- Top of page
OBJECTIVE: A previous study described the effect of a collaborative care intervention on improving adherence to antidepressant medications and depressive and functional outcomes of patients with persistent depressive symptoms 8 weeks after the primary care physician initiated treatment. This paper examined the 28-month effect of this intervention on adherence, depressive symptoms, functioning, and health care costs.
DESIGN: Randomized trial of stepped collaborative care intervention versus usual care.
SETTING: HMO in Seattle, Wash.
PATIENTS: Patients with major depression were stratified into severe and moderate depression groups prior to randomization.
INTERVENTIONS: A multifaceted intervention targeting patient, physician, and process of care, using collaborative management by a psychiatrist and a primary care physician.
MEASURES AND MAIN RESULTS: The collaborative care intervention was associated with continued improvement in depressive symptoms at 28 months in patients in the moderate-severity group (F1,87 = 8.65; P = .004), but not in patients in the high-severity group (F1,51 = 0.02; P = .88) Improvements in the intervention group in antidepressant adherence were found to occur for the first 6 months (χ2(1) = 8.23; P < .01) and second 6-month period (χ2(1) = 5.98; P < .05) after randomization in the high-severity group and for 6 months after randomization in the moderate-severity group(χ2(1) = 6.10; P < .05). There were no significant differences in total ambulatory costs between intervention and control patients over the 28-month period (F1,180 = 0.77; P = .40).
CONCLUSIONS: A collaborative care intervention was associated with sustained improvement in depressive outcomes without additional health care costs in approximately two thirds of primary care patients with persistent depressive symptoms.
Several studies have shown that only approximately 40% of primary care patients with major depression who are accurately diagnosed and started on antidepressant medication by their primary care physicians are significantly improved (50% decrease in initial symptoms) at 4 to 6 months.1–3 Recent evaluations of enhanced depression care interventions have shown significant improvement in the percent of patients who recover.1,2,4–6 We recently reported that a stepped collaborative care intervention resulted in significantly greater improvement in depressive and functional outcomes over a 6-month period compared to usual primary care in patients with persistent symptoms 2 months after initiating antidepressant medication treatment with their family physician.7,8
Because prior research had demonstrated that severity of depression was one of the best predictors of outcomes of depressive episodes in primary care,9 randomization of patients with persistent depression in the above trial was stratified by severity on the Hopkins Symptom Checklist depression items10 (symptom check list [SCL]-20 of <2.0 and >2.0). A second paper based on these 2 severity strata showed that severity of depression was a predictor of response to treatment.11 Analyses revealed a significant intervention effect by 3 months that continued at the 6-month follow-up among those with moderate depressive severity (mean SCL depression score of 1.0 to 2.0), but did not continue at the 6-month follow-up among those with greater symptom severity.11
The higher severity group represented about one third of the sample and was found to significantly differ from the moderate-severity group on 3 main clinical variables: the percent with comorbid panic disorder (odds ratio [OR], 5.8); percent reporting childhood emotional abuse (OR, 2.1); and percent feeling more lonely (OR, 2.6).11 Analysis of prescription refills for antidepressant medications over the 6-month period revealed improved adherence in intervention patients compared to controls in both high and moderate groups, suggesting that a worsening depressive course in the high-strata group between 3 and 6 months was not due to changes in medication adherence. These findings suggest that the higher depressive severity subgroup, characterized by increased loneliness and anxiety, was unlikely to show long-term benefits from the collaborative care intervention, whereas the moderate-severity group might show sustained benefits.
This paper will test several questions about the long-term effects of a stepped collaborative care intervention among persistently depressed primary care patients.
Among those in the moderate-severity strata, does the intervention (I) group sustain the 6-month improvement in depressive and functional outcomes over 28 months of follow-up as compared to usual-care (UC) patients?
Do the moderate- and high-severity intervention groups sustain the 6-month improvements in adequacy of dose and duration of antidepressant medication over 28 months of follow-up as compared to usual care?
What are the differences in total ambulatory care costs between intervention and control patients over this long-term follow-up?
- Top of page
A total of 2,699 letters were mailed to eligible patients in the 4 Group Health primary care clinics, with 336 (12.4%) refusing to be interviewed and 312 (11.5%) patients who were ineligible or who couldn't be contacted. Patients agreeing to be interviewed (n = 2,051; 76.1%) did not differ in age or gender from patients refusing to be interviewed.
Of the 2,051 patients completing the screening, 272 (13.3%) were eligible for the persistence study and 694 (33.9%) were eligible for a parallel study on relapse prevention14 (based on having 0 to 3 DSM-IV symptoms and either recurrent depression or dysthymia). Of the 272 patients eligible for the persistence study, 176 (64.7%) received a baseline interview and 159 (90.3%) were successfully randomized to the persistence study. Ninety-six (35.3%) patients did not receive a baseline interview. Of these 96 patients, 30 refused, 30 did not have time to participate in an intervention program, 27 could not participate for other miscellaneous reasons, and 9 could not be contacted. Patients refusing baseline interview did not differ in age or gender from those agreeing to be interviewed.
Of the 694 patients eligible for the baseline interview for the relapse prevention study based on screening interview, 472 (68%) completed the interview and 69 (14.6%) were offered and accepted randomization to the persistence study based on an SCL of 1.5 or more. Patients refusing the baseline interview for the relapse prevention study (222 (8.1%)) did not differ in age or gender from those agreeing to be interviewed.
Of the 228 patients randomized, 209 (91.7%) completed the 1-month follow-up, 193 (84.6%) completed the 3-month follow-up, 192 (84.2%) completed the 6-month follow-up, and 171 (75%) completed the 28-month follow-up. There were no significant demographic or clinical differences between the patients who missed completing at least 1 follow-up and the patients completing all 4 follow-up interviews.
There were no significant differences between the 114 intervention and 114 usual-care patients on the following demographic variables, including age (I, 47.2 ± 14.0 years vs UC, 46.7 ± 13.4 years), percent with 1 or more years of college (I, 77.2% vs UC, 78.1%), percent employed full- or part-time (I, 72.6% vs UC, 64.9%), and percent Caucasian (I, 79.8% vs UC, 80.7%). There was a significant difference between intervention and control patients in the percent of female subjects (I, 67.5% vs UC, 81.6%, χ2 (1) = 5.20; P = .02), which was one of the covariates controlled for when analyzing differences in outcomes between the 2 groups.
There were also no significant differences between intervention and control patients on chronic disease score (I, 1,191 ± 979 vs UC, 1,368 ± 1,293), NEO Neuroticism score (I, 22.7 ± 5.5 vs UC, 23.0 ± 5.5), SCL-Depression score (I, 1.9 ± 0.5 vs UC, 1.9 ± 0.5), percent with recurrent depression (I, 76.3% vs UC, 83.3%), or percent with a history of dysthymia (I, 50.0% vs UC, 59.8%).
There were no significant differences in age, gender, randomization or strata groups, or baseline depression level between the 187 patients used in the cost and adherence analyses and the 41 patients who disenrolled at some point during the 30 months. There were no significant demographic or clinical differences between control and intervention patients in the cost and adherence analyses.
Effects of Intervention on SCL Depression Score
The longitudinal random regression model for SCL depression resulted in a significant 3-way interaction of time × treatment × strata (z = 2.16; P= .03). This was due to significant interactions of time × treatment (z = 1.94; P = .05) and time × strata (z = 3.16; P = .002). In this model, the main effects are not directly interpretable. Baseline depression, CDS, and NEO were significant covariates. On the basis of these results, we stratified by baseline severity in order to examine 28-month depression. The planned post hoc ANCOVAs for the 28-month SCL-Depression showed a significant treatment effect for patients in the moderate-severity strata (F1, 87 = 8.65; P = .004), with the adjusted mean for the control group (1.23 ± 0.62) significantly higher than that of the intervention group (0.88 ± 0.52) at the 28-month follow-up (seeFig. 1). In the high strata, treatment differences in SCL-Depression at 28 months were not statistically significant (F1, 51 = 0.02; P = .88] (seeFig. 2). The adjusted means were 1.16 ± 0.85 and 1.19 ± 0.72 for the intervention and control groups, respectively, at the 28-month follow-up.
Effects of Intervention on Sheehan Disability Scale
The longitudinal random regression model for Sheehan disability resulted in a significant 3-way interaction of time × treatment × strata (z = 3.08; P = .002). This was due to significant interactions of time × treatment (z = 2.06; P = .04) and time × strata (z = 3.69; P < .001), and treatment × strata (z = 2.41; P = .02). In this model, the main effects are not directly interpretable. CDS was the only significant covariate. On the basis of these results, we stratified by baseline severity in order to examine 28-month disability. The ANCOVAs for the Sheehan Disability Scale at the 28-month follow-up were not statistically significant. In the moderate strata, the control group reported more disability (adjusted mean = 3.58 ± 2.37) in comparison to the intervention group (adjusted mean = 3.09 ± 2.30) (F1, 87 = 1.21; P = .27). In the high strata, there were no significant differences between the intervention (adjusted mean = 3.41 ± 2.61) and control groups (adjusted mean = 3.20 ± 2.66) (F1, 51 = 0.09; P = .76).
Effects of Intervention on Dosage and Duration of Antidepressant Medications
The longitudinal ordinal random regression model examining patients meeting criteria for at least 90 or more days of an adequate dosage of antidepressants in each of five 6-month periods did not result in a significant 3-way interaction of time × treatment × strata (z = 1.79; P = .07). When this term was dropped, and the model was refit, the only significant 2-way interaction was time × treatment (z = 3.62; P < .001). In this model, the main effects of time and treatment are not directly interpretable. The strata main effect was very significant in the model (z = 4.49; P < .001). On the basis of this result, we stratified by baseline severity in order to examine 28-month adherence to an adequate dosage of medication. For the high-severity strata, intervention patients were significantly more likely to adhere to 90 days or more of antidepressants at the lowest dose consistent with Agency for Health Care Policy and Research guidelines compared to usual-care patients during the first and second 6-month blocks of time. In the high strata during the first 6 months, 72% (n = 24) of the intervention patients and 40% (n = 14) of the controls were adherent to an adequate dosage of medication (χ2 (1) = 8.23; P < .01). This trend was also seen in the second 6-month period: 70% (n = 23) of the intervention patients and 37% (n = 13) of the controls were adherent to an adequate dosage of medication (χ2(1) = 5.98; P < .05). For the moderate-severity strata, intervention patients were only more likely to adhere to 90 days or more of adequate dosage of antidepressants during the first 6-month block of time (76% of the intervention patients versus 46% of the controls, χ2(1) = 6.10; P < .05) Similar, but nonsignificant, trends were observed for the second 6-month block. For the other three 6-month periods, the percentages were very similar for the treatment groups in both strata.
Effects of Intervention on Costs
Table 1 describes the unadjusted difference in health care costs between intervention and control patients. On the basis of linear regression models, there were no significant differences between intervention and control patients in total ambulatory costs (F1,180 = 0.77; P = .40), total health care costs (F1,180 = 0.91; P = .34), depression treatment costs (F1,173 = 2.65; P = .10), or non–depression-related outpatient costs (F1,180 = 0.11; P = .74). In the descriptive unadjusted data, intervention patients were found to have nonsignificant trends toward higher outpatient depression costs over the 30-month period, whereas controls had nonsignificant trends toward higher total nondepression costs and total outpatient costs. The incremental depression costs in the intervention group were primarily due to the increased costs of longer term use of serotonin reuptake inhibitors.
Table 1. Unadjusted Annualized Cost Data for the Control and Intervention Groups (N = 187)*, †
| ||Controls (n = 92)||Intervention (n = 95)|
|Strata||Mean, $||95% CI, $||Mean, $||95% CI, $|
| Antidepressant prescriptions||821||523 to 1120||1,398||940 to 1,856|
| Specialty mental health visits||616||353 to 880||469||273 to 666|
| Primary care visits with mental health diagnosis||317||238 to 394||265||205 to 326|
| Intervention visits|| || ||185||168 to 201|
|Outpatient depression treatment costs||1,754||1,289 to 2,220||2,317||1,710 to 2,924|
| Primary care visits without mental health diagnosis||1,617||1,340 to 1,893||1,341||1,109 to 1,572|
| Diagnostic tests (lab and radiology)||809||575 to 1,043||657||487 to 826|
| Specialty medical visits||1,272||909 to 1,635||1,230||918 to 1,544|
| Emergency visits||354||134 to 574||289||109 to 470|
| Pharmacy not including antidepressants||1,719||1,273 to 2,164||1,060||714 to 1,407|
| Other outpatient costs||999||573 to 1,424||892||448 to 1,336|
|Total outpatient nondepression costs||6,769||5,351 to 8,188||5,470||4,431 to 6,510|
|Total outpatient costs||8,524||5,059 to 9,989||7,787||6,595 to 8,980|
|Inpatient care (medical + mental health)||1,247||486 to 2,008||1,362||633 to 2,090|
| Total health services costs||9,799||7,763 to 11,834||9,192||7,504 to 10,880|
Another cost of an intervention program for persistent depression would be the cost of instituting and maintaining a tracking system. We estimated that a program that would need to be developed by an HMO to screen patients 8 weeks after initiation of primary care physician antidepressant prescriptions would add approximately $67 per patient to the cost of the intervention.
- Top of page
This study demonstrated the long-term (28-month) effectiveness of a collaborative care intervention among patients with moderate depression severity. Most trials testing mental health or collaborative care interventions versus usual primary care in patients with major depression have found a significant effect in reducing depressive symptoms over 3 to 6 months compared to usual care that tended to decrease over the next half year.1,2,5,30 This is probably because major depression in most primary care patients is a relapsing-remitting illness with most episodes lasting less than 6 months.9 Thus, even depressed patients in usual primary care who are less likely to receive evidenced-based care tend to improve over a 6- to 12-month period. Our stepped-care program, however, selected patients with a higher risk of chronicity by requiring that patients have 4 or more DSM-IV symptoms approximately 8 weeks after initiation of antidepressant medication by the primary care physician. Our data from structured interviews showed that this methodology selected a persistently ill population; approximately 50% had double depression (dysthymia and major depressive episodes), and approximately 75% had experienced 3 or more major depressive episodes.7 A recent trial that showed long-term improvements over a 1-year period also selected patients for 2 years of high utilization and depression; these eligibility criteria also likely selected patients who had more persistent depressive symptoms.31 A second trial that showed longer term improvement in depressive symptoms over 12 to 18 months differed from the current trial in that patients were selected by screening for depression in primary care, with less than half of patients in the usual-care arm receiving depression-specific treatment.32
In the current study, the significant improvement in depressive symptoms in the moderate-strata intervention versus control group (with similar trends in function) persisted for 28 months despite the fact that intervention patients demonstrated significantly better adherence to adequate dosage of antidepressant medications for only the first 6 months. It may be that the more complete recovery of intervention patients in the first 6 months in the moderate-severity strata was associated with less risk of relapse over the 28-month period. Residual depressive symptoms have been found to be one of the most important risk factors for predicting relapse of depression in primary care patients with depression.33,34 Another factor associated with enhanced outcomes in intervention patients may have been the education and resulting activation regarding self-management of depression provided by the videotape, the book, and specialist counseling. In the high-severity strata, there were large differences in medication adherence for the first 12 months that then dissipated. In this more difficult to treat group, these large differences in medication adherence were inadequate to produce sustained improvements in depressive symptoms relative to usual care.
A strength of the study was the population-based provision of collaborative care to primary care patients who were persistently ill 8 weeks after initiation of pharmacologic treatment. Our previous collaborative care trials have shown that these interventions markedly improve outcomes for patients with major depression, but not minor depression.1,2 About half of patients diagnosed with depression in primary care and started on antidepressants have minor depression, and 65% to 70% of these patients recover over 1 to 3 months in usual primary care.1,2 Approximately 40% of patients with major depression also improve over 3 to 4 months in usual primary care. By closely monitoring 8-week outcomes of primary care treatment of depression, we targeted specialty mental health resources to the care of patients who had the most need for additional treatment. We found that approximately 22% of over 2,000 patients diagnosed and started on antidepressant medication by primary care physicians met our criteria for persistent symptoms, and most of the patients benefited from the short-term addition of specialty mental health care.7 Our results suggest that approximately one third of patients with persistent symptoms who have higher initial severity (and a high prevalence of comorbid anxiety with less social support)11 did not benefit from this brief intervention; these patients represent about 7% of patients diagnosed with depression and treated by primary care physicians.
The most conservative interpretation of the cost data suggests that for no greater total ambulatory costs, this stepped-care intervention was associated with improved outcomes in the moderate-severity-strata patients, who represent about two thirds of the total sample. In general, higher outpatient depression costs in intervention patients were balanced by higher outpatient nondepression costs in usual-care controls. This same pattern was seen in both intervention and control patients in both severity strata. For instance, in the moderate-severity strata, the total outpatient costs were $8,016 (95% confidence interval [95% CI], $6,568 to $9,464) in intervention patients and $8,824 (95% CI, $6,677 to $10,970) in usual-care patients; in the high-severity strata, the intervention patient total outpatient costs were $7,358 (95% CI, $5,159 to $9,556) versus $8,035 (95% CI, $6,293 to $9,778) in usual-care patients. This pattern of health care costs could be interpreted as evidence for a cost-offset effect (i.e., the increased resources provided for depression treatment lead to an off-setting reduction in general medical utilization). An important caution here is the lack of precision in estimates of total ambulatory costs. The 95% CIs increase progressively as one moves from estimates of depression costs to total ambulatory costs to total health care costs. The increase in depression costs in the intervention group was primarily due to better adherence to serotonin reuptake inhibitors. This increase in depression costs of approximately $500 based on pharmaceutical costs should decrease by 50% over the next 1 to 2 years due to increased use of generic serotonin reuptake inhibitors.
Several limitations in this study must be noted. First, the research was completed in 4 large HMO clinics staffed by family physicians, and implementing this intervention model may be more difficult in primary care networks that do not integrate psychiatric services into primary care. Second, the population was largely Caucasian, working, and middle class. The intervention may not generalize to other socioeconomic or ethnic groups. Third, this was a multifaceted intervention, and we are unable to state which components of the intervention were most important to its success. This limitation must be balanced by evidence that multifaceted interventions aimed at patient education and activation, physician education, and changing the process of care have been shown to be most effective in improving chronic disease management.35 Fourth, the study was underpowered to evaluate statistical differences in total ambulatory costs, which may require populations of over 1,000 patients given the large standard deviations in cost data.28 Finally, the CDS suggested more medical comorbidity in controls, which may have influenced the depression cost differences; however, our health care analyses controlled for CDS as well as for 6-month costs prior to randomization.