The Downside of More Effective, Fast-acting Antidepressants


Even a "magic bullet" leaves a wound that requires a period of recovery.

"Laugh, and the world laughs with you; weep, and you weep alone." -Ella Wheeler Wilcox

When you imagine the life of someone who has been weeping alone for 20 years, you are picturing the plight of those with chronic treatment-resistant depression.

Such patients continue to swallow another pill, meet another doctor, and endure another hospitalization with the dimmest of hopes that this next thing may stop the endless nightmare. For some, there is no hope — just a sense of guilt, obligation to someone else, or some unexplainable drive to continue living.

Now, imagine there is a medicine that can almost instantly lift that oppressive weight. The patient’s tears dry up and she feels a sense of awakening and clarity. It sounds wonderful, but when she looks around, she sees with new eyes the surrounding devastation and the casualties of an incapacity to do anything about her growing problems. Then, she feels completely overwhelmed by the herculean tasks ahead.

This is one unintended consequence of more effective, fast-acting antidepressants. For the first time in 50 years, novel therapeutics that may offer relief to patients suffering from chronic refractory illness are being developed. One such agent is intravenous ketamine, but over the past few years of administering it to those with treatment-resistant depression, I have seen the above vignette borne out many times.

Does this mean patients with chronic refractory illness should not bother getting well? Of course not, as it is possible to rebuild one’s life even under extraordinary circumstances. However, the seeming impossibility of it all is akin to a poorly prepared survivor of a nuclear apocalypse stepping out of his bunker into a lonely world of destruction.

The potential for this rude awakening calls for some preparation and forewarning on the part of physicians. It may be possible to help someone understand that even good change is stressful and that decreasing depressive symptoms is only the first step in a long path towards building a life that feels meaningful.

However, this explanation cannot actually sink in when you do not expect the treatment to work in the first place and you have no other perspective than the depressive position. Regardless of whether a treatment involves ketamine infusions or the next fast-acting antidepressant in the pipeline, “take 2 of these and call me in the morning” is not sufficient in this case. Even a “magic bullet” leaves a wound that requires a period of recovery.

About the Author

Steven P. Levine, MD, is a board-certified psychiatrist and therapist. He received his psychiatry training at New York Presbyterian Hospital and Memorial Sloan Kettering Cancer Center and currently practices in Princeton, NJ.

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