Can Cough Medicine Treat Depression?

NOVEMBER 12, 2013
Steven P. Levine, MD
One of the most promising recent developments in psychiatry has been intravenous (IV) ketamine infusion for the rapid treatment of severe treatment-resistant depression. But even though multiple studies have demonstrated and replicated the safety and efficacy of the off-label use of the 50-year-old anesthetic, their findings remain limited to acute treatment.
 
Longer-term maintenance studies on ketamine are not being done, based in part upon the premise that a medication with a similar mechanism to ketamine will emerge as a more widespread antidepressant. Those drugs are currently in development, and if all goes well, they may be available to us within the next few years.
 
In the meantime, some clinicians have begun to treat severe treatment-resistant depression patients with IV ketamine without evidence-based guidance for maintaining long-term dramatic responses. The rough solution to that problem is to continue what has worked by infusing IV ketamine on a less frequent maintenance basis while weighing the unknown risks of ongoing infrequent exposure to the drug against the risks of recurrence of depressive symptoms. An additional solution is to find another off-label yet orally available medication with a similar mechanism to ketamine that may be sufficient to maintain response.
 
Several drugs that fit the profile have been studied, either directly following ketamine or on their own. Each of those medications — which include riluzole, scopolamine, amantadine, and memantine — has an unrelated indication approved by the US Food and Drug Administration (FDA) and, like ketamine, promotes activity at the N-methyl-D-aspartate (NMDA) receptor.  However, clinical studies on the drugs’ effects in depression have been limited and the results have been somewhat disappointing, which is why I considered another medicine that brings my story full circle.
 
A few years ago, I met with a patient for a second-opinion consultation. She was on the unfortunately common path of having tried multiple treatments for long-standing depression and anxiety that either failed or had intolerable side effects. However, there was an interesting wrinkle in the case, as the patient had found that over-the-counter cough medicines with cough suppressant dextromethorphan helped her mood and anxiety better than anything else. So, she asked me, “Why can’t I just keeping taking DayQuil?”
 
At the time, I advised against it because she required relatively high and frequent doses to achieve the effect that, over time, could be toxic. However, it made me curious about the mechanism of dextromethorphan that might account for the patient’s observations. Investigating that mechanism led me to a literature search of similar drugs and their safety and efficacy in depression. It turned out that there were several, including the aforementioned medicines; but when I read the ketamine studies, I knew there was something of value to further explore.
 

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