Background
Depression and diabetes mellitus (DM) are two of the most prevalent chronic diseases around the world, which frequently co-occur [
1‐
5]. Approximately 20% of patients with DM meet diagnostic criteria for depression [
4,
5]. Diabetic patients with depression are associated with decreased glycated hemoglobin control, lower adherence to diet, exercise and taking medications, comparing with those without depression [
6‐
9]. Moreover, depression had an increased risk in diabetes development and adverse diabetes outcomes, such like microvascular and macrovascular complications [
10,
11].
Patients with diabetes and depression are usually poorly managed in primary care [
7,
12]. Depression is associated with failures to detect and diagnose in diabetic patients [
13]. Diabetes also weaken the effectiveness of depression treatments [
14,
15]. Depression care needs to be improved especially in people with diabetes and vice versa. The most common method of treatments for diabetes and depression in primary care are taking medications of oral hypoglycemic agents and antidepressants. However, diabetes patients with depression are more likely to have problems and concerns with medication, such like fear of side effects and addiction, than those patients without depression [
1,
15‐
17]. Conventional psychological interventions fail to improve both physical and mental health outcomes in diabetes patients with depression [
18].
Collaborative care is a new model pointing out coordinated care management in primary practices, which involving primary care physicians, nurses and other specialists or professionals who provided patient-orientated and guideline-based management to patients at the primary care level [
12,
19‐
22]. It is originally conducted on depressive patients. More studies of collaborative care have been diversified to those patients with chronic illnesses [
19,
23]. Nowadays, collaborative care attracts a worldwide interest in its potential effectiveness in achieving certain clinically improvements and public health benefits [
12,
19‐
21,
24,
25]. Several randomized controlled trials (RCTs) indicated that collaborative care significantly improved control of both depression and diabetes [
19,
26,
27]. However, some studies concluded that collaborative care improved depression outcome alone [
23,
28]. There is no consensus on these results. We still do not know whether collaborative care work as a truly integrated intervention that improve both depression and diabetes outcomes.
We therefore conducted a systematic review and meta-analysis to examine whether a primary care based collaborative care would improve depression and diabetes outcomes in patients with both depression and diabetes.
Discussion
The present study comprehensively summarized current evidences from 8 RCTs to examine if collaborative care can work as a truly integrated intervention to improve both depression and diabetes outcomes, comparing with usual care. We found that collaborative care significantly improved depression outcomes, as well as adherence to antidepressant medication and oral hypoglycemic agent. Though there were significant heterogeneity in the meta-analyses, we found results from large RCTs were consistent [
19,
31,
32], which strengthened the robustness of our conclusion.
Our study showed that collaborative care improved depression treatment response of diabetic patients with depression. All combined results showed positive effects on depression treatment response at 6 months, 12 months and the end of follow up. Moreover, the improvement in the outcome at the end of follow up compared favorably with response rates in collaborative care trials, which included patients with and without long term conditions. For example, a previous meta-analysis of 79 RCTs of collaborative care for depression showed a RR of 1.29 (95% CI = 1.18-1.41) [
12] versus a RR of 1.33 (95% CI = 1.05-1.68) in our study.
Collaborative care model was also significantly associated with higher rates of both adherence to antidepressant medication (RR = 1.79, 95% CI = 1.19-2.69) and oral hypoglycemic agent (RR = 2.18, 95% CI = 1.61-2.96) in depressed patients with diabetes. These results are encouraging. Previous studies showed that depression was significantly associated with poor adherence to medication in diabetic patients [
8,
15,
39]. In view of the challenges that faced by physicians in primary care practices, collaborative care are most likely helpful to improving adherence rate of medication among depressed patients with diabetes.
The effects of collaborative care on depression remission rates were limited at the end of follow up. According to our combined results, it seems that collaborative care did not benefit long term depression remission (RR = 1.15, 95% CI = 0.87-1.52). This data was mainly based on the crude RRs or crude odds ratios (ORs) that reported in original RCTs. Most of the authors of these original RCTs only reported the crude RRs or ORs without adjusting the potential confounders (for example, age, base line SCL-20 and HbA1c values). In study of Ell et al [
32], the authors anticipated these confounders and provided the adjusted analysis for collaborative care versus usual care, which showed a signification increase in depression remission at the end of follow up (adjusted RR = 1.53, 95% CI =1.11-2.12). However, the data could not be combined since there was only one study reported the adjusted results of this outcome. In the future, the trialists are recommended to report both adjusted and unadjusted results to prevent the potential selection bias [
40,
41]. In addition, our meta-analysis showed that collaborative care also improved treatment remission rates at 6 months follow up, but this effect was modest.
Out meta-analyses showed that the improvements of outcomes of depression were not accompanied by significant differences in HbA1c values between patients in collaborative care and usual care group. HbA1c values were not affected at 6 months, 12 months and the end of follow up. Of the trials included in qualitative synthesis, three of them [
19,
26,
27] had found that collaborative care was associated with improved HbA1c values, and two of them was significant [
19,
26]. Given that diabetic patients with depression usually have more macrovascular and microvascular complications and higher numbers of risk factors than diabetic patients without depression, the collaborative care that focuses on improving management of both depression and diabetes are likely to be needed in the future, to improve clinical outcomes at a population level in both of chronic illnesses [
19].
Limitations of the review
Combining the results from different trials generated significant variations in outcomes. In meta-analyses of primary outcomes, there existed a significant heterogeneity in the overall results of depression treatment response. The values of I
2 are 54%, 52% and 59% for treatment response at 6 months, 12 months and the end of follow up respectively, which were all represented moderate levels of heterogeneity [
42]. We therefore used random effects models to combine the data of these outcomes. Collaborative care is a kind of complex intervention with a considerable variability involving separate mechanisms, which is difficult to specify and define [
29]. Nevertheless, compared with previous reviews [
22,
43], which using broader inclusion criteria for collaborative care, this review was based on more precise definition of collaborative care [
12,
30].
We were unable to collect addition information from authors who were responded for the original studies. There might be some missing data. In addition, using the Cochrane Collaboration’s tool for assessing risk of bias, we have identified methodological limitations in the studies. For example, all studies were rated as high risk of bias for blinding of participants and personnel.
Last but not least, this meta-analysis was based on 8 RCTs with 2,238 patients from different primary care practices in the United States, which might not be representative of all patients with both diabetes and depression around the world. Further research is needed to help clarify whether collaborative care can be implemented outside the United States.
Conclusions
In summary, collaborative care model significantly improves depression outcomes and adherence to medication in diabetic patients with depression, comparing with usual care. Collaborative care is recommended for patients with both depression and diabetes in the future.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
AG and YH conceived and designed the experiments. YH, AG, XW, TW and RC involved in the interpretation of the results. YH and AG performed the experiments. YH, XW, TW and RC analyzed the data. YH and AG wrote the paper. All authors read and approved the final manuscript.