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Wednesday, April 11, 2012

Ketamine for Bipolar Depression Treatment

The debate continues over the best way to treat bipolar depression.  To a large extent, most of the antidepressants prescribed for bipolar depression are suspect with respect to their efficacy and tolerability.  

Looming in the background are a handful of emerging psychiatric antidepressants that demonstrate efficacy and rapid response time (hours or days).  I touched on this subject in a December post about seven novel treatment medications for bipolar depression.  In a post from last month I wrote about another potentially awesome drug, scopolamine.  I even tried it!

Meanwhile, the emergent drug ketamine has been studied in the scientific literature for the treatment of mood disorders.  Most studies focused on relief from major depressive order with only a few evaluating bipolar depression treatment.

Ketamine is a very rapid (as fast as 40 minutes) treatment for bipolar depression with acknowledged short term efficacy.  While its overall safety profile and tolerability seem positive, concerns about a few side effects (e.g., hallucinations) seem to persist.

Drug Background

Ketamine is used routinely as an animal tranquilizer and an anesthetic for surgery.  Unfortunately, it's also infamous for being used routinely in the recreational drug scene.  So, it comes with a bad rap to begin with.

The media recently published some curious stories about using ketamine as an add-on antidepressant for "difficult-to-treat" depression.  At the end of January NPR did a story about a severely depressed person's ketamine experience.  

I thought it glossed over the serious adverse effects. Also, this is an account of the experience of only one person who is not bipolar.  Bipolar treatment experiences are highly variable among individuals and unique for each brain.  Check out the story and you be the judge.   

The scientific literature affirms ketamine is a rapid acting and effective antidepressant.  And although the drug is well tolerated overall, some side effects still cause concern.  Potentially serious side effects reported are hallucinations, increased blood pressure, confusion, and respiratory stress. 

This is only some general information about ketamine.  If you want more facts and information check out my ketamine hubpage.

Ketamine Studies
There are dozens of scientific studies of ketamine going back 40 years.  However, most of the early studies were done to assess ketamine for use as an anesthetic during surgery, not as an antidepressant.

Fortunately, within the last decade or so there have been a good number of  studies involving ketamine for treatment of major depression, treatment resistant depression, and bipolar depression.
A recently completed trial showed a rapid and significant improvement in mood when using ketamine for bipolar depression.  It demonstrated rapid and significant improvement in depressive symptoms for the 79% of participants that responded to ketamine infusion.  Improvements remained significant through day 3.  The most common side effect was dissociative symptoms that occurred only at 40 minutes post-dosing. 

A 2010 study of 18 individuals having treatment-resistant bipolar depression found ketamine produced robust (71% responded to treatment) and rapid (response within 40 minutes) antidepressant effects from a single intravenous dose.  The researchers found ketamines effect of improved moods remained significant through day 3.   

Research in 2010 showed that multiple doses (6 infusions over 12 days) of IV administered ketamine (0.5 mg/kg over 40 minutes) administered to 10 treatment resistant, depressed individuals was robust (90% met positive response criteria) and tolerable.  Psychotic symptoms (e.g., hallucinations) were minimal and side effects are reported as generally mild.  However, three participants (30%) experienced "significant but transient dissociative symptoms."  Eight people relapsed between 6 and 45 days after ending ketamine treatment.  One had only minimal depressive symptoms for over three months! 

A 2006 trial used ketamine for treatment-resistant major depression.  The placebo-controlled, randomized, double-blind crossover trial concluded that ketamine is a rapid (less than 2 hours response time) and robust antidepressant when administered as a single intravenous dose.  The 17 trial participants were diagnosed DSM-IV major depression (treatment resistant).  Results show that 71% met response criteria and 29% were in remission (no symptoms) when measured the following day.  Also, following the trial 35% maintained a positive response for at least 1 week. 

Even with over 10 years of research on ketamine for treatment of depression, further studies are still required to better understand proper therapeutic dosages, administration methods, side/withdrawal effects, and other relevant factors.  There needs to be more data with statistical relevance (e.g., larger sample sizes) analyzed for treatment efficacy, tolerability, and safety.

  1. Ketamine has established itself as a novel, rapid, and robust antidepressant with seemingly unresolved tolerability concerns;
  2. Further trials are needed to substantiate earlier findings from some of the smaller studies; 
  3. Additional trials are needed to investigate the possibility of using ketamine for longer treatment duration.  Specifically, the long term treatment that may be needed for effective acute and chronic bipolar depression treatment in some individuals;  
  4. Clinical trials data is needed to develop dosing guidelines and administration techniques; and
  5. A couple of side effects are still a concern, but otherwise ketamine is tolerated well.
Conclusion There are no safe and effective antidepressants available that have the rapid and powerful onset like ketamine.  We have scientific studies of the drug's mood changing effects going back over a decade.  It's not like ketamine is new to the block.  I think it's time to accelerate the advancement of promising treatments like ketamine. 

I'm not optomistic about ketamine's future.  Research and clinical trials are taking way too long.  It's reputation as a recreational drug doesn't help matters.  Ketamine could very well end up stuck in limbo between initial lab studies and your medicine cabinet    So, would you consider particpating in a ketamine study?  I know I would!  Take care friends and take your meds.


  1. I have being researching about depression and reading your blog, I found your post very helpful. Usually when I get depressed I close my eyes for 2 min and relax my mind or if its not work I use to take generic aventyl to treat depression.

  2. Hi Mark! I like your idea of closing one's eyes and just relaxing for a moment or two. Thanks for stopping by. I don't have personal experience with Nortriptyline. Do you still take it and does it work well for you? Take care, Jeff

  3. Ketamine is widely used as an alternative in treating depression but many patient dislike to use if because of its effect. Hallucination is one of its effect and many are avoiding of being addicted to it.

  4. Hey Jason -

    I haven't heard much about ketamine from the patient's persepective. Thanks for the info!

    - Jeff

  5. Hi Jeff,

    I just came across your blog, thanks for this effort and please keep up the good work. You make a good point that Ketamine's reputation as a recreational drug slows down research and clinical trials, and it's really too bad. It wasn't until my mid-20's that my docs and I finally figured out I have atypical BP rather than regular depression (though you would think my crazy reaction to an SRI would have tipped off the pros sooner.) I abused ketamine a lot when I was in my teens, though now I think of this more as an attempt to "self-medicate" than seek "recreation." If only the medical community would better appreciate how much of "recreational" drug abuse is actually a reflection of undiagnosed and untreated mood disorders. Anyway, thanks for your thoughts on this. I'll keep visiting.


  6. Hello Anon -

    Glad you stumbled upon my blog. I agree that the use of "street" drugs by folks with mental illness is more often than not an attempt to self medicate. We're just looking for some relief! I ran across this a few months back. It has some hopeful insights into Ketamine and the glutamate neurotransmitter systems. Yes, let's get fast acting antidepressants and stop the prolonged suffering and in some cases suicide. Remember to never, never, never quit!


  7. I received ketamine for surgery I had 10 years ago, I had what can only be described as a great trip, though I must confess I have never done LSD or any other drugs, (beer, wine and rum excepted) in my life.

    I felt great for many days or even weeks afterwards.

    My doctors had no explanation so consequently I researched the internet and found that it was recently observed, however it would take some years of study before it could be approved.

    Now 10 years later its still 10 years away from use?

    Since ketamine is a horse tranquilizer, that out of patent protection, I suspect that ten years from now it will still be under study, or at least until "Big Pharma" find out which part of the ketamine molecule is causing the anti-depressive effect, at that point it will be patented and cost the patients thousands of dollars per annum.

    Your thoughts will be appreciated on this subject,


    1. Hey Anon!

      Thanks for sharing your experience. From what I can tell Ketamine should be in stage III trials and beyond by now. From this page it seems Ketamine and Riluzole and FDG (new to me) have been undergoing phase II testing at NIMH since 2004 with results expected in 2014! That's all I know about Ketamine trials at this time. Keep on keeping on!

      - Jeff