Mood disorders affect up to fifteen percent of the population, any given year. Today’s treatment options are plagued with low response and high relapse rates, and can be time and resource intensive. Further, up to one third of patients suffering from major depression do not respond to standard treatments. New treatment options that alter the brains level of neuroplasticity (its ability to adapt to change and reconfigure itself) show promising results, but either show transient effects or require multiple and/or maintenance treatments. Here we wish to combine two methods that induce neuroplasticity, intravenous sub-anesthetic ketamine infusion and transcranial magnetic stimulation (TMS), in a one day protocol for treatment of depression. The planned clinical RCT will involve one treatment of ketamine, followed by two sessions of ‘theta-burst stimulation’ (TBS; an approved therapeutic TMS protocol), controlled by an active placebo group (sub-anesthetic midazolam infusion) and sham-TMS. The hypothesis is that one method (TMS) can strengthen the effect of the other (ketamine) such that the anti-depressant effect is stronger and/or lasts longer. A positive result may reduce the need for multiple treatments or increase the time interval between treatments.