Ketamine Treatment for Treatment-Resistant Depression

Ketamine is a new and effective treatment option for the treatment of Treatment-Resistant Depression (TRD).

SASOP released a statement in 2022 that addresses some of the pitfalls of ketamine administration, including:

1. Ketamine is registered in South Africa as an anesthetic agent, and therefore, the use of ketamine for the treatment of depression and suicidality is off-label.
2. Although there is evidence for efficacy in treating TRD, long-term data regarding safety are needed, and its position in treatment algorithms still needs to be established.
3. The recommended route of administration is ivi, and for safety reasons, ketamine should be administered by an anesthetist or suitably qualified general practitioner (diploma in anesthetics).
4.  The diagnosis of TRD is in the sole domain/ Scope of Practice of psychiatrists, as only psychiatrists review the
   efficacy of the previous treatment (and thus diagnose “true” treatment resistance).
5. Patients should, therefore, formally be referred by a psychiatrist to the medical practitioner who administers the ketamine. Psychiatrists should follow up with patients who have received ketamine.
6.  Organizations promoting the ethical and safe use of ketamine, such as SASA (South African Association of Anesthesiologists), have released statements that SASOP supports.

As the number of patients receiving ketamine has increased dramatically, the following concerns have been identified:

1.  Ketamine has been advertised extensively, e.g., on social media. This has enabled patients with depression to obtain ketamine on demand without an evaluation by a psychiatrist. Thus, the diagnosis of TRD for many patients has not been established. This exposes patients to side effects, possible worsening of their mental health condition, and numerous other adverse effects.
2. As only psychiatrists can diagnose TRD, this implies health practitioners such as psychologists and general practitioners recommending and administering ketamine are practicing out of scope of practice. They are exposing patients to risks and themselves to litigation.
3.  The use of ketamine is evidence-based for adults. However, it has been mentioned in the media as a treatment option for children.
4.  SAPHRA (South African Health Products Regulatory Authority) has ruled that because the use of ketamine for TRD is off-label, ketamine may not be advertised or even mentioned online. Although factually correct, this stance makes it difficult to educate the public.
5. Due to the increased use of ketamine, the supply of ketamine has become problematic. Fresenius Kabi does not condone the off-label use of ketamine for psychiatric patients, except when under strict supervision of a psychiatrist.
6. Only psychiatrists can diagnose TRD and prescribe ketamine, while only anesthetists and GPs with diplomas can administer ketamine. This scenario has, unfortunately, created conflict and communication breakdown between the relevant medical practitioners. This is not to the advantage of our patients.

In summary:

The first SASOP statement regarding the use of ketamine for TRD remains applicable.
We anticipate an increased demand for ketamine as a therapeutic modality, which will lead to additional challenges with interpretation and compliance with existing guidelines will likely accompany.
Adherence to the recommendations of the initial SASOP position statement remains critical.
All relevant stakeholders, e.g., psychiatrists, psychologists, general practitioners, anesthesiologists, and patients, should be informed about the
ethical and safe use of ketamine in the treatment of TRD.