What are the Side Effects of Ketamine in Depression?

Ketamine therapy has rapidly gained recognition as a breakthrough treatment for treatment-resistant depression, especially for those who haven’t found relief with traditional antidepressants.  

Once used primarily as an anesthetic, ketamine is now offered in low, controlled doses for severe depression treatment at clinics across Denver, Boulder, and Westminster to help alleviate severe depressive symptoms.  

In this guide, you’ll learn exactly how ketamine therapy works, what side effects to expect (from mild to rare), difference between ketamine or Esketmaine (which one to choose), how it differs from traditional antidepressants, and how clinics like Axis Integrated Mental Health keep you safe.  

Understanding Ketamine and Esketamine 

How does ketamine work? 

Ketamine targets the ‘N‑methyl‑D‑aspartate (NMDA) receptor’, part of the glutamatergic system.  

By blocking this receptor, ketamine increases glutamate levels, which in turn stimulates new connections between brain cells.  

This process is believed to reset depressed neural circuits and relieve symptoms quickly, often within hours or days instead of weeks.  

Traditional antidepressants primarily affect serotonin, norepinephrine, and dopamine, which can take several weeks to work.  Ketamine rewires the mind by improving neuroplasticity through synaptic growth. 

Types of ketamine therapy 

There are two main forms of ketamine treatment for depression: 

• IV or intramuscular ketamine: A low dose of ketamine is infused into your bloodstream or injected into a muscle. Sessions typically last 40–60 minutes. A course of treatment may involve six to eight sessions over two to four weeks, followed by maintenance infusions as needed. 

• Esketamine nasal spray (Spravato®): Esketamine is a variant of ketamine approved by the U.S. Food and Drug Administration (FDA) for treatment‑resistant depression. Patients self‑administer the nasal spray under supervision in a clinic. After using Spravato®, they are adviced to remain under observation for at least two hours. 

 Why Ketamine at Home Should be a BIG NO? 

So many companies are willing to send you ketamine at home. But there are risks for doing so. Read our blog on 7 critical dangers of at-home ketamine to make an informed choice.

Common Side Effects of Ketamine  

During Treatment 

Ketamine’s effects begin quickly, often within minutes of administration.  

During this time, you might experience: 

• Dissociation or feeling “floaty”: Many people describe sensations like watching themselves from outside their body or feeling detached from reality. This is temporary and usually subsides soon after the infusion ends. 

• Dizziness or lightheadedness: Some people feel dizzy. Clinics monitor blood pressure to ensure safety. 

• Blurred vision or double vision: Vision changes are common but short‑lived. 

• Nausea or vomiting: Eating lightly before treatment and taking anti‑nausea medication can help. Clinics often provide medication to reduce nausea. 

• Increased blood pressure and heart rate: Ketamine can temporarily raise blood pressure and pulse. This is why vital signs are closely monitored. People with uncontrolled high blood pressure may need adjustments or different treatments. 

• Strange sensations: You might feel tingling, warmth, heaviness or euphoria. These sensations diminish after treatment. 

After Treatment 

Following ketamine therapy, you may experience: 

• Fatigue: It’s common to feel tired or groggy for the rest of the day. Plan to rest and avoid driving or operating machinery. 

• Headache: Mild headaches can occur. Drinking water and resting in a dark room can help. Over‑the‑counter pain relievers may be used but check with your provider first. 

• Mood swings: Some people feel emotional or tearful after treatment. This is often part of the brain’s adjustment process. Communicate your feelings with your healthcare provider. 

• Confusion or cognitive changes: You may feel fuzzy or slow. Avoid making major decisions or signing contracts until the next day. 
• Bladder or urinary issues: Frequent urination or urgency can happen but are usually temporary. Long‑term bladder issues from ketamine are more common with high, frequent recreational use, not medical treatment. 

Ketamine aftercare is an important state in ketamine therapy. Learn what to do after ketamine therapy to maximize the experience.

Less Common but Serious Side Effects 

Serious side effects are rare but important to recognize: 

• Severe blood pressure changes: Ketamine can cause significant increases or decreases in blood pressure. People with heart disease or uncontrolled hypertension should discuss the risks with their provider. 

• Allergic reactions: Signs include rash, itching, swelling or difficulty breathing. Clinics are equipped to handle allergic responses. 

• Substance misuse risk: Ketamine has potential for misuse when taken outside of medical supervision. Treatments follow strict protocols to prevent dependence. Always adhere to your provider’s recommendations. 

• Mania or psychosis: In rare cases, ketamine may induce manic or psychotic symptoms, especially in people with bipolar disorder. Screening for bipolar disorder prior to treatment helps reduce this risk.  

Why Side Effects Matter? 

In the U.S., 14.5 million adults experienced a major depressive episode with severe impairment in 2021.  

Because standard therapies don’t work for everyone, ketamine offers hope.  

But it’s important to weigh the benefits against potential side effects.  

Discuss your medical history, medications, and concerns with your healthcare provider before starting treatment. 

Comparing Ketamine to Traditional Antidepressants 

Traditional antidepressants like SSRIs and SNRIs can cause side effects such as:  

• Sexual dysfunction 

• Weight gain 

• Gastrointestinal issues  

• Emotional numbing.  

Ketamine’s side effects are typically short‑term and subside within hours.  

While SSRIs may take weeks to work, ketamine can provide rapid relief.  

However, ketamine requires clinic visits, medical monitoring and has the potential for dissociation.  

Deciding between treatments depends on individual needs, medical history and how urgently the relief is needed. 

Safety and Monitoring During Ketamine Administration 

At Axis Integrated Mental Health, patient safety is our top priority.

Before your first session, you’ll receive a thorough evaluation to determine if ketamine or esketamine is appropriate.

During treatment we monitor blood pressure, heart rate and oxygen levels.

You’ll rest in a comfortable chair while a provider stays close.

After the session, you’ll stay for observation until any immediate side effects subside.

We work with your prescribing physician to coordinate ongoing care and adjust other medications as needed.

Your treatment plan may include ketamine, therapy, lifestyle changes and, if appropriate, Transcranial magnetic stimulation (TMS) or Spravato®. 

Who Should Avoid Ketamine?

Ketamine may not be appropriate for everyone. Individuals with uncontrolled high blood pressure, active substance use disorders, certain heart conditions or untreated psychosis should discuss alternatives with their provider. Pregnant or breastfeeding people should avoid ketamine unless the benefits outweigh risks. Always share your full medical history and medication list with your healthcare team.  

Frequently Asked Questions 

1. Are the side effects of ketamine permanent?

No. Side effects are typically temporary and resolve within hours. Rare long‑term effects are generally associated with chronic misuse, not medically supervised treatment. 

2. How soon will I feel better?

Some people notice improvement within hours or days. Others may need several sessions to experience significant relief. Your provider will monitor your progress. 

3. Can I drive after ketamine treatment?

No. You should not drive or operate machinery until the day after treatment. Arrange for someone to take you home. 

4. How many treatments will I need?

A typical course involves six to eight infusions or nasal spray sessions over two to four weeks. Maintenance treatments may follow. The exact number depends on your response and your provider’s recommendations. 

5. What is ketamine therapy? 

Ketamine is a medication that alters the way certain brain receptors work, leading to rapid improvements in mood. It’s administered in low doses—either through intravenous (IV) infusion, intramuscular injection or as a nasal spray (esketamine). These treatments are typically used for Treatment‑resistant Depression, which affects about 30% of people diagnosed with major depressive disorder. Ketamine works differently from traditional antidepressants; it stimulates glutamate, a neurotransmitter linked to mood and learning. 

6. Are side effects common? 

Most people experience some side effects during or shortly after ketamine treatment. Common effects include mild dissociation (feeling detached from reality), dizziness, blurred vision, nausea and increased blood pressure. These effects are usually temporary and subside within an hour or two. Serious side effects are rare when treatment is given in a controlled medical setting. 

7. Is ketamine therapy safe? 

When administered by trained professionals in a medical clinic, ketamine therapy is generally safe. Patients are monitored before, during and after each session. Blood pressure, heart rate and oxygen levels are checked to ensure stability. Because ketamine can impair thinking and motor skills for several hours, you’ll need someone to drive you home and should avoid driving or operating heavy machinery until the next day. 

Still not sure if Ketamine is for you? Reach out to our experts and get clarity!