, summaries, and abstracts), review articles, notes, letters, book chapters, interactive tutorials, or surveys; publications involving animal or in vitro studies; and publications on pediatric populations were excluded.

| Article selection process
The title and abstract of each retrieved article were independently screened against eligibility criteria by one author. Selected full-text articles were then divided between the authors for detailed review and inclusion assessment. Figure 1 shows the article selection process.

| Article selection
The search retrieved 104 articles; 30 were determined ineligible based on screening of titles and abstracts, and 74 were selected for full-text review. Forty articles met the eligibility criteria and were included in the qualitative data analysis (Figure 1).

| Risk of publication bias
Several authors and research groups authored multiple articles identified in this review (Table 1 and Table 2), indicating the potential for publication bias.

| Cross-sectional studies
Of the 20 cross-sectional studies included in this review, 9 (all published between 2002 and 2016) used the GAF as the sole functioning scale. 27,28 Four of these studies compared overall functioning between patients with euthymic BP-I or BP-II vs healthy controls, 27,32,33 and four compared functioning between BP-I, BP-II, and/or healthy controls or between patients with BP-I and BP-II with different mood states (ie, depression, major depression, mania, hypomania, and euthymia) or functioning (ie, low vs high). [29][30][31] The remaining study 28  The WHOQOL-BREF evaluates treatment efficacy by assessing overall quality of life in the areas of physical health (pain and discomfort, sleep and rest, energy and fatigue, mobility, activities of daily living, dependence on medicinal substances and medical aids, work capacity), psychological health, social relationships (personal relationships, social support, sexual activity), and environment (freedom, physical safety and security, home environment, financial resources, health and social care, opportunities for acquiring new information and skills, participation in and opportunities for recreation/leisure activities, physical environment, and transport)

(3)
Young Schema Questionnaire Short Version 48 (YSQ-S3) 2005 The YSQ-S3 uses a Likert-type ranking to assess 18 schemas, patterns that when triggered make the person feel intense emotions in the areas of disconnection and rejection, autonomy and performance, self-control, directedness, and overvigilance and inhibition UCLA Social Attainment Survey 73 1973 The UCLA Social Attainment Survey rates the social adjustments of patients based on same-sex peer relationships, leadership in same-sex peer relations, opposite-sex peer relations, dating history, sexual experience, outside activities, and participation in organizations Family Assessment Device 84 (FAD) 1983 The FAD includes seven scales assessing problem solving, communication roles, affective responsiveness, affective involvement, behavior control, and general functioning between psychosocial functioning and ≥1 cognitive domain (eg, attention, learning and memory, executive function, language).
Five of these studies also assessed correlations between the GAF and demographic 27,31 and/or clinical variables, 27,28 such as duration of illness, number of hospitalizations, number and type of episodes, symptom type and severity, and medications. One study also evaluated the relationship between psychosocial functioning and theory of mind, the ability to perceive other people's mental states. 27 The ninth study 35 used the GAF to assess functioning and symptoms in patients with BD.
In addition to these nine studies using only the GAF, one study 36 used the GAF along with the Self-reported Social Functioning Scale

Publication
Year Description Studies, n (%) Interpersonal Support Evaluation List 85 (ISEL) 1983 The ISEL includes the following four subscales: tangible assistance (perceived availability of material aid), appraisal (perceived availability of someone to talk about one's problems), self-esteem (perceived ability of a positive comparison when comparing one's self to others), and belonging (perceived availability of people with whom one can do things)

(3)
Self-reported Self-reported Social Functioning Scale 37 (SFS) 1990 The SFS assesses the areas of functioning that are crucial to the community maintenance of individuals with schizophrenia. It provides a detailed assessment of strengths and weaknesses of individuals in comparison with reference groups based on the following seven functional domains: social engagement/withdrawal, interpersonal behavior, prosocial activities, recreation, independence-competence, independence-performance, and employment/occupation Work and Social Adjustment Scale 47 (WSAS) 2002 The WSAS is a short self-report questionnaire that measures work and social adjustment on the following five domains: work ability, home management, social leisure activities, private leisure activities, and the ability to form and maintain close relationships The SAS-SR surveys the patient's role as a spouse, a parent, and a member of a family unit to assess the patient's performance, interpersonal relationships, frictions, feelings and satisfaction in work, and in social and leisure activities with the extended family 1 (3)

Residential and vocational data
Residential Status Index (RSI) Vocational Status Index (VSI) 57 2003 The RSI and the VSI serve as proxies of functional recovery by operationalizing ratings for current residential and vocational status that equate or exceed the patient's previous highest residential and vocational status  and in patients with BP-I, BP-II, and BD not otherwise specified after first or multiple affective episodes. 52 The two observational studies that used both the GAF and the   are several early studies that utilized the GAF, which likely set precedence for its use in later longitudinal and cross-sectional studies.

| Longitudinal interventional studies
One key study used the GAF along with the MVSI and MLCI to measure global functioning, occupational status, and residential status, respectively, over 4 years 78 in patients with BD; the aim of the study was to identify factors contributing to long-term outcomes.
The reliability and validity of the GAF, however, depend on the rater's training and expertise, and GAF scores have been observed to correlate more with symptom severity than functional impairment. 79 The FAST was introduced in 2007 as a simple interview to assess the following 6 domains of functioning considered to be the main problem areas for patients with mental illness, including BD: autonomy, occupational functioning, cognitive functioning, finances, interpersonal relationships, and leisure time. 22  ipation, for clinical evaluation of disability. 82 We see the adoption of the WHODAS as a valuable addition to the field as it provides more specific measures of functioning. On the other hand, the GAF provides an overall rating that includes functioning which in some cases may be useful because of its ease of use. As with any scale, investigators will need to decide which scale best meets their needs. This systematic review has several limitations. Although the search parameters were designed to be comprehensive, it omitted non-English articles and articles published before 2000, which could have limited its scope. In several areas of the literature, particularly studies using the GAF and FAST, multiple studies were published by the same research groups or authors at the same institutions. Although an effort was made to omit duplicate publications, it is important to recognize the potential for bias due to multiple publications by the same investigators.
In conclusion, this review shows high utilization of the GAF and