Problems & criticisms of using Ketamine

Prescribing 'off-label' medications

Ketamine is an 'off-label' treatment therapy for treatment resistant depression, anxiety, and other mental health conditions. ‘Off label’ means that the manufacturing company has not obtained government approval for the use of ketamine for depression. There are many reasons for this, including the fact that ketamine's patent expired long ago, meaning that the cost of applying for such an indication would be greater than any financial reward.

However, Esketamine, the S-enantiomer of ketamine, has been patented as a nasal spray and has successfully applied to the United States Food and Drug Administration for an indication to treat depression. Medsafe New Zealand have also granted an indication for esketamine to be used in patients with treatment-resistant depression. With the involvement of a major pharmaceutical company, it is likely that greater resources will be available to establish the role of a form of ketamine in treating mental health problems.

Side effects

Ketamine can have side effects. These include frightening dissociative symptoms, difficulty walking, and transient hallucinations. As a result, patients need to have at least their first dose of oral ketamine under medical supervision to check that it can be given safely at home.

Esketamine and injectable forms of ketamine require medical supervision after each dose.


There are concerns about the possibility of abuse of ketamine. In this regard, ketamine is similar to many other drugs with medical uses. In clinical use of oral ketamine, it is rare for patients to build tolerance or to ask for increasing frequency of dosing. It is more likely that as ketamine exerts its effect on depression and anxiety, patients will space out their doses and eventually stop taking ketamine altogether.

Giving patients a small amount of ketamine at a time and closely supervising response and use of ketamine helps to reduce the chance of developing a significant substance use problem. Ketamine is abused via insufflation of concentrated powder (‘snorting’) or injection, and doses are typically much greater than those used for therapeutic purposes. The oral route is not preferred by abusers.

Finding the correct dosage

Ketamine has a wide dose range. Some patients will respond to low doses of ketamine, others require higher doses to obtain any response. Finding the right dose takes time, effort and close follow up from an experienced professional.

Esketamine (Spravato) has a relatively rapid titration protocol.

The role of ketamine in treating mental health conditions has not been fully researched. Although there is excellent evidence for short term efficacy Many questions remain unanswered, including important questions about how best to maintain a response.

Ketamine requires intensive input from a team of mental health professionals. Patients need to be assessed by a psychiatrist with experience in the area, in-office titration of an oral dose or administration of intravenous, intranasal or subcutaneous doses, and frequent follow-up to tailor the treatment for each individual. Ketamine is a labour intensive and therefore costly treatment for self-funding patients, and may not be covered by some insurers.