Ketamine for Depression: The Main Clinical Question Is Usually Suitability, Not Speed

Ketamine attracts attention because of its rapid effects in some people with depression, especially compared with standard antidepressants. But clinically, the more important issue is where it sits in the treatment pathway. The 2022 VA/DoD major depression guideline places ketamine or esketamine among options to consider only after a patient has shown partial or no response to an adequate initial pharmacological treatment trial. NICE also does not recommend esketamine nasal spray with an SSRI or SNRI for treatment-resistant depression within its appraisal framework.

That does not mean ketamine has no role. It means it is better understood as a specialist treatment rather than a routine first-line option. This is where patient selection becomes important. Comorbidity, prior treatment response, functional status, psychosis risk, substance use, and the practical ability to attend repeated monitored sessions are all relevant to whether treatment is realistic and appropriate. The FDA label for Spravato states that because of the risks of sedation, dissociation, and respiratory depression, patients must be monitored for at least 2 hours after each treatment session. It is also available only through a REMS programme.

This monitoring requirement is not a minor detail. It shapes who can access treatment and how burdensome the pathway may feel. A therapy that requires repeated clinic attendance, post-dose observation, and transport planning is very different from a standard outpatient prescription. The FDA label also notes abuse and misuse potential, which adds another layer to clinical decision-making.

So the most useful way to write about ketamine is not as a breakthrough in the abstract. It is as a treatment with a specific place, a clear monitoring burden, and a narrower suitability profile than the marketing language sometimes suggests.