In March 2019, the Food and Drug Administration approved a depression treatment based on ketamine, bringing the first new psychiatric drug to market in more than 30 years. This innovative approach to treating depression, a condition the World Health Organization has deemed the leading cause of disability in the world, is now available at Pacific Mind Health.

What is ketamine?

Ketamine has long been used as anesthetic, as it has a quick onset and creates a dissociation from the body that leads to a diminished or absent sense of pain. There are two types of ketamine used to treat major depression.

• Racemic ketamine is administered as an intravenous infusion. It is a combination of two mirror-image molecules, "R" ketamine and "S" ketamine.
• Esketamine is administered intranasally in a spray. Esketamine is only comprised of the "S" molecule.

Research is ongoing about the efficacy of each type of ketamine and the variability of side effects, as the two forms affect receptors in the brain in different ways. Esketamine was recently brought to market, but racemic ketamine has been utilized for decades off-label as a psychiatric medication. Dosages given for treatment of depression are far less than those given for analgesia.

What does ketamine treat? 

Studies have proven ketamine’s value for treatment-resistant patients who are unable to find relief for depression through other treatments. Depression is the leading cause of disability worldwide, with an estimated 16 million adults experiencing a major depressive episode each year in the United States. Suicide rates have risen by more than 30% in half of the states in the country in the last 20 years, and ketamine's rapid action could have life-saving effects for acutely suicidal patients. 

Ketamine also shows promise as a treatment for depression combined with anxiety, OCD, PTSD, bipolar disorder, chronic pain management, and other treatment resistant disorders. Mental health providers will evaluate patients to identify candidates who may benefit from ketamine therapy. 

How does ketamine work?

Ketamine works differently than antidepressants currently on the market. Standard antidepressants target one of the monoamine neurotransmitters -- serotonin, norepinepherine, and dopamine -- but ketamine increases glutamate, the brain’s most prevalent chemical messenger, by binding to NMDA receptors in the brain. Glutamate plays an important role in synaptic changes that occur in response to experiences that underlie learning and memory. Although its mechanism is not totally clear, ketamine's interaction with glutamate appears to trigger connections in the AMPA receptor, which leads to synaptogenesis and affects cognition, mood, and thought patterns. 

Studies are ongoing to identify exactly how ketamine works, but it is likely that it works in a myriad of ways. Research indicates it may reduce signals that cause inflammation, which is a known contributor to mood disorders. 

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How long does it take for ketamine to work?

Ketamine infusions typically demonstrates an effect on patients within the first three infusions. If no effect is experienced within the first three infusions, it is unlikely to have an effect with additional infusions and other treatment modalities will be recommended. 

Pacific Mind Health recommends an infusion schedule of 2 to 3 infusions per week for 6 to 8 infusions. While patients may feel relief after 1 to 3 infusions, additional treatments can prolong the positive effects of ketamine. The additional infusions will not typically provide the same dramatic relief as the initial infusions, but they should help sustain the relief.

After the initial infusion schedule is complete, the patient and doctor will determine if treatments should stop, taper, or continue. 

What are the side effects of ketamine?

Ketamine, like all drugs have side effects. When given by infusion, ketamine may cause:

• Nausea and vomiting
• High blood pressure
• Perceptual disturbances (time seems to pass very slowly or very quickly; noises, colors, and textures may be unusually stimulating; vision may be blurry)
• Dissociation (sometimes called out-of-body experiences); rarely, a person may feel as if they are looking down on their body, for example.

Perceptual disturbances and dissociation are often felt most during the first infusion and stop quickly after the infusion finishes. If at any point during an infusion a patient feels overwhelmed by these side effects, the infusion can be discontinued to halt the experience in 5 to 30 minutes depending on the age, body mass, metabolic rate, dosage, and route of administration. Ketamine is rapidly metabolized by the liver, giving the drug a half life of 2.5 hours in adults and near elimination from the system in about 10 hours.  

Side effects of ketamine that require emergency medical care include: 

• Trouble peeing, or bloody or cloudy pee
• Pale or bluish lips, skin, or fingernails
• Chest pain, discomfort, or tightness
• Shortness of breath
• Altered mental status, including confusion, delusions, or convulsions 
• Trouble swallowing or swelling to the eyelids, face, lips or tongue
• Skin rash or itching
• Irregular heartbeat

Is ketamine addictive?

Ketamine, like opioids, has addictive properties and may not be indicated for patients with a history of substance abuse. Its dissociative qualities has made it a drug of abuse for those looking to have hallucinogenic experiences. Mental health providers will consider substance abuse history when weighing the risks and benefits of ketamine. 

What should I expect during an infusion?

Upon arrival to your appointment, you will be taken to a treatment room and prepared for infusion. This involves collecting your weight, height, vital signs, and health history, including allergies. A nurse will start an IV that will be used to administer ketamine intravenously. You will sit in a recliner and be provided with an eye mask and noise cancelling headphones that will play soothing music. You can bring your own eye mask, headphones, playlist, and blanket if you prefer. Once you are comfortable, the nurse will attach equipment to monitor your heart, breathing, and blood pressure during the infusion. The nurse will then prepare and administer your infusion via a pump. The treatment takes about an hour.

Each patient's response to ketamine can be as unique as the patient. If at any time you feel unmanageable distress, you can alert the nurse and the infusion will be stopped or slowed depending on your response and preference. 

After the infusion is complete, you will have a period of recovery during which the nurse will monitor you for adverse side effects. You will likely feel back to normal a few minutes after the infusion is complete, but you will need someone to take you home from your appointment for your safety.