Elsevier

Biological Psychiatry

Volume 73, Issue 12, 15 June 2013, Pages 1204-1212
Biological Psychiatry

Priority Communication
Rapid Effects of Deep Brain Stimulation for Treatment-Resistant Major Depression

https://doi.org/10.1016/j.biopsych.2013.01.034Get rights and content

Background

Treatment-resistant major depressive disorder is a prevalent and debilitating condition. Deep brain stimulation to different targets has been proposed as a putative treatment.

Methods

In this pilot study, we assessed safety and efficacy of deep brain stimulation to the supero-lateral branch of the medial forebrain bundle in seven patients with highly refractory depression. Primary outcome criterion was severity of treatment-resistant major depressive disorder as assessed with the Montgomery-Åsberg Depression Rating Scale. General psychopathologic parameters, social functioning, and tolerance were assessed with standardized scales, the Global Assessment of Functioning scale, quality of life (Short-Form Health Survey Questionnaire), and neuropsychological tests.

Results

All patients showed strikingly similar intraoperative effects of increased appetitive motivation. Six patients attained the response criterion; response was rapid—mean Montgomery-Åsberg Depression Rating Scale of the whole sample was reduced by>50% at day 7 after onset of stimulation. At last observation (12–33 weeks), six patients were responders; among them, four were classified as remitters. Social functioning (Global Assessment of Functioning) improved in the sample as a whole from serious to mild impairment. Mean stimulation current was 2.86 mA; all side effects (strabismus at higher stimulation current, one small intracranial bleeding during surgery, infection at the implanted pulse generator site) could be resolved at short term.

Conclusions

These preliminary findings suggest that bilateral stimulation of the supero-lateral branch of the medial forebrain bundle may significantly reduce symptoms in treatment-resistant major depressive disorder. Onset of antidepressant efficacy was rapid (days), and a higher proportion of the population responded at lower stimulation intensities than observed in previous studies.

Section snippets

Methods and Materials

The Institutional Review Board of the University of Bonn approved of this study; the protocol is registered at ClinicalTrials.gov with the identifier NCT01095263. All patients gave written informed consent, and their individual inclusion criteria were reviewed by a psychiatrist not related to our group.

Demographic and Clinical Characteristics

All seven patients were diagnosed as severely treatment-resistant, with a mean length of current major depressive episode of 7.6 years (SD 5), and had 14 medical treatment courses on average (SD 3.5) with an antidepressant treatment resistance score (Modified Antidepressant Treatment History Form score) above 3 defining an adequate treatment dose and length, including augmentation and combination therapy. At the time of implantation, the mean number of antidepressant medications was 4 (SD 3.9).

Discussion

In this article, we report on effects of DBS to the slMFB in an unblinded trial in seven patients with extreme forms of treatment-resistant major depression. This approach and the results obtained are noteworthy for several reasons; the target selection was hypothesis-based, individual deterministic diffusion tensor imaging was used to identify target sites in each patient, the onset of antidepressant response was unexpectedly rapid, and last, the short-term antidepressant effects were more

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    Authors TES and VAC contributed equally to this work.

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