Exploring the effectiveness of family-based interventions for psychosis in low- and middle-income countries: a systematic review

Purpose Of the 80% people with psychosis living in low- and middle-income countries (LMICs), up to 90% are left to the care of families. The World Health Organization has recommended the inclusion of families in community-based rehabilitation and while there is evidence of its implementation in LMICs, this has not been reviewed yet. This study aims to describe the key features and implementation strategies of family-based interventions in LMICs, and appraise their effectiveness. Methods Included are people with psychosis in LMICs who receive any form of family-based intervention, compared to their usual or absence of treatment, with patient outcome measures. We searched (August 2021) through Embase, MEDLINE, Global Health, PsycInfo, Social Policy and Practice, and Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as from grey literature and hand-searched records. Risk of bias was assessed through the Integrated Quality Criteria for Review of Multiple Study Designs (ICROMS) and Consolidated Health Economic Evaluation Reporting Standards (CHEERS), then analyzed narratively. Results 27 studies were included from the 5254 records. Psychotherapeutic features, systems approach and task-sharing were key intervention elements. Delivery strategies included preliminary research, sustained family engagement, and cultural adaptation. There were positive health impacts across four outcome domains. Conclusion All studies recommended family-based interventions, with limitations in heterogeneity and 70% of them rated high risk of bias. Other Review was registered in PROSPERO (CRD42021256856). The authors did not receive funding for this research. Supplementary Information The online version contains supplementary material available at 10.1007/s00127-022-02309-8.


Introduction
Despite the growing evidence on the global burden of psychosis [1][2][3][4], there is still an urgent need to scale up services to support people with psychosis and their families in lowand middle-income countries (LMICs) [5]. Pharmacological treatment may be the cornerstone treatment for its practicality in administration, but this is challenged by low adherence and side effects [6]. Social determinants may significantly impact the prevalence of psychosis [7]; a biopsychosocial approach is therefore needed. Apart from this, the availability of second-generation antipsychotics, and in some cases any medication, is variable [8]. Among psychological interventions, cognitive behavioral therapy (CBT) shows encouraging evidence in some contexts [9,10], but negative symptoms may not be effectively addressed [11]. The World Health Organization (WHO), through the Mental Health Gap Action Plan (mhGAP), has endorsed community-based rehabilitation especially for rural areas in LMICs [8]. However, the challenge for low-resource settings is to provide access to this service, which is made more difficult due to a limited number of mental health specialists [9].
Of the almost 80% of people with psychosis living in LMICs, 90% are primarily cared for by their families [8,[12][13][14][15][16]. Recently, there has been strong emphasis on engaging the family in advancing global mental health interventions [5,17,18] and specifically for early onset psychosis [19]. To reinforce community-based rehabilitation, it makes sense to draw upon social capital by task-sharing to family carers, who may be the people working closest with the person with psychosis. Family-based interventions essentially tap the family member(s) of a person with psychosis to be the main delivery agent of care, whether through psychoeducation, family counselling/therapy, or through a combined program with pharmacological treatment [20,21]. Clinically, when psychoeducation is given in family therapy, negative aspects of expressed emotion (EE), or more specifically, the critical, hostile and emotional over-involvement of the family environment, was effectively reduced and caring for the person with psychosis was improved [22]. Evidence over the past decade has recorded favorable outcomes for family intervention, particularly clinical outcomes, medication compliance, social functioning, family outcomes, and quality of life [23][24][25]. Additionally, economic analyses point to agreeable outcomes in net household savings and cost-effectiveness [26,27].
Across cultures, various efforts in implementation have illustrated the feasibility and effectiveness of family-based intervention [20,25,[28][29][30][31][32][33][34][35]. In high-income countries, there have been challenges in bringing family-based intervention to routine care, but it has already been widely incorporated into mental health services [36]. In scaling up communitybased programs, psychoeducation in India [32,37], Pakistan [38,39], Ethiopia [40], China [41], and other low-resource countries [42] have benefitted in utilizing key family members. Robust evidence in HICs supports family-based interventions and is being implemented in mental health care facilities. Growing evidence provides a basis for optimism for the uptake of family-based intervention in mental healthcare interventions in LMICs, but a synthesis of delivered family-based interventions and their effectiveness has not yet been conducted. Focusing on the studies in LMICs provides a substantial contribution to the literature of psychosis interventions.
This systematic review aims to (i) describe FBI for psychosis studied in LMICs, which synthesizes intervention features and delivery strategies, and (ii) appraise the evidence of family-based interventions in LMICs. Exploring intervention elements and its delivery could help identify active ingredients in family-based interventions to enable its incorporation within the LMIC context. The output of this systematic review will inform communities in mental health research, clinical practice as well as non-practitioners involved in psychosis interventions and policies.

Methods
Protocol for this review was approved by the London School of Hygiene and Tropical Medicine Ethics Committee and registered to PROSPERO (CRD42021256856), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and completed the PRISMA 2020 checklist [43]. A stepwise process of screening the titles and abstracts, then the full-text articles according to the eligibility criteria was performed.

Eligibility criteria
The study population is people with psychosis in lowand middle-income countries, who received any form of family-based intervention compared to their usual, or absence of, treatment. Broad direct and indirect patient outcomes were included, i.e., from clinical outcomes to a shift in the behavior or the attitude of the family that in turn affects patient outcomes. Since the study aims to explore the existing evidence on family-based intervention in LMICs, it sought to include all relevant studies that reported outcomes related to the people with psychosis. Therefore, cost-effectiveness outcomes were also included. This review was not limited to the year of publication nor a specific time frame, and all study designs were included.
Eligibility criteria were assigned to the following domains: (A) family-based interventions, (B) people with psychosis, and (C) low-and middle-income countries. Family-based intervention is defined as any intervention that involves one or more family member(s) as recipients of the service and agents of its effectiveness on the patient. It includes, but not limited to, family intervention, family therapy, family psychoeducation, family workshops, "crisis intervention support for the family" [44], and "familyfocused intervention" [23]. Family therapy, a type of group psychotherapy, is defined as treatment of more than one family member in the same session [45]. Psychoeducation in this review denotes the structured learning of the patient and their family about psychosis and how to manage this within their lives. Within the framework of psychotherapy, its content ranges from the nature of the mental illness, managing symptoms, effective caregiving for the person with psychosis, problem-solving, and treatment modalities. Psychosis is a mental condition characterized by cognitive impairment, disorganized behavior, and a disconnect from reality, including hallucinations and delusions as experiences of positive symptoms and marked unresponsiveness as negative symptoms [46,47]. Diagnoses were done by mental health practitioners and researchers. In this review, we define a person with psychosis as someone who has been diagnosed with the aforementioned symptoms at any age after onset with early onset, acute or chronic psychosis. The medical subject headings (MeSH) term used for this review is "psychotic disorders", including schizophrenia and bipolar disorder as they are the most common types. Psychosis due to substance abuse was excluded. Lastly, low-and middle-income countries were defined from the World Bank income division [48], crossvalidated with the Organization for Economic Cooperation and Development (OECD) and the LMIC Filters of the Cochrane Database of Systematic Reviews [49]. All the 109 country names and the derivative terms for LMICs, both former and recently used, were included in the search.

Information sources and search strategy
Studies were searched through the following bibliographic databases: Embase, MEDLINE, Global Health, PsycInfo, Social Policy and Practice, and Cumulative Index to Nursing and Allied Health Literature (CINAHL), through Ovid platform. Scopus and Google Scholar were used to unpublished reports. Relevant Chinese conference proceedings and records that were unavailable were hand-searched from Wangfang Data, a Chinese bibliographic database, Research-Gate, a social networking site for researchers, and through the British Library collection. The electronic search strategy covered the three domains to accommodate the specific database syntax. Consistent with the population, intervention, comparator, outcomes (PICO) approach adopted, search terms were: (A) psychosis (e.g., psychos?s or brief reactive psychos?s or bipolar disorder* or schizoaffective disorder* or schizophren*), (B) family-based interventions (e.g., family-based intervention* OR family therap* OR family-based OR parent* OR mother* OR father* OR primary care-giver* OR sibling*), and (C) low-and middle-income countries (e.g., yemen OR yugoslavia OR zambia OR zimbabwe OR global south OR sub-saharan africa OR lmic OR lmics OR third world OR lami countr*). All terms were combined by the Boolean term "OR" within the domains and "AND" when key terms per domain were combined.

Selection process
All authors participated in the two-tier screening process for eligibility for preliminary (title and abstract) and fulltext articles. HM screened all articles on both stages and SL co-screened all titles and abstracts and 30% of the full-text articles, above the recommended 20% cut-off [50]. Agreement between raters was at least 97.6% inter-rater agreement with Kappa = 0.78. Four discordant articles were resolved by referencing the eligibility criteria and consultation with CH. HM performed an update of the search one year after and CH co-reviewed the included full-text articles, where full agreement of additional included articles was made. Eligibility assessment was performed for all included studies on an individual blinded standardized manner via Rayyan (https:// rayyan. ai/), a free web-based collaboration and reviewing tool.

Data collection process
A preliminary scoping review exercise surveyed similar published studies through PROSPERO (International Prospective Register of Systematic Reviews), Ovid, and Google Scholar in January 2020. The first search was in June 2020 and an updated search was completed in August 2021. Search terms were manually generated and inputted onto the databases. Citation chaining was performed to allow for the forward and backward research trail of potentially relevant studies, where they were retrieved through the mentioned information sources. Results of the database search were catalogued in a referencing manager (EndNote X9) and then transferred to Rayyan where the records were de-duplicated. Finally, resulting records underwent the two stages of screening. To minimize language bias, included studies written in Chinese and Spanish in the first and second screenings were translated twice by different native-speaker researchers before deciding at the full-text screening stage.

Data items
Study outcomes were within 1.5-24 months. We included all outcomes, coded and conceptually mapped them, and then categorized into four domains: (a) patient condition, (b) self-management, (c) social, and (d) delivery outcomes. Patient condition outcomes are related to the symptoms of the patient. Symptomatology, relapse rate, medication adherence, depression comorbidity, recovery and stabilization, rehospitalization, disability-adjusted life years, and cognitive functioning are categorized under this domain. Second, selfmanagement outcomes denote the wellbeing and health promotion of the patient. It includes self-management outcomes that include self-care, knowledge about psychosis, quality of life, psychosocial functioning, and ability to seek medical consultation/help. Third, social outcomes are others-oriented and involve or affect their wider sphere, comprising of family environment, EE, social and occupational functioning, and psychosocial functioning. And fourth, delivery outcomes refer to intervention administration, included attendance rates and service user satisfaction.

Study risk of bias assessment
We used the Integrated Quality Criteria for Review of Multiple Study Designs [ICROMS; [51]] to accommodate for the variability in design, and the Consolidated Health Economic Evaluation Reporting Standards [CHEERS; [52]] for the two economic evaluations. ICROMS work as a point system according to study-specific quality criteria based on a decision matrix, where mandatory items and a minimum score for each study design are added to reach a decision for the study. For the CHEERS checklist, the markings are 1 score for Yes if it is reported, 0 for No if otherwise, and 0.5 for partially reported. NA indicates not applicable. The scores are tallied and averaged after omitting counts for NA. The midpoint, described as average, is 17 of the 24 items. All studies were included regardless of scores.

Data extraction and analysis
A data extraction table was developed based on the Cochrane Data Collection Form for Intervention Reviews: RCTs and non-RCTs and from the data headings of Sin et al. [53]. Information was extracted from each included study on: (A) study specifics (authors, publication year, study source, geographical context, study design and study aim); (B) participants (number of participants and attrition rate, age range, diagnosis); (C) theoretical basis (general underpinning theory or concept, specific theory or rationale behind approach); (D) intervention specifications (delivery platform, delivery agents, intervention program specifics, and recommendations); and (E) outcome measures (outcome definition, time points measured, outcome results).
A narrative approach was used to synthesize the data [54]. Synthesis was performed after extracting data from the included articles to remain inclusive in reviewing the records. Because of the heterogeneity across studies, further analysis was performed using the thematic framework as an interpretive method to categorize information from variable studies to maximize generation and exploration of overarching themes according to the research questions [55]. These stages of fractioning the main themes of the results through codes, and then clustering them into intervention features and strategies, aimed to highlight active ingredients from different the family-based interventions.

Study characteristics
Resulting studies from database searches were 5254 records, with 2815 titles and abstracts for the first screening phase and 72 full-text articles. There were four records related to one study (Study 1), including a doctoral dissertation, two articles written in Chinese and one article in English journals that reported the same study aims and outcomes, therefore the first English publication (Study 1) was selected for this review while the rest were excluded. Two other non-English articles were in Serbo-Croat but could not be translated. We were open to including conference abstracts to the review, but only contained limited information. Records that did not deliver the intervention were excluded as well. Lastly, we excluded a PhD dissertation and three more records because it reported the same information as the core study. This rationale applies to study 21 which had a 14-year follow-up record. Published journal articles and one book chapter were included in this review. This led to 27 studies (with corresponding numbers 1-27 listed in Table 1). Figure 1 illustrates the PRISMA flow chart diagram for the process and reasons for exclusion.
Geographical settings were distributed in urban, rural, and multisite settings. Sixty-nine percent of the intervention sites were in rural settings (e.g., studies 14,19,24) and four studies were multisite (e.g., studies 6 and 20). Seventy-four percent were based on community sites (i.e., for home visits; seven studies), as outpatient (e.g., studies 21-23), as combination of in-and out-patient facilities (studies 3 and 17), and conducted within non-government organizations where people with psychosis resided (studies 15 and 18), and an orphanage (study 24). Twenty of the 27 studies included participants diagnosed with schizophrenia, three studies included participants with schizophrenia and bipolar disorder (studies 2-3 and 16), one included participants with schizophrenia and schizoaffective disorders (study 7), and one included participants with bipolar disorder (study 19).

Synthesis of results
Results were coded and narratively synthesized according to an emergent thematic framework based on the research objectives to describe family-based interventions and to explore how this is evidenced in LMICs. They were clustered into intervention features with the study outcomes, as well as the delivery strategies in different LMIC contexts.

Intervention features
The conceptual or theoretical underpinnings are the rationale for implementing family-based interventions. Two overarching themes emerged: psychotherapeutic components and task-sharing. Psychotherapeutic components address symptoms of psychosis psychologically, i.e., through processing or talking about mental and emotional distress. In the studies, three main components were salient: psychoeducation, therapeutic technique, and family systems approach. Twenty-four studies cited psychotherapeutic components as the basis for family-based intervention (studies 1-8, 10-25), 22 of which were based on psychoeducation (studies 1, 3-12, [14][15][16][18][19][20][21][22][23][24][25]. Twelve studies utilized therapeutic techniques, specifically, three studies employed individual therapy for family members with psychosis (studies 6, 13, and 24) and nine studies utilized family therapy (studies 2, 4, 6, 8-9, 13, 17, and 24-25), with one study that had multiple family therapy (study 22). Format of psychoeducation sessions included workshops (e.g., studies 5 & 12) and interactive discussions (e.g., study 6 & 18) within the time frames of three to 14 regular lectures lasting 15 min to two hours. The content generally includes a series of lectures about schizophrenia (e.g., study 11), different treatments and rehabilitation (e.g., study 21), caring for a family member with psychosis (e.g., 9), coping strategies, and how to care for the carers (e.g., study 22). Second, the family systems approach highlights the dynamics within the family, addressing the interaction among members to affect the outcomes of the person with psychosis. Studies specifically mentioned expressed emotion (EE; e.g., study 19) and communication/interaction patterns. For example, Zhang [77] aimed to decrease family stress and EE, thereby reducing relapse rates. Yang and Pearson [68] proposed to manage symptoms by reducing EE, and Asmal et al. [69] associated greater family support to reduced EE. Finally, task-sharing in this review pertains to assigning care and support by family members, to provide quality aftercare (e.g., study 3) and community networking, such as care networks (study 7) and social support networks (studies 2 and 18). Aftercare was a feature to strengthen the patient-family relationship and to provide support for other families in similar situations. Four studies (studies 3, 9, 11, and 15) employed home visits either to encourage sustained participation in the intervention (e.g., study 9) or to perform home-based therapeutic support (e.g., study 15). Family-based interventions in LMICs reported multiple outcomes for each study. Among the 27 studies, patient condition was mentioned 46 times from 26 studies, all reporting positive health impacts. For example, study 23 reported three patient outcome measures: recovery rate, symptom severity (negative symptoms), and relapse rate. Only studies 3, 12, and 18 reported no change for their specified patient conditions. Second, self-management outcomes appeared 17 times from 11 studies, all reporting positive health impacts. Study 16 for instance measured increased knowledge about schizophrenia and self-care skills. Third, social outcomes were mentioned 12 times from 15 studies, with studies 3, 12 and 13 reporting no change in social outcomes. Lastly, three studies (studies 10, 14 and 26) presented positive delivery outcomes, measuring an increase in attendance rates and service user satisfaction.

Delivery strategies
All the studies had more than two delivery agents for the intervention, except for one clinical study with one clinical psychologist in the individual family sessions [68]. Sixtyeight percent of the interventions were employed by mental health professionals, specifically, psychiatrists, clinical psychologists or therapists, and psychiatric nurses, while the rest were employed by social workers, researchers, and non-government organization staff. Intervention endpoints ranged from three to 24 months. Seventy-four percent of the studies cited their own preliminary research on the topic (e.g., studies [17][18]26) and population (e.g., study 8), and robustness of the method (e.g., study 22) as contributing factors to implementation. One-third of the studies underscored the importance of sustained family engagement in family-based interventions (e.g., studies 4 and 13), and a quarter attributed favorable delivery to cultural adaptation (e.g., studies 2 and 12). On the other hand, the studies also mentioned challenges in implementation, particularly those that lack robustness of research method (e.g., studies 8 & 10), including stigma held by family and community members (e.g., studies 7 and 27), and waning family involvement (studies 6 and 21). Lastly, authors of the studies offered improvements to the evaluations, such as longer follow-ups (e.g., study 3), and to the interventions, such as to use less and briefer sessions (e.g., study 26), to integrate in routine clinical settings (e.g., study 2), to task-share care and obtain support from family (e.g., study 24), to ensure cultural appropriateness (e.g., study 13), and to allocate a public health budget for it (e.g., studies 15, 26 and 27).

Discussion
To the best of our knowledge, this is the first review that synthesized the various family-based interventions in LMICs. It aimed to describe intervention features with their study outcomes, to identify the delivery strategies within the different LMIC contexts, and to appraise this evidence.

Summary of findings
Almost all studies examined family-based intervention as a stand-alone complex intervention; with only two studies utilizing antipsychotic meditation alongside family-based intervention (studies 10 and 21). Between 1993 and 2021, it appears that there was an increased delivery in LMICs, with 60% of the recorded evidence from the recent decade (2011-2020). It is encouraging to see an increase in number of reported studies, which also varied in design: trials and noncontrolled intervention studies, qualitative research, and economic evaluation from national data. While it appears ripe to adopt this intervention to low-resource contexts, systematic and scientific approach to planning it is essential. Most of the trials and before-after studies had methodological issues in randomization and in minimizing reporting bias. Despite this constraint, family-based intervention was still recommended by all included studies because of its cited effectiveness in individual studies, primarily in symptom reduction and improved family dynamics. A majority of the studies also reported decreased relapse rate, consistent with the evidence from HICs [33,53,83]. Additionally, patient outcomes related to decreased EE [20,22,84] that have been observed in HICs were also evident in the LMICs. It seems universal that being mindful of EE within the family unit could optimize involvement of family members when aftercare is dependent on them, increasing the quality of task-sharing from family members.
Even with the diversity of the geographical settings, key features in the family-based interventions were also similar to those administered in HICs, particularly psychoeducation and therapeutic components. Psychoeducation was the most common intervention feature in delivering familybased intervention across the different kinds of studies and    CBA controlled before-after study, cRCT cluster randomized control study, NCBA non-controlled before-after study, RCT randomized control trial study contexts, which could be implemented in different locations and by at least one delivery agent (i.e., by a psychologist in a psychotherapy session). This may not be surprising for psychosis interventions in HICs, but it is notable that this review highlights psychoeducation for utilizing family-based intervention in LMICs, coinciding with mhGAP recommendations for priority interventions for psychosis [85][86][87]. Moreover, recent suggestions to fill in gaps for early psychosis intervention and research involve the family [7,88]. Finally, cultural appropriateness was identified as an essential foundation in intervention features and implementation, consistent with previous literature on implementing family-and community-based interventions in LMICs [9,[89][90][91][92]. This review illustrated how anecdotes and stories in psychoeducation workshops were adapted for religious and cultural considerations as well as Western theoretical and conceptual bases contextualized to suit their population and therapeutic aims.

Strengths and Limitations
Our inclusion criteria captured and represented all relevant studies from LMICs. In addition, language bias was minimized by screening Spanish and Chinese articles and eventually including a Chinese-written article, but we were unable to translate two publications in Serbo-Croat found in the first screening. Synthesis was obtained narratively because of the variability of study outcomes. Three RCTs with low risk bias may not be enough to meaningfully pool them and would not satisfy the objectives of representing the current state of family-based interventions in LMICs. Further analysis could investigate the direction of effectiveness through  [93,94]. One limitation that developed in the analysis phase was that the included studies are classified as lower-or uppermiddle-income countries, thus indicative of a research gap in the records of family-based intervention for psychosis in low-income countries. Lastly, majority of the included studies had a moderate to high risk of bias mainly due to their methodological quality, therefore conclusions about the effectiveness of this intervention is limited by this. Recommendations from the studies for scaling up include quality research methodology and further research work.

Directions for practice and research
The evidence from this review suggests that participation of the family caregiver was essential in facilitating the familybased intervention in LMICs. Since up to 90% of aftercare is from family [5,12,95], whether by choice or convenience, the quality of engagement of the family caregiver with the person with psychosis is significant. The impetus to adapt family-based intervention in community-based rehabilitation in LMICs has been suggested and there seems to be a momentum in adopting and endorsing it in various parts of the world [8,96]. Therefore, an inventory of the evidence of family-based interventions in LMICs contributes both in research and in practice. Contributing factors in delivery, such as brief and culturally adapted intervention features and advanced and formative methodological preparations, mentioned in this review can be considered for implementing family-based programs. Task-sharing within the family for example, has augmented out-patient care and medication adherence [88]. LMIC-based mental health interventions and practice can tap into the family as an underutilized resource [97] and build their capacities as allies in providing quality care, while they also are taught techniques to care for themselves. Thus far, findings suggest that family-based intervention was implemented in communities and mostly outpatient facilities and can be delivered by at least one mental health professional or non-professionals. Consistent to general recommendations in family-based approaches in mental health intervention [10,21], recommendations to engage policymakers (studies 8,13,15,27) and to advance investment on this intervention (studies 15, 26-27) potentially enable scale-up. Active ingredients of delivered family-based interventions in LMICs fundamentally share key elements with the general literature, particularly on the content of sessions (e.g., psychoeducation, skills training), adapting to the cultural settings of the family, and a less rigid delivery strategy (e.g., time frame can be from months to years and delivery agent, and cooperation of a family member), and therapeutic techniques (e.g., talking therapies and family systems approach) [98]. While presenting the current state of family-based interventions in LMICs may prove significant, it would be worthwhile to add contextual definitions of effectiveness to the discourse.

Conclusion
A salient theme that emerged was the methodological strengths and weaknesses of the included studies and how these appear to impact the delivery of family-based interventions. Recommendations to refine interventions that involve the family can be gathered from this review. The evidence presented can further provide more definitive information on how to overcome barriers to implementation in LMICs. Large randomized controlled trials could provide more decisive evidence but depending on the context, careful consideration should be evaluated for the feasibility of conducting these. Cultural adaptation contributes to implementing this in LMIC contexts, and perhaps a challenge could also be in the conceptualization phase of the intervention, utilizing indigenous and evolving concepts of family structure and support, as well as contextualizing aftercare and recovery, to strengthen features of family-based interventions. Adopting a culturally grounded family-based intervention strategy can be a foundation to facilitate a robust community-based rehabilitation. Taken together, these findings may inform policymakers, healthcare providers, and academics to improve patient outcomes through a cost-effective intervention that can promote more effective task-sharing of quality care with the family.
Author contributions HM conceptualized the study, protocol and design. CH supervised the review. Search, screening, data extraction, quality assessment, analysis and interpretation were performed by HM. SL screened titles and abstracts and full articles, and assessed the quality of studies. CH screened the updated search. The first draft of the manuscript was written by HM, and CH and SL commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Conflict of interest
The authors declare that they have no conflict of interest.
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