Can ketamine help when antidepressants don’t? A closer look at the off-label drug that’s in the spotlight

You may have seen ketamine making headlines recently as a promising drug therapy for treatment-resistant depression, or “TRD.” (What’s TRD? Health care professionals define it as receiving at least two different antidepressants– for at least six weeks in a row, and at an adequate dosage – but experiencing less than a 50% improvement in depressive symptoms.)

So, how does it work and what does the research show so far? Get the facts below — plus find some helpful insight on side effects and more from PatientsLikeMe members who have tried ketamine.

 

Let’s back up — what is ketamine?

Ketamine has been around since the 1960s, and over the years it has been used as an anesthetic, treatment for some types of pain and a sedative in certain instances. It’s also been abused as a “party drug” due to its hallucinogenic high. But in the 2000s, researchers discovered that ketamine could also have rapid antidepressant effects — in as little as 24 hours — for those with TRD when administered in a small, single dose IV infusion.

A number of clinical trials have since linked the effects of ketamine with improvement in symptoms of major depressive disorder (MDD), as researchers continue to find the optimal dose and the best administration routes (like potentially a nasal spray). Ketamine continues to be studied further in other mood disorders like PTSD and OCD with a focus on its long-term safety.

How does ketamine work?

Researchers are still figuring out the specifics, but the drug seems to affect receptors in the brain, including two called NMDA and AMPA:

• Ketamine stimulates the AMPA receptor, which increases levels of the protein BDNF (brain-derived neurotrophic factor). This protein helps form new neurons and synapses in the brain, which is thought to improve certain mood conditions such as MDD.
• Ketamine also blocks the NMDA receptor, which in turn causes an increase in glutamate levels (glutamate is an important neurotransmitter in the brain) and results in a cascade of positive neurobiological changes.
• Both of these pathways and possibly others that still aren’t fully understood are related to the way ketamine works as an antidepressant.

The research looks promising…

There are currently several ongoing clinical trials involving ketamine and MDD and PTSD — and here’s a breakdown of what other recent research has found:

• One Cochrane review looked at 25 randomized controlled trials involving ketamine’s effects on brain receptors in people with severe depression. It found that while other antidepressants can take 6 to 8 weeks to become effective, ketamine may offer rapid effects in comparison to a placebo. The authors noted that the initial studies are small and there’s uncertainty about how long ketamine’s effects last.
• Another 2016 study of 14 patients with TRD found that after 3 weeks of twice-weekly ketamine infusions, 7 (50%) experienced remission from suicidal thoughts. Two of these 7 people maintained remission for 3 months.
• There isn’t quite as much data about the use of ketamine to treat PTSD, but one trial that has been published showed a significant reduction in PTSD symptoms.

The patient perspective: Real-world reviews of ketamine

• “I am currently receiving IV racemic ketamine once every 2-2.5 weeks at a 0.5mg/kg dose,” says one PatientsLikeMe member. “I haven’t been successful at spacing treatments further out than once every three weeks and 2-2.5 weeks seems to be the sweet spot for me, and I don’t have significant crashes.”
• Another member says, “Ketamine has saved my life. After failing so many medication trials and ECT, I thought I had run out of options. I am so lucky to be able to access this treatment.”
• “I am currently receiving IV ketamine 0.5mg/kg every other week in an outpatient setting,” says one member. “I am feeling very well, probably better than I ever have in my life. Ketamine has been a game changer for me.”

Ketamine’s long-term effectiveness

Despite positive findings on ketamine’s rapid effectiveness, researchers are unsure if the antidepressant effects are sustained beyond two weeks and what the consequences of relapse are. Take one PatientsLikeMe member’s experience:

“I received ketamine as part of a clinical trial. Within 24 hours I felt like ‘myself’ again and was able to experience pleasure and internalize positive experiences. The effects lasted about 9 days and then all my previous symptoms returned.”

Side effects, cost, and other things to consider

Ketamine is currently only FDA-approved for surgical anesthesia, so it must be prescribed off-label (not for its intended use). And because it’s off label, it must be administered by a specialty clinic, which means it may not be covered by insurance and can come with a hefty price tag at $400-$800 per infusion. Learn more about available clinical trials here (and be sure to talk to your doctor before changing anything about your treatment regimen).

And what about side effects? In short, more data and research is needed. But here’s what other members who have tried ketamine for MDD have said:

• “The worst side effect is nausea, but I receive ondansetron before the infusion and that helps significantly. I have only had one ‘bad trip’ or ‘K-hole’ while getting the infusion, but it quickly subsided.”
• “I have found that during an infusion, external stimuli intensifies and I can get quickly overwhelmed. To avoid this, I always wear headphones and have music that is very familiar to me playing, and I typically have my eyes closed for much of the time. This also mitigates most of the perceptual disturbances that might occur during an infusion. I am a person who does not like feeling out of control, so I limit my exposure to external stimuli and that helps significantly.”

Have you tried ketamine or been involved in a ketamine clinical study? Join or sign in to PatientsLikeMe to jump in the conversation today.