Ketamine for Depression

Ketamine has 9.1x higher odds vs placebo of a clinical response for depression at 24 h, 6.8x at 3 days, and 4.9x at 7 days, from a single dose. [1]
What if there was a depression treatment that was largely unknown, solely because it was no longer patentable, and therefore no drug companies want to promote it?


What is Ketamine

Ketamine is
a) an NMDA receptor antagonist
b) a recreational drug
c) one of the most widely used anaesthetics
d) "on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system"
e) a drug that appears highly effective for treating depression.


Does it work?

It seems that Ketamine has a significant, but short-lived benefit for treating depression.
"For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days."[2]
"Overall, depression scores were significantly decreased in the Ketamine groups compared to those in the control groups (SMD = -0.99; 95 % CI -1.23, -0.75; p < 0.01)."[3] (For context, an SMD of 0.2 is small, >0.5 is medium, and >0.8 is large. This is 0.99!)


Is this illegal?

No — you can go to a doctor or medical clinic and have prescription Ketamine treatments. Ketamine is approved by the FDA as an anaesthetic. There are many legal Ketamine clinics that use prescription Ketamine. They are generally expensive.

What does the research show?

IV (intravenous, into veins) Ketamine
Results: "For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days."[2]
Dosage: 0.5 mg/kg typically.
Regimen: Most research uses either a single dose, or 6 doses over two weeks (Mon-Wed-Fri x2).

Oral Ketamine
How it was taken: Ketamine was swallowed in a syrup, nightly for 28 days.
Dosage: up to 0.5 mg/kg per night.
Results: Significant response by day 3 for anxiety, and day 14 for depression.[4]


Ketamine Comparison Chart

Diana Benedetti/The Epoch Times


Is this FDA approved?
Yes — Ketamine is FDA approved as an anaesthetic, and not yet as a depression aid.

Can my doctor prescribe this for depression legally?
Yes — Ketamine is FDA approved. Off-label prescription means a physician can prescribe Ketamine "when they judge that it is medically appropriate for their patient."

Why isn't this yet a widespread treatment?
Because Ketamine for depression is still in Phase 2 trials with the FDA. However the FDA has granted "breakthrough therapy status" to esKetamine (on August 16, 2016), which would speed the approval process for depression.

Why is Ketamine still in Phase 2 trials?
Ketamine's patent has expired. This means drug companies will find it difficult to make lots of money from selling it, compared to other patentable drugs. The government funds Phase 2 research for Ketamine via grants, however the cost of a Phase 3 trial is so high that government grants are not sufficient to fund this work. There are only two paths for Ketamine being FDA approved for depression: a) a drug company develops a similar drug that works the same way as Ketamine, but is different enough that they can patent it and make lots of money (this is what is happening with esKetamine) or b) a wealthy individual funds the Ketamine Phase 3 trials out of the goodness of their own heart.

What protocols and dosages are used in research?
Almost all use 0.5-mg/kg dosages. Most studies are done intravenously. Some studies do Monday-Wednesday-Friday infusions.

Is there research on oral Ketamine, instead of nasal or IV?
One study used 0.5-mg/kg daily and found significant improvement in both depressive symptoms and symptoms of anxiety in all eight subjects. Dosage was daily. Depression symptoms improved significantly by day 14 until the end (day 28), and anxiey symptoms improved significantly by day 3 until the end (day 28). "The response rate for depression is similar to those found with IV Ketamine; however, the time to response is more protracted." — basically, it worked similarly well for depression as IV Ketamine, though took longer to take effect.[4]

What are the side effects?
"None of the studies included in the current meta-analysis documented major adverse effects, but side effects such as transient headache, dizziness and nausea were commonly reported; such side effects reportedly dissipated fairly quickly, usually once the infusion was complete."[2]

What are the worst things about this? Why might this not work?
"Middle- and long-term efficacy and safety have yet to be explored. Extrapolation should be cautious: Patients included had no history of psychotic episodes and no history of alcohol or substance use disorders, which is not representative of all the depressed patients that may benefit from this therapy."[3] Also, it's important to realize that one dose won't solve your depression forever.

Does Ketamine work for everyone who has depression?
No. Seems like it works for around ~70% of people in research so far.[2]


  1. Mcgirr A, Berlim MT, Bond DJ, Fleck MP, Yatham LN, Lam RW. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of Ketamine in the rapid treatment of major depressive episodes. Psychol Med. 2015;45(4):693-704. PubMed
  2. Coyle CM, Laws KR. The use of Ketamine as an antidepressant: a systematic review and meta-analysis. Hum Psychopharmacol. 2015;30(3):152-63. PubMed
  3. Fond G, Loundou A, Rabu C, et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl). 2014;231(18):3663-76. PubMed
  4. Irwin SA, Iglewicz A, Nelesen RA, et al. Daily oral Ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial. J Palliat Med. 2013;16(8):958-65. PubMed
  5. Han Y, Chen J, Zou D, et al. Efficacy of Ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies. Neuropsychiatr Dis Treat. 2016;12:2859-2867. PubMed
  6. Clements JA, Nimmo WS, Grant IS. Bioavailability, pharmacokinetics, and analgesic activity of Ketamine in humans. J Pharm Sci. 1982;71(5):539-42. PubMed

Unfortunately, given that drug companies don't make money from promoting Ketamine (because the patent has expired), there is no marketing budget to tell people that it has this level of effectiveness for depression.

You may or may not want to privately mention this to someone you know who would be interested.