4 Therefore, a key research question is whether evidencebased psychotherapeutic and pharmacologic treatment that are efficacious in depressed patients without chronic medical illness are as effective in patients with BEZ235 depression and comorbid illnesses such as diabetes and CHD. A recent meta-analysis of randomized trials of depression interventions in patients with diabetes and depression found five studies that tested the efficacy of psychotherapy and seven that tested the efficacy of antidepressant medications.139

Four of the five psychotherapy studies were quite small with 60 or fewer patients, and all Inhibitors,research,lifescience,medical of the antidepressant trials had less than 90 patients. The meta-analysis showed both evidence based depression psychotherapies and antidepressants were efficacious in treating depression among patients Inhibitors,research,lifescience,medical with diabetes with moderate to large effect sizes compared with control treatments.139 The meta-analysis also examined the results of three large collaborative depression trials that provided a choice of starting with

antidepressants versus problemsolving therapy (PST) and used stepped care principles to increase intensity of depression treatment based on lack of response Inhibitors,research,lifescience,medical to initial treatment.63,98,140 In each trial, a care manager supervised by a psychiatrist worked with the primary care physician to enhance exposure to evidence-based depression treatments. Thus, if the patient chose PST and showed a lack of response an antidepressant medication could be added, and if they chose medication and depressive symptoms did not improve, either PST could be added, another

medication could be started, or a second antidepressant could be added as an augmenting agent. These collaborative care trials enrolled 329 to 417 patients each with Inhibitors,research,lifescience,medical few exclusion criteria and in all three trials, collaborative care was more effective in reducing depressive symptoms compared with usual primary care.63,98,140 Thus, collaborative care is an effective health service model to improve exposure to evidence-based depression Inhibitors,research,lifescience,medical care and depression outcomes ADAMTS5 in large primary care populations with comorbid depression and diabetes. In patients with comorbid depression and either CHD or CHF there have been four large antidepressant trials.141-143 The SADHEART trial randomized 369 patients with major depression after acute MI to sertraline versus placebo.141 Patients treated with sertraline had significantly greater improvement on the Clinical Global Impression (CGI) scale (67% vs 53% (P=.01) responders) but not on the Hamilton depression rating scale (HAM-D) (P=.14). In the subsample of patients with a history of recurrent major depression, both CGI and HAM-D measures were significantly improved in those assigned to sertraline versus placebo.141 A Dutch trial randomized 91 patients post-MI with comorbid major or minor depression to mirtazapine versus placebo.