Ketamine is an injectable anesthetic (a medicine that puts people to sleep during surgical procedures). Ketamine is related to the recreational drug phencyclidine (PCP).
Studies have found that low doses of ketamine can quickly reverse symptoms of depression. But so far, the U.S. Food and Drug Administration (FDA) has not approved it for depression or any other mental health condition.
Ketamine Treatment for Depression
Ketamine is taken off-label (meaning the FDA does not approve it) for depression that hasn’t responded to traditional antidepressants. This type of depression is known as treatment-resistant depression (TRD). About 30% of people with depression experience TRD.
- How ketamine works for depression: We don’t know precisely how ketamine helps treat depression. We do know that it affects several different signal pathways in the body that are associated with depression. At low doses, ketamine primarily blocks the N-methyl-D-aspartate (NMDA) receptor. Research suggests that NMDA receptors in the brain are overactive in depression. If taken at higher doses, ketamine also affects opioid and dopamine receptors. See the table below for more details, keeping in mind that research is ongoing.
- Types of ketamine treatment: There are different ways ketamine can be administered for depression. Ketamine infusions can be injected intravenously (IV) for depression two or three times a week in a hospital or outpatient setting like a ketamine clinic. Mail-order ketamine products like capsules, tablets, and lozenges are also gaining popularity. Taking ketamine by mouth is not as effective as having it infused. And though self-administering ketamine can be tempting, keep in mind that without appropriate monitoring by a healthcare provider, ketamine can be dangerous. It carries legal and health risks. Be aware that Spravato (esketamine) is a similar medicine that the FDA has approved as a nasal spray for TRD. It is not exactly the same as ketamine.
- What to expect during treatment: A ketamine infusion typically lasts about 40 minutes. During the treatment and for at least an hour afterward, you’ll be monitored for side effects like high blood pressure, high heart rate, or hallucinations. When your vital signs (heart rate, blood pressure, and oxygen saturation) are stable, and the healthcare team has determined you are not experiencing psychological side effects, you can leave the facility if it’s an outpatient clinic. Be sure to arrange transportation home because you should avoid driving for the rest of the day.
| How Ketamine May Work for Depression | |
|---|---|
| Action | Effects |
| Blocks NMDA receptors | Increases glutamate, dopamine, and serotonin |
| Increases brain-derived neurotrophic factor (BDNF) release | Helps change brain synapses |
| Changes gene expression | Promotes resilience to stress |
| Activates opioid receptors | Reduces pain |
Understanding Depression
Depression is the most prevalent mental health condition in the United States. It affects over 8% of adults and nearly 20% of those between ages 18 and 25.
Depression is a common but serious mental health condition. It’s characterized by a sad mood and lack of interest in activities for at least two weeks. Depression interferes with daily life and can be debilitating. Symptoms of depression vary but may include fatigue, feelings of hopelessness, irritability, and trouble concentrating.
Depression is typically treated with psychotherapy (such as cognitive behavioral therapy or interpersonal therapy), antidepressant medications, or both. Some examples of antidepressant medications include but are not limited to Prozac (fluoxetine), Zoloft (sertraline), and Cymbalta (duloxetine).
Finding the proper treatment for it is crucial to improve daily life and prevent complications like suicide.
Benefits and Risks of Ketamine Treatment
Before starting ketamine treatment, there are some essential benefits and risks to be aware of, including:
- Benefits of ketamine for depression: Ketamine has antidepressant effects that begin within hours of taking it. This is an essential advantage over most traditional antidepressants, which can take four to eight weeks to kick in. The effects of a single dose of IV ketamine can last for up to two weeks, but they often start to wear off before this.
- Potential side effects: Ketamine is a dissociative medicine, which means it can cause you to feel disconnected from pain or out of control of your environment. It may cause serious side effects, including but not limited to sedation (drowsiness), high blood pressure, fast heart rate, slow or shallow breathing, dissociation (disconnected thoughts or feelings), hallucinations, urinary tract complications, and nausea. Side effects are more likely with higher doses of ketamine.
- Precautions: Avoid ketamine if you have heart problems or high blood pressure that’s not controlled by medications. It may also potentially cause drug abuse (using too much of a medicine) or dependence (where your body needs a drug to function).
- Potential interactions: Ketamine may interact with other medicines that cause sleepiness, such as anxiety medicines like benzodiazepines or opioid pain medicines. And importantly, we don’t fully understand the long-term effects of using ketamine. More research is necessary to know if it’s safe.
- Who should consider ketamine treatment: Discuss ketamine treatment with your healthcare provider if you have tried at least two other antidepressants that haven’t worked. Also, consider ketamine if you have severe depression or suicidal thoughts. Ketamine is fast-acting and can bring quick relief to some people. Do keep in mind that because ketamine can cause hallucinations, it carries risks for people with mental health conditions like psychosis or schizophrenia. Most research on ketamine for depression has not included people with these conditions. That said, limited data suggests that ketamine may be an option for them.
- Microdosing ketamine: “Microdosing” refers to taking very low doses of ketamine or other psychedelic medicines. This is a popular trend, and though it makes sense that a low dose could be a safer option, there’s no clinical evidence yet to prove it. Animal studies have shown that low doses of ketamine led to minimal improvement in motivation and attention. Clinical trials in humans are necessary before this method can be routinely recommended.
Accessing Ketamine Treatment
There are several challenges associated with taking ketamine for depression, from finding a provider to affording the treatment. Here’s a closer look:
- Ketamine legality: Ketamine is a Schedule III controlled substance in the U.S., meaning it requires a prescription from a healthcare provider to be legal. Taking ketamine without a prescription is illegal across the board. You may hear of illicit ketamine by street names that include Kit Kat, Special K, and Cat Valium. Avoid taking these.
- How to find a provider: Your healthcare provider may refer you to a ketamine clinic. If they don’t, consider a ketamine provider directory like the one from the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3). When researching a ketamine clinic, be sure to look into factors like the healthcare provider’s expertise and how long the clinic has been open.
- Cost and insurance considerations: Ketamine infusions can be pricey. Insurance companies often pay a lower percentage for them than for other therapies. The price you are charged may depend on the type of facility that provides your infusions. For instance, if you are hospitalized when you receive ketamine, you may be charged less for it than if you get an infusion at a ketamine clinic. Before starting ketamine treatments, ask your insurance company for information about the prices you can expect to pay.
- Alternative treatments: If you have TRD, your healthcare provider may add another medicine that is not an antidepressant to help manage your depression. This is called augmentation. Often, lithium, thyroid hormone, or an antipsychotic are taken to augment antidepressants. Other treatments for TRD include electroconvulsive therapy (electric currents shock the brain and produce a seizure), deep brain stimulation (an implant is placed in the brain to activate specific parts of it), and psilocybin (a psychedelic derived from mushrooms). Be sure to discuss the legality, benefits, risks, and availability of these medicines and procedures with your healthcare provider before use.
Summary
Ketamine is a medicine approved for surgical anesthesia. It is taken off-label for depression.
In contrast to other antidepressants, ketamine begins to work within hours. For this reason, it is a good option for people with severe depression or those with suicidal thoughts.
Ketamine is usually given as an IV infusion in a healthcare setting like a hospital or specialized clinic.
Keep in mind that ketamine is a Schedule III controlled substance in the U.S. and requires a prescription from a healthcare provider to be legal.
Serious side effects of ketamine include high blood pressure and heart rate, drowsiness, cognitive problems, and hallucinations or dissociation.
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