There is a growing body of clinical evidence that has shown how ketamine works to produce antidepressant effects in those with treatment-resistant depression (TRD). These studies have used a common subanesthetic dose of 0.5 mg/kg over a period of 40 minutes when administered through an IV. An outpatient study from 2018, published in Molecular Psychiatry, recently added onto this body of research in order to find the optimal dose for antidepressant effects in those with TRD. They found that single IV doses of ketamine of 0.5 mg/kg and 1 mg/kg proved to be more effective than an active placebo in reducing depression over a 3-day period.
The double-blind placebo-controlled study randomly assigned 99 participants to one of five infusion types (single subanesthetic dose over 40 min): ketamine 0.1 mg/kg, ketamine 0.2 mg/kg, ketamine 0.5 mg/kg, ketamine 1.0 mg/kg, or midazolam 0.045 mg/kg (active placebo). The participants who were on prohibited psychotropic agents underwent a washout period before the doses were administered. In other words, the other drugs were “washed out” of their systems in order to provide a cleaner slate for the ketamine or active placebo to work on.
To assess for safety and efficacy, the researchers evaluated participants’ scores on various scales and questionnaires, such as the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression-Scale 6, throughout the length of the study (3 days), as well as 5, 7, 14, and 30 days after.
The results found that participants who received ketamine IV treatments had significant improvement when measured on the Hamilton Depression Scale, compared to those who received the active placebo (midazolam). However, after controlling for multiple comparisons using post hoc analysis, only the standard dose (0.5 mg/kg) and high dose (1 mg/kg) of ketamine were superior to active placebo. Conversely, the low dose (0.1 mg/kg) was significant only before adjustment, and the 0.2 mg/kg dose did not show any significant effects compared to active placebo. Therefore, their results suggest clinical evidence for antidepressant effectiveness from the 0.5 mg/kg and 1.0 mg/kg doses of ketamine, but no conclusive evidence for lower doses.
At Reset Ketamine, we use ascending doses of ketamine to achieve the maximal effects for our patients. Typically, we start at 0.5 mg/kg and then titrate upwards, depending upon patient effect and safe vital sign assessments. We believe higher doses will lead to non-ordinary states of conciousness, which may lead to a more potent, profound, and prolonged effect. Each patient is different, so we tailor the dose specifically for that person to achieve the maximal benefits.
Fava, Maurizio, et al. “Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine as Adjunctive Therapy in Treatment-Resistant Depression (TRD).” Molecular Psychiatry, 2018, doi:10.1038/s41380-018-0256-5.