Ketamine for Depression - An Overview

What Is Ketamine?

Ketamine or ketamine hydrochloride is a preferred medication for both humans and animals for its typical properties such as pain-relieving, sedation, and amnesia. It is chiefly administered to induce and maintain anesthesia before surgery. The state of anesthesia they generate is known as dissociative induction. With a sub-anesthetic dose, ketamine aids in pain and treatment-resistant depression (depression resistant to anti-depressant drugs). World Health Organization (WHO) recognizes ketamine as one of the essential medicines. Ketamine was discovered in 1962 and approved by the Food and Drug Administration (FDA) in 1970. Early, ketamine was used commonly on dogs and horses, as well as during the Vietnam War.

How Does Ketamine Perform?

Ketamine is an N-Methyl D Aspartate (NMDA) receptor antagonist that inhibits or antagonizes the action of NMDA. They disrupt glutamate, a chemical substance that transmits signals over the brain via neurotransmitters and involves memory, comprehension, and pain recognition. However, research and further studies are going on on the mechanism of action over depression.

What Are the Types of Ketamine?

The chemical structure of ketamine exhibits two forms, R ketamine, and S ketamine. They are isomers-same bonded atoms but with different dimensional orientations.

• Racemic Ketamine - It is the equal proportion of R and S ketamine. R-S ketamine has been used as an anesthetic and pain reliever for over fifty years. Available in many forms as oral, sublingual, rectal, nasal, subcutaneous, intramuscular, and intravenous.

• S-ketamine - It is available as a nasal spray.

How Does Ketamine Help Fight Depression?

Depression is a neurological mood disorder characterized by a constant feeling of sadness (low mood) and loss of interest in daily activities leading to impairment. Depression is often debilitating and affects millions worldwide in health, wealth, and socioeconomic status. Pharmacological therapy as antidepressant drugs conventionally shows improvement only after 4 to 12 weeks. Recent studies have concluded that glutamate, NMDA, and serotonin receptors play significant roles in depression disorder. Most of those studies accepted the position of drugs in depression exhibiting modification through NMDA receptors. Ketamine is a voltage-dependent NMDA receptor and calcium channel blocker whose low dose is evident for depression and, in higher doses, mimics psychotomimetic action and anesthesia.

When and How to Infuse Ketamine for Depression?

Ketamine is a robust and fast-acting antidepressant that also relieves extreme depression, anxiety, and life-threatening suicidal ideation.

• Ketamine as a slow IV infusion by infusion pump may show good improvement in mood within 4 hrs and reach a peak at 24 hrs in patients experiencing treatment-resistant depression.

• Some evident studies show that an infusion of 0.5mg/kg/min for about 40 minutes gives a favorable output.

• Ketamine inhibits suicidal ideation for up to three days of injection.

• Ketamine may partially relieve depression in bipolar patients.

With Clinical Evidence.

• After three clinical trials, the FDA approved s-ketamine as a nasal spray in March 2019 for treatment-resistant depression. However, the FDA also cautioned in February 2022 about ketamine-containing nasal spray intended to treat depression.

• The European Medicines Agency approved ketamine as an antidepressant.

• S-ketamine is a third-line of depression treatment, says the Canadian Network for Mood and Anxiety Treatment.

• Cochrane Medical Research on randomized trials reviewed that people under ketamine or S-ketamine showed improvement and remission of symptoms within one to 7 days than placebo did.

• Few studies have inspected the action of ketamine in anxiety.

A Drawback of Ketamine Over Depression.

Though some patients show complete remission of depression over days, in others, the effect of ketamine tends to decline after seven days and may result in a relapse of depression after ten days. So, the main drawback can be the period that lasts the effect after the course of treatment. The compensation would be the maintenance of ketamine initiation from twice a week and then lowering to once a week.

What Are the Other Health Benefits of Ketamine?

In addition to depression, ketamine is primarily directed to treat various medical conditions. As a result, the drug has been shown to be effective in these states.

1) Anesthesia:

• The primary manifestation of ketamine is anesthesia. Unlike other drugs, ketamine stimulates circulatory functions. The effects of ketamine on the respiratory system include preserving the airway and breathing reflexes. They are one of the typical anesthetic agents used in the Vietnam War.

• Ketamine is the drug of choice for the person experiencing traumatic shock with hypotension as it elevates blood pressure.

• As ketamine shows moderate bronchodilation, it aids in respiratory conditions like asthma, bronchospasm, and chronic obstructive pulmonary disorder.

• As a sedative drug in the emergency department to calm the patient abruptly.

2) Pain:

The lower dosage of ketamine, referred to as the sub-anesthetic dose, aids in relieving acute pain in the emergency department and perioperative refractory pain. In addition, they are effectively used due to their low risk of respiratory depression.

3) Near-Death Experience:

The personalized experience or dreams about one’s death or impending death is the near-death experience. Unfortunately, people under ketamine anesthesia seldom have the same features of dreaming.

4) Seizure:

Few shreds of evidence show that ketamine also helps in relieving status epilepticus.

What Are the Contraindications of Ketamine?

Have a concern about taking ketamine when you are at the following certain illnesses and conditions.

• Pregnancy.

• Neonates below three months.

• Cardio-related conditions like unstable angina.

• Uncontrollable hypertension.

• Increased intracranial or intraocular pressure.

• Poorly controlled psychotic disorders.

• Chronic liver diseases like cirrhosis.

• Recent liver transplantation.

What Are the Side Effects of Ketamine?

Though ketamine has numerous health benefits to look at, it possesses several adverse effects when taken.

• Short-term side effects include nausea, vomiting, impairment in memory, dizziness, drowsiness, diplopia (double vision), dreams, flashbacks, perceptual disturbances, and rarely hallucinations.

• Long-term adverse effects are stomach ache, renal problems, elevated blood pressure, amnesia, liver toxicity,

Conclusion

Hence, a fact presumes that people experiencing depression or treatment-resistant depression can get relieved by slow intravenous (IV) infusion of ketamine or S-ketamine followed by sustained maintenance. Nevertheless, future literature would contribute to the effects and actions of ketamine for depression.