Can Oral Ketamine Help Treat Severe Depression When Other Treatments Fail?

What you need to know

Oral ketamine may be helpful for some patients with severe depression that hasn’t responded to other treatments
Ketamine appeared to improve not only depression symptoms, but also obsessive-compulsive and psychotic symptoms in this patient
More research is needed on ketamine for depression, especially in patients with complex symptoms or other health conditions

Background on treatment-resistant depression

Depression is a common mental health condition that can significantly impact a person’s quality of life. While there are many effective treatments available, some people continue to struggle with depression symptoms even after trying multiple medications, therapies, and other approaches. This is known as treatment-resistant depression.

Treatment-resistant depression can be very challenging to live with. It’s associated with a lower quality of life and higher risk of suicidal thoughts. Researchers are always looking for new treatment options that might help people who haven’t found relief from standard depression treatments.

A promising new approach: Ketamine

In recent years, there’s been growing interest in using ketamine as a treatment for depression. Ketamine is a medication that has been used as an anesthetic for many years. At lower doses, it appears to have rapid antidepressant effects in some people with treatment-resistant depression.

Most research on ketamine for depression has looked at giving it through an IV infusion. However, some recent studies have explored giving ketamine orally (by mouth) instead. Early results suggest oral ketamine may also be helpful for depression while being more convenient than IV infusions.

A complex case of treatment-resistant depression

This case report describes a 55-year-old woman with very severe, long-standing depression. In addition to depression, she also experienced obsessive-compulsive symptoms and auditory hallucinations (hearing things that aren’t there).

Over more than 20 years, she had tried many different treatments without much improvement:

Multiple antidepressant medications
Cognitive behavioral therapy and other psychotherapies
Electroconvulsive therapy (ECT)

She had even participated in a clinical trial of deep brain stimulation, an experimental treatment that involves implanting electrodes in the brain. Unfortunately, none of these approaches provided significant relief from her symptoms.

Trying oral ketamine as a last resort

With the patient continuing to struggle and feeling increasingly hopeless, her doctors decided to try oral ketamine as a “compassionate use” last resort treatment. This means using a medication that isn’t officially approved for that purpose because other options have failed.

The patient started taking S-ketamine (a particular form of ketamine) orally twice a week. The dose was gradually increased over time. She continued taking her other psychiatric medications and the deep brain stimulation remained active.

Surprising improvements across multiple symptoms

After 6 weeks of oral ketamine treatment, the patient showed major improvements:

Her depression symptoms decreased substantially based on standardized rating scales
She reported feeling able to function and enjoy life again for the first time in years
Interestingly, her auditory hallucinations and obsessive-compulsive symptoms also decreased

The patient has now been taking oral ketamine twice weekly for 18 months and remains in remission from her depression. Her doctors continue to monitor her closely for any side effects or safety concerns with long-term use.

What this case suggests about ketamine for depression

This complex case provides some intriguing insights about the potential of ketamine for treating severe, treatment-resistant depression:

Oral ketamine may be effective even when many other treatments have failed. This patient had not improved with numerous medications, therapies, ECT, or even experimental deep brain stimulation. Yet she showed significant improvement with oral ketamine.
Ketamine may help with symptoms beyond just depression. In this case, the patient’s obsessive-compulsive and psychotic symptoms also improved. This is particularly interesting since people with these types of complex, combined symptoms are often excluded from clinical trials of new depression treatments.
Oral ketamine was able to be safely combined with other psychiatric medications and even with deep brain stimulation. The patient did not experience any concerning interactions.
Ketamine’s benefits may be sustained with ongoing treatment. This patient has maintained improvements for 18 months of twice-weekly dosing.

Important considerations and unanswered questions

While this case report is encouraging, it’s important to keep in mind that it only describes one patient’s experience. Much more research is needed to better understand the effects of oral ketamine for depression, especially:

How well it works for larger groups of patients
The optimal dosing schedule
Long-term safety and efficacy
Whether it’s helpful for most patients with psychotic or obsessive-compulsive symptoms

It’s also crucial to note that ketamine can have side effects and risks. In this case, the patient only experienced mild, temporary dizziness. But ketamine can potentially cause more serious side effects in some people, including dissociation (feeling detached from reality) and increased blood pressure.

Additionally, there are concerns about the potential for ketamine misuse or addiction with repeated use. Careful monitoring by medical professionals is essential.

Ketamine and childhood trauma

One interesting point the authors make is that some research suggests ketamine may be especially effective for depression in people with a history of childhood trauma. Childhood trauma is a known risk factor for developing treatment-resistant depression later in life.

While this particular case report doesn’t mention whether the patient had experienced childhood trauma, it’s an intriguing area for further study. If ketamine is indeed more helpful for depression in people with past trauma, it could potentially help identify who is most likely to benefit from this treatment.

The patient’s perspective

The case report includes a quote from the patient describing her experience:

“Since the ketamine treatment, my mood changed. I am able to enjoy activities again. I started feeling emotions again that I have not felt since my depression started, such as enjoyment, sadness and missing my dog. My obsessive and compulsive symptoms have decreased since this mood improvement; they are still there but I can cope now.”

This highlights how profound the changes were for this individual who had been suffering with severe symptoms for decades. Being able to feel a range of emotions and cope with remaining symptoms represents a major improvement in quality of life.

Conclusions

Oral ketamine may be a promising option for some patients with severe, treatment-resistant depression, even when many other treatments have failed
Ketamine appeared to improve not only depression, but also obsessive-compulsive and psychotic symptoms in this patient
More research is needed on the safety and effectiveness of oral ketamine for depression, especially in patients with complex symptoms or other health conditions
While encouraging, this single case report cannot tell us how well ketamine will work for most patients - larger clinical trials are necessary