DBS for Depression

Deep brain stimulation for depression

Depression is a major psychiatric disorder in which, the prominent symptom is a disturbance of mood which is a constant feeling that is experienced internally and that influences a person’s attitudes, thinking, behavior and perception. It is marked by depressed moods where one loses interest in things that once excited them, impaired cognition (think brain fog and slowed speech), difficulty sleeping, and a loss of appetite. While our collective interest in mental health has now made “depression” a household term, it is a serious diagnosis that can be completely debilitating without proper treatment. Treatment typically consists of psychotherapy and medication. But that isn’t a fit for everyone. This means that after initial trial and error, talk therapy and medication are not providing relief and debilitating symptoms that impact day-to-day functioning are persisting. These are called “treatment-resistant depression (TRD)”. Electroconvulsive therapy (ECT) and transcranial magnetic therapy (TMS) can be used in case of TRD nonetheless some patient may have recurrence despite of multiple sessions. Deep brain stimulation (DBS) is beginning to gain steam for treatment of depression and accumulate data proving its efficacy.

How DBS works in depression?
DBS was developed in the late 1980s. It is used to treat Parkinson’s disease and several other disorders for several years. However, over the past two decades, data showing its safety, feasibility and efficacy piled up. The promise of DBS in disorders of motor circuitry has driven its investigation in depression. Furthermore, while neurotransmitters, such as serotonin, norepinephrine, and dopamine, are undoubtedly implicated in depression, pharmacotherapy is often a wholesale approach affecting virtually all brain regions. More focused approaches, such as DBS, target specific anatomic circuits underlying emotional processing and offer an additional therapeutic option. Depending on which brain areas are targeted for stimulation, different types of brain functions (such as movement, or anxiety, or emotion) can be affected.
The electrodes are planted onto that part of the brain, though specific electrode placement will depend upon the treatment plan. Once the “generator” is functioning, it will begin to fire off electric pulses to the impacted parts of the brain. These pulses reset the brain’s metabolism by blocking malfunctioning neurons. Protocols of surgery, type of anesthesia, implant selections etc. differs vary according to different centers and patients.

Patient selection
Patient selection is crucial to the success of DBS. It is important that the patient be offered surgical evaluation at an appropriate center which has the expertise of evaluating such patients. Preferably two neuropsychiatrists should establish if the disease is indeed incurable with medical treatment and the patient has been offered adequate trial of best medical therapies.

How is DBS done for depression?
Planning of DBS in depression is an extensive exercise. It requires an experienced team of functional neurosurgeon, neuropsychiatrist, neuropsychologist, neuroscientist, neurophysiologist, neuroanesthesia team, neuroradiologist, functional neurosurgery specialist nurse etc. Planning usually starts several days before surgery. Patient is evaluated by neuropsychiatrist and neuropsychologist for severity and treatment-resistance. Functional neurosurgeon associated with neuroradiologist, and neuroscientist decides most effective target for DBS electrodes implantation. Finally, after fitness from neuroanesthesia, patient is scheduled for surgery.

In DBS, electrodes are planted into the target areas of the brain during surgery. These electrodes begin to regulate abnormal brain activity through a series of electrical pulses. Surgery to implant the electrode takes about four hours. The electrodes are controlled by a device called a generator. It is often compared to a pacemaker because it is planted in the upper chest and is connected to the electrodes by a wire running from the chest to the brain. Engaging in DBS is a process. There is a recovery period from the surgery that takes a few weeks.

After DBS
DBS is effective in properly selected patient for depression nonetheless it may be recommended that the medication and other treatments like counselling, psychotherapy, rehabilitation, etc., be continued even after the DBS. Follow up with functional neurosurgery team and neuropsychiatrist is required for optimum medical management and programming of “electric pulse generator”. Patient will not have any restriction related to diet or activity due to DBS. Although new devices are magnetic compatible, it may interfere with function of some devices. Therefore proper instruction should be followed from device manufacturers.

Clinical literature
In 2005, Mayberg et al. presented the first clinical study of DBS in depression. The hypothesis to stimulate Broadman area 25 was acquired from observations that showed hyperactivity of the subgenual cingulate cortex (Brodmann area 25; Cg25) in chronic depressed patients. It was thought that this area plays a primary role in processes like learning, memory, motivation, and reward—behaviours that change with depression. In this novel study by Mayberg et al., six patients were implanted and stimulated with parameters adjusted to the apparent optimal benefit. After 6 months, in 67% of patients, a reduction of more than 50% on the Hamilton depression rating scale (HDRS) was seen, with a total or partial remission in three patients. Clinically, improvement was referred as an increase in energy, interest, psychomotor speech and decrease of apathy and anhedonia. In addition, imaging studies showed normalization in the cerebral blood flow of Cg25 and other areas which appear to be related with depression. Schlaepfer et al. published the positive results of DBS of the nucleus accumbens for depression in three patients. The positive behavioural changes in these patients were supported by positron emission tomography imaging that correlated symptomatology with an augmentation of metabolism in the nucleus accumbens, amygdala, and dorsolateral and dorsomedial prefrontal cortex, and reduced metabolism in the ventral and ventrolateral medial prefrontal cortex.

Indian study on DBS for depression
Doshi et al. have operated three patients with TRD using Cg25 as their target. The follow-up ranges from 1.5 to 3 years. At the last follow-up, their HDRS (17) improved from 27 to 4, the Hamilton anxiety scores improved from 26 to 4 and two patients were only ON stimulation and OFF all medications.
Since DBS is a ray of hope for many, but still not the right treatment for every person caught in the anguish of this disorder, it is important to continue the research and clinical trials on the subject. Many hope that a close understanding of DBS and how it works on the brain can provide researchers with the insight they need to find a cure for depression and other psychopathic diseases.
Having said that, DBS is emerging as a potential intervention for patients with severe depression for whom no reasonable treatment options are available. Beyond simple demonstration of safety and efficacy, a growing number of human and animal studies are beginning to delineate potential mechanisms of action for DBS for TRD. With careful and considered study, the hope is that DBS might become an important treatment option for some of the most severely affected patients with neuropsychiatric diseases, as it has in the field of movement disorders.