Neurophilosophy

ResearchBlogging.org

Depression is a common neuropsychiatric disorder which affects at least 1 in 7 adults. The condition can have a major effect on patients’ quality of life, and is a major cause of both disability and suicide.

Many patients with depression can be treated effectively with antidepressant medications, such as the specific serotonin re-uptake inhibitor (SSRI) fluoxetine (more popularly known as Prozac). However, a significant proportion of patients – up to 20% – do not respond to these drugs, or to other forms of treatment.

Now a study published online in the journal Biological Psychiatry suggests that patients with treatment-resistant depression could benefit from a technique called deep brain stimulation, in which an electrode is implanted into the brain.

Deep brain stimulation (DBS) is an experimental surgical technique which involves the implantation of a device called a brain pacemaker into a specified area of the brain. The device is attached by a thin wire to a small battery which is often placed under the skin on the chest. It generates rhythmic pulses of electricity which modulate the activity in the targeted brain region.

In 2002, the U.S. Food and Drug Administration approved DBS as a treatment for Parkinson’s Disease, a neurodegenerative disease characterized by muscle rigidity and tremors, and since then has been used to successfully alleviate those symptoms in approximately 40,000 patients with that condition.

DBS has also been used to treat other conditions such as chronic pain and Tourette’s Syndrome. And it is not the first time that it has been used to treat depression: in 2005, the same team reported their results from a trial involving 6 patients and last year, researchers from the Cleveland Clinic in Ohio reported their preliminary data from a trial involving 17 patients.

The current study is the largest clinical trial to date of the efficacy of DBS as a treatment for severe depression. Between May 2003 and November 2006, Andrez M. Lozano and his colleagues implanted electrodes into the brains of a total of 20 patients (9 men and 11 women) with major depressive disorder, all of whom were referred to the researchers from hospitals or community psychiatrists, after failing to respond to antidepressants, psychotherapy or electroconvulsive therapy.

The surgery, carried out at Toronto Western Hospital, involved implanting the electrodes into a region of the brain called the subcallosal geniculate cingulate gyrus (SCG), which is thought to be involved in regulating mood and has been shown in functional neuroimaging studies to be over-active in depressed patients.

The SCG was identified in the patients by magnetic resonance imaging; holes were then drilled on both sides of the patients’ skulls, and the electrodes inserted through them. The precise locations at which the researcher left the electrodes were determined by behavioural tests – the patients were given a local anaesthetic prior to the surgery, and so remained conscious throughout the procedure. They could therefore report how their mood changed with electrical stimulation of different parts of the SCG.

12 out of the 20 patients reported significant long-term improvements in their condition. This was corroborated by neuropsychological assessments which measured, among other things, the patients’ mood, anxiety levels and sleeping patterns. These improvements were observed within 1 month and, importantly, persisted for at least 12 months after the treatment, by which time 7 of the patients had gone into full remission.

However, the exact mechanism by which DBS exerts its effects at the cellular level is unknown. PET scans performed following the treatment suggested that the alleviation of symptoms was caused by stimulation of the SCG white matter (which contains bundles of nerve fibres), leading to both activation and inhibition of multiple distant brain areas. But other studies have targeted other regions of the brain, such as the nucleus accumbens, at it remains to be seen which of these substrates is the optimal target for treatment of depression. It is also unclear why 8 of the patients did not respond to the treatment.

Even so, the study shows that DBS can improve many of the symptoms of severe depression, and that it is a safe procedure that was tolerated well by the patients involved: although the surgical wound became infected in 3 of the patients, and 1 of them experienced a seizure on the evening of the surgery, 7 patients reported no adverse effects whatsoever, and none of those who did not respond to the treatment reported a worsening of their condition.

Related:


Lozano, A. M., et al (2008). Subcallosal Cingulate Gyrus Deep Brain Stimulation for
Treatment-Resistant Depression. Biol. Psychiatry. DOI: 10.1016/jbiopsych.2008.05.034.

Comments

  1. #1 Dr Shock MD PhD
    July 24, 2008

    Isn’t it time for some randomized trial, switching the device on and off?
    Great post, regards Dr Shock

  2. #2 Mo
    July 24, 2008

    According to this Nature News story, the Texas-based company Advanced Neuromodulation Systems is “sponsoring a double-blind, controlled phase III trial on up to 200 patients at three centres in the United States.”

  3. #3 Left_Wing_Fox
    July 24, 2008

    I think I first heard about this last year through Canada’s Quirks and Quarks science show. One thing I’ve found interesting is what appears to be a resurgence and rehabilitation of Electroconvulsive therapy as a treatment for serious depression. Is that something that I’m just stumbling into conincidentally, or do you think it’s a treatment that’s making a resurgence?

  4. #4 nothing ventured
    July 24, 2008

    Left Wing Fox: EV is definitely resurgent in the US and is applied much more specifically in cases of severe depression that does not respond to medication and/or talk therapy. The “dosages” are much lower than in the past with the same results. To use a very bad analogy, it’s a reboot. Works in some cases, not in all.

  5. #5 eddie
    July 24, 2008

    Compare and contrast this;

    http://www.sentienttimes.com/08/08_june_july/brain.html

    which suggests that all you need do is listen to audio output from your brainwaves.

    Yes, the noise it makes when you are “istening to continually-changing musical tones that reflect the continually-changing electrical activity of the surface layer�the cerebral cortex�of your own brain” is;

    woooooo…

  6. #6 The Neurocritic
    July 25, 2008

    The surgery … involved implanting the electrodes into a region of the brain called the subcallosal geniculate (SGC)…

    You mean subcallosal cingulate gyrus (SCG), aka subgenual cingulate in their previous publications.

  7. #7 Mo
    July 25, 2008

    I certainly do. Thanks Neurocritic.

  8. #8 Ryan Morehead
    July 25, 2008

    There is a third group in Germany who stimulated the Nucleus Accumbens in an attempt to relieve anhedonia, a major symptom of major depression: http://www.nature.com/npp/journal/v33/n2/abs/1301408a.html.

    They only had three subjects, but the results seem promising. Their choice of stimulation site makes me wonder, however, if any of them have turned into compulsive gamblers.

  9. #9 Amiya Sarkar
    July 30, 2008

    Instead of “specific serotonin re-uptake inhibitor (SSRI)”, the term ‘selective serotonin re-uptake inhibitor (SSRI)’ is more accurate.
    A very interesting read.

  10. #10 Joseph Brenner
    August 4, 2008

    Does Epilepsy fall among the other disorders?

  11. #11 isaac h
    April 16, 2010

    I just finished my second, and final, surgery at the cleveland clinic two days ago for bilateral implantation of the medtronics device leading to the ventral striatum. I am very sore and stiff but relieved to be through the tough part of the process. I am told the device will be programmed and I will be randomized in one month following the last surgery, so I am anxiously waiting for the return to cleveland. I hope to have good news to report soon. Let me know if you have any questions about the procedure, hopefully I could answer some of them.
    Isaac

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