In this Post:
- What Is Ketamine?
- The Trouble Treating Anxiety with Standard Meds
- How Does Ketamine Work for Anxiety?
- What Does the Research Say About Ketamine for Anxiety?
- Comparing Ketamine Treatments for Anxiety
- Ketamine Side Effects
- Bottom Line
- Ketamine Q&A
Ketamine is a dissociative anesthetic that can relieve anxiety by helping a person feel calm and relaxed. It can also change their perceptions and reduce reactivity by targeting chemical messengers in the brain that increase neuroplasticity. This effect can “rewire” the brain and disrupt problematic thought patterns that contribute to anxiety-related disorders.
This article examines why ketamine therapy has emerged as a prominent contender for alleviating anxiety. It covers how ketamine works for anxiety relief, what the research says about its effectiveness, and the various administration routes available.
What Is Ketamine?
Ketamine is a rapid-acting intravenous dissociative anesthetic drug that the U.S. Food and Drug Administration (FDA) approved in 1970. Three decades later, groundbreaking research revealed its potential to treat major depressive disorder as well, opening the door to new psychiatric applications.
Since 2000, clinicians have increasingly prescribed ketamine off-label for depression, suicidality, bipolar disorder, chronic pain, OCD, and anxiety, conditions that often overlap. For many patients, ketamine has provided relief when traditional antidepressants and anti-anxiety medications have fallen short.
The Trouble Treating Anxiety with Standard Meds
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.
One key reason behind the inefficacy is heterogeneity. In other words, anxiety disorders encompass a spectrum of conditions with varying neurobiological underpinnings, making it challenging to develop universal treatments.
Studies also suggest that traditional medications may not address anxiety’s full spectrum of underlying factors. Anxiety is linked to abnormalities in neurotransmitter systems, particularly the gamma-aminobutyric acid (GABA) and glutamate systems, and SSRIs do not directly impact these systems. Ketamine does.
How Does Ketamine Work for Anxiety?
Ketamine relieves anxiety by targeting GABA and glutamate, two neurotransmitters that regulate stress and mood. It also supports neurogenesis and synaptic plasticity, helping repair brain regions affected by chronic anxiety.
Let’s break it down function by function:
GABA
GABA is the most common inhibitory neurotransmitter in the central nervous system, meaning it can block chemical messages and decrease brain activity. It is known for producing a calming effect and playing a major role in controlling nerve cell hyperactivity associated with anxiety, stress, and fear. Ketamine strengthens GABA’s calming effects, helping to slow down overactive brain circuits and restore balance.
Glutamate
Glutamate is the brain’s primary excitatory neurotransmitter that’s essential for mood regulation, cognition, and neuroplasticity. It helps neurons communicate and adapt, but overactive glutamate activity is linked to anxiety and stress-related disorders. Ketamine blocks excessive glutamate activity that reinforces anxiety-related brain patterns.
This blockade also triggers a secondary effect—a surge in glutamate release through other receptors, particularly AMPA receptors. This modulated increase strengthens neural connections, promotes neuroplasticity, and helps the brain form new, healthier pathways that reduce anxiety.
Brain Repair & Neuroplasticity
Chronic anxiety can cause structural damage to the hippocampus and prefrontal cortex, impairing memory, emotional regulation, and decision-making. Ketamine stimulates BDNF (brain-derived neurotrophic factor), which supports dendritic growth, synaptogenesis, and neurogenesis. This effect helps repair neural circuits, reversing some of the long-term damage associated with anxiety disorders.
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 back up its effectiveness in this area.
01. Ketamine for Multiple Anxiety-Related Conditions
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 symptom improvement than baseline.
- Among patients with comorbid SAD and GAD, 60% of participants achieved treatment response after receiving ketamine compared to 0% in the control group.
02. Weekly Ketamine Treatments Improve General Anxiety Disorder
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 weekly showed significant potential.
- In one reviewed study, 83% responded to 0.5-1 mg/kg doses.
- In another study, 66% experienced treatment response (50% or greater improvement)
03. Oral Ketamine Reduces Anxiety in Hospice Patients
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 potent 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 14 dropped out.
04. Ketamine Treatment Displays Long-Lasting Stability
In a 2023 analysis, scientists analyzed data on people treated with ketamine infusion therapy (KIT) from 2017 to 2020.
Key Result: IV ketamine significantly reduced anxiety symptoms compared to other treatments. Also, the improvement remained stable over a year of follow-up monitoring.
- Infusion patients experienced a significantly greater reduction in depression symptoms at eight weeks compared to patients starting standard antidepressant therapy.
- Increases in symptoms in ketamine patients were minimal for up to a year.
05. Ketamine Relieves Anxiety Quickly in a Single Dose
A systematic review performed by Hartland and colleagues in 2023 examined the effects of a single dose of ketamine on anxiety in randomized placebo-controlled trials (RCTs).
Key Result: Ketamine consistently showed anxiety improvement in less than 24 hours, while it can take 2 to 6 weeks for traditional anti-anxiety medications to work,
- Researchers found significant improvement in anxiety in under 12 and within 24 hours that was sustained for 7 to 14 days.
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’s effectiveness varies depending on the person and their symptoms. Its efficacy can also rely on the form, including oral preparations, intranasal sprays, intramuscular (IM) shots, and intravenous (IV) infusions.
Let’s review.
Intravenous (IV) ketamine infusions
Ketamine IV therapy is the most evidence-based and well-studied administration route for depression and anxiety. IV ketamine involves injecting the medication directly into the bloodstream for immediate and fully bioavailable effects.
Protocol:
- Typically, 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 an observation period before the patient goes home.
The Benefits:
- Ketamine IV infusion is very effective and fast, with results usually in minutes, making it ideal for those needing a rapid and substantial effect.
- 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!”
Intramuscular (IM) shots
Intramuscular (IM) shots involve injecting ketamine into a large muscle, such as the thigh or upper arm.
Protocol:
- Typically, IM ketamine treatment requires multiple injections per treatment session for the first few sessions. It can start with two treatments per week for the first four weeks, then one treatment per week for the following two weeks, then one treatment every other week or as needed.
- Patients must stay for at least one hour of post-administration monitoring at each appointment.
The Benefits:
- 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.
Considerations:
- IM injections take longer to kick in because the ketamine must travel through muscle tissue for the bloodstream to absorb it.
- Premeasured IM shots mean the dosage is limited to a specific volume, so there is no ability to adjust when the entire dosage “hits” all at once. Patients who are uncomfortable have no option but to ride out the experience.
Esketamine Nasal Spray
Esketamine (Spravato) is a ketamine-derived medication approved by the FDA for treatment-resistant depression (TRD). It comes as an intranasal spray and targets glutamate pathways to rapidly improve mood. Doctors often prescribe Spravato alongside traditional anti-anxiety medications to enhance its effectiveness.
Protocol:
- 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.
- Spravato requires treatment at a hospital or doctor’s office, and a physician must administer it and monitor any side effects.
- Clinicians must monitor Spravato patients for two hours post-treatment, making it a two-and-a-half-hour experience overall.
The Benefits:
- Spravato is FDA-approved for those with TRD and major depressive disorder (MDD) with suicidal ideation, so most insurance will accept it if treatment history meets the criteria.
- Spravato is a good option for those uncomfortable with injections. Many people find relief and prefer this route due to its convenience, easy administration, and rapid onset.
- However, esketamine 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.
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.
Ketamine Side Effects
Ketamine therapy shows promise in treating anxiety symptoms and is incredibly safe. It also 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, but they can include:
- Increased blood pressure
- Dizziness and disorientation
- Blurred vision
- Confusion
- Diplopia, or seeing double
- Dysphoria, or feeling significant uneasiness and dissatisfaction
- Nausea
- Vomiting
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
Does ketamine work for anxiety?
Research and clinical observations show that a single ketamine infusion can significantly reduce anxiety symptoms in adults. Many experts now view ketamine as a promising treatment alternative for people whose anxiety has not responded to traditional treatments.
How fast does ketamine work for anxiety?
There is no single protocol for how quickly ketamine relieves anxiety. However, ketamine infusions work significantly faster than traditional treatments. Some patients notice improvements within an hour of their first session, while others may need two to three infusions to experience relief.
How many ketamine treatments do you need for anxiety?
Typically, the initial “loading dose” for ketamine treatments is six to 10 infusions over three to four weeks. After that, some patients will continue with booster sessions, either monthly or as they see their anxiety symptoms begin to creep back up.
Can ketamine be used with other anxiety medications?
Most clinical experts agree that ketamine is safe to use with nearly all antidepressants and may even enhance their effects. However, potential interactions and side effects vary, so patients should always consult their healthcare provider before combining treatments.
At Avesta, our team works closely with patients’ doctors and psychiatrists to ensure ketamine therapy is safe to integrate with existing 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.
