Intravenous Ketamine Therapy

Depression affects millions of people worldwide, and while traditional antidepressants have helped many, a significant number of individuals continue to struggle with symptoms despite multiple treatment attempts. This condition—known as treatment-resistant depression (TRD)—has prompted researchers and clinicians to explore new and faster-acting solutions.

Among the most promising of these options is intravenous ketamine therapy, a treatment that uses low doses of ketamine, a long-established anesthetic, to relieve depression symptoms quickly. Unlike most antidepressants, which can take weeks to show an effect, intravenous ketamine therapy often provides noticeable improvement in mood within hours or days.

A recent article on Medscape, titled “Intravenous Ketamine Outperforms Intranasal Esketamine in Depression,” presents new evidence that IV ketamine may be more effective and act faster than its intranasal counterpart. Let’s explore what this means for patients and the mental health community.

What Is Intravenous Ketamine Therapy?

Intravenous ketamine therapy involves delivering a controlled, low dose of ketamine directly into the bloodstream through an IV infusion. The treatment is done in a medical setting under the supervision of trained professionals.

Ketamine works differently from traditional antidepressants. While medications like SSRIs (such as Prozac or Zoloft) target serotonin or norepinephrine, ketamine acts on the brain’s glutamate system, which is linked to learning, memory, and emotional regulation. This unique action helps restore healthy communication between brain cells and promotes new neural connections—processes believed to be disrupted in depression.

In simple terms, intravenous ketamine therapy helps the brain “reset” itself, offering rapid relief from symptoms when other medications have failed.

The Study: IV Ketamine vs. Intranasal Esketamine

The Medscape article summarizes a retrospective chart review involving 153 adults diagnosed with treatment-resistant depression. Participants were divided into two groups:

• 111 patients received intravenous (IV) ketamine infusions twice a week for four to five weeks.

• 42 patients received intranasal esketamine treatments during the same period.

Both groups were monitored to measure how quickly and how much their depression symptoms improved.

Key Findings

The results showed that intravenous ketamine therapy led to faster and stronger improvements than intranasal esketamine:

Faster results: Patients receiving IV ketamine showed a clear reduction in depression scores after just one session. In contrast, those using intranasal esketamine typically didn’t experience notable improvement until after the second session.

Greater symptom relief: By the end of the treatment phase, the IV ketamine group had nearly a 50% reduction in depression severity scores, while the intranasal group saw about a 40% improvement.

Comparable safety: Side effects and dropout rates were similar for both groups, indicating that IV ketamine was well-tolerated when administered properly.

What It Means

While both forms of ketamine can help people with difficult-to-treat depression, this study suggests that intravenous ketamine therapy may offer a quicker and more robust effect, making it a valuable option for those who need faster relief.

Why Speed Matters in Depression Treatment

One of the most challenging aspects of depression treatment is the time it takes for traditional antidepressants to work. Many medications require six to eight weeks before patients feel a difference. For someone in the depths of depression—or struggling with suicidal thoughts—that wait can feel unbearable.

In contrast, intravenous ketamine therapy can work within hours to days, offering a potential lifeline to those who’ve found little relief elsewhere. Some patients report feeling a lift in mood or decreased hopelessness even after a single session.

This rapid effect makes ketamine therapy especially important in cases where immediate symptom reduction could prevent a crisis or hospitalization.

How Intravenous Ketamine Therapy Works

Ketamine acts primarily on NMDA (N-methyl-D-aspartate) receptors in the brain, which are part of the glutamate signaling system. By blocking these receptors, ketamine triggers a chain reaction that increases glutamate release and activates other receptors called AMPA receptors.

This process stimulates the production of brain-derived neurotrophic factor (BDNF)—a protein that supports the growth and survival of brain cells. Essentially, it helps repair and rebuild neural connections that may have weakened due to chronic depression.

For patients, the result can be a noticeable improvement in mood, energy, and motivation in a much shorter timeframe than traditional antidepressants allow.

What to Expect During Intravenous Ketamine Therapy

If a doctor recommends intravenous ketamine therapy, here’s what a typical treatment process might look like:

Before the Session

• Patients undergo a thorough medical and psychiatric evaluation to confirm that ketamine therapy is appropriate.

• Vital signs, medical history, and current medications are reviewed to ensure safety.

  
  

During the Session

• A low dose of ketamine—usually around 0.5 mg per kilogram of body weight—is infused through an IV over about 40 minutes.

• The patient remains awake but may experience mild dissociation, lightheadedness, or dreamlike sensations.

• A trained clinician monitors the patient’s heart rate, blood pressure, and comfort throughout the infusion.

  
  

After the Session

• Most patients rest for about 30–60 minutes after the infusion to allow any side effects to subside.

• Some may feel tired or slightly disoriented for the rest of the day, so driving immediately afterward is not recommended.

• Effects on mood are often noticed within hours or the next day.

  
  

A standard treatment plan often involves six to eight infusions over three to five weeks. Some patients continue with “maintenance” infusions once a month or as needed, depending on how long the benefits last.

Who Can Benefit from IV Ketamine Therapy?

Intravenous ketamine therapy is not for everyone—it’s specifically intended for those who haven’t found relief from conventional treatments. Candidates may include:

• Adults with major depressive disorder (MDD) or bipolar depression who haven’t improved after at least two antidepressant trials.

• Individuals experiencing severe depressive episodes where fast symptom relief is crucial.

• Patients without major medical contraindications (such as uncontrolled high blood pressure, psychosis, or active substance abuse).

  
  

Doctors carefully screen candidates to make sure the treatment is safe and appropriate.

Possible Side Effects and Safety Considerations

While intravenous ketamine therapy is generally safe when performed in a clinical setting, it’s not without risks. Common short-term side effects include:

• Mild dissociation or “out-of-body” sensations

• Dizziness or blurred vision

• Nausea

• Temporary increase in blood pressure or heart rate

  
  

These effects typically wear off within an hour after treatment. Serious complications are rare when therapy is administered by qualified professionals who follow strict monitoring protocols.

However, because ketamine has a history of recreational misuse, it’s important that treatments take place in licensed medical facilities with professional oversight.

What Are the Limitations of Intravenous Ketamine Therapy?

Despite its promise, intravenous ketamine therapy is still considered an off-label treatment for depression in most countries. While research continues to show positive outcomes, several limitations remain:

• Duration of effect: Some people may relapse weeks or months after treatment without maintenance sessions.

• Cost and accessibility: IV therapy can be expensive, and insurance coverage varies widely.

• Lack of standardization: Protocols differ between clinics—there’s no universal agreement on dosage, frequency, or maintenance.

• Long-term safety: While short-term results are encouraging, researchers are still studying the potential cognitive and physical effects of repeated treatments.

  
  

For these reasons, intravenous ketamine therapy should always be part of a broader mental health plan that includes ongoing support, therapy, and follow-up care.

The Future of Intravenous Ketamine Therapy

The findings highlighted by Medscape add to a growing body of evidence that intravenous ketamine therapy may become a cornerstone treatment for severe, treatment-resistant depression.

Researchers are now exploring several key areas:

• Personalized dosing: Determining the ideal dosage and frequency for individual patients.

• Combination approaches: Pairing ketamine therapy with psychotherapy to prolong results.

• Predictive markers: Identifying which patients are most likely to respond to the treatment.

• Expanded applications: Studying its use for anxiety, PTSD, and chronic pain conditions.

  
  

As evidence builds, the hope is that more patients will gain access to this potentially life-changing treatment under safe, standardized protocols.

A Balanced Perspective

While the results are promising, it’s important to approach intravenous ketamine therapy with realistic expectations. Not every patient will respond, and some may need additional treatments or alternative approaches.

The best outcomes often occur when ketamine therapy is combined with other supportive treatments—such as talk therapy, lifestyle changes, and ongoing psychiatric care.

If you or a loved one is considering this treatment, the first step is to consult a qualified psychiatrist or ketamine clinic. They can explain the process, evaluate your individual situation, and determine whether intravenous ketamine therapy could be right for you.

Final Thoughts

Intravenous ketamine therapy represents one of the most exciting developments in modern depression treatment. The study discussed by Medscape shows that IV ketamine not only works faster but may also provide stronger relief than intranasal esketamine for people who’ve struggled with other options.

For individuals living with treatment-resistant depression, this therapy offers a renewed sense of hope—a chance to experience meaningful improvement and regain quality of life.

As research continues, intravenous ketamine therapy is poised to become an increasingly important part of the mental health landscape, offering rapid, effective relief for those who need it most.