Can Childhood History Predict Best Treatment for Depression?

In May 2000, a research group led by Martin Keller reported an important study in The New England Journal of Medicine, the leading clinical research journal in the world. The authors had studied 681 patients with chronic major depression, recruited from 12 academic centers, who received either antidepressant medication, brief psychotherapy, or a combination of the two. Their results demonstrated that the two individual treatments were equally effective (which was consistent with previous research), but that their combination was significantly better than either alone. This surprised few clinicians, but was good news for those psychotherapists who noticed it, insofar as it provided an “evidence base” for the essential role of psychotherapy as at least one component in the optimal treatment of depression. Psychoanalysts noted, of course, that it was not a psychoanalytic psychotherapy (which is yet to be tested), but still it was a first step.

The next step turned out to be surprising, and, to me, even more interesting. In November 2003, six of the original authors, led by Charles Nemeroff, joined by eight additional colleagues, reported a further analysis of the same data in the prestigious Proceedings of the National Academy of Sciences (not the usual setting for psychotherapy research). They divided the original 681 patients into two groups—about two-thirds who had a history of early childhood trauma (“loss of parents at an early age, physical or sexual abuse, or neglect”) and one-third who had no such history.

For the traumatized group, but not the others, psychotherapy alone was clearly superior to pharmacotherapy alone, and, in fact, was almost as effective as the combination of the two treatments, while the combination was clearly superior to pharmacotherapy alone. In sum, psychotherapy was essential for the effective treatment of chronically depressed patients with histories of childhood trauma.

Childhood history thus becomes one of the relatively few predictors of differential treatment response in chronic depression.

First Step in Research Strategy

This is an important advance, because the search for clinically relevant subtypes of depression that predict responses to different treatments has been surprisingly unsuccessful until now. Nemeroff and colleagues discuss these results in the context of the neurobiological sequelae of early trauma which they believe may predispose to later psychopathology, but it would be easy for a psychoanalyst to hypothesize psychodynamic factors that might contribute to predispositions or pathogenesis as well. What is exciting is that we have the first step in a research strategy that can help us to differentiate between these models and evaluate their relative importance, and in so doing enrich our understanding of development and further refine our ability to select the most desirable treatment for a given patient.

I have left out the methodological details, such as how the investigators dealt with comorbidity and with dropouts, how they assessed childhood trauma, the parameters of the treatments, what outcome measures were used, the duration of follow-up, and others, but as in all such studies these are all critical. We can be somewhat reassured in that the authors of these studies include some of the nation's leading experts on the assessment of psychiatric treatment, among them four psychiatry department chairs. Their results have been reviewed and summarized in a paper by Craighead and Nemeroff now in press in a special issue of Clinical Neuroscience Research devoted to research relevant to psychoanalysis. The opening sentence of that paper states, “Most patients who have experienced sexual abuse or early loss of a parent are optimally treated with psychotherapy as a core component of their treatment.”

The original Keller article in The New England Journal of Medicine elicited two accompanying editorials. The first, by Jan Scott of Glasgow, emphasized the difficulty of treating chronic depression, along with the paucity of relevant data and the limitations of the Keller study. The second, by Marcia Angell, then editor, explained why the Journal had to go to Scotland to identify the editorial writer. It was difficult to find a research psychiatrist expert on the treatment of depression who did not have financial ties to drug companies that make antidepressants, which would have conflicted with the Journal's conflict of interest policy. It also described a disturbing corollary of the eminence of the authors. Their ties with such companies were so extensive that the Journal published a list of them on its Web site rather than with the article.

My own conflict of interest: I have no financial ties to companies that make antidepressants, but I was on the editorial board of The New England Journal of Medicine when the Keller et al paper was published and, along with Steve Roose, am the co-editor of the special issue of Clinical Neuroscience Research that will publish the Craighead and Nemeroff paper.