Rajamannar Ramasubbu, MD; Susan Anderson, RN; Angela Haffenden, PhD; Swati Chavda, MBBS, MCh; Zelma H.T. Kiss, MD, PhD
Ramasubbu — Department of Psychiatry and Clinical Neurosciences, Faculty of Medicine, University of Calgary, Hotchkiss Brain Institute, Calgary, Alta.; Anderson — Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alta.; Haffenden — Department of Psychology, Alberta Health Services, Calgary, Alta.; Haffenden, Chavda, Kiss — Department of Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, Calgary, Alta., Canada
Background: Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD.
Methods: Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17). In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes.
Results: Longer pulse widths (270–450 μs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded.
Limitations: Limitations include small sample size, weekly changes in stimu lus parameters, and fixed-order and carry-forward effects.
Conclusion: Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.
Submitted Aug. 19, 2012; Revised Sept. 12, 2012; Jan. 16, 2013; Accepted Jan. 18, 2013.
Acknowledgements: This study was supported by a grant from the Hotchkiss Brain Institute (HBI) Clinical Research Unit, Faculty of Medicine, University of Calgary, and Calgary Health Region, Calgary, Alberta, Canada, to R. Ramasubbu and Z.H.T. Kiss. Z.H.T. Kiss is a Clinical Scholar of the Alberta Heritage Foundation for Medical Research. S. Chavda was the Denyse Lajoie Lake Fellow of the HBI. We thank Dr. G. MacQueen for screening patients, Dr. M. Eliasziw for assistance in study design, Dr. Y. Starreveld for stereotactic planning, and Haifeng Zhu for statistical assistance. Preliminary results were presented as a poster at the annual conference of Society of Biological Psychiatry at New Orleans, May 2010.
Competing interests: As above for R. Ramasubbu, who also declares having received an investigator-initiated grant from AstraZeneca and from Lundbeck for the WORKER study, speaker’s hon or aria from AstraZeneca and payment for developing educational presentations from the Canadian Network for Mood and Anxiety Treatments. S. Chavda declares having won competitive fellowships from HBI as above and from the University of Calgary (International Resident Fellowship award). As above for Z.H.T. Kiss, who also declares receiving grant support through her institution from Medtronic Australia and St. Jude Australia, as well as travel support from Medtronic Inc. None declared for A. Haffenden.
Contributors: R. Ramasubbu and Z.H.T. Kiss designed the study, ana lyzed the data and wrote the article. R. Ramasubbu, S. Anderson, A. Haffenden and S. Chavda acquired the data. All authors reviewed the article and approved its publication.
Correspondence to: R. Ramasubbu, Department of Psychiatry and Clinical Neurosciences, University of Calgary, Mathison Centre for Mental Health Research and Education, TRW Bldg., Room 4D64, 3280 Hospital Dr. NW, Calgary AB T2N 4Z6; firstname.lastname@example.org