Summary: One of the largest studies yet shows that sublingual ketamine (melted under the tongue) with telehealth works even better than IV ketamine given in a clinic. It was tested for anxiety and depression. Ketamine brings fast relief and helps rewire the brain, so the relief lasts. Most other drugs take a long time to help and must be taken for a long time. Mood problems like anxiety and depression are the top cause of disability. Many studies show that IV ketamine works for depression.
Ketamine was first made as an anesthetic, to put people to sleep for surgery. In recent years, it has drawn notice as a possible way to treat mood problems like anxiety and depression. It acts on a certain brain receptor called the N-methyl-D-aspartate (NMDA) receptor. That sets it apart from the usual antidepressants, like SSRIs (selective serotonin reuptake inhibitors). So it is being tried in people the usual drugs did not help. Right now, the FDA has approved ketamine for treatment-resistant depression (depression that does not respond to other drugs), and for surgery. Research is now looking at ketamine for more mood problems, such as anxiety and post-traumatic stress disorder (PTSD). More and more proof suggests it may be safe and work well, mainly in people the usual drugs did not help. One good way to give ketamine is through telehealth, or care by video. Telehealth has some real perks. It has grown popular as a way to make care easier to get and cheaper. If you have a mood problem, it lets you get care at home, with your care team still checking in and watching how you do.
Does sublingual ketamine work for depression and anxiety?
In the last ten years or so, the use of ketamine for mood disorders has grown a lot. There is a reason researchers are so interested in it. Until now, most drugs for anxiety and depression raise the brain’s serotonin. These drugs work slowly, over weeks and even months. They only work when taken every day, with no end, and they cause many side effects. But some new studies show that ketamine is quite different from current antidepressants. Early studies show that a ketamine infusion can bring lasting relief from depression and anxiety. Ketamine seems to help rewire the brain, especially when combined with cognitive behavioral therapy. But a ketamine infusion has one big drawback: it can only be given in a clinic. So in recent years, researchers have begun testing ketamine by mouth for mood disorders. The under-the-tongue route is of special interest, because it works fast. Drugs taken under the tongue also skip the liver’s first round of breakdown (first-pass metabolism). The new study is one of the largest clinical trials of sublingual ketamine for depression and anxiety. It included 1,247 patients. The findings were remarkable. Sublingual ketamine eased anxiety and depression in 89% of patients. Even more striking, 63% of the participants said their symptoms dropped by more than 50%. And 30% of all participants reached complete remission of depression and anxiety after just four sessions. That means they had almost no symptoms. The benefits were especially striking in patients with suicidal thoughts. At the start of the study, 62% of those with depression had suicidal thoughts. By the end, none did. These findings are hopeful in many ways. The results are much better than those from other drugs and talk therapy. They are even better than results from IV ketamine. Sublingual ketamine with telehealth and remote monitoring seems to be one of the most effective ways to manage mood disorders. Of course, more studies are needed before sublingual ketamine can be approved for mood disorders. Larger and longer studies are also needed to learn about its long-term safety and benefits. It is worth exploring whether this approach could, in the long run, cure people with depression and anxiety.
Frequently asked questions
Does sublingual ketamine work for depression?
In one of the largest studies to date, 1,247 patients with moderate to severe anxiety and depression took ketamine under the tongue with telehealth support. Symptoms eased in 89% of them. 63% said their symptoms dropped by more than half. And 30% reached remission after four sessions. Longer and larger studies are still needed to confirm its long-term safety and benefit.
What is the difference between sublingual and IV ketamine?
IV ketamine drips into a vein, so it can only be given in a clinic. Sublingual ketamine melts under the tongue. It works fast. It also skips the liver’s first round of breakdown (first-pass metabolism). It needs no IV line, so it can be paired with telehealth and remote checks.
How does ketamine work for depression?
Ketamine acts on the NMDA receptor in the brain. That is a different target from SSRIs and other antidepressants that raise serotonin. It was first made as an anesthetic, to put people to sleep for surgery. Since it works in a new way, it is being tried in people the usual drugs did not help. It also seems to help rewire the brain, mainly when paired with cognitive behavioral therapy.
How fast does ketamine work for depression?
Much faster than the usual drugs. Most drugs for anxiety and depression raise serotonin and take weeks or even months to help. And they only work while you take them every day. Ketamine brings fast relief from mood symptoms. In the sublingual ketamine study, 30% of participants reached complete remission after just four sessions.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
