Antidepressant Controversy 4: Tolerance and Kindling: Can Antidepressants Stop Working?

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Continuing, looking at evidence supporting the kindling concern (continued from the main Antidepressant Controversies page):

Dr. Rif El-Mallakh, head of the Mood Disorders Clinic at the University of Louisville, Kentucky, published concern about “loss of response” (sometimes called “Prozac poop-out”, or more Greek: antidepressant tachyphylaxis) to antidepressants several years ago: “Can long-term antidepressant use be depressogenic?” El-Mallakh Another of his papers on antidepressant-associated worseningEl-Mallakh,b includes an excellent literature review on this entire subject. However, even Dr. El-Mallakh seems to stop short of saying that antidepressants might permanentlyworsen a person’s mood disorder. One of the only published descriptions of this concern I’ve found, though I’ve heard it voiced many times (generally by psychiatrists with a lot of clinical experience and willingness to speak out against prevailing beliefs), states directly my concern: namely that antidepressants could make people “treatment-resistant”, even when they started out with a good response, and even when they started out looking “unipolar”, not bipolar.Sharma 2006

Then there’s that case report of mine, cited in Controversy 3.Phelps (We added a very low dose of lithium to the quetiapine (Seroquel) she had improved on earlier, and her depression lifted. She ultimately added tap dancing to the activities her excellent therapist had encouraged her to pursue. She remains well, nearly symptom-free, 9 years later).

My opinion? Obviously I’m expressing it by including this concern on this page and providing these references, as scant as they are. I fear there may be some people who are indeed “kindled” by antidepressants, so that they experience a form of bipolar disorder they might not have experienced until later in their lives, or perhaps might never have experienced at all. To my mind, this is just a matter of adding two plus two: antidepressants can clearly induce hypomania and/or mania; and manic episodes, at least — and perhaps hypomania as well — may in some patients cause later episodes to be more severe and more likely to recur (the “kindling” concept). Therefore shouldn’t we worry that antidepressant-induced mania or hypomania could “bump” some people forward along the curve of their illness?

I’m not alone in this concern. Dr. Fred Goodwin, one of the most respected bipolar experts in the world, echoed it in a recent interview (Primary Psychiatry, July 2005):

[Primary care doctors] tend to think of antidepressants as light, easy, uncomplicated drugs, and mood stabilizers as heavy drugs that should be reserved for a last resort. But in fact, recent data suggests that we may have to reverse that order of preference, or at least put them on an equal plane. [emphasis mine]

He then concludes:

When it comes to selecting treatment, the first do no harm” principle should govern all of medicine… If you create [by giving an antidepressant] a bipolar patient, that patient is likely to have recurrences of bipolar illness even if the offending antidepressant is discontinued.

Next (and final chapter)… Antidepressants: Should you continue or taper them?

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