Ketamine: A Potential Ray of Light For Those With Serious Depression


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The three mood chemicals seem linked in the brain, If one neurochemical is affected, so are the other two. The novel use of ketamine has shed light upon the mechanisms of depression. Further investigations are warranted. Copyright Image by John A. Jaksich

For those who suffer from clinical depression or bi-polar disorder, a loss of hope often accompanies these illnesses.

Loss of hope is dangerous because it often leads to suicide ideation. The symptoms of suicide ideation can lead to extreme acts of violence not only upon oneself but upon those within the reach of the afflicted.

It is in that stage of irrationality where chemists and biochemists pin their hopes for treatment: intravenous infusion of ketamine. Clinical trials have shown ketamine to quickly – but temporarily -reverse thoughts of suicide ideation.

Ketamine is not a new drug, but its use for depression is gaining a foothold. The drug has the potential to shorten hospitalization stays, and if a successful analog molecule is synthesized from ketamine, it may allow the severely depressed to live normal lives.  Moreover, clinical success would allow psychiatrists to attend to ill patients that are judged as un-treatable.

Depression Comes in Different Forms

To most of us, depression has one of two colors: a bleak gray or black. The afflicted acts lethargically and may be seen crying (or as angry). Most depressions originate in the brain and are understood to be polymorphic. Polymorphic means that the biochemistry of depression often has more than one site where normal brain chemistry has gone awry. This complex neurochemistry is slightly tweaked by the person’s DNA.

Some patients take Prozac to improve mood; science understands Prozac by its actions in the brain. Prozac is an SSRI-a Selective Serotonin Re-uptake Inhibitor. It helps when a person’s brain has too many receptors, which sequester the feel-good chemical, serotonin from acting correctly.

In another case, the anti-depressant Effexor (a SNRI)- a Selective Norepinephrine Re-uptake Inhibitor allows the feel-good chemical, norepinephrine to act correctly.

How do Norepinephrine and Serotonin Differ in their Chemistries?

Up until a 10 years ago, the differences between Norepinephrine and Serotonin were fairly mysterious-they were known as neurochemicals that governed one’s mood. Now, however, we understand the differences between Norepinephrine and Serotonin to be the following:

  • Serotonin allows you to feel good (it allows for pleasure and happiness).
  • Norepinephrine is a stimulant-there is far less lethargy.

Norepinephrine stimulates the reason to seek pleasure and happiness. It is derived from adrenaline-the stimulant allowing one to flee or find the courage to fight.  Norepinephrine and Serotonin act together to alleviate the worst aspects of depression. Included in the feel-good chemicals is Dopamine The roles between the three are synergistic. The differences lie in how each govern aspects of mood. [A success stimulates pleasure – that gives the brain the signal to seek more success, and hence pleasure.]

Managing Depression in a Bi-Polar Disorder Diagnosis

Presently, extremely ill patients are treated with a prescribed drug cocktail. Drug ‘cocktails’ often include a mood stabilizer, along with anti-depressant and anti-psychotic medications. A typical example of a drug cocktail resembles the following: Valproate (mood stabilizer), Effexor (anti-depressant), and  Zyprexa (anti-psychotic).

Drug cocktails act to boost serotonin, dopamine, and norepinephrine levels in the brain. These medications pass through the gut and the mucosa lining of the stomach first. Drug metabolites from the gut then reach the brain. Eventually, the drugs allow the afflicted to feel hopeful and experience fewer mood swings that are characteristic of Bi-polar disorder.

However, in certain cases of Bi-polar disorder, the depression is so deeply seated that drugs are ineffective, and Electroconvulsive Therapy (ECT) is the primary course of treatment. The side effects of ECT are extreme, however, so ketamine may be less traumatic alternative.

Managing Clinical Depression Outside Bipolar Disorder

While people with Bipolar Disorder suffer from mood swings with possible psychotic symptoms, the clinical depressive suffers from primarily depression with the potential for psychotic behavior. Although psychosis occurs with the clinically depressed, it occurs in the extreme cases. The lingering darkness of depression pervades all aspects of life; it darkens all actions of the afflicted.

The standard treatment for depression are pills that alter brain chemistry-the anti-depressants. Typical regimens may include an SSRI (Prozac), SNRI (Effexor), and the atypical anti-depressants (Asendin).

How Does Ketamine Affect Depression?

The new treatment that shows so much promise is the molecule, ketamine. Researchers have found that ketamine can be directly injected into the bloodstream, to eliminate suicidal ideation in those who suffer both clinical depression and Bi-polar disorder. The drug modulates the flow of Calcium and Magnesium in the brain, which allows the general flow of feel-good neurochemicals in the brain, as opposed to SSRIs and SNRIs that act to allow specific chemicals.

Ketamine also affects blood glucose levels and possibly  LDL cholesterol levels (bad cholesterol).  As with SSRIs and SNRIs, the spike in blood glucose and cholesterol levels are not new but offer clues to how depression acts upon the body. Researchers are currently working to understand the connections between blood glucose/cholesterol and anti-depressants.

Often times, the most marginalized of society suffer depression and slip through the cracks towards obscurity. Image by AmyFisherLittle

Ketamine has been shown to reverse depression within hours – but aside from cholesterol and blood glucose, there’s another downside. Patients apparently build a resistance to the drug, so it is only administered once. That means maintaining the remission of suicidal thoughts with other means must be aggressive.

In addition, ketamine is a drug that may readily be abused-it is addictive, and toxic, as well.

Ketamine: A Ray of Hope for Many

Fast-acting ketamine gives hope to many, but there are hurdles that need to be surmounted if ketamine is to become a main-stream pharmaceutical. While Medicinal chemists have taken ‘lead molecules’ like ketamine and developed them into robust pharmaceuticals- the scientific findings linking glucose and cholesterol (LDL) to certain anti-depressants are troubling.

The scientific and medical communities have found important insights into how the depressed brain works-that may be the most important take-away for the present moment.

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