Abstract: The disclosure provides novel compositions comprising ketamine and/or pharmaceutically acceptable salts, enantiomers, derivatives or metabolites thereof as an active pharmaceutical agent for use in the treatment, control or prevention of depressive disorders, including, for example treatment resistant depression (TRD). The disclosure further provides method and uses of combined doses of ketamine showing exceptional efficacy in the treatment of depressive disorders (including TRD) and in the control and duration of remission from the same.