Ketamine for Depression

Mindpath Health’s Julian Lagoy, MD, discusses ketamine therapy and why it’s used to treat depression. See highlights below or read the full article with sources here. 

Healthcare professionals first began using ketamine as an anesthetic in the 1960s. Before long, they noticed it didn’t just cause a sedative effect. Some people also reported improvements in their mood after receiving ketamine, says Kyle Keller, LICSW, a CIIS-certified psychedelic-assisted psychotherapist in Minnesota and founder of Intero Psychedelic Therapy. 

During the 2000s, medical professionals began researching ketamine as a possible treatment for depression, according to Hans Eriksson, a clinical psychiatrist and chief medical officer at HMNC Brain Health. 

In 2019, the Food and Drug Administration (FDA) approved the use of an esketamine nasal spray called Spravato for treatment-resistant depression. Esketamine is a more potent form of ketamine, so doctors can prescribe it at lower doses that have a similar effect. 

Treatment-resistant depression refers to depression symptoms that don’t respond to two or more types of antidepressant medication. Estimates suggest up to 30% of people with major depression have treatment-resistant depression. 

Antidepressants aren’t the only treatment option for depression symptoms, of course. You may have also tried: 

• psychotherapy 
• hypnotherapy 
• meditation 
• acupuncture 

These approaches don’t always relieve severe depression symptoms, including thoughts of suicide — and that’s where ketamine could make a difference. 

How it treats depression

Ketamine works by binding to receptors in the brain that produce a chemical called glutamate, explains Faisal Tai, a board-certified psychiatrist and medical director of geriatric psychiatry at HCA Houston Healthcare Tomball. In other words, it helps activate glutamate in your brain. 

Ketamine can also stimulate the production of brain-derived neurotrophic factor, Eriksson says. This protein plays a role in neuroplasticity, or your brain’s ability to adapt as you experience new things. By supporting neuroplasticity, ketamine may help change negative thought patterns that contribute to depression. 

Another major advantage lies in the fact that ketamine works very quickly, Eriksson says. With traditional antidepressants, it may take weeks before you notice improvement in your symptoms. Ketamine may offer relief in as little as 1 hour. 

Ketamine may also help treat: 

• anxiety 
• obsessive-compulsive disorder (OCD) 
• post-traumatic stress disorder (PTSD) 
• bipolar disorder 

Types of ketamine:

• Nasal spray: You can use Spravato nasal spray once or twice a week for up to 4 weeks. After 4 weeks, your care team will typically study your symptoms before recommending further treatment. 
• Intravenous (IV) therapy: A slow, continual IV drip delivers ketamine directly into your bloodstream. 
• Intramuscular (IM) injections: You may receive shots of ketamine into a large muscle, such as your shoulder or thigh. 

• Lozenges: You may receive a prescription for oral ketamine tablets, which dissolve slowly under your tongue, to take at home. You can take these tablets between IV or IM treatments, or on their own. It may take longer to notice an effect, since your digestive system has to process the ketamine first. 

You can only receive esketamine nasal spray, IV therapy, and IM injections at a clinic or hospital. This allows healthcare professionals to monitor your response and any side effects you experience. 

What does the research say?

A growing body of research supports the benefits of ketamine for depression. 

In a small 2019 study, men with severe depression who received six ketamine injections over 2 weeks experienced a significant improvement in depression. This effect set in just 1 hour after their first dose and lasted as long as 1 month after their last dose. 

In a 2020 study, participants with treatment-resistant depression received either six ketamine infusions or five placebo infusions followed by one ketamine infusion over a 12-day period. Those who received only ketamine doses experienced greater improvements in their depression — but when the placebo group received their dose of ketamine, they reported a similar level of improvement. 

In a 2022 study, people with depression and thoughts of suicide received six IV ketamine infusions at three separate clinics over 21 days. Within 6 weeks of starting treatment, 20% of people with depression were considered “in remission,” meaning their depression symptoms had greatly improved, and 50% of people who had thoughts of suicide no longer experienced them. 

In a small 2022 study, people with treatment-resistant depression who received three IV ketamine infusions in 1 week found it easier to replace certain negative beliefs with more optimistic ones. Updating these beliefs seemed to help improve depression symptoms, according to the study authors. 

Important 

While these results show promise, research on ketamine for depression remains in the early stages, says Julian Lagoy, MD, a California-based psychiatrist with Mindpath Health. 

More studies are needed to figure out the ideal treatment dosages and frequencies to maximize the benefits of ketamine while minimizing its side effects. 

Safety and side effects

Side effects of ketamine therapy tend to be fairly mild. According to a 2021 review the most common side effects include: 

• nausea 
• dizziness 
• headaches 
• dissociation, or feeling disconnected from your body, thoughts, and feelings 
• vertigo, or the feeling of spinning and losing your balance when you’re not moving 
• drowsiness 
• dysgeusia, or altered sense of taste 
• psychosis, which may include hallucinations and delusions 

In rare cases, ketamine can cause adverse events, such as: 

• panic attacks 
• mania 
• ataxia, or poor muscle control or coordination 
• akathisia, or difficulty sitting still 
• thoughts of self-harm 
• autoscopy, or out-of-body experiences 

Long-term ketamine use has been linked to bladder dysfunction and memory loss. 

Is ketamine right for everyone?

Since ketamine can increase blood pressure, it’s not recommended for people with hypertension, Eriksson says. 

Keller advises avoiding ketamine treatment if you or your family has a history of psychosis. Ketamine can cause disassociation, which experts have linked to hallucinations and other symptoms of psychosis. 

You may also want to ask your healthcare professional about whether or not it’s safe to take ketamine if you have: 

• heart disease 
• history of increased intracranial pressure 
• history of substance use disorder 

How to try it

You can find freestanding clinics and online services that offer ketamine, but Safai cautions that many of them don’t offer adequate supervision. 

“This is dangerous, as it’s important to be monitored for side effects by a nurse or doctor during the treatment,” she says. 

Again, oral ketamine tablets are the only form of ketamine you can take at home. Your prescribing clinician will likely recommend having a friend, partner, or other trusted person present when you take them, just in case you experience any uncomfortable side effects or a negative reaction. 

If you do try a ketamine clinic on your own, the American Society of Ketamine Physicians, Psychotherapists, and Practitioners recommends making sure it meets the following criteria: 

• It’s been open for more than 2 years. 
• It has board-certified physicians with mental health experience on staff. 
• It offers additional mental health support services, such as individual or group therapy. 
• You’re required to complete at least one or two consultations before starting ketamine therapy. 

How much does it cost?

Since the Spravato nasal spray is the only FDA-approved treatment at this time, insurance companies often won’t cover other forms — though they may cover other types of ketamine treatment in cases of very severe depression, according to Lagoy. 

The cost of other types of ketamine therapy can vary, depending on where you live, what form and dose you take, and other factors. 

The cost of 1 month of Spravato treatment may run as high as $6,800 if you receive treatment twice a week. That said, insurance programs may offer some support with covering the cost of Spravato.