Ketamine in severe, highly treatment-resistant depression—a retrospective case study and a perspective

Abstract

Ketamine is a well-known and widely available general anesthetic from the 1960s that, in sub-anesthetic doses, has been adopted in a limited manner for the treatment of acute suicidality and treatment-resistant depression. Its short onset time and short duration of action make it feasible for use at outpatient clinics. In the US, it has a long history of off-label use and was officially approved for depression treatment in 2019. In Finland, it has been administered to selected hospitalized patients in the public healthcare system since 2010 and became available at a private outpatient clinic very recently. In Norway, it has been administered off-label at a private clinic for approximately 500 patients since mid-2010s and at a public clinic for approximately 300 patients since 2020, with plans on opening more clinics in 2024. In the US, the treatment has been administered to hundreds of thousands of patients. The retrospective ethnographic inquiry part of this study features a Finnish woman in her twenties who suffered from treatment-resistant depression, rooted in her insecure childhood and having been bullied at school, as well as income insecurity and excessive workload in adulthood. Eventually, she was violently raped, which induced an obvious post-traumatic stress disorder and exacerbated her depression, incapacitating her. In the course of approximately five years, she was prescribed ten different anti-depressive medications and seventeen other medications, including various antipsychotic medications and lithium. These failed to provide an anti-depressive effect but resulted in 'massive' adverse effects instead, including 60% weight gain and psychotic hallucinations. Eventually, esketamine spray treatment at a private outpatient clinic resolved her depression in a single session. A weekly re-administration process was ongoing. In this case, repeated esketamine administration alleviated depression by producing accumulating corrective emotional experiences without the need to re-experience previous traumatizing events. In a few months to a year, the transient but accumulating anti-depressive effect typically leads to the resolution of depression in most cases, if the patients' living conditions no longer constantly re-traumatize them. It is necessary to adopt ketamine more widely as an emergency measure while more effective, non-addictive alternatives and complements are prepared for adoption. The cost of this specific pilot program implementation was unscalable, but costs can be reduced by approximately 90% by modifying the implementation details. Ketamine and its more effective alternative, 5-MeO-DMT, can serve a major role in facilitating a rebirth of public and private mental healthcare systems, with treatment efficacy multiplied and treatment costs simultaneously reduced.