Ketamine: antidepressant, analgesic, anti-inflammatory

April 15, 2014

Ketamine is used to induce and maintain anaesthesia, for humans and animals. Its mechanism of action is relatively complex with effects on many different pathways and receptors within the body. Given this it is not overly surprising that ketamine has many potential indications and a range of properties. Secure storage is required as it is a potential drug of abuse (‘Special K’). The three articles below highlight some of the exciting new indications and properties of ketamine that are currently being explored.

1. Ketamine’s evolving role in the treatment of depression

1 in 7 Australians report depression at some point during their life (1), and 70% of patients fail to respond to standard antidepressant therapy after twelve weeks (2). Intravenous ketamine may provide some hope.

In the last decade several randomised controlled trials have shown a single intravenous ketamine injection can relieve severe depression and reduce suicidal thoughts within hours(2).

Studies to date have focused on the response of patients with major depressive disorder, depression associated with bipolar disorder and treatment resistant depression (including patients unresponsive to ECT). Results from these studies suggest ketamine infusions are twice as effective as standard anti-depressive therapy (3).

The low dose used for depression has been well tolerated with only a small number of patients experiencing brief undesirable effects on their cardiovascular system (3). However, it’s important to note that medically unstable patients were excluded from these trials.

Ketamine’s rapid effect makes it potentially very useful in acutely suicidal patients who present to the emergency department. Unfortunately its rapid effect it is not sustained – regular infusions are required. In addition there is great inter-patient variability. Some patients relapse within 24 hours of a single infusion while others maintain the benefit for several weeks (3). The reason for this is currently unknown.

There are many clinical trials in progress that hope to answer some important questions including;

  • Can other dosage forms (eg. intranasal) be used for long-term maintenance treatment,
  • Can we predict the likelihood of a patient to respond, and
  • Could ketamine be used as an adjunct to speed up response to ECT?

2. Ketamine’s potential role in speeding up return to mobility following knee surgery

It is well known that ketamine has a role in perioperative multi-modal analgesia management. Its opioid-sparing effects and subsequent reduction in post-operative nausea and vomiting has been well demonstrated. However, its intraoperative use in small doses (0.15mg/kg) to speed up patients’ return to mobility following knee surgery is not so well known or studied. Three studies have demonstrated the positive effect of ketamine use in varying types of knee surgery. The latest study by Adam followed a group of 40 patients who underwent total knee arthroscopy, 20 of whom received intraoperative ketamine. The median time to return to 90 degrees of knee flexion following surgery was 7 days in those who received ketamine and 12 days in those who did not receive ketamine – a significant outcome (p < 0.03) (4).

3. Ketamine’s anti-inflammatory effect

During surgery the body experiences some damage and the result is the production of a signalling molecule called IL-6. IL-6 is primarily involved in initiating inflammation. Measuring the amount of IL-6 in someone’s blood is an indicator of inflammation(5).

High concentrations of IL-6 post-surgery have been associated with increased post-operative complications. Researchers are looking for a drug that decreases IL-6 levels, while still allowing the body to heal. Ketamine is the current forerunner.

Collectively studies to date have shown that ketamine does have anti-inflammatory effects and the concentration of IL-6 in the blood within the first 6 hours following surgery is significantly less when a dose of ketamine (at least 0.15mg/kg) is given immediately prior to operating(6). The dose of ketamine required, long term outcomes and the exact way this drug exerts its anti-inflammatory effect still needs more research.


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(1)    Australian Bureau of Statistics (2009). National Survey of Mental Health and Wellbeing: Summary of Results, 4326.0, Canberra

(2)    Kaplan A (2013) New Claims and Findings for Ketamine in Severe Depression, Psychiatric Times,

(3)    Aan Het Rot M, Zarate CA Jr, Charney D, Mathew S (2012), ‘Ketamine for Depression: Where Do We Go from Here?’, Biological Psychiatry, issue 72, pp537–547

(4)    Adam, F, Chauvin, M, Du, MB, Langlois, M, Sessler, DI & Fletcher, D 2005 ‘Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty’, Anesthesia and analgesia, vol. 100, no. 2, pp. 475.

(5)    Ohzato H, Yoshizaki K, Nishimoto N, Ogata A, Tagoh H, Monden M, Gotoh M, Kishimoto T, Mori T. 1992 Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery, accessed 5/11/13

(6)    Dale, O, Somogyi, AA, Li, Y, Sullivan, T & Shavit, Y 2012 ‘Does intraoperative ketamine attenuate inflammatory reactivity following surgery? A systematic review and meta-analysis’, Anesthesia and analgesia, vol. 115, no. 4, pp. 934.

Posted in Blog by Douglas Fahlbusch