Depression can be chronic and long-lasting, and many sufferers try several different treatments and medications before finding one that works for them. Typically, depression treatment includes antidepressant medication, often in combination with behavioral therapy. Although antidepressants can be life-changing for many people with depression, some people may experience delays or difficulty finding effective treatment.
Some of the criticisms of traditional antidepressant treatments are:
- Response to medication varies from person to person
- Negative side effects
- Slow to be effective
To address some of these shortcomings, researchers and clinicians have trialed other types of treatments. Recently, ketamine treatment for depression has gotten attention as an alternative to other slower-acting antidepressants.
Table of Contents
What Is Ketamine?
Ketamine was originally used as an anesthetic medication. More recently, it has been used as a fast-acting antidepressant, with reports suggesting it may be effective in as little as a few hours, and its effects may last for days or weeks. Ketamine therapy is beneficial for people who have not responded to other forms of treatment and are thought to have treatment-resistant depression. For people with severe or treatment-resistant depression, or with an immediate risk of suicide, ketamine therapy may be a life-saving treatment option.
How Is Ketamine Used to Treat Depression?
Most antidepressant medications are taken in pill form; ketamine, however, is most frequently delivered intravenously. It is typically used in cases of treatment-resistant depression, where multiple other attempts to alleviate depression symptoms have been unsuccessful.
Before ketamine is prescribed, a detailed medical history is collected that typically includes, among other pieces of information, details about any previous psychiatric illness and medications taken. Ketamine for depression is typically administered for 40 minutes, three times per week in a clinical setting. Patients are monitored closely for any signs of an adverse reaction.
History of Ketamine Treatment
Ketamine’s primary medicinal use has been as an anesthetic, and it was used heavily for pain management for soldiers during the Vietnam war. At some doses, ketamine can cause hallucinogenic or dissociative features and has been used to “model” schizophrenia in research settings.
Because of these side effects, ketamine (often referred to as “K” or “Special K”) has often been used and abused recreationally. It became a popular recreational drug in the 1970s and was common in rave culture. Recreational use and abuse of ketamine have been associated with cardiovascular, gastric and urinary health problems.
More recently, there has been increasing research into the antidepressant effects of ketamine. In 2000, an important study showed that participants who had been given a low-dose infusion of ketamine had significant improvements in their depression symptoms compared to those who had an infusion of a saline solution. Since then, there have been many more clinical trials evaluating the use of ketamine in depression. These trials have demonstrated the effectiveness of the drug, and ketamine infusions or injections are now offered as treatment options in some cases of depression. Most recently, a similar drug called esketamine has also been approved for use in clinical settings.
Ketamine vs. Traditional Antidepressants
Ketamine is thought to be effective in cases where other types of treatment have failed to provide significant improvements in depression symptoms because it targets different biological mechanisms than other depression treatments. Traditional antidepressants target the monoamine system, a group of chemicals that include serotonin or dopamine, and can take weeks to be effective. In contrast, ketamine acts on glutamate, which can be effective almost immediately. This difference can be life-saving for those experiencing suicidal ideation.
Ketamine also differs from traditional antidepressants when it comes to its side effect profile. While conventional antidepressants may have unpleasant side effects, the effects of ketamine may be more intense, acute or severe, with a heightened risk of abuse.
Ketamine Side Effects
Although there have been many therapeutic benefits to the use of ketamine, there are also several side effects that warrant consideration. For example, adverse effects may include:
- Psychiatric conditions, including schizophrenia symptoms or mania
- Increase in blood pressure
- Feeling intoxicated or having lowered inhibition
- Disruptions to memory
- In rare cases, toxicity
In many cases, these symptoms, much like the antidepressant effects of ketamine, appear during ketamine administration and wear off within a short time. However, it’s important to consider these side effects when deciding on depression treatment.
As a result of the rapid antidepressant effects and some of the potential sensory-altering effects, ketamine is sometimes used recreationally or abused. Because of this, a prescription for ketamine may not be provided to those with a history of substance use problems.
FDA Approval of Esketamine
Given the challenges of adequately addressing treatment-resistant depression, there’s great interest in making ketamine or similar drugs available to the public. As a result, many trials have tested the effects of esketamine, a drug similar to ketamine. Esketamine has been tested for use through a nasal spray, rather than the more burdensome intravenous delivery. Trials have shown that it is effective in rapidly alleviating depression symptoms.
In 2013, the Food and Drug Administration (FDA) approved the use of esketamine for treatment-resistant depression, particularly in cases where suicide is an imminent risk. The FDA approval of a nasal spray for depression shows important progress in making the drug more accessible for those who may urgently need it. However, while the drug has been approved, it is still under restricted distribution to prevent abuse and is only available from certified doctors and clinics.
Cost of Ketamine Treatment
The cost of ketamine can be a significant barrier to access. Just a single dose of esketamine can cost $500 or more, with additional costs for properly trained personnel or appropriate equipment. Given that the benefits of the drug may be fairly short term, the price of repeated ketamine treatment may be unaffordable for many people.
The Future of Ketamine Treatment for Depression
Use of ketamine can be life-saving for severely depressed patients. However, questions remain surrounding the long-term safety and health outcomes of extended ketamine use. There is also ongoing research to examine whether alternative drugs with similar effects may be safe for use, and may reduce the risk of abuse associated with ketamine.
Aan Het Rot, M., et al. “Ketamine for depression: where do we go from here?” Biol Psychiatry, 2012. Accessed May 10, 2019.
Sanacora, G., et al. “A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders.” JAMA Psychiatry, 2017. Accessed May 10, 2019.
Morgan, C. J., et al. “Ketamine use: a review.” Addiction, 2012. Accessed May 10, 2019.
Berman, R. M., et al. “Antidepressant effects of ketamine in depressed patients.” Biol Psychiatry, 2000. Accessed May 10, 2019.
Rasmussen, K. G., et al. “Serial infusions of low-dose ketamine for major depression.” J Psychopharmacol, 2013. Accessed May 10, 2019.
Katalinic, N., et al. “Ketamine as a new treatment for depression: a review of its efficacy and adverse effects.” Aust N Z J Psychiatry, 2013. Accessed May 10, 2019.
Daly E. J., et al. “Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial.” JAMA Psychiatry, 2018. Accessed May 10, 2019.
U.S. Food and Drug Administration. “FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.” March 06, 2019. Accessed May 10, 2019.
Ying X., et al. “Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis.” International Journal of Neuropsychopharmacology, November 17, 2015. Accessed May 10, 2019.
Sassano-Higgins, S., et al. “A review of ketamine abuse and diversion.” Depression and Anxiety, 2016. Accessed May 11, 2019.