Comparative effect of collaborative care, pain medication, and duloxetine in the treatment of depression and comorbid pain in outpatient care: results of a randomized, placebo-controlled, multi-center trial

Objective: Evidence exists for efficacy of collaborative care (CC) against MDD, for efficacy of consequent use of pain medication against pain, and for efficacy of duloxetine against both MDD and neuropathic pain. However, their relative effectiveness in comorbid major depression (MDD) and pain has never been established so far. This study evaluates the effectiveness of CC, pain medication and duloxetine, and CC, pain medication and placebo, compared to duloxetine alone, on depressive and pain outcomes. Methods: Three armed cluster randomized multi-centre placebo controlled trial in consecutive patients presented at three specialized mental health outpatient clinics who screened positive for MDD. All interventions lasted 12 weeks. In the CC groups duloxetine or placebo was prescribed. Pain medication was administered according to an algorithm that avoids opiate prescription as much as possible as an alternative to the current WHO pain ladder, with paracetamol, COX inhibitors and pregabalin as steps before opiates are considered. Patients who did not show up for three or more sessions were registered as noncompliant. Explorative, intention-to-treat and per protocol, multilevel regression analyses were performed. The trial is listed in the trial registration (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1089; NTR number: NTR1089). Results: This study was prematurely terminated because of massive reorganisations and reimbursement changes for mental health care during the study. 60 patients completed the study. Patients in all treatment groups reported significant less depressive and pain symptoms after 12 weeks. CC with placebo condition showed the fastest decrease of depressive symptoms compared to the duloxetine alone group (b = -.78; p = .01), Noncompliant patients did not improve over the 12 weeks period. Pain outcomes did not differ between the three groups. Conclusions: In MDD and pain, compliance of patients and placebo effects are more important than choice of one of the three treatments. Active pain management in CC with COX inhibitors and pregabalin as alternatives to Tramadol or other opiates might provide an attractive alternative to the current WHO pain ladder as it avoids opiate prescription as much as possible. The study was sufficiently powered to show an exploratory result, but the generalizability is limited due to the small sample size. Larger studies are needed