The International Journal of Neuropsychopharmacology

A randomized trial of low-frequency right-prefrontal-cortex transcranial magnetic stimulation as augmentation in treatment-resistant major depression

Paul B. Fitzgerald a1a2c1, Stephen Huntsman a3, Ranil Gunewardene a4, Jayashri Kulkarni a1 and Z. Jeff Daskalakis a5
a1 Alfred Psychiatry Research Centre, The Alfred and Monash University Department of Psychological Medicine, Melbourne, Victoria, Australia
a2 The Victoria Clinic, Prahran, Melbourne, Australia
a3 Palm Beach Currumbin Clinic, Currumbin, Gold Coast, Queensland, Australia
a4 Mosman Private Hospital, Mosman, New South Wales, Australia
a5 Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada

Article author query
fitzgerald pb   [PubMed][Google Scholar] 
huntsman s   [PubMed][Google Scholar] 
gunewardene r   [PubMed][Google Scholar] 
kulkarni j   [PubMed][Google Scholar] 
daskalakis zj   [PubMed][Google Scholar] 


Low-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) appears to have antidepressant properties although the effectiveness of this treatment in clinical practice has not been assessed nor have the optimal stimulation parameters been adequately defined. A total of 130 patients with treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over the right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk extension. Non- responders were randomized to either 5- or 10-Hz left PFC rTMS. Overall, 66 patients (51%) achieved response and 35 (27%) remission criteria. For right-sided treatment, depression significantly improved but there was no between-group difference. Twenty-eight (42%) patients in the 1-Hz group and 33 (53%) patients in the 2-Hz group achieved response criteria (χ2=1.40, p>0.05). Depression symptom scores also improved for patients who crossed over to left-sided treatment but there was no significant difference in response between 5- and 10-Hz rTMS. Despite a heterogeneous sample, a significant proportion of patients met clinical response criteria following treatment but response to 1 and 2 Hz did not differ. 2-Hz right PFC rTMS has antidepressant properties but offers no advantage over 1 Hz despite doubling pulse number.

(Received May 17 2006)
(Reviewed June 11 2006)
(Revised June 22 2006)
(Accepted July 7 2006)
(Published Online September 7 2006)

Key Words: Antidepressant; depression; prefrontal cortex; remission; repetitive transcranial magnetic stimulation; response.

c1 Alfred Psychiatry Research Centre, First Floor, Old Baker Building, The Alfred, Commercial Rd, Melbourne, Victoria, Australia, 3004. Tel.: 61 3 9276 6552 Fax: 61 3 9276 6588 E-mail: