Deep Brain Stimulation (DBS) currently
is under investigation for treatment of sever, treatment-resistant
depression (TRD). It is not really news. I wrote
about it in 2005. The background information in the
earlier post still is pertinent, so I won't repeat that now.
Briefly, though, the treatment consists of surgical
implantation of a pacemaker-like device. The device has wires
that go into the brain (area 25, the subgenual cingulate area).The study reported in 2005 was promising, but it included only six patients. Four patients responded, and maintained response for six months. That is kind of neat, but the number of patients and the duration of response were both way too small to get excited about.
In the meantime, we've seen reports about the application of DBS for Parkinson's disease; for persons with a minimally-conscious state after traumatic brain injury (1 2); and for Alzheimer's Disease (1 2)
In May, Dr. Shock provided an update on the cognitive safety of DBS when used to TRD. Bottom line: it is very safe, with no cognitive problems noted. That is obviously good, especially if one also plans to use it for treatment of dementia.
In July, Mo, writing at Neurophilosophy, provided a nice summary of the more recent report about the use of DBS for TRD; this report described the results with more patients, with a longer follow-up period.
At that time, the article had been epublished-ahead-of-print, and only the abstract was openly available. Now, the final published article is available. Not only that, but the journal selected it to be one of their few open-access articles.
Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression
Background
A preliminary report in six patients suggested that deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) may provide benefit in treatment-resistant depression (TRD). We now report the results of these and an additional 14 patients with extended follow-up.
Methods
Twenty patients with TRD underwent serial assessments before and after SCG DBS. We determined the percentage of patients who achieved a response (50% or greater reduction in the 17-item Hamilton Rating Scale for Depression [HRSD-17]) or remission (scores of 7 or less) after surgery. We also examined changes in brain metabolism associated with DBS, using positron emission tomography.
Results
There were both early and progressive benefits to DBS. One month after surgery, 35% of patients met criteria for response with 10% of patients in remission. Six months after surgery, 60% of patients were responders and 35% met criteria for remission, benefits that were largely maintained at 12 months. Deep brain stimulation therapy was associated with specific changes in the metabolic activity localized to cortical and limbic circuits implicated in the pathogenesis of depression. The number of serious adverse effects was small with no patient experiencing permanent deficits.
Conclusions
This study suggests that DBS is relatively safe and provides significant improvement in patients with TRD. Subcallosal cingulate gyrus DBS likely acts by modulating brain networks whose dysfunction leads to depression. The procedure is well tolerated and benefits are sustained for at least 1 year. A careful double-blind appraisal is required before the procedure can be recommended for use on a wider scale.
The bottom line is that it still is too early to get excited, but it is OK to allow yourself to get a warm glow of anticipation. In a population of patients with TRD, a response rate of 60% is astonishingly good. A remission rate of 35% is equally remarkable. The fact that those results held up for one year is highly encouraging.
Treatment response was seen in the whole package of symptoms:
Deep brain stimulation was associated with global improvements in depressive symptomatology as measured by the mood, anxiety, somatic, and sleep subcomponents of the HRSD scale.
The authors point out that the treatment "is adjustable and stimulation is reversible." This is different than other types of psychosurgery, which are irreversible. (1 2)
As sort of an added bonus, Lozano et. al. performed neuroimaging (PET) in addition to the clinical outcome studies.
This shows definite, specific changes in brain activity. Moreover, it shows that the changes progress over time. (The changes are relative to baseline.)
The authors note that the changes is the immediate vicinity of the electrodes are not the same as the effects downstream:
Of interest, opposite metabolic changes were present at the target of stimulation, the subcallosal cingulate white matter, and the immediately adjacent gray matter. In contrast to our previous report using blood flow where only decreased SCG activity was observed, we noted focal increases in metabolism in the immediate vicinity of the stimulating electrode with decreases in metabolism in the adjacent caudal subcallosal gray matter consistent with the previous blood flow results (Figure 3, sagittal image, left). These results suggest that there is a direct activation of the white matter at target that can lead to either metabolic activation or inhibition in distinct remote brain areas.
While this may not have immediate clinical significance, this kind of descriptive study can turn out to have implications for further research in basic neuroscience.
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Groovy citation:
A LOZANO, H MAYBERG, P GIACOBBE, C HAMANI, R CRADDOCK, S KENNEDY (2008). Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression Biological Psychiatry DOI: 10.1016/j.biopsych.2008.05.034
Brain & Behavior
Comments
Is it true that psychiatrists have psychic powers? Do all psychiatrists have this gift, or only some? It's not a prerequisite for being a psychiatrist, is it?
Posted by: stumpy | September 4, 2008 11:47 AM
Did the authors of this study examine potential changes in autonomic nervous system activity that might be produced by direct stimulation of this region of cingulate cortex? (Sorry, I don't have immediate access to the article.)
There is a wide range of evidence that this cortical region can directly influence heart rate, blood pressure and similar functions through inhibition of the sympathetic nervous system. This effect is believed to be mediated by direct projections from area 25 to the nucleus of the solitary tract and other brainstem nuclei (at least in rats). It seems to me that it might be important to examine this cortical-autonomic link because the autonomic nervous system plays an important role in emotions.
Posted by: Gary Fisk | September 4, 2008 1:54 PM
If psychiatrists had psychic powers, they would not need to use PET scans.
I did not see any mention in the article of assessment of autonomic function. I would like to think that adverse effects such as bradycardia or postural hypotension (or the opposite) would have been obvious, and would have been mentioned if they occurred, but that is an assumption.
Posted by: Joseph j7uy5 | September 6, 2008 12:56 AM