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Intranasal Ketamine for Treatment Resistant Depression

What is Ketamine?

Ketamine is in a category of medications called dissociative anesthetics. It has been used since 1970 by anesthesiologists to help keep patients, usually children, asleep and free of pain in surgery. More recently, however, it was discovered that depressed patients who were given ketamine during surgery would find their depression symptoms rapidly improved. This prompted a wide range of scientific studies supporting the use of ketamine – intravenously – for rapid treatment of severe depression. In doses used to treat depression, it is neither dissociative or anesthetic.

At higher doses, Ketamine has also been used by people for its psychedelic effects, and for that reason is a controlled substance. It almost never leads to addiction and compulsive use, however, because does not directly stimulate dopamine pathways like most other addictive substances.

What is Intranasal Ketamine?

Ketamine can be absorbed the bloodstream in several ways: orally, intramuscularly, intranasally and intravenously. Spraying ketamine into the nostrils can help get small doses of ketamine into your bloodstream via the small blood vessels in the nasal sinuses. Although most research has studied intravenous ketamine at moderate doses, research does exist that suggests intranasal ketamine can be helpful for treatment-resistant depression too. Some physicians also advocate treatment by intramuscular injection.  Dosing through the nose is less reliable than intravenous dosing as people’s breathing, nasal mucosa (lining) and blood flow differs, and the drug passes through the liver before getting to the brain. However, nasal dosing is much cheaper and easier to get and a good first step.

How Does Ketamine Work?

How Ketamine works for depression is not fully established, and there are several theories. It is well known that ketamine is an NMDA glutamate antagonist but also affects brain growth factors and opioid receptors. It may work either by interfering with the pain system, diminishing mental anguish, or by temporarily inhibiting a part of the brain that is typically overactive in depression (the lateral habenula, also known as the “anti-reward center”), so that life can indeed feel hopeful again. Stress, the common antecedent for depression, affects cellular activity in part via the glutamate and opioid systems. Perhaps the ketamine is modulating this effect.

How Much Does Ketamine Treatment Cost?

It is legal to use ketamine when prescribed by a physician. However, it is not yet FDA approved for depression. For this reason, it can be prescribed but is not currently covered by insurance for depression, in any form. Intravenous ketamine treatment is typically costly to administer (patients have an IV put in, and are monitored for the duration of the infusion) and for that reason can cost a client $500-$1000 per infusion.  A series of 6 infusions are typically recommended over the course of 2 weeks. If it works then treatment is ongoing. Intranasal ketamine, on the other hand, is given at lower doses and is far less costly (approximately $50-$150 for 1 month supply, self-administered, typically every other day).

Is Ketamine for Me?

At Psych Garden we do a careful evaluation with a therapist and psychopharmacologist to determine whether ketamine will be appropriate for you. Typically clients with moderate to severe depression who have not benefited from multiple antidepressant trials have a good chance in benefiting from Psych Garden’s intranasal ketamine program. At Psych Garden we know that medications are crucial but not always sufficient so we will encourage you to engage in comprehensive treatment. This may include other medication changes, psychotherapy, and wellness coaching.

Is it Safe?

Ketamine is quite safe even at high anesthesia doses. It is not toxic to the heart or brain and is not addictive. Some people have a small increase in blood pressure during the procedure. Some people who have misused massive doses of ketamine for a while develop a cystitis. Our intranasal ketamine doses are from 20-30x times less than anesthetic doses. They are quite tolerable, resulting in sensations of time and thinking distortion that usually lasts around 30 minutes. At Psych Garden, the first dose and dose increases will always be monitored by us to ensure you can safely tolerate the doses we prescribe. You would need to wait for several hours after dosing to ensure you are ready to drive home.

Is it Effective?

Ketamine has been and continues to be studied but there are now numerous double-blind placebo-controlled studies showing it to be safe and effective, rapidly improving depression symptoms, and especially suicidality, in the short term. Because this drug is cheap and readily available, there is no reason a pharmaceutical company will finance a study of effectiveness, so studies are being done at academic centers. Some studies use esketamine, an isomer of racemic ketamine that is only available in research settings. It is not clear why that should work differently if it does. The vast majority of research has been done with intravenous ketamine. Research on intranasal dosing is much scarcer. Because doses are less robust and steady, it may be less effective than intravenous. However, it is much easier to give and much cheaper to receive and side effects will only be lower with this route.  

What is it like?

Right after administering the drug, people say they feel a bit out of it. Most sit down and relax for a half hour during which they may find it hard to gather their thoughts, and time can feel slowed down. They are always aware of where they are. Most people are not anxious during this, but neither is it an experience that they’d call fun. The effects last 20-40 minutes and people are fine to walk around after. Our patients tend to report a rapid response that they describe as getting a respite from their negative thinking, a separation from those depressed pessimistic parts of themselves, during which they are able to get on with the tasks and relationships they have been unable to motivate or enjoy. While the effects may only last that day at first, such hopeful respites from depression permit people to make real-world changes – exercising, getting work done, interacting, etc – which people feel proud of, further lifting them out of depression. By combining intranasal ketamine at the right dose, with the appropriate antidepressants and psychotherapy, rapid and sustained remission of depression symptoms can be achieved.

What if I Have an Addiction?

There is no evidence to date that using ketamine for depression causes or worsens addiction symptoms. Ketamine is indeed being studied for the treatment of addictions with some promising results. More clinical trials will be needed to know with certainty that it is helpful for addictions. At this point, we do not see addiction as an absolute contraindication for intranasal ketamine and treat these clients on a case-by-case basis depending on what their addiction patterns are, monitoring use, misuse, and benefits.

What is Involved in the Ketamine Program at Psych Garden?

The Ketamine Program for Treatment-Resistant Depression at Psych Garden involves a comprehensive approach for depression tailored to your unique situation. Your first appointment at Psych Garden will be a 90-minute evaluation with both a psychotherapist a psychopharmacologist. In this appointment, we will assess your situation and discuss a comprehensive treatment approach, including but not limited to Ketamine treatment.

Among the options considered will be adjunctive medication to help address depression symptoms, specialized psychotherapy to address emotional, behavioral and thought patterns that accompany depression, individualized lifestyle modification with a case manager who can help your lifestyle support recovery from your particular condition, professional consultation to your family members on how they may best support your treatment and independence, couples or family therapy to aid with external relationships that often have tremendous opportunity effect depression in positive ways ways, and groups that can often address social patterns such as isolation and avoidance that can contribute to depression. We typically do not recommend intranasal ketamine alone as an effective treatment for depression. We will also discuss providers for intravenous ketamine in the Boston area.

After a treatment plan is agreed upon, we will set you up with providers to help support this plan, as well as a first-time ketamine administration appointment with our registered nurse. Your first dose will be monitored at Psych Garden, after which, in most cases, you will be given ketamine for self-administration every other day at the prescribed dose. Your progress will be monitored by regular appointments with a psychopharmacologist, and any dose changes will first be given in our facility. We will work with you to adjust the treatment plan as needed until you have arrived at the solutions needed to conclude treatment at your pace.