Oral Ketamine for Depression and Anxiety in Hospice

by: Alex Smith, @alexsmithMD

Journal of Palliative Medicine recently published a nice exploratory open label study of daily oral ketamine for depression and anxiety in hospice patients.  We discussed this paper in our last palliative care fellow‘s journal club, with the esteemed fellow Dr. Virginia Dzul-Church presiding.

I won’t regurgitate the whole article – although Eric Widera just pointed out that one of the take home points of discussing this article is the importance of actually reading the article.  In brief, the wonderful Dr. Scott Irwin recruited 14 hospice patients with depression and anxiety and treated them with 0.5mg/kg of ketamine by mouth daily.  He found a significant reduction in both anxiety (starting at day 3) and depressive symptoms (starting at day 14) with few adverse side effects.

Sounds great, right?

Some points to consider:

• No placebo.  Without a placebo we can’t tell how well this drug would have performed above and beyond the placebo effect.  SSRI antidepressants are effective something like 45% of the time.  Placebo is effective something like 30% of the time.  So you’re really talking about a small additional benefit,  ~15%, from the active ingredients.
• Regression to the mean.  Symptoms have a normal variation.  Depression gets worse, depression gets better.  When do we tend to start medications on patients?  Or notice that they have severe symptoms and consider them for a trial?  When they have severe depression.  And yet, just due to the natural variation in symptoms, we would expect depressive symptoms to decrease over time.    Voila!  It appears the treatment worked.  But by doing nothing, the symptoms would likely have improved.
• Intention to treat.  The above impressive results on depression and anxiety were for the 8 out of 14 subjects who completed the study.  What happened to the other 6?  4 withdrew after day 14 due to lack of response, and two withdrew due to changes in condition unrelated to the medication (that happens in hospice!).  But if you include the subjects you intended to treat, the results would be much less impressive.

All that said, consider – you have a hospice patient.  The patient is depressed and anxious, and has a short time to live.  You’ve tried methylphenidate, it didn’t work.  Raise your hand if you’d consider trying oral ketamine?

My hand is going up.  

Why?  We don’t have many good options for treatment of depression and anxiety on a short time frame.  SSRI’s take weeks to work.  IV ketamine has been shown to work for depression but IV isn’t great for the hospice setting.  When used for pain, oral ketamine at these doses has relatively few side effects.  And then we have this flawed data suggesting it might work, and isn’t too harmful.  

What would you do?