To Treat or Not to Treat: The Debate Over Residual Symptoms

How vigorously should we treat depression?

Research in the last two decades, and here the trend is overwhelming, shows that patients with “residual symptoms,” indicators of depression that persist even when by standard definitions mood disorder is no longer present, are likely to become depressed more rapidly — and then to suffer the consequences of a “career” of chronic disability and disease. This risk extends even to seemingly minor symptoms like insomnia.

On the other hand, depression can be hard to treat. Eradicating every last symptom is a demanding goal, one likely to expose patients to multiple medication trials and, if they can afford it, extended periods of psychotherapy. Thoughtful doctors have suggested that the risk from complex treatment is unknown and that despite the problems of chronicity it may be more helpful, and more realistic, to leave some patients in an intermediate state in which they are “better but not well.”

This argument is certain to persist until we have access to new, more effective treatments. In the meanwhile, an in-advance-of-publication article in the Journal of Affective Disorders weighs in on the “treat to remission” side of the argument.

The authors looked at over 1500 patients with bipolar disorder and found 310 to be in an episode of major depression, while 112 were in a “subsyndromal” state — that is, they had depressive symptoms that were not numerous or severe enough to trigger a diagnosis. These figures are typical. Bipolar patients spend about a third of their adult lives depressed — and it is depressive, not manic symptoms that are the best predictor of poor functioning in manic depression.

The histories of these patients differed in the direction you would expect. Those in remission had fewer past episodes of depression; those with frank depression had the most. The patients with partial depressions often suffered other disorders and symptoms, like anxiety. Oddly, the remitted patients were most likely to have experienced a psychosis in the past; it may be that these patients then received the most vigorous treatment. In terms of measurable personality traits, the three groups were comparable.

It was the measures of impairment in daily living that were surprising. Both partial and full (subsyndromal and syndromal) depression led to bad outcomes, in terms of work, relationships, recreation, and overall life satisfaction — and the two groups looked remarkably similar. The diagnosed depressives lost more days at work, but otherwise, low-level depression, among bipolar patients, looked as harmful as full-blown episodes. The authors observe that “patients with sustained continued symptoms experience essentially the same functional burden as those experiencing a full episode of depression.” In terms of particular residual symptoms, sadness, lassitude, and the inability to experience pleasure were especially harmful.

This study would seem to argue for vigorous interventions for of residual depression in bipolar patients — but there are caveats. Antidepressants can make bipolar patients manic. It may even be that some of the disability in bipolar patients with low-level depression arises from their treatment, if it gives them hypomania, or low-level manic symptoms.

A note on the study and its funding and authorship: These results arise as part of the STEP-BD research, a multi-site investigation (conducted at major universities) fully funded by the National Institute of Mental Health. The lead author of the current article is Lauren Marangell, who during the trials was at the Baylor College of Medicine; she has since been hired by Eli Lilly. That corporate name can make readers leery. But in the world of research, a multi-site NIMH-sponsored study is about as good as it gets.

The take-home message — and many other studies lead to the same conclusion — is that, in bipolar patients, residual depression is not just a risk factor for future illness; it is also a predictor of current misery. It is reasonable to argue that we just don’t know what the tradeoffs may be when doctors press onward, treating symptoms in order to prevent future illness. But doctors are likely to want to make those efforts for another reason: their patients are floundering here and now.