The SCAMP trial has several important findings. First, optimized antidepressant therapy coupled with a pain self-management program produced substantial reductions in depression severity as well as enhanced response and remission rates. Second, the intervention also resulted in moderate reductions in both pain severity and pain-related disability. Third, the benefits on both depression and pain outcomes were sustained over the 12 months of the trial, including the 6-month continuation phase.
The effect size of the SCAMP intervention on depression outcomes was similar to that seen in patient populations without chronic pain. In a systematic review of 28 randomized controlled trials of multi-component interventions for primary care patients receiving acute-phase treatment for depression, Williams et al found an 18.4% median absolute increase in patients with a 50% improvement in symptoms (range, 8.3–46%) and a median absolute increase of 16.7% (range, 10.6–40%) in remission from depression.39
The median absolute increases in SCAMP were 20.9% for a 50% response (i.e., 37.4% response in the intervention group vs. 16.5% in the usual care group) and 13.2% for remission (17.9% vs. 4.7%). Also, the number needed to treat (NNT) of 4.8 to achieve a treatment response for depression is similar to the NNT of 4 in a Cochrane review of antidepressants compared with placebo or no treatment in medically ill adults.51
Some of the reasons for improved depression outcomes in SCAMP may be that intervention patients were on antidepressants more months than usual care patients (9.3 vs. 2.0 months), were more likely to be on an antidepressant all 12 months of the study (67.5% vs. 3.9%), and more likely to have an antidepressant switched or added during the study (35% vs. 17%). Continuing an antidepressant at least 6-12 months is known to enhance depression outcomes, and STAR*D and other trials have taught us that an inadequate response to the initial antidepressant is not uncommon and may require a change in medication.39,52
The assessment of antidepressant use may have been more accurate in intervention patients whose medication was provided by the nurse care manager and documented in the study logs, while antidepressant use in usual care patients depended entirely on refill information in the electronic medical record. However, it is unlikely that group differences as large as we found for antidepressant usage are entirely due to ascertainment bias.
The effect size of the SCAMP intervention on pain outcomes − 0.54 for pain severity and 0.62 for pain interference was notable. Chronic pain is difficult to treat and a 30% reduction is typically judged a clinical response – as determined by patient-rated quality of life and perceptions of analgesic efficacy53
– in contrast to the 50% reduction required for depression. Using this threshold, a clinical response in pain was much more likely in the intervention compared to the control group (41.5% vs. 17.3%, or a NNT of 4.1). Impressively, when rating overall change in pain, 47.2% of intervention patients reported improvement at 12 months, compared to only 12.6% of control patients. Thus, the SCAMP intervention showed benefits in terms of 3 pain outcomes considered relevant in clinical trials: pain severity, pain interference, and global pain improvement. It is possible that pain improvement in our trial reflected a main effect of improved mood (i.e., an antidepressant effect on mood rather than an analgesic effect), and that as depression lifts, patients may experience pain as being less intense and less disabling. Conversely, it is also possible that the improvement in depression was mediated by an improvement in pain (i.e., as pain improves, patients feel less depressed) or that both depression and pain lessened as a result of treatment effects on a common pathway.
The largest reductions in depression and pain were seen early (i.e., during the first month of optimized antidepressant therapy) and were sustained during the remainder of the trial. Thus, the added value of the pain self-management program cannot be ascertained in SCAMP. We had postulated that improvements in pain that might occur with optimized antidepressant therapy would be further enhanced with a behavioral intervention designed to improve pain coping and other self-management skills. It is possible that, without the pain self-management program, patients whose pain initially improved might have suffered a relapse. However, it is also possible that antidepressant continuation, as occurred in SCAMP, is sufficient. To test whether pain self-management provides any benefits beyond optimized antidepressant therapy would require a parallel group or factorial trial design rather than the sequential approach used in the current study.
While the between-group differences (i.e., treatment effect) were similar to previous depression trials, the absolute response and remission rates in both intervention and control groups were low compared to other depression care management studies.39,54
and closer to that seen in populations with more medical comorbidity.22,51
Indeed, secondary analyses of two collaborative care interventions found that high baseline pain reduces depression improvement rates.55,56
A secondary analysis of patients with comorbid pain in a geriatric depression trial57
found a much more modest ES for pain outcomes than for depression. Thus, additional interventions to co-manage pain (e.g., optimized analgesic management) may be necessary to further improve response and remission rates. For example, Dobscha and colleagues recently found that a collaborative care intervention for chronic pain that included clinician education, patient education and activation, symptom monitoring, feedback and recommendations to clinicians, and facilitation of specialty care produced modest improvement in both pain and depression outcomes.58
In addition to improving depression and pain outcomes, the SCAMP intervention also demonstrated benefits in terms of secondary measures such as anxiety, functional impairment, and quality of life. There was also a nonsignificant trend towards fewer pain-related disability days. Since pain and depression are among the two leading causes of decreased work productivity59,60
, interventions that improve both of these symptoms as well as their adverse impact on functional status might be particularly desirable from not only the patient but also the employer and societal perspectives.
SCAMP used an antidepressant algorithm rather than a single antidepressant, and more than half of the patients discontinued or switched from their initial antidepressant by 12 months. Therefore, the superiority of one antidepressant over another in comorbid depression and pain cannot be determined. Studies to date have failed to establish differential efficacy among antidepressants in terms of depression outcomes.21,52
For pain, tricyclic antidepressants (TCAs) may be somewhat more effective than SSRI antidepressants.6,61,62
However, head-to-head comparisons are few, previous trials are short in duration, and many trials have used lower doses of TCAs than are normally required for an optimal effect on depression. Several SNRI antidepressants now have FDA indications for treating neuropathic pain and fibromyalgia7
but their efficacy in the painful conditions studied in our SCAMP trial (low back pain and osteoarthritis of the hip and knee) requires further research. Also their relative superiority compared to other antidepressants in terms of improving pain is less certain63
and would require active comparator trials. Notably, all antidepressants used in our SCAMP trial are now available in generic formulations.
Neither data from electronic medical records nor patient self-report suggested that group differences were significantly confounded by co-interventions. The average intervention patient averaged slightly more than one care manager contact per month over the 12-month study, with most of these (82%) occurring by telephone. Health care use was slightly higher for intervention patients in a few categories of visits, but these differences did not appear clinically significant. Though we did not design our single-site study to conduct a formal cost-effectiveness analysis, the care manager contacts together with greater antidepressant use and no decrease in health care use certainly indicates there was some added cost to achieve the improved depression and pain outcomes in the intervention group. This is consistent with many other primary care trials comparing enhanced depression care to usual care,64,65
. However, a recent multi-center trial with sophisticated cost analyses found that the cost per quality-adjusted life year for enhanced depression care compared favorably with many other medical interventions66
and it is possible that increased costs incurred during the first year may be recouped with cost savings in subsequent years.67
Our study has several limitations. First, since patients were enrolled from urban underserved and veteran clinics, the generalizability of our results to other primary care populations needs to be demonstrated. However, adverse socioeconomic factors more prevalent in our sample tend to make treatment of depression and pain more difficult, so the substantial effects we observed are noteworthy. Second, since only one-third of eligible patients agreed to enroll, the extent to which the benefits we found are generalizable to patients not desiring participation in a trial is uncertain. Third, SCAMP is a multi-component effectiveness trial. Therefore, to what degree benefits can be specifically attributed to the antidepressant-behavioral intervention vs. the nonspecific effects of care manager contacts cannot be precisely determined. Also, the lack of blinding in an effectiveness design may inflate somewhat the benefits specifically attributable to the intervention. However, a recent literature synthesis of depression care management trials showed that, like our SCAMP study, an effectiveness trial with a usual care control group has been the most common study design.39
Also, a number of patients in the usual care group received antidepressants which might tend to reduce the effect size of the intervention. Importantly, the two treatment groups did not differ in terms of self-reported pain or depression co-interventions over the 12-month trial.
In summary, SCAMP showed that optimized antidepressant therapy coupled with pain self-management in patients with comorbid pain and depression can produce substantial improvements in both depression and pain. At the same time, additional interventions may be needed to produce larger improvements in pain and higher depression response and remission rates. Strategies might include optimized analgesic management, cognitive-behavioral therapy6,68
, or augmentation strategies.41
While numerous trials have shown that enhanced care for depression is equally or more cost-effective than the treatment of chronic medical diseases, the lack of parity for mental disorders leads some payers to insist that depression care must be cost-neutral or even cost-savings.64,65
A recent trial demonstrated that depression care management improved workplace as well as clinical outcomes.69
Since pain and depression are among the leading causes of decreased work productivity, an intervention that is effective for both conditions may further strengthen the “business case”. Also, an intervention that allows a care manager to cover several conditions rather than a single disorder may enhance its implementation and cost-effectiveness. Given the prevalence, morbidity, disability, and costs of the pain-depression dyad, the SCAMP results have important implications.