The acute antidepressant effect of racemic ketamine is at the level of electroconvulsive treatment and is not inferior compared to esketamine. Maitenance ketamine treatment or ketamine-assisted psychotherapy are indispensable to sustain the antidepressant, anxiolytic and antisuicidal effects of prior acute treatment with racemic ketamine.
Several international retrospective and prospective studies have focused on maintenance treatment with racemic ketamine by intravenous, intramuscular, subcutaneous, intranasal, sublingual and oral administration. In these studies, ketamine has been administered from 3 times weekly to once every 12 weeks, depending on the effect and tolerance.
No placebo- or comparator-controlled long-term study on ketamine maintenance therapy in patients with treatment-resistant depressive disorder has been published to date. Thus, a direct comparison of the effectiveness of ketamine with other interventions is lacking.
Interim observations beyond 1 year do not provide information on adverse effects, other than those described during acute ketamine treatment. Some caution has been raised regarding the dependence development, considering a tendency to increase doses in some self-administrating patients, who had been given ketamine home.