Abstract: We identified 18 RCTs examining a range of complex interventions for people with multimorbidity. Nine studies focused on defined comorbid conditions with an emphasis on depression, diabetes and cardiovascular disease. The remaining studies focused on multimorbidity, generally in older people. In 12 studies, the predominant intervention element was a change to the organisation of care delivery, usually through case management or enhanced multidisciplinary team work. In six studies, the interventions were predominantly patient-oriented, for example, educational or self-management support-type interventions delivered directly to participants. Overall our confidence in the results regarding the effectiveness of interventions ranged from low to high certainty. There was little or no difference in clinical outcomes (based on moderate certainty evidence). Mental health outcomes improved (based on high certainty evidence) and there were modest reductions in mean depression scores for the comorbidity studies that targeted participants with depression (standardized mean difference (SMD) −2.23, 95% confidence interval (CI) −2.52 to −1.95). There was probably a small improvement in patient-reported outcomes (moderate certainty evidence) although two studies that specifically targeted functional difficulties in participants had positive effects on functional outcomes with one of these studies also reporting a reduction in mortality at four year follow-up (Int 6%, Con 13%, absolute difference 7%). The intervention may make little or no difference to health service use (low certainty evidence), may slightly improve medication adherence (low certainty evidence), probably slightly improves patient-related health behaviours (moderate certainty evidence), and probably improves provider behaviour in terms of prescribing behaviour and quality of care (moderate certainty evidence). Cost data were limited. This review identifies the emerging evidence to support policy for the management of people with multimorbidity and common comorbidities in primary care and community settings. There are remaining uncertainties about the effectiveness of interventions for people with multimorbidity in general due to the relatively small number of RCTs conducted in this area to date, with mixed findings overall. It is possible that the findings may change with the inclusion of large ongoing well-organised trials in future updates. The results suggest an improvement in health outcomes if interventions can be targeted at risk factors such as depression, or specific functional difficulties in people with multimorbidity.

Plain-language summary: We searched the literature up to September 2015 and identified 18 generally well-designed randomised controlled trials meeting the eligibility criteria. Nine of these studies focused on specific combinations of health conditions (comorbidity studies), for example diabetes and heart disease. The other nine studies included people with a broad range of conditions (multimorbidity studies) although they tended to focus on elderly people. The majority of studies examined interventions that involved changes to the organisation of care delivery although some studies had more patient-focused interventions. All studies had governmental or charitable sources of funding. Overall the results regarding the effectiveness of interventions were mixed. There were no clear positive improvements in clinical outcomes, health service use, medication adherence, patient-related health behaviours, health professional behaviours or costs. There were modest improvements in mental health outcomes from seven studies that targeted people with depression, and in functional outcomes from two studies targeting functional difficulties in participants. Overall the results indicate that it is difficult to improve outcomes for people with multiple conditions. The review suggests that interventions that are designed to target specific risk factors (for example treatment for depression) or interventions that focus on difficulties that people experience with daily functioning (for example, physiotherapy treatment to improve capacity for physical activity) may be more effective. There is a need for further studies on this topic, particularly involving people with multimorbidity in general across the age ranges. All of the included studies were randomised controlled trials. The overall quality of these studies was good though many studies did not fully report on all potential sources of bias. As definitions of multimorbidity vary among studies, the potential to reasonably combine study results and draw overall conclusions is limited. Overall, we judged that the certainty or confidence we can have in the results from this review is moderate but due to small numbers of studies and mixed results we acknowledge the uncertainty remaining and the potential that future studies could change our conclusions.