How Long Does Ketamine Work for Depression?

Ketamine can provide rapid relief for some patients with depression and certain other mental health concerns. But how long does ketamine work for depression, and what happens when its effects wear off?

Learn more about our Georgia mental health programs or verify your insurance now. 

History of Ketamine

Ketamine is a powerful drug that medical doctors and veterinarians have been using for decades to prepare patients for surgery and ease post-operative pain. In recent years, it has gained additional attention for its potential mental health benefits.

Key moments in the history of ketamine include:

• 1962: Ketamine is synthesized for the first time as part of an effort to find an anesthetic that is as effective as phencyclidine (PCP) but that doesn’t cause the problematic side effects that PCP does. 
• 1966: The first clinical study of ketamine as a human anesthetic is published.
• 1970: The U.S. Food and Drug Administration approves ketamine as an anesthetic for human patients.
• 2019: The FDA approves Spravato, a nasal spray that contains a ketamine variant called esketamine, for people with treatment-resistant depression. This approval requires the spray to be used in combination with an oral antidepressant.
• 2025: The FDA approves Spravato as a standalone treatment for major depressive disorder (MDD).

Depression remains the only FDA-approved use of ketamine as a mental health medication, but studies have shown that it may also be beneficial for people with:

• Bipolar disorder
• Anxiety disorders
• Posttraumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)
• Suicidal ideation
• Substance use disorders (addictions)
• Eating disorders

In addition to prescribing Spravato, some doctors also offer ketamine infusion therapy, which delivers the drug directly into the patient’s bloodstream. This is legal when done by a qualified medical professional, but since it has not yet been approved by the FDA it is considered an off-label use of the drug.

How Does Ketamine Work for Depression?

Experts believe that ketamine’s ability to ease depression may be due to its interaction with N-methyl-d-aspartate (NMDA) receptors. These receptors are typically associated with glutamate, which is the body’s primary excitatory neurotransmitter.

As an excitatory neurotransmitter, glutamate increases activity in nerve cells throughout the central nervous system (CNS). It plays an essential role in functions such as learning, memory, and neuroplasticity, which is the brain’s ability to make structural and functional changes in response to experiences and injuries.

It appears that when ketamine molecules block NMDA receptors, this causes increased glutamate levels in certain areas of the brain, including the prefrontal cortex. This increase has been linked with a variety of mental health benefits, including improved mood, and an easing of suicidal thoughts. 

How Long Does Ketamine Work for Depression?

From a mental health perspective, one particularly promising aspect of ketamine is the speed with which it produces results:

• Patients who receive ketamine infusion therapy frequently report benefits within two to 24 hours after their first session. 
• For Spravato, the nasal spray that contains esketamine, positive results are often felt within 24-48 hours, or one to two days.

Top put this into context: With commonly prescribed antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), patients typically have to take the medication for six to eight weeks before they notice improvements in their symptoms.  

Rapid relief is clearly a significant benefit, but does this relief last for an extended period? In other words, how long does ketamine work for depression?

Ketamine infusions

An April 2022 review in the journal Discover Mental Health reported the following about how long patients experienced antidepressant benefits from ketamine infusions:

• A meta-analysis of nine studies involving ketamine infusions found that antidepressant effects began approximately 40 min post-infusion, peaked approximately 24 hours later, and lost superiority to placebo after 10–12 days.
• Two randomized studies involving patients with depression due to bipolar disorder also found that antidepressant effects occurred within about 40 minutes of the infusion. Those studies reported that these effects lasted two to three days.

Spravato

Various sources have reported that the effects of a Spravato session can last from a few days to a week or longer. But patients who receive Spravato rarely take the medication just one time.

Typically, during what clinicians refer to as the induction or initiation phase of treatment, patients take Spravato twice a week for four weeks. Those who show improvements then often shift to a maintenance phase, which involves taking the drug once a week for the next four weeks.

During Spravato sessions, patients self-administer the medication by inserting a small device into their nostril and pressing a plunger to deliver the nasal spray. However, the FDA’s approval of this medication requires patients to be in a doctor’s office under the supervision of a qualified professional when they administer it.

Therapies for Depression

Many patients who take Spravato or receive ketamine infusions also take part in therapy to help them manage their depression symptoms. Depending on the nature and severity of a person’s symptoms, they may benefit from therapies such as: 

• Individual psychotherapy
• Group therapy
• Family counseling and support
• Cognitive behavioral therapy (CBT)
• Dialectical behavior therapy (DBT)
• Red light therapy 
• Biofeedback therapy
• Yoga, art, music and other holistic therapies
• EMDR and other trauma-focused therapies

There is no single medication, type of therapy, or course of treatment that is ideal for every person who has depression. This is why it is so important to find a provider who will assess your history, needs, and goals, then use that information to develop a truly customized treatment plan for you. 

Learn More About Depression Treatment in Atlanta

If you’ve been struggling with depression, another mental health condition, or a substance use disorder (addiction), Time Wellness Georgia is here for you.

Treatment options at our outpatient center in Atlanta, GA, include a partial hospitalization program (PHP), an intensive outpatient program (IOP), and an evening IOP for adolescents. Each program is staffed by a team of experienced professionals who are committed to providing personalized care within a safe and welcoming environment.

To learn more about how we can help you or a loved one, or to schedule a free assessment, please visit our Contact page or call us today.