Written by Dr. Ladan Eshkevari, PhD, CRNA, LAc, FAAN.
In this Post:
- What Is Ketamine?
- The Trouble Treating Anxiety
- Ketamine’s Glutamate Action
- What the Research Says About Ketamine for Anxiety
- Comparing Ketamine Treatments for Anxiety
- Best Ketamine Protocols for Anxiety
- Can ketamine be used in conjunction with other anxiety medications?
- Can ketamine cause anxiety?
- Can recreational doses of ketamine help anxiety?
Novel approaches to managing anxiety disorders are critically needed in today’s mental health system. Ketamine, a dissociative anesthetic traditionally used for anesthesia and pain management, has emerged as a prominent contender.
This article examines how ketamine therapy can alleviate anxiety, covers various administration routes, and explores research-backed protocols.
What Is Ketamine?
Ketamine is a rapid-acting intravenous dissociative anesthetic drug FDA approved in 1970. Doctors initially administered the drug in surgical and medical settings due to its ability to induce anesthesia and relieve pain.
In 2000, a proof-of-concept study indicated ketamine could also effectively treat major depressive disorder. Since then, clinicians have begun prescribing it as an off-label drug for this purpose. “Off-label” refers to prescribing or using a medication for a purpose that is not officially approved by the U.S. Food and Drug Administration (FDA), which is extremely common with various medications. For example, gabapentin was initially FDA-approved for use as a muscle relaxant and muscular pain reliever but is used extensively “off-label” in psychiatry for its effects as an anti-anxiety medication.
Over the last two decades, countless patient stories and clinical studies have shown ketamine can rapidly alleviate depression symptoms, suicidality, bipolar disorders, and OCD. Research also shows the benefits of anxiety, which commonly occurs alongside depression.
Incredibly, ketamine has been utilized to support patients where traditional antidepressants and therapeutics have failed.
The Trouble Treating Anxiety
Various medications, like SSRIs and benzodiazepines, purport to treat anxiety. However, research suggests around 50% of people undergoing therapy for generalized anxiety disorder (GAD) are “treatment-resistant,” meaning they don’t experience any improvement after a course of anti-anxiety medication.
Researchers are exploring several hypotheses to explain this issue. One key factor is heterogeneity. In other words, anxiety disorders encompass a spectrum of conditions with varying neurobiological underpinnings, making it challenging to develop universally effective treatments.
Studies also suggested that abnormalities in neurotransmitter systems, particularly the gamma-aminobutyric acid (GABA) and glutamate systems, may contribute to anxiety disorders. Traditional antidepressant medications may have downstream effects on GABA– and neurotransmission. But they primarily work by increasing serotonin activity.
GABA and glutamate’s role in anxiety underscores the value of interventions, like ketamine, that target these systems.
Ketamine’s Glutamate Action
Glutamate is one of the brain’s primary chemical messengers, and it plays an important role in numerous functions, including mood regulation, memory, and learning. Glutamate also supports neuroplasticity, the brain’s ability to adapt, learn, and change with new experiences.
Ketamine quickly increases glutamate activity in the brain by blocking glutamate-related NMDA receptors.
- Reduces stress: NMDA receptors are intricately involved in the brain’s stress response, and research indicates that altering their function could provide a critical step in relieving acute and refractory anxiety disorders.
- “Rewires” the brain: By increasing neuroplasticity, ketamine can help “rewire” the brain to form new pathways that disrupt problematic or harmful thought patterns. This opening can allow space for people to “rewrite” their story and reframe the traumatic experience into something they can heal from.
- Acts rapidly: Unlike traditional anti-anxiety medications that take two to six weeks to work, ketamine can relieve symptoms in as little as two hours.
What Does the Research Say About Ketamine for Anxiety?
Ketamine research often focuses on depression and suicidality. However, clinical evidence for anxiety has been growing steadily, and many studies are available that back up ketamine’s effectiveness in this area.
A 2021 review of six ketamine trials focusing on social anxiety disorder, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD) concluded that ketamine was safe and effective.
Key Result: In four out of the six trials, ketamine demonstrated significant improvements in anxiety rating scores when compared to control groups.
- In the SAD group, 28.94% achieved 50% or greater improvement in symptoms compared to baseline.
- Among patients with comorbid SAD and GAD, 60% of participants achieved treatment response after receiving ketamine compared to 0% in the control group.
Another systematic review in 2022 analyzed eighteen studies with 513 participants experiencing GAD or GAD and depression.
Key Result: Single-dose infusions were not particularly effective overall. However, studies using ascending subcutaneous ketamine doses once weekly showed significant potential.
- In one reviewed study, 83% responded to .5- 1mgkg doses.
- In another study, 66% experienced treatment response (50% or greater improvement)
In a small 28-day open-label proof-of-concept trial on hospice residents with depression and anxiety, oral ketamine significantly reduced anxiety symptoms.
Key Result: Patients receiving daily oral ketamine experienced a strong antidepressant and anti-anxiety response with minimal adverse events.
- The response rate for depression was similar to that observed with intravenous (IV) ketamine, but the time to respond was somewhat longer.
- 100% of subjects who completed the trial responded to ketamine treatment for both anxiety and depression. However, six of fourteen dropped out.
Other Findings
Most ketamine infusion studies showed a dose-response relationship, with doses equal to or greater than 0.5 mg/kg showing more substantial reductions in anxiety rating scores than lower doses. Ketamine maintenance therapy was associated with sustained anxiolytic (anxiety-reducing) effects and improvements in social and/or work functioning.
Comparing Ketamine Treatments for Anxiety
Ketamine therapy comes in many administration routes that vary in effectiveness depending on the person and their symptoms. These include oral preparations, such as tablets, intranasal sprays, and intramuscular (IM) and intravenous (IV) infusions.
Here is what each method entails, with pros and cons for anxiety.
Intravenous (IV) ketamine infusions
Ketamine IV therapy is the most evidence-based, and well-studied administration route. IV ketamine involves injecting the medication directly into the bloodstream for immediate and fully bioavailable effects.
IV infusions, which can only be done in a hospital or clinic setting, deliver a carefully dosed, constant drip that clinicians can titrate up or down based on the patient’s needs.
Research shows the best practice for IV therapy involves six sessions over two to three weeks. However, Avesta creates tailored protocols for patients based on their condition and response to the medication.
IV infusion visit takes approximately 90 minutes, including the 40-60 minute session and observation period before the patient goes home.
Avesta has served nearly 1,000 patients in its Maryland and Virginia ketamine clinics. It has witnessed incredible results from this powerful protocol.
The Benefits:
- Ketamine IV infusion is very effective and fast, with results usually in minutes.
- IV infusion is easily adjustable because it can be increased, decreased, or stopped depending on the patient’s response during the treatment.
- Intravenous ketamine is the most bioavailable method, meaning the patient absorbs 100% of the medicine.
“I can’t overstate how helpful my treatment has been in dealing with my anxiety (of which there’s been cause for plenty as of late), Or how comforting an environment the whole team has made in what would otherwise be an intimidating experience!”
– Avesta patient, Danny T.
Intramuscular (IM) shots
Intramuscular (IM) shots involve the injection of a ketamine dose into a large muscle, such as the thigh or upper arm.
IM ketamine treatment might require multiple injections per treatment session. Usually, patients complete a series of five to six sessions.
- Intramuscular administration has shown similar rates of effectiveness to IV infusion. That said, research on IM ketamine for anxiety is scarce compared to the IV route.
- Still, IM injections take longer to kick in because the ketamine must travel through muscle tissue for the bloodstream to absorb it.
- Additionally, premeasured IM shots mean the dosage is limited to a specific volume, and there is no ability to adjust when the entire dosage “hits” all at once. If a patient is uncomfortable, they have no option but to ride out the experience.
Esketamine Nasal Spray
Another type of ketamine is called “esketamine” operating under the brand name Spravato.
Spravato is an intranasal ketamine-derivative spray specifically developed for treatment-resistant depression. Spravato also requires treatment at a hospital or doctor’s office for a physician to administer it and monitor any side effects.
Patients use the spray once or twice weekly for the first eight weeks and then only once every week or two in the maintenance phase. Doctors often prescribe Spravato in combination with traditional anti-anxiety medications.
- Eseketamine nasal spray dosages are typically lower than IV infusion and IM shots and are fixed doses prescribed by the manufacturer, which may be less effective.
- Additionally, clinicians must monitor esketamine patients for two hours post-treatment, making it a two-and-a-half-hour experience overall.
- Despite these challenges, some people find relief and prefer this route due to its convenience, easy administration, and rapid onset.
Sublingual tablets
Sublingual ketamine tablets, or troches, deliver the medicine under the tongue.
Doctors can prescribe oral ketamine tablets off-label for home use as a stand-alone treatment or for maintenance in between IV or IM treatments.
Patients put the tablet under their tongue and allow it to dissolve slowly.
- Oral doses of ketamine can be effective. However, it takes longer for the body to absorb because it must travel through the digestive system. Additionally, research-backed oral ketamine protocols do not exist.
- Avesta does not offer ketamine tablets for patients as their first treatment option. However, it will prescribe troches as a supplement for chronic pain patients, who benefit from IV ketamine and would like to extend the time between sessions.
Best Ketamine Protocols for Anxiety
IV ketamine therapy shows promise in treating anxiety symptoms and is incredibly safe. In
particular, it displays fewer issues than traditional anti-anxiety medications, which can cause sleep disturbances, delayed effects, and abuse.
Ketamine’s side effects are typically minor and short-lived, including:
- Increased blood pressure
- Dizziness and disorientation:
- Blurred vision
Ketamine is a powerful tool for rapid relief. But it is not a permanent cure.
Most medical professionals note ketamine is most effective for anxiety when paired with talk therapy as part of a larger treatment plan. Ketamine tones down anxiety’s uncomfortable mental and physical symptoms, while therapy can help people address the underlying issues.
Patients looking to get the most out of IV ketamine treatment should seek clinics that offer integrative care, including mental health support, group therapy, and medication management.
Bottom Line
Growing evidence supports using ketamine as an anxiety treatment, especially if traditional medications aren’t working. Ketamine is fast and effective, often relieving symptoms within a few hours. When combined with talk therapy, ketamine can help patients overcome anxiety symptoms while they work to solve the root of their condition.
Ketamine Q&A
Can ketamine be used in conjunction with other anxiety medications?
Most medical professionals agree that ketamine is safe to combine with almost every antidepressant on the market, and it might even have synergistic effects with other medications. However, patients should always consult healthcare professionals before combining drugs due to possible interactions and side effects.
At Avesta, our clinicians collaborate with patients’ doctors and psychiatrists to ensure they can safely combine ketamine with current medications.
Can ketamine cause anxiety?
Studies show that some ketamine patients experience adverse reactions. For example, they may feel triggered, sensitive, anxious, or depressed during or after a ketamine infusion session. Fortunately, IV ketamine providers can reduce the dosage quickly to provide immediate relief. IM and nasal spray dosages cannot be adjusted.
Combining ketamine with traditional therapy can also negate adverse feelings and help patients integrate the experience into meaningful insights.
Can recreational doses of ketamine help anxiety?
Recreational ketamine use can be dangerous for various health and safety reasons. For example, it can lead to dependence and overdose. It can also worsen anxiety symptoms and lead to enduring mental harm. People struggling with anxiety must seek professional support from reputable ketamine clinics that follow research-based protocols.
Avesta offers cutting-edge IV ketamine treatment for patients with treatment-resistant anxiety. Contact our patient-centered care team for a free consultation today.
