Objective: To determine the impact of clustered maintenance transcranial magnetic stimulation (TMS) on irritability occurring in treatment-resistant major depressive disorder (MDD).

Method: A naturalistic study of 106 courses that includes pre- and posttreatment assessments of subjective and objective depression and a subjective measure of irritability developed for this study.

Results: Forty-six participants (35 females), mean age 43.2 years (14.3), completed 106 courses. There was a significant reduction in irritability and depression scores (p < .001). The change in irritability scores was significantly correlated with the change in depression scores, r = .40, p < .001.

Conclusion: TMS has the capacity to reduce the irritability co-occurring with treatment-resistant MDD, known to be responsive to TMS. This increases the possibility of using TMS in the treatment of irritability co-occurring with other disorders or standing alone (should irritability be categorized as a stand-alone disorder).