Worldwide, 349 million people are estimated to be care-dependent, of whom 18 million (5%) are children aged under the age of 15 years, and 101 million (29%) are older people 60 years of age and over. Care-dependence is defined as the need for frequent human help or care beyond that habitually required by a healthy adult. In older people, coexisting chronic diseases (multimorbidity) is frequently associated with the need for health and social care (1). In most countries, care for older people is provided by informal caregivers (including spouses, adult offspring and other relatives or friends), and the majority of primary caregivers are women (2). Evidence shows that caregivers of people with severe declines in capacity are at high risk of experiencing psychological distress and depression (3). In many low-and middle-income countries, formal systems of long-term care are poorly developed; the negative effects of caregiving therefore have a strong impact on the physical, emotional and economic status of family caregivers (2).
In the past two decades, psychosocial interventions to support informal caregivers have been extensively studied. Psychosocial support includes different types of service provision, such as psychoeducational, counselling, skill-building and information or emotional support, which may be provided through agency-based settings or in the carer's home (4). These interventions focus on improving the carer's ability to manage everyday caregiving tasks (4). Furthermore, recent research has explored technologybased interventions, including the use of telephone and computer services, to provide adequate support and education to caregivers, with accessibility being a key advantage (5). Another popular intervention is respite care, defined as the provision of a temporary break in caregiving activities for the informal carer aimed at reducing distress and improving the carer's well-being (6). Respite can be delivered in different ways, including in-home services, adult day care or in institutions, such as care homes or hospices (7). Evidence from earlier reviews suggest that most trials of caregiver interventions were from high-income countries and were largely dominated by a range of programmes and services developed to assist caregivers of people with dementia. Therefore, the effectiveness of these interventions in different social, cultural and geographical contexts is unclear (2). Of all the chronic diseases, dementia is a particularly important contributor to caregiver strain. However, the extent to which these interventions can be administered to informal caregivers of care-dependent older people is unknown.

# Search strategy
The search for studies using combined intervention terms was conducted on October 2015 in Ovid MEDLINE (see Annex 1). The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials databases were searched, using combinations of the following terms:
( Excluded from GRADE tables and footnotes (12,13) -Lopez-Hartmann M, Wens J, Verhoeven V, Remmen R.

# Narrative description of the studies that went into analysis
Respite care and psychosocial interventions

# GRADE table 1
Mason et al. conducted a systematic review and meta-analysis to examine the effectiveness and cost-effectiveness of respite care for caregivers of frail older people (8). An extensive literature search was conducted and relevant studies were identified and assessed for methodological quality by two of the authors. A total of 22 studies were included: 10 randomized controlled trials (RCTs), seven quasi-experimental studies and five uncontrolled studies. Noticeably, even though the search was not restricted to a particular disease, most of the studies included older people with cognitive impairment exclusively (n = 13). Although physical impairment was also described as a common condition, it was inconsistently reported. Moreover, different types of respite care were covered across the different trials including adult day care, multidimensional packages, respite packages, in-home respite, host-family respite, institutional respite and video respite.
Caregiver burden and caregiver depression were the two main outcomes measured. Pooled estimates obtained from four RCTs and four quasi-experimental studies (N = 989) assessing respite package (n = 1), in-home respite (n = 2) and adult day care (n = 5) found no statistically significant effect of respite on caregiver burden (SMD: 0.15, 95% CI: -0.36 to 0.05). On the other hand, pooled estimates from one RCT and two quasi-experimental studies (N = 295) examining caregiver depression showed a statistically significant positive effect (SMD: 0.32, 95% CI: -0.62 to -0.02).This overall beneficial effect was attributed mainly to results in one trial on day care, however, which undermines the reliability of the pooled results.
The authors concluded that there is evidence suggesting that respite for caregivers of frail older people may have a small positive effect reducing caregiver depression and burden (although the latter effect was not significant when including RCTs in the analysis). They found no reliable evidence that respite care may delay institutionalization or may be more cost-effective than usual care. However, it should be noted that several limitations have been reported by the authors regarding the methodological quality of the studies and the variability of relative effects based on structural differences in the interventions provided.

# GRADE table 2
Shaw et al. conducted a systematic review and meta-analysis to assess the effectiveness of respite care on the well-being of informal carers of frail and disabled older people living in the community (9). An extensive search was conducted, including qualitative studies, and methodological quality was assessed by two authors independently. From a total of 104 quantitative studies selected, 16 were included in the meta-analysis (9 RCTs and quasi-experimental studies and seven longitudinal before-and-after studies). All the studies were conducted in high-income countries, the majority assessing day care and mixed respite care interventions, while some assessed in-home care and institutional care. Overall, care recipients included frail older people or older adults with dementia or experiencing mixed problems. Two RCTs and a quasi-experimental study assessing day care respite showed

# (continued next page)
ICOPE guidelines -World Health Organization no significant effects of respite care on caregiver burden after a six-month follow-up period (SMD: 0.11, 95% CI: -0.38 to 0.17). However, even though studies were rated as moderate to high quality, sampling characteristics of one of the trials were not generalizable to the carer population and another study presented limitations as the uptake of respite was low in the sample. In addition, caregiver depression was assessed as a primary outcome. Due to significant heterogeneity in the studies, random effect model results were used and these are presented in the GRADE tables. Authors found no significant results in favour of day care respite to address carer depression either at short-term (six months) or long-term follow-up (12 months) (SMD: -0.23, 95% CI: -0.49 to 0.03; and SMD: -0.08, 95% CI: -0.41 to 0.24, respectively). Although the overall quality of studies in this group was moderate, authors remarked that the low level of respite provision in two of the studies might explain the intervention's low impact.
Further analysis revealed no significant benefits of respite in terms of caregiver anxiety (SMD: 0.27, 95% CI: -0.28 to 0.82) and singlegroup studies indicated that carer's quality of life was worse after respite use. However, pooled estimates derived from one moderate-quality RCT and one quasi-experimental study providing day care showed that anger was significantly lower after three months post-intervention in the intervention group (SMD: -0.38, 95% CI: -0.60 to -0.17).  (11). In addition to the interventions analysed in their previous article (10), the authors also included measures such as: (i) counselling/case management, (ii) psychoeducation stratified into active participation or information provision only and (iii) structured and unstructured multicomponent approaches. Furthermore, authors added institutionalization as a main outcome measure. A detailed analysis of the evidence reported in this study is presented in the WHO mhGAP guidelines on interventions for carers of people with dementia (14). Overall, when evidence from both studies is compared (10,11), similar findings can be observed showing that psychoeducation is significantly beneficial for all the outcomes across both studies and, similarly, psychotherapy (e.g. cognitive behavioural therapy had significant effects in terms of reducing caregiver burden and depression in all caregivers. However, while respite care showed significant benefits for improving burden, depression and subjective well-being (SWB) for dementia caregivers (SMD: -0.26, 95% CI: -0.39 to -0.12; SMD: -0.12, 95% CI: -0.24 to 0; SMD: 0.27, 95% CI: 0.03 to 0.51, respectively) (11), no positive effects remained when only RCTs were analysed for older people's carers (10).
GRADE a Indirectness: Downgraded once as trials recruited unselected target population; caregivers for older people with and without dementia were included, therefore it is difficult to distinguish the effect. Included trials were from high-income countries, therefore data may not be generalizable to resource-poor settings. b Imprecision: Downgraded twice as sample size was very small (less than 100 participants). c Number of participants recruited in the control group was not reported. b Indirectness: Downgraded once as included trials were from high-income countries, therefore, data may not be generalizable to resourcepoor settings. Trials recruited unselected target population: both caregivers for older people with and without dementia were included, therefore, it is difficult to distinguish the effect. c Imprecision: Downgraded once as sample size was small (less than 200). d Imprecision: Downgraded twice once as sample size was small (less than 100). e Number of participants recruited in the control group was not reported. a Inconsistency: Downgraded once as Chi 2 test indicates heterogeneity (P = 0.05), but I 2 value was not reported. b Indirectness: Downgraded once as trials recruited unselected target population; caregivers for older people with and without dementia were included, therefore it is difficult to distinguish the effect. Included trials were from high-income countries, therefore data may not be generalizable to resource-poor settings. c Imprecision: Downgraded twice as sample size was very small (less than 100). d Imprecision: Downgraded once as sample size was small (less than 200).

# GRADE table 6: Support interventions compared with no intervention for carers of older adults

# GRADE table 8: Multicomponent interventions compared with no intervention for carers of older people
Evidence profile: caregiver support ICOPE guidelines -World Health Organization

# Additional evidence not mentioned in GRADE tables

# Psychosocial interventions
Yin et al. conducted a systematic review and meta-analysis to examine the effectiveness of group and individual interventions on reducing the burden experienced by carers of frail older people (15). A total of 26 studies were included (17 RCTs and nine quasi-experimental studies) with sample sizes ranging from 20 to 486 (total N = 1970). Caregiver mean age was 60.1 years, nearly 80% of participating caregivers were female and more than 80% reported living with the care recipient. On the other hand, the mean age for care recipients was 78.7 years and 54% of the total sample had a diagnosis of dementia. Eighteen studies explored group interventions of which more than 90% combined an educational component with a support programme. Duration of the interventions varied from two weeks to one year and 33% of the studies included up to six month of follow-up. Moreover, the eight studies examining individual interventions (N = 472) had a duration ranging from one single session to eight months follow-up. All studies included caregiver burden as a primary outcome measure and the Zarit Burden Interview (ZBI) was mostly employed as a measure scale.
The authors calculated that the weighted mean effect size was 0.41 (95% CI: 0.32 to 0.51), showing a significant beneficial treatment effect for group interventions. Moreover, they found that the effect size remained significant when only RCTs were included (mean: 0.26, 95% CI: 0.15 to 0.37, n = 11). However, the homogeneity test was significant (Q17 = 56.37, P < 0.0001), which could indicate variations in the different study effect sizes attributable to study characteristics. Furthermore, similar results were observed for individual interventions where the weighted effect size was 0.48 (95% CI: 0.30 to 0.67), indicating a positive treatment effect. Nevertheless, the authors reported that most of the studies were flawed: six trials showed high risk of bias due to uncertainties around randomization and seven studies failed to report features significant to study outcomes which may jeopardize the generalizability of the results.

# Information and communication technology support
There is very limited evidence regarding the effectiveness of technology-based interventions for caregivers who care for people exclusively with chronic diseases other than dementia. Klemm et al. conducted a randomized longitudinal study to evaluate whether psychosocial outcomes in family caregivers of people with chronic disease who participate in online support groups (OSGs) differ from those who are non-active participants in OSGs (16). A total of 86 caregivers were randomized into two types of OSGs (professionally facilitated/ psychoeducational or moderated/peer-directed OSGs). Nonactive participants were those who completed informed consent and questionnaires, but did not actively participate in the online discussions. The OSG programmes had a duration of 12 weeks, and outcomes were measured at baseline and at two later time pointswith outcomes including depression measured by the Center for Epidemiology Studies -Depression Scale (CES-D), burden measured by the Caregiver Strain Index (CSI) and quality of life measured by the Caregiver Quality-of-Life Index (CQoL-I). The authors found that both professionally facilitated/psychoeducational and moderated/peer-directed OSGs reduced depressive symptoms and improved quality of life for caregivers who actively participated (P = 0.018 CES-D;
(continued next page) ICOPE guidelines -World Health Organization P = 0.046 CSI; 0.004 CQoL-I). Moreover, they found no significant differences in the effectiveness of the two types of OSGs. However, generalizability of the results may be limited considering the sample characteristics (most caregivers were middle-aged white women who read and spoke English) and considering the fact that the intervention is limited to those who have access to a computer and the Internet and who have some degree of computer literacy. Moreover, risk of bias is unclear due to high attrition rates, mainly in the non-active participant group. Economic incentives were awarded to those who completed the study. The authors suggest that future caregiver research should target men and minorities.

# Evidence from technology-based interventions for dementia caregivers
Mahoney et al. conducted a small RCT (n = 100) to examine the effectiveness of a computer-mediated automated interactive voice response (IVR) intervention for assisting caregivers of people with disruptive behaviours associated with Alzheimer's disease (17). Caregivers were randomized to a 12-month intervention group or a control group. IVR provided stress monitoring and counselling information, personal voicemail linkage to Alzheimer's disease experts, a telephone support group and a distraction call for care recipients. Outcomes including depression, anxiety, mastery and bothersome nature of caregiving were measured at baseline, 6, 12 and 18 months. Authors found a significant effect for caregivers with lower mastery at baseline on all the other outcomesbother (P = 0.04), anxiety (P = 0.01) and depression (P = 0.007)meaning this intervention could be particularly beneficial for caregivers with these characteristics.
Moreover, another study based on the REACH programme (Resources for Enhancing Alzheimer's Caregiver Health) explored the efficacy of technology-based interventions and family therapy in reducing depression among dementia caregivers (18). A total of 225 (114 Cuban and 111 American) caregivers were randomized to receive a structural family therapy (SFT), a combined intervention (SFT plus computertelephone integrated system or minimal support (control group). The CTIS system covered several aspects including: regular or conference phone calls with family or friends living far apart, monthly web-based telephone conferences with other caregivers, access to voicemail box, therapist appointment reminders and access to the Alzheimer's Association Resource Guide. Randomization was stratified according to the ethnicity of the caregiver and the REACH core battery of assessments (i.e. the CES-D, the Revised Memory and Behaviour Problems Checklist  to measure burden, activities of daily living  scale, Mini-Mental State Examination  and a Likert scale to measure global satisfaction) was administered at 6, 12 and 18 months. All measures were adequately translated to Spanish for Spanish-speaking participants. Authors found that at the six-month follow-up depressive symptoms in caregivers were significantly reduced among those who had received the combined intervention. Information and communication technology support interventions, such as professionally facilitated/psychoeducational or moderated/peer-directed online support groups (OSGs) reduced depressive symptoms and improved the quality of life for carers of people with chronic diseases who actively participated in the OSGs. Moreover, computer-mediated automated interactive voice response (IVR), as well as a combined structural family therapy and computer-telephone integrated system (CTIS) intervention, showed some beneficial effects. However, these findings are based on single RCTs conducted in high-income countries and aimed at caregivers of people with dementia.
No harm was identified.

# Values and preferences/acceptability Explanation
Is there important uncertainty or variability about how much people value the options? Most of the available studies analysed did not focus specifically on interventions for caregivers of frail older people; there was frequently a preponderance of caregivers of people with dementia in the samples. No subgroup analysis was conducted in most of the studies. Moreover, the lack of studies comparing interventions limits our understanding as to whether some interventions are more effective than others.
When assessing the effectiveness of respite interventions, respite care was not found to significantly reduce the caregiver's burden, depression or anxiety. Further analysis including only RCTs showed similar results, as well as finding no significant effects of respite care on caregivers' subjective well-being, ability and knowledge, or on the reduction of the care recipients' symptoms. However, positive results for reducing caregivers' burden, depression and improving their subjective well-being were observed when the analysis was not limited to RCTs. Significant beneficial effects of respite care on reducing caregiver depression were described in another meta-analysis. However, the reliability of these results remains unclear as only one RCT was included in the analysis. Further research is required to explore the effectiveness of respite care interventions for caregivers of frail older people exclusively, as well as an appropriate subgroup analysis within the caregiver population and for each type of respite care service provided (i.e. day care, residential home, etc.).

# Feasibility/resource use Explanation
How large are the resource requirements? Considering that these interventions are frequently resource intensive, implementation of such approaches would be more difficult to achieve and would vary according to the resources available at each different location.
- Psychotherapeutic interventions (including counselling and/or cognitive behavioural therapy) should be offered when indicated, assuming that specialists accredited in the approaches or trained and supervised non-specialists are available to deliver the interventions. - The evidence for information and communication technology (ICT) interventions (mainly) from the field of dementia suggests ICT technology as a potentially useful means, with increasing coverage due to the low cost. - The vast majority of the primary studies available were carried out in high-income countries. Moreover, few available trials focused specifically on caregivers of older adults with chronic or disabling conditions other than dementia. Therefore, more research concentrating on the effectiveness of interventions for this particular group is required, as well as subgroup analyses within the caregiver population (children and other relatives, friends, neighbours, and so on). - Further studies are also needed to explore the different types, content, duration and format of delivery of each intervention.
- Psychoeducational interventions delivered by trained non-specialists could represent a feasible and effective alternative, which could be beneficial to all health systems worldwide, given the increasing health demands in the context of ageing populations.