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.

Findings

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.