His research (mostly in collaboration with Robert J. DeRubeis) has found that cognitive therapy is as efficacious and more enduring than antidepressant medications in the treatment of unipolar depression.
It was in graduate school that he developed his interest in the nature and treatment of depression with a particular emphasis on work by Aaron T. Beck (cognitive theory and therapy), Martin E. P. Seligman (learned helplessness), and Gerald Klerman (controlled clinical trials).
When he moved to Philadelphia to work with Beck in the mid-1970s, he joined a group that was studying the effectiveness of cognitive behavioral therapy (CBT) for the treatment of depression.
[10] After he moved to Minnesota, he and DeRubeis conducted a clinical trial that again showed that CBT was as efficacious as adequately implemented antidepressant medications[11] and once again more enduring.
[16] Hollon has contributed to four of the seven trials (out of eight total) that have found prior cognitive therapy has an enduring effect relative to antidepressant medications following treatment termination.
[17] In 2006, Hollon joined with Sona Dimidjian in the aftermath of Neil Jacobson’s untimely death to bring a placebo-controlled trial to closure that found behavioral activation as efficacious as medications[18] and as enduring as CBT.
[19] A subsequent trial in rural India conducted by Vikram Patel indicated that a brief 6 to 8 session culturally adapted version of behavioral activation called the Healthy Activity Program (HAP) conducted by non-professional lay counselors was more efficacious than enhanced usual care among depressed patients in primary care[20] with little indication of relapse over the nine months following treatment termination.
[25] His recent interests have gravitated toward optimizing treatment selection (moderation), global mental health, and evolutionary theory with respect to depression.