Ketamine-Assisted Psychotherapy for Hard-to-Treat Depression: What We Know

Depression can be particularly frustrating when traditional treatments don't seem to help. In fact, about one in three people with depression don't get better with standard treatments like antidepressants and talk therapy. But there's new hope on the horizon: Ketamine-Assisted Psychotherapy (KAP) is showing promising results, especially for people who haven't found relief through other methods.

When we talk about depression that doesn't improve with standard treatments, doctors call this "treatment-resistant depression." It's a serious condition that can make it hard to work, maintain relationships, and enjoy life. People with this type of depression often try multiple medications and therapies without finding the relief they need.

New Ways to Use Ketamine

While doctors have been studying ketamine given through an IV for depression, there's growing excitement about simpler methods - specifically, taking it by mouth or under the tongue (called sublingual). These approaches could make treatment more convenient and potentially allow for at-home use under proper medical supervision.

What the Research Shows

Taking Ketamine by Mouth:

- A careful study by Domany and colleagues in 2019 looked at 41 people with hard-to-treat depression. They found that taking ketamine by mouth three times a week made a real difference compared to a placebo.

- Another study by Al Shirawi's team in 2017 found that more than three-quarters of their 22 patients felt significantly better after six weeks of treatment.

Taking Ketamine Under the Tongue:

- Research by Lara and their team in 2013 found that this method could help people feel better in as little as 40 minutes, with most patients showing major improvements.

- When Arabzadeh's group in 2018 compared under-the-tongue ketamine to a common antidepressant (sertraline), they found ketamine worked faster and better over a six-week period.

How Does It Compare to IV Ketamine?

A big review by Rosenblat and colleagues in 2019 looked at all the different ways to take ketamine. While they found that IV ketamine had the strongest evidence behind it, taking it by mouth or under the tongue also showed good results and might be safer.

Getting the Right Amount

Finding the right dose is crucial. Research by Andrade in 2019 showed that oral doses usually range from 0.5-1.5 mg per kilogram of body weight, while under-the-tongue doses can be lower because the body absorbs it better this way. Hartberg's team in 2018 even developed guidelines for safe at-home use, though this requires careful medical oversight.

Long-Term Results

The good news about longer-term use comes from Azhar's research in 2021. They followed 30 people using under-the-tongue ketamine for six months. More than half of the patients maintained their improvement, and there weren't any major side effects.

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