Ketamine for Bipolar: Potential Risks and Benefits

Could a dangerous and abused recreational drug be a miracle cure for a psychiatric disorder?

This is what seems to be one of the latest buzzes in the popular mental health blogosphere. Ketamine, also known as Special K, is being touted as a possible cure for major depression and bipolar disorder. Is it true? Is it worthwhile? Should you consider trying it?

What Is Ketamine?

Ketamine is a drug of a class called dissociative anesthesia.

That basically means that it changes perception (a hallucinogen) and dulls pain. If you have ever been given laughing gas at the dentist you might have had a taste of something similar. But this stuff is much stronger. It is used in animal medicine and sometimes used in human medicine especially for chronic pain (particularly in cancer patients) and sometimes as a local anesthesia. And yes even in some dental procedures.

As a super strong laughing gas, one can easily understand why it is also used as a recreational drug. It enhances other hallucinogens such as LSD but since it is basically a “downer” it can (theoretically) prevent some wild consequences of LSD. This is at least the rumor, but I have not seen any real evidence of it. Since it can also induce amnesia it has been used as a date rape drug. Doesn’t sound nice to me.

Research Findings

The news started about three years ago with a report of a very small trial of 18 treatment resistant patients suffering from bipolar disorder. 

The article, by Dr. Carlos A. Zarate Jr., hit the major newsfeeds and reported pretty amazing results. Nobody would suggest serious treatment after just eighteen trials. But the news was that this worked really really fast (within an hour) and abated all the symptoms!

It just sounded too good to be true. And you know what they say: “If it sounds too good to be true, it probably is!” However, Dr. Zarate emphasizes that the research is far from becoming ready as a treatment protocol.

He is continuing his research and he replicated his findings and published a study in December 2012, and this new study is all important for two reasons.¹

1. First, it seems that for severely suicidal patients one dose might help reduce the suicidality in as little as 40 minutes. No other treatment can come close to such a claim. 
   
2. Secondly, it works in a way that is completely different from all the other medicines. Almost all antidepressants work on building serotonin while this works on something called NMDA.

Pros and Cons

The exciting possibilities of Ketamine for bi-polar disorder, if it actually becomes a realistic treatment option, include:

• It is extremely fast working: the effects are seen within an hour
• It does not stay in the body for a long time, usually about three days. This means that it probably does not cause neurological toxicity
• It seems to have few major side effects (dizziness and nausea)

There are a few real problems with this miracle drug.

• First of all, nobody knows what effects it might have when used for a long period of time
• We know that people can get addicted to ketamine and that is it is a pretty ugly addiction
  
• It does not stay in the body for a long time. This means that it has to be administered every three days. We do not know what happens when a dose is missed

Will It Work for Everyone with Bipolar?

There is still another issue that needs to be considered in this whole discussion. We are talking about using a specific drug, Ketamine, for a specific disorder, bipolar disorder. But is bipolar a specific disorder? Besides the distinction between bipolar I and bipolar II, is it a disease treatable in the same way as a strep throat?

We know that for many people with a diagnosis of bipolar disorder there is a history of childhood trauma.² We also know that there are people who have bipolar that do not have such a history. Are these actually two different diseases? Since we can't answer this important question we obviously can't know if novel treatments would work for all people labeled with bipolar.

A Research Case Study on a Special Population

When I worked in the children’s psychiatric department in a local hospital we had a six year old patient who clearly had bipolar disorder. Most of the time she was quite a pleasant little girl. But she could not sleep through the night without terrible nightmares and during the day she acted out terrible fears. She talked of killing her parents and dismembering them in the kitchen. She had no history of trauma. Her mood swings were generally a few times a day.

Demitri Papolos is currently the Director of Research at Juvenile Bipolar Research Foundation at the Albert Einstein college of medicine. He sees a lot of bipolar children like the one I met years ago in the children's psychiatric hospital. I heard a story on NPR this past month (March 25, 2013) where Dr. Papalos describes treatment of bipolar disorder in children with ketamine. He talks about children whose rage is triggered by extreme fears. They seem to be constantly vigilant for fear of life itself. This is what triggers the rapid manic symptoms.

There is also an additional symptom that is often overlooked. They have a problem with heat. The show describes a boy that needed an ice pack on his head in order to fall asleep. Dr. Papalos realized that Ketamine calms fears and lowers body temperature. He tried it on patients like this and it seems to cure the patients very rapidly. Like in less than an hour, and with small doses every three days the patients remains completely symptom free.

Dr. Papalos’s published article only cites a dozen clinical trials.³ This means that the same caveats for the use of ketamine cited above are also relevant. But here are two differences. First, this is a well defined subset of bipolar disorder that might not be bipolar at all. Second, it is partially defined by a symptom that is not behavioral at all.

Uncertainty...But a Lot of Promise

Yes, ketamine is an addictive drug and we do not know how it will affect these patients in the long run. But I cannot forget that little girl in the hospital. If it were my daughter, I would definitely consider Ketamine.