Deep Brain Stimulation for Treatment Resistant Depression

Deep brain stimulation (DBS) is an experimental surgical treatment involving the implantation of a medical device that sends electrical impulses to specific parts of the brain. DBS has been approved for treating tremor (a disease where parts of the body, usually the hands, shake when someone is intentionally moving), dystonia (a disorder where muscle contractions cause twisting and repetitive movements or abnormal postures), and Parkinson's Disease. DBS has also shown some promise in helping people with treatment-resistant depression.

The pacemaker or stimulator that controls DBS is placed in specific areas of a person's brain (mapped out ahead of time using imaging technology such as a CT scan or MRI) during a surgical procedure where the patient is anesthetized (i.e., feels no pain), but awake. The device is then calibrated to provide optimal amounts of stimulation for each person. After approximately 3 to 5 years, the brain pacemaker must be replaced, because the batteries wear out across time.

In individuals with treatment resistant depression, the pacemaker is placed in the subgenual cingulate region (SCR or Brodmann's area 25) or the nucleus accumbens (a part of the brain that controls our ability feel pleasure). It is unclear why the treatment works, but the stimulation of these brain regions seems to help with emotional regulation and decreasing depressive thoughts and feelings. Preliminary research results are promising; DBS patients experienced a remission in depression symptoms for 6 months. However, the procedure is still considered experimental; very few people have undergone this type of treatment for depression.

Exactly how deep brain stimulation can affect depression isn't clear. Researchers theorize that certain regions deep within the brain influence mood and depression. They believe that the areas associated with depression may be overactive in certain people. Sending electrical impulses to these areas may "reset" them to normal functioning.

Risks

Any surgical procedure carries risks. Because deep brain stimulation involves brain surgery, the procedure may be especially risky, posing some serious health risks. Also, the brain stimulation itself may cause side effects.

Possible surgical complications

Complications of surgery may include:
  • Bleeding in the brain
  • Stroke
  • Infection
  • Breathing problems
  • Nausea
  • Heart problems
  • Incision scarring

Possible side effects after surgery

Side effects and adverse health problems associated with deep brain stimulation include, but may not be limited to:
  • Bleeding in the brain
  • Seizure
  • Infection
  • Delirium
  • Unwanted mood changes, such as mania and depression
  • Movement disorders
  • Lightheadedness
  • Insomnia
  • Dizziness
  • Device malfunction
  • Temporary tingling in your face or limbs
Also, people who have undergone deep brain stimulation to treat Parkinson's disease have reported a variety of problems, including:
  • Panic attacks
  • Mania
  • Speech difficulty
  • Movement problems
  • Increased suicidal thoughts and behavior
The long-term risks and side effects of deep brain stimulation for depression aren't known.

How you prepare

Because deep brain stimulation is experimental, it's available only through participation in clinical trials. Because of the risks involved, its use is limited to people who have severe, debilitating depression that has not improved with standard treatments.

First, weigh the pros and cons

Deep brain stimulation is a serious and potentially risky procedure because it requires brain surgery. Even if you might be eligible for a clinical trial to test deep brain stimulation, you and your doctors must carefully weigh the pros and cons of the procedure. If your depression prevents you from going about your daily activities or is life-threatening, you may be more willing to face the risks involved with deep brain stimulation. But you still must be screened by a team of medical professionals to make sure deep brain stimulation is a good and safe option for you.

Next, preparing for surgery

Before surgery, you need a medical evaluation with your doctor or neurosurgeon to make sure it's safe for you and a good option in your case. You may need a full physical and psychiatric evaluation. This may include neuropsychological evaluations to determine your level of intellectual and cognitive ability before the procedure so that potential changes can be monitored over time. You also need brain-imaging studies, such as an MRI, before the surgery.

What you can expect

During the surgery

Deep brain stimulation requires two surgical procedures:
  • Surgery on your brain to implant electrodes
  • Surgery on your chest to implant a neurostimulator device
Because the procedure is new and experimental for depression, it may not be performed exactly the same way everywhere. In general, here's how surgery for deep brain stimulation works.

Brain surgery 

For the brain surgery portion, you're given local anesthetics to numb the areas being operated on. You remain awake and alert, however, so that the surgeon can talk to you to make sure the proper areas of your brain are being stimulated.
Your head is placed in a special frame to keep it still during surgery. Two holes are drilled in your skull. Guided by imaging techniques, the surgeon implants electrodes on both sides of your brain. You may undergo testing during the surgery to see how your mood is affected by the stimulation.

Chest surgery

During the second portion of surgery, the surgeon implants the neurostimulator in your chest, near your collarbone. You're put to sleep with general anesthesia for this surgery. Wires from the brain electrodes are placed under your skin and guided down to the battery-operated neurostimulator.

After the procedure

After the surgeries, you may need to take antibiotics to lower the risk of infection. A week or so after the surgeries, the neurostimulator in your chest is activated in your doctor's office. This sends electrical signals to the electrodes in your brain, affecting areas related to mood.

The amount of stimulation is customized to your situation, based on your mood and side effects. Stimulation is generally constant, 24 hours a day. The neurostimulator, which runs on battery power, can be easily programmed from outside your body.

You're given a hand-held magnetic device to use at home. With this, you can temporarily turn off stimulation by holding the magnet over the area of your chest where the neurostimulator is implanted. When you move the magnet away, stimulation restarts.
You must visit your doctor periodically to make sure that the neurostimulator is working correctly and that it hasn't shifted out of position. If necessary, the neurostimulator can be replaced or removed in a simple surgical procedure. The neurostimulator device may need replacement after a few years.

Results

If deep brain stimulation works as hoped, your depression symptoms will improve or go away completely. It may take several months of treatment with deep brain stimulation before you notice any improvements in your depression symptoms, though. And not everyone with chronic depression, especially those who have had depression for years, gets better with deep brain stimulation. Additional research is needed to learn more about how deep brain stimulation works and how safe and effective it is for depression.

St. Jude Medical Study

According to the latest data in a clinical study supported by St. Jude Medical, Inc., deep brain stimulation (DBS) therapy for depression may provide sustainable improvement in depression symptoms among patients with major depressive disorder. Study results was presented at the American Psychiatric Association (APA) meeting in San Francisco.

This study profiles 21 patients with DBS therapy in the area of the brain known as Brodmann Area 25, most of whom have completed one year of post-surgery evaluation. At six months, 62 percent of the patients experienced at least a 40-percent decrease in symptoms of depression as measured by a standardized test called the Hamilton Rating Scale for Depression. Of these patients, 92 percent maintained this improvement at their last follow-up visit (typically at one year). Additionally, 71 percent of all patients in the study exhibited at least a 40-percent decrease in symptoms of depression as measured by the Hamilton scale.

"Typically these patients do not maintain responses to traditional approaches such as medications and electroconvulsive therapy," said Peter Giacobbe, M.D., psychiatrist with the University Health Network in Toronto and presenter of the study results. "We are encouraged that this data indicates DBS therapy may provide sustainable improvement in the quality of life for these patients."

Ongoing at three leading Canadian academic medical centers, the study utilized the St. Jude Medical Libra Deep Brain Stimulation System to deliver stimulation to an area of the brain known as Brodmann Area 25, which appears to become overactive in severely depressed people. The pilot study builds upon the research of Helen Mayberg, M.D., and Andres Lozano, M.D.

Patients in the study had suffered from depression for an average of 20 years, had tried in excess of 12 depression medications and were considered disabled or unable to work at the time of enrollment. At the 12-month evaluation point, eight of the study patients had returned to daily life activities such as school, work and sustaining relationships with family and friends, and two patients were considered to be in remission.

"These results are important as they contribute to the growing body of research about the potential benefits deep brain stimulation may provide this patient population," said Chris Chavez, president of the St. Jude Medical Neuromodulation Division. "We are committed to expanding our research into the field of depression and to completing the BROADEN study to determine whether stimulation of Brodmann Area 25 is clinically significant in treating severely depressed patients who have exhausted other treatment options."

Heidelberg University Hospital Study

A team of neurosurgeons at Heidelberg University Hospital and psychiatrists at the Central Institute of Mental Health, Mannheim have for the first time successfully treated a patient suffering from severe depression by stimulating the habenula, a tiny nerve structure in the brain. The 64-year-old woman, who had suffered from depression since age 18, could not be helped by medication or electroconvulsive therapy. Since the procedure, she is for the first time in years free of symptoms.

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Source: Heidelberg University Hospital.

The habenula is a tiny double structure in the diencephalon. For stimulation two electrodes are implanted. The picture shows the pathway of an electrode in the brain.

Scientific studies have shown that the habenula is hyperactive in depression, the idea was to downregulate this structure by deep brain stimulation. The surgical procedure is based on a hypothesis of how the habenula is involved in depression that was first formulated by Dr. Alexander Sartorius, psychiatrist at the Central Institute for Mental Health.

The success of the procedure was confirmed when the electrode was accidentally switched off: the patient had a bicycle accident which required surgery for which an ECG had to be made as preparation. The brain pacemaker was switched off and was not reactivated for a few days, and the depression promptly returned. A few weeks after reactivation, the patient completely recovered again.

The neurosurgeons in Heidelberg and the psychiatrists in Mannheim now want to build on this positive experience and are planning a clinical study in which the habenula stimulation is to be implemented for severely depressive patients at five psychiatric-neurosurgery centers in Germany. “We aim to show that habenula stimulation has a better success rate than other target areas attempted for depression and that it is also safe to use,” says Dr. Sartorius, Coordinating Investigator of the proposed study.



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