It is of small consolation to these sincere critics when I reply, as I usually do, along the following lines:
“Well, yes: when antidepressants are prescribed by the wrong doctor to the wrong patient, and for the wrong reason, serious problems can occur. Patients with bipolar disorder may indeed become irritable, aggressive, or manic, and in general, should rarely be treated with antidepressants.17 And, yes: when patients are not carefully monitored, they can become excessively sedated, just as they may experience prolonged sexual dysfunction that is not detected by the prescribing physician—who is very likely not a psychiatrist.
“And, it is true that when a physician discontinues an antidepressant too rapidly, the patient may experience a very uncomfortable, flu-like syndrome that may last for days or weeks—rarely longer—which can nearly always be avoided by using a very slow tapering schedule, over several months. These are problems mainly related to poor medical practice, and only partly related to the properties of the medications themselves. These are problems that arise, in part, from inequities in our health care system, and the lack of affordable and accessible psychiatric care in this country.”
I don’t blame disgruntled patients for finding this apologia unconvincing, if not downright insensitive. When you have been made miserable by an inappropriate or poorly monitored medication, you are not likely to be mollified by the explanations of those prescribing—and not ingesting!—the drug in question. Ironically, given the complaints of these critics, the growing popularity of antidepressants in the United States18 does not suggest that physicians are getting a strong “Cease and desist!” signal from the vast majority of patients. On the contrary: the evidence suggests that most patients are generally satisfied with their antidepressant treatment. For example, a recent study by pharmacists found that among monitored patients taking antidepressants,
“Fifty-seven percent of patients reported feeling better a lot of the time, and an additional 30% reported feeling better some of the time. Nearly 75% reported that the antidepressant did not bother them or only bothered them a little of the time. Being very satisfied was reported by 47% of patients, and an additional 28% were satisfied with the antidepressant.”19
There is also encouraging news on the level of molecular biology. Antidepressants do not merely rev up levels of neurotransmitters, along the lines of the now outdated “chemical imbalance” hypothesis.14 Rather, ADs may work at the level of the gene, by promoting production of various neurotrophic peptides, such as brain-derived neurotrophic factor (BDNF). These factors, in turn, may enhance neuronal growth and survival, and appear to underlie the mechanism of several antidepressants.20
Rather than damaging the brain, ADs may actually work to enhance “neuroplasticity,” improve stress tolerance, and facilitate learning.21 That said, there are some concerns that in a small subset of patients who are treated long-term with ADs, a syndrome of “tardive dysphoria” may develop. Such a delayed, “pro-depressant” effect might reflect some as yet poorly understood “rebound” phenomenon in the brain.22 Clearly, we need more research on this troubling possibility.
Nonetheless—and contrary to the claims of critics—there is some evidence that patients treated with ADs report improvements in “quality of life” (QOL) and overall satisfaction with their lives. For example, a Belgian study of depressed or anxious patients taking the AD escitalopram(Drug information on escitalopram) found that treatment resulted in a significant improvement in quality of life enjoyment and satisfaction.23 However, we need many more studies examining QOL in patients taking antidepressants. HAM-D scores alone do not tell us whether a depressed patient has moved beyond mere remission to a full and flourishing recovery.
And so, overall, what is my verdict on antidepressants? In my estimation, our present medications for depression are only mediocre. For moderate to severe, and especially melancholic, cases of major depression, ADs are effective and sometimes lifesaving, particularly when part of a comprehensive treatment plan that includes psychotherapy. And, there is convincing evidence that ADs prevent relapse at least during the 6 months or so after a bout of major depression. For mild, non-melancholic cases of depression, I generally favor beginning with psychotherapy, given the “costs” of antidepressant side effects. In this regard, we urgently need to find antidepressants that are more effective and better tolerated. Recent research suggests that agents that modulate the N-methyl-D-aspartate (NMDA) system (eg, ketamine(Drug information on ketamine)) are worth further exploration.24 In sum: I do not hear loud applause for our current antidepressant armamentarium. I believe I hear the sound of one hand clapping.
So what is next? We need to improve access to psychiatric care, so that patients who need antidepressants are seen by those best trained and most knowledgeable in their use. We need to work more closely with our colleagues in primary care, so that they become more proficient in the diagnosis and treatment of depression. We need to investigate carefully even the very rare side effects of antidepressants, so that we do not lose the confidence of the general public. We need to avoid even the appearance of conflicts of interest, related to “Big Pharma.” And perhaps most important, we need to listen attentively and respectfully when our patients tell us they are not happy with their treatment.
Acknowledgment—Thanks to James Knoll, MD, for his reading of an earlier draft of this paper. Thanks also to Nassir Ghaemi, MD, for providing me with insights into the Kirsch4 data.
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