Ketamine has been making headlines for years, from the death of actor Matthew Perry to Elon Musk’s reported microdosing, to its portrayal in Hulu’s “The Secret Lives of Mormon Wives.” Ketamine, primarily known as a longtime party drug and anesthetic, has reemerged as a controversial treatment for depression.
Its rise in popularity underscores the truth that treating depression isn’t always cut and dry. To the everyday person, a depression diagnosis might seem straightforward: symptoms of a persistent sad mood, lack of energy and little enjoyment in pleasurable activities, all to be remedied by psychotherapy and a medication. However, it’s not so simple.
Depression is a complex condition, impacted by genetics and other factors. Given the complexity of the diagnosis, any additional tool — such as ketamine — in the therapeutic arsenal is helpful. It might end up as the most successful treatment for an individual, finally alleviating their depressive symptoms.
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What Is Ketamine?
Ketamine is a powerful medication that has been safely used in medical and veterinary science for over a century, mainly as an anesthetic. Ketamine can induce a state of sedation, or feeling calm and relaxed. It may also induce immobility, relief from pain, hallucinations and amnesia. It has gained recent popularity for treating depression.
Ketamine is short for ketamine hydrochloride, which the Drug Enforcement Administration considers a Schedule III controlled substance, meaning it has the potential for abuse and dependence.
Which ketamine is FDA approved?
There are various formulations of ketamine. Ketamine is a mixture of two molecules called R-ketamine and S-ketamine, sometimes referred to as arketamine and esketamine, respectively. Among these, only esketamine in the form of a nasal spray, marketed as Spravato, has been approved by the Food and Drug Administration for the treatment of depression.
Specifically, Spravato is “approved as a nasal spray for treatment-resistant depression in adults and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior,” as stated in a press release from the FDA on October 10, 2023. Spravato may be taken in conjunction with an oral antidepressant or as a standalone therapy.
Currently, other forms of ketamine outside Spravato are considered on-label only for anesthesia.
According to the FDA’s press release, “Ketamine is not FDA approved for the treatment of any psychiatric disorder. FDA is aware that compounded ketamine products have been marketed for a wide variety of psychiatric disorders (e.g., depression, anxiety, post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder); however, FDA has not determined that ketamine is safe and effective for such uses.”
While ongoing research may lead to broader approvals for other forms of ketamine and other uses, no additional indications have been approved to date.
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What Types of Depression Is Ketamine Therapy Used for?
Ketamine is primarily used for a type of depression called treatment-resistant depression. TRD is a type of major depressive disorder that doesn’t respond to traditional first-line treatment, like antidepressant medications, including selective serotonin reuptake inhibitors, such as Prozac or Zoloft.
Ketamine therapy can be effective for some patients, says Dr. Helen Lavretsky, professor of psychiatry in-residence at the David Geffen School of Medicine at UCLA. She’s also director of the Late-Life Mood, Stress and Wellness Research Program and director of the Integrative Psychiatry Clinic.
“Ketamine use should be reserved for truly treatment-resistant patients who failed to respond to two or more antidepressants administered in the optimal dose for at least two to four months,” she says.
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How Does Ketamine Therapy Help With Depression Symptoms?
The reputation of ketamine being a party drug and a horse tranquilizer may cause some skepticism, says Dr. Martha Koo, Manhattan Beach, California-based founder and chief medical officer at Neuro Wellness Spa and a board-certified provider in psychiatry and addiction medicine.
Ketamine is in a drug class called dissociative anesthetics, and ketamine is specifically an N-methyl-D-aspartate receptor antagonist. Koo explains that this means that ketamine acts on the glutamatergic system in the brain, which is responsible for:
— Growing new pathways and connections between brain cells, called neuronal growth
— Maintaining neuroplasticity, which is the ability to learn new skills and become better at them
— Helping different parts of the brain work together as a team, called neuronal interconnectivity
— Helping you feel energized and focused while also maintaining a sense of calm
With ketamine giving a boost to the glutamatergic system, it may help people struggling with depression to feel like their brain is working more harmoniously, giving them energy, strength and focus to be able to face the day.
Is Ketamine Effective for Depression?
Research suggests that ketamine administered through the nose (Spravato) or taken orally requires two to four weeks of treatment before taking effect. Other forms of ketamine used off-label, such as intravenous or intramuscular injections, can offer faster relief.
The effects of ketamine depend on the individual, the type of ketamine they received and the dosage. The body will eliminate ketamine in a matter of hours, but the effects of it may last for more time, up to a week or longer.
Ketamine dosage and frequency
There are a few routes and types of medications for ketamine for depression. In the FDA’s October 2023 press release, the agency emphasized that “compounded drugs, including compounded ketamine products, are not FDA approved, which means FDA has not evaluated their safety, effectiveness or quality prior to marketing. Therefore, compounded drugs do not have any FDA-approved indications or routes of administration.” The FDA reiterated this guidance in October 2024.
This means there are no FDA-regulated routes or dosages for ketamine, except in the case of FDA-approved Spravato. But, here are some of the typical routes of administration and dosages that health care providers may use:
— Intramuscular ketamine. Ketamine can be given as a shot into the muscle, usually in the upper outer gluteus. A standard IM dose is 0.25 to 0.5 milligrams per kilogram of body weight. IM ketamine peaks in about five minutes.
— Oral ketamine. A standard dose is 1 mg/kg of body weight. Oral ketamine peaks around 15 to 30 minutes.
— Ketamine lozenges. Ketamine lozenges are a simple, noninvasive way to administer ketamine at home. Standard dosing varies.
— Intranasal ketamine (Spravato). As this is the only FDA-approved formulation of ketamine for depression, there is standard dosing. The dose for TRD is 56 mg for adults, which may increase to 84 mg. For major depressive disorder or suicidal ideation, the dose is 84 mg for adults. Spravato is taken nasally for six months, or longer if the medication is effective. A medical provider will provide a nasal spray device, similar to one you might use for a stuffy nose.
— Intravenous ketamine. Koo says that IV ketamine works the fastest, with symptom relief within a few hours. IV ketamine doses are weight-dependent and commonly administered at 0.5 mg/kg. IV ketamine peaks between one and five minutes. Because of its rapid onset and precise dosing, it is often the administration method of choice in most health care settings.
Ketamine administered intravenously — which can involve up to six infusions — has shown positive effects in patients within a few hours, relieving depressive symptoms and suicidal thoughts, Lavretsky says. Intravenously administered ketamine can quickly resolve “depressive symptoms and suicidal ideations” in patients under 65 years old, she adds.
“However, the need for IV access and physician monitoring limits its uses. In addition, the medication’s long-term use efficacy and safety are not well known,” she points out.
Since the other forms of ketamine are off-label, there aren’t regulated treatment durations. Your doctor may recommend that you have more ketamine treatments in the beginning, and then have the treatment less often as a maintenance therapy. Treatment duration and frequency depend on the discussion between a patient and their medical provider.
Microdosing ketamine
Microdosing ketamine — meaning taking less than the recommended therapeutic dose of ketamine — has recently become a topic of discussion, after reports of Elon Musk microdosing ketamine have surfaced. Musk has publicly stated that microdosing ketamine helps him get out of a negative frame of mind.
However, it’s important to note that microdosing ketamine is not FDA approved for any medical or psychiatric use, and its safety and effectiveness have not been established for this purpose. Taking ketamine, even when under the therapeutic dose, should always be done under medical supervision. Even at low doses, there are still side effects and risks that may occur with ketamine.
Ketamine Benefits
Using ketamine for depression has a few key benefits:
— Relief from depression symptoms. Especially with TRD, other treatments may not be working. Ketamine may be the treatment to finally provide relief from depression.
— Rapid onset. FDA-approved Spravato may take a few weeks for you to start feeling the full effects. However, you may feel some relief from Spravato within 24 to 48 hours, which is faster than you would get with oral antidepressant medications.
— May be combined with psychotherapy. Because ketamine can induce an altered state of consciousness, individuals may be more receptive to emotional processing and therapy.
Ketamine Side Effects and Risks
Using ketamine for depression also has side effects and risks:
— Medical surveillance is needed after treatment. All patients require some level of medical surveillance after treatment, such as staying in the clinic so the staff can watch vital signs and assess for loss of consciousness. Koo also says that patients cannot drive post-session for at least 24 hours.
— Dissociative effects. The effects differ between individuals, but some may experience emotional numbness or detachment, out-of-body experiences or hallucinations.
— Nausea. Nausea is one of the most common side effects, and usually, the side effect is mitigated with medications prior to treatment.
— Headaches. Headaches are another common effect, also treated with medicine beforehand.
— Abuse potential. Proper screening and ongoing monitoring are essential with ketamine administration. It’s vital that people work with licensed psychiatric clinicians who can prescribe appropriately and watch for signs of misuse or dependence.
Is ketamine addictive?
Dr. Leonardo Vando, the Maryland-based medical director of Mindbloom, a platform that provides services to affiliated psychiatric medical practices in more than 35 states, says that ketamine is “not physically addictive in the way that substances like alcohol and nicotine are. However, it is possible to become psychologically dependent on ketamine — especially when it is taken without proper clinical supervision.”
Are there ketamine withdrawal symptoms after treatment ends?
When ketamine for depression is taken under medical supervision, withdrawal symptoms are less common. The dosage of ketamine administered is not meant to induce physiological dependence.
When ketamine is abused, American Addiction Centers cites common symptoms may include:
— Mood swings
— Nausea
— Shakiness
— Sweating
Who Is Eligible for Ketamine Therapy?
Ketamine therapy is usually for individuals with depression who have not responded to other types of treatment or those with active suicidal thoughts.
Beyond that, anyone considering ketamine therapy would need additional medical clearance. This process includes:
— Patient intake. Your provider will take a complete medical history, family history, surgical history, medication list and allergies.
— Rule out contraindications. Your provider will need to make sure you don’t have a condition that makes taking ketamine unsafe, like pregnancy or breastfeeding, heart disease, uncontrolled high blood pressure, untreated thyroid disease, schizophrenia, dementia, acute drug intoxication or acute mania. There are also some concerns about the long-term effects of ketamine on the still-developing adolescent brain, Lavretsky says.
— Psychological assessment. Your provider will want to ensure that other mental health medications or mental health conditions would not interact with ketamine. In addition, they will want to screen for your risk or history of substance use.
— Assessment of developmental and trauma history. It’s important for your provider to understand what treatment you have tried in the past and your support system you have at home while taking ketamine.
— Informed consent. Everyone needs to sign consent forms and agree that they understand the risks and benefits of ketamine therapy and the importance of regular medical follow-ups.
Does Insurance Cover Ketamine?
Insurance sometimes covers ketamine therapy for treatment-resistant depression.
Spravato is FDA approved for depression, so it may be a covered benefit under your insurance plan if you meet the inclusion criteria. Out of pocket, Spravato costs between $500 and $1,000 per single dose. Spravato does have a program called Spravato withMe to assist with cost coverage, navigation and pharmacy services if you need support. Medicare and Medicaid may also help with cost-sharing for Spravato.
Outside of FDA-approved Spravato, ketamine is still considered off-label for depression. This means that insurance companies are unlikely to cover the medication, as your plan would likely consider it an investigational treatment.
With continued research on safety and efficacy, insurance coverage may improve.
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What Is Ketamine and Is It Effective for Depression? originally appeared on usnews.com
Update 07/02/25: This story was previously published at an earlier date and has been updated with new information.
