Marcelo T Berlim1, Alexander McGirr2, Frederique Van den Eynde3, Marcelo P A Fleck4, Peter Giacobbe5. 1. Neuromodulation Research Clinic, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada; Depressive Disorders Program, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada. Electronic address: nrc.douglas@me.com. 2. Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada. 3. Neuromodulation Research Clinic, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada. 4. Neuromodulation Research Clinic, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada; Depressive Disorders Program, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada. 5. Department of Psychiatry, Toronto General Hospital, University Health Network, Toronto, Canada.
Abstract
BACKGROUND: Deep brain stimulation (DBS) applied to the subgenual cingulate cortex (SCC) has been recently investigated as a potential treatment for severe and chronic treatment-resistant depression (TRD). Given its invasive and experimental nature, a comprehensive evaluation of its effectiveness and acceptability is of paramount importance. Therefore, we conducted the present systematic review and exploratory meta-analysis. METHODS: We searched the literature for English language prospective clinical trials on DBS of the SCC for TRD from 1999 through December 2012 using MEDLINE, EMBASE, PsycINFO, CENTRAL and SCOPUS, and performed a random effects exploratory meta-analysis using Event Rates and Hedges׳ g effect sizes. RESULTS: Data from 4 observational studies were included, totaling 66 subjects with severe and chronic TRD. Twelve-month response and remission rates following DBS treatment were 39.9% (95% CI=28.4% to 52.8%) and 26.3% (95% CI=13% to 45.9%), respectively. Also, depression scores at 12 months post-DBS were significantly reduced (i.e., pooled Hedges׳ g effect size=-1.89 [95% CI=-2.64 to -1.15, p<0.0001]). Also, there was a significant decrease in depression scores between 3 and 6 months (Hedges׳ g=-0.27, p=0.003), but no significant changes from months 6 to 12. Finally, dropout rates at 12 months were 10.8% (95% CI=4.3% to 24.4%). LIMITATIONS: Small number of included studies (most of which were open label), and limited long-term effectiveness data. CONCLUSIONS: DBS applied to the SCC seems to be associated with relatively large response and remission rates in the short- and medium- to long-term in patients with severe TRD. Also, its maximal antidepressant effects are mostly observed within the first 6 months after device implantation. Nevertheless, these findings are clearly preliminary and future controlled trials should include larger and more representative samples, and focus on the identification of optimal neuroanatomical sites and stimulation parameters.
BACKGROUND: Deep brain stimulation (DBS) applied to the subgenual cingulate cortex (SCC) has been recently investigated as a potential treatment for severe and chronic treatment-resistant depression (TRD). Given its invasive and experimental nature, a comprehensive evaluation of its effectiveness and acceptability is of paramount importance. Therefore, we conducted the present systematic review and exploratory meta-analysis. METHODS: We searched the literature for English language prospective clinical trials on DBS of the SCC for TRD from 1999 through December 2012 using MEDLINE, EMBASE, PsycINFO, CENTRAL and SCOPUS, and performed a random effects exploratory meta-analysis using Event Rates and Hedges׳ g effect sizes. RESULTS: Data from 4 observational studies were included, totaling 66 subjects with severe and chronic TRD. Twelve-month response and remission rates following DBS treatment were 39.9% (95% CI=28.4% to 52.8%) and 26.3% (95% CI=13% to 45.9%), respectively. Also, depression scores at 12 months post-DBS were significantly reduced (i.e., pooled Hedges׳ g effect size=-1.89 [95% CI=-2.64 to -1.15, p<0.0001]). Also, there was a significant decrease in depression scores between 3 and 6 months (Hedges׳ g=-0.27, p=0.003), but no significant changes from months 6 to 12. Finally, dropout rates at 12 months were 10.8% (95% CI=4.3% to 24.4%). LIMITATIONS: Small number of included studies (most of which were open label), and limited long-term effectiveness data. CONCLUSIONS: DBS applied to the SCC seems to be associated with relatively large response and remission rates in the short- and medium- to long-term in patients with severe TRD. Also, its maximal antidepressant effects are mostly observed within the first 6 months after device implantation. Nevertheless, these findings are clearly preliminary and future controlled trials should include larger and more representative samples, and focus on the identification of optimal neuroanatomical sites and stimulation parameters.
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