When treating patients suffering from complex regional pain syndrome (CRPS) with a low-dose (subanesthetic) ketamine infusion, it was observed that some patients made a significant recovery from associated depression. This recovery was not formally documented, as the primary concern was the treatment of the patient's pain. It was not possible to quantify to what degree depression recovery was secondary to the patient's recovery from CRPS. Based on this result, it was thought that a low-dose (subanesthetic) infusion of ketamine was worth a trial in patients who were suffering from treatment-resistant depression without other physical or psychiatric illness.
Animal studies have shown that ketamine and other NMDA receptor antagonists have antidepressant effects in different animal models of depression. About a decade ago, Berman et al.[9] described the first double-blind, placebo-controlled (crossover) study, which showed that an intravenous ketamine infusion (0.5 mg/kg) resulted in significant and rapid but short-lived antidepressant effects in seven patients with major depression.
The problem with using ketamine more widely to treat depression has been the fact it has to be given intravenously under medical supervision, and it can also cause short-term psychotic symptoms.
