Updates on Ketamine for Depression and Other Mental Health Disorders

In recent years, ketamine has emerged as a groundbreaking treatment for depression and other mental health disorders. Originally developed as an anesthetic, ketamine's potential as a rapid-acting antidepressant has garnered significant attention. This blog delves into the latest updates on the use of ketamine for treating depression and other mental health disorders, exploring its mechanisms, efficacy, safety, and future directions.

The Rise of Ketamine for Depression

Ketamine was first synthesized in the 1960s and has been widely used in medical and veterinary practice for its anesthetic properties. When I go on medical missions to Africa or Central America, I sometimes use it as a stand along anesthetic.  Its journey from an anesthetic to a promising psychiatric treatment began in the early 2000s when researchers discovered its rapid antidepressant effects. Unlike traditional antidepressants, which can take weeks to show benefits, ketamine can alleviate depressive symptoms within hours.

Mechanism of Action

Ketamine primarily acts as an NMDA receptor antagonist, which sets it apart from traditional antidepressants that target serotonin, norepinephrine, and dopamine pathways. By blocking NMDA receptors, ketamine enhances glutamate transmission and promotes synaptic plasticity. This leads to the formation of new neural connections, which is thought to underlie its rapid antidepressant effects.

Additionally, ketamine influences the brain's reward and mood regulation systems, potentially reversing the neural changes associated with chronic stress and depression. It also modulates the HPA axis, reducing the production of stress hormones like cortisol, which can have a profound impact on mood and anxiety.

Efficacy in Treating Depression

Major Depressive Disorder (MDD)

Ketamine has shown remarkable efficacy in treating Major Depressive Disorder (MDD), particularly in treatment-resistant cases. Studies have demonstrated that a single intravenous (IV) infusion of ketamine can produce rapid and significant reductions in depressive symptoms within hours, with effects lasting up to a week. Repeated administrations have been found to prolong the antidepressant effects.

Bipolar Depression

Bipolar depression is notoriously difficult to treat, often requiring a combination of mood stabilizers and antidepressants. Ketamine has shown promise in this area, offering rapid relief from depressive episodes without inducing manic symptoms. This has provided a new avenue of hope for patients with bipolar disorder who struggle with frequent and severe depressive episodes.

Suicidal Ideation

One of the most compelling benefits of ketamine is its ability to reduce suicidal ideation rapidly. Traditional antidepressants often fall short in addressing acute suicidality due to their delayed onset of action. Ketamine's rapid effects make it a valuable tool in crisis situations, providing immediate relief and potentially preventing suicide.

Emerging Applications in Other Mental Health Disorders

Anxiety Disorders

Anxiety disorders, including generalized anxiety disorder (GAD), social anxiety disorder, and post-traumatic stress disorder (PTSD), have also been responsive to ketamine treatment. Its rapid anxiolytic effects can significantly reduce symptoms and improve the quality of life for patients who do not respond to conventional therapies.  I do feel that Stellate Ganglion Block (SGB) may be a better option as it blocks the sympathetic nervous system (fight or flight) temporarily.


Post-traumatic stress disorder (PTSD) is a debilitating condition that can severely impact daily functioning. Ketamine's ability to modulate glutamate transmission and enhance synaptic plasticity has shown promise in alleviating the intrusive thoughts, hyperarousal, and emotional numbing associated with PTSD. Preliminary studies indicate that ketamine can provide rapid symptom relief and improve overall functioning in PTSD patients.  We typically pair SGB with ketamine in complex cases.

Obsessive-Compulsive Disorder (OCD)

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors. Traditional treatments, including selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT), often provide only partial relief. Recent research suggests that ketamine can reduce OCD symptoms, potentially by modulating glutamate pathways and enhancing synaptic plasticity.

Administration and Treatment Protocols

Ketamine can be administered in various forms, including intravenous (IV) infusions, intranasal sprays, oral tablets, and intramuscular injections. IV infusions are the most commonly studied and used method due to their rapid onset and controlled dosing.

Intravenous (IV) Infusions

IV infusions typically involve a sub-anesthetic dose of ketamine administered over 40 – 60 minutes (can be longer for chronic neuropathic pain). Patients often undergo a series of infusions, starting with a loading phase (e.g., six infusions over two – three weeks) followed by maintenance infusions at longer intervals/as needed.  This is a very safe way to microdose ketamine, especially in the hands of an experienced physician board certified in anesthesiology.

Intranasal Sprays

In 2019, the FDA approved esketamine (Spravato), an intranasal formulation of ketamine, for treatment-resistant depression. Esketamine offers the convenience of self-administration under medical supervision.  The dosing starts at 56mg and can go up to 84mg.  It should be noted that bioavailability of Spravato is only approximately 48%.  This can be a very expensive alternative however, if not covered by insurance.

Oral and Intramuscular Administration

Oral and intramuscular ketamine are less commonly used due to variability in absorption and slower onset of action. However, these methods may offer alternatives for patients who cannot access IV or are afraid of needles.  

Safety and Side Effects

While ketamine has shown great promise, it is not without risks. Common side effects include dissociation, dizziness, nausea, and increased blood pressure. These effects are typically short-lived and resolve shortly after the infusion ends.  A patient will be closely monitored with non-invasive blood pressure device and pulse oximeter.  Any side effect will be treated with IV medication as needed, or simply pausing the anesthesia pump that delivers ketamine.

Long-term safety remains a concern, particularly regarding potential abuse and dependency. Ketamine is a Schedule III controlled substance, and its potential for abuse necessitates careful monitoring and adherence to treatment protocols. However, the risk of addiction appears to be low when ketamine is used in a controlled medical setting.  

Research and Future Directions

The growing body of research on ketamine continues to expand our understanding of its potential benefits and mechanisms. Ongoing studies are exploring optimal dosing regimens, long-term safety, and the development of biomarkers to predict patient response.

Combining Ketamine with Psychotherapy

One promising area of research involves combining ketamine with psychotherapy. The rapid mood improvements induced by ketamine may enhance the effectiveness of psychotherapeutic interventions, creating a synergistic effect that promotes lasting recovery. Trials are currently underway to evaluate the benefits of this combined approach.

Understanding Individual Variability

Not all patients respond to ketamine, and understanding the factors that influence individual variability is crucial. Researchers are investigating genetic, neurobiological, and psychological factors that may predict response to ketamine treatment. This personalized approach aims to optimize treatment outcomes and reduce the trial-and-error process associated with antidepressant therapy.  Certain medications and social habits can also affect intravenous ketamine therapy, which is discussed at consultation.

Expanding Indications

Beyond depression and anxiety, ketamine's potential applications are being explored in other areas, such as chronic pain, substance use disorders, and neurodegenerative diseases. Preliminary findings suggest that ketamine may have neuroprotective and anti-inflammatory properties, opening new avenues for its use in a broader range of conditions.  We have had excellent results for our patients struggling with addiction as well as chronic pain as it works on blocking NMDA receptors in the central nervous system.


Ketamine has revolutionized the treatment landscape for depression and other mental health disorders, offering rapid and effective relief for patients who have not responded to traditional therapies. Its unique mechanism of action, targeting glutamate transmission and promoting synaptic plasticity, sets it apart from conventional antidepressants and provides hope for those struggling with treatment-resistant conditions.

While ketamine's potential is immense, it is essential to approach its use with caution, ensuring rigorous monitoring and adherence to evidence-based protocols. As research continues to advance, we can look forward to a deeper understanding of ketamine's therapeutic potential and the development of more refined and personalized treatment approaches.

In the coming years, ketamine's role in psychiatry is likely to expand, offering new hope for patients with a range of mental health disorders. For those struggling with depression, anxiety, PTSD, and other conditions, ketamine represents a beacon of hope, promising rapid relief and a path toward recovery.

At StrIVeMD Wellness and Ketamine in Illinois (Chicago, Skokie, St. Charles Champaign), Frisco/Dallas, and now Dublin/Columbus Ohio, we are helping to transform lives with compassionate care and innovative treatments- IV Ketamine therapy/IV ketamine infusions as well as ultrasound-guided stellate ganglion blocks to help with PTSD, depression, anxiety, and other complex treatment resistant mental health disorders.  With a team comprised of physicians board-certified in adult and pediatric anesthesiology, pain medicine, and functional medicine, advanced practice nurses and certified registered nurse anesthetists (CRNA), we are the most comprehensive team from the nation’s best medical institutions to take care of patients of any age including adolescents and geriatric patients.  We work with your mental health provider to ensure safety and effectiveness of our program. If you or someone has a mental health disease that is worsening, or fighting a chronic medical condition, please consider potentially transformative solutions for mental health challenges or chronic pain that have resisted conventional treatments.  your healthcare provider or go to the emergency room.  In the meantime, if you have any questions, please feel free to email us at info@strivemdwellness.com.