Wednesday, November 18, 2009

Good News/Bad News Update on Nucleus Accumbens DBS for Treatment-Resistant Depression

Taken from Fig. 1 (Bewernick et al., 2009). Hamilton Depression Rating Scale (PDF) over time.

Two and a half years ago, The Neurocritic wrote about the very early results of deep brain stimulation (DBS) in the nucleus accumbens for severe, refractory depression. You can read about the details of the procedure and its scientific motivation here:

More About the Nucleus Accumbens

NAcc Localization for DBS

Briefly, the nucleus accumbens (NAcc) is considered one of the brain's PLEASURE CENTRES:
When the cortex has received and processed a sensory stimulus indicating a reward, it sends a signal announcing this reward to a particular part of the midbrain–the ventral tegmental area (VTA)–whose activity then increases. The VTA then releases dopamine not only into the nucleus accumbens, but also into the septum, the amygdala, and the prefrontal cortex.

The nucleus accumbens then activates the individual’s motor functions, while the prefrontal cortex focuses his or her attention.
It makes sense as a DBS target region from the standpoint of anhedonia (inability to experience pleasure from normally pleasurable life events) in major depression. Why not stimulate the "pleasure center" when you're feeling blue? Extensive research in animals and humans has demonstrated "hedonic hot spots" in the NAcc.

The current paper by Bewernick et al., 2009 reports on the results from 10 patients who received NAcc-DBS for at least 12 months. These patients were severely ill and completely non-responsive to any other treatment. On average, they had been continuously depressed for 10 years, were completely unable to work, had been hospitalized numerous times, had failed over 20 medication treatment courses, were currently on 4 different drugs, had received over 20 electroconvulsive therapy (ECT) treatments, and 316 hours of therapy, all to no avail.

The primary results are illustrated in Fig. 1 above. Half the patients (n=5) were considered "treatment responders" who experienced a 50% reduction of depressive symptom severity as assessed by the HDRS, and half did not respond. Anxiety scores also declined in the responders, and engagement in pleasant activities increased.

There were some adverse events related to the surgical procedure (swollen eye in 6 patients, pain and dysphasia in 3), as well as transient adverse events related to stimulation parameter changes e.g., anxiety (n=3), hypomania, paresthesia, and agitation (all n=2). Nonetheless, the authors concluded on a positive note:
DBS to the nucleus accumbens had clinically relevant antidepressant and antianhedonic effects in a patient population that was at least as treatment-resistant as those reported on in other studies of DBS in major depression (Lozano et al., 2008; Malone et al. 2009). The efficacy to adverse event ratio in this small group was favorable. Site-specific antianxiety effects also could be demonstrated.

By targeting one site in a network of brain regions implicated in processing of affective stimuli, it was possible to manipulate anhedonia in particular. Additional studies with larger sample sizes and rigid selection criteria are needed to analyze effects of stimulation to different targets on specific symptoms and clinical phenotypes of depression. In the future, symptom-based DBS therapy, adapted to the individual needs of the patients, could be a plausible treatment option for severe TRD.


Bewernick, B., Hurlemann, R., Matusch, A., Kayser, S., Grubert, C., Hadrysiewicz, B., Axmacher, N., Lemke, M., Cooper-Mahkorn, D., & Cohen, M. (2009). Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression. Biological Psychiatry DOI: 10.1016/j.biopsych.2009.09.013

Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH. (2008). Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 64:461-7.

Malone DA Jr, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, Rauch SL, Rasmussen SA, Machado AG, Kubu CS, Tyrka AR, Price LH, Stypulkowski PH, Giftakis JE, Rise MT, Malloy PF, Salloway SP, Greenberg BD. (2009). Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry 65:267-75.

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