There Are Newer Brain Therapies Approved For The Treatment Of Depression Other Than ECT

I understand there are newer brain therapies approved for the treatment of depression other than ECT. What are they and should I consider them if I’m not getting better?

There are two new therapies approved by the U.S. Food and Drug Administration (FDA) and one that remains experimental but has been performed in Canada. The first two are transcranial magnetic stimulation (TMS) and vagal nerve stimulation (VNS), whereas the third is deep brain stimulation (DBS).

TMS

TMS is a noninvasive procedure that applies weak electric currents to the head, thereby exciting neurons in the brain. If performed repetitively, TMS can be used as a therapeutic tool to produce longer lasting changes. This is also referred to repetitive TMS, or rTMS. Potential therapeutic uses include the treatment of migraines, stroke, Parkinson’s disease and other movement disorders, as well as depression. With respect to depression, a large number of studies have demonstrated at most a very modest effect, and none compared favorably with ECT.

However, in October 2008 the procedure was approved by the FDA for use in adults with major depression who failed to improve with medication. The short-term risks are minor. There can be mild pain in the area of stimulation to the scalp and rarely mild burns from over-heating when used in conjunction with electroencephalographic electrodes. In patients with epilepsy there is a very low risk of seizure induction.

Other dis-comforts are hearing the noise generated by the machine, somewhat similar in experience to the knocking sound of an MRI machine. The long-term risks are currently unknown, but so far there is no evidence of cognitive impairment from receiving this treatment. In conclusion, the treatment is benign and its benefits modest at best.

VNS

VNS is used adjunctively primarily for the treatment of certain intractable seizure disorders. In 2005 the FDA approved its use for treatment refractory depression.

However, despite its approval and the endorsement by the American Psychiatric Association, its use has been limited because in the only randomized controlled trial, which is considered the gold standard of scientific studies, VNS failed to perform any better than placebo. In this case the study included a placebo group of patients who had VNS implanted but not activated.

Implanting the device is performed as an outpatient procedure. An incision is made in the upper left chest and the generator is placed under the left clavicle, sim-ilar to a pacemaker. Another incision is made in the left neck where the surgeon places the generator leads around the left branch of the vagus nerve. The genera-tor then sends electrical signals to the leads at regular intervals similar to a pacemaker, stimulating the vagus nerve.

The left vagus nerve is used because the right vagus nerve stimulates the heart; cardiac effects are thus minimized. The theory behind VNS is that signals are sent via the vagus nerve back to the brain, which affect various areas of the brain, as well as neurotransmitter systems that play a role in mood and sei-zure control. Obviously, there are immediate risks associated with the surgery and potential complications resulting from that, as well as placing a foreign object in the body. But the most significant risk has been the development of obstructive sleep apnea.

This occurs because the laryngeal nerves are also stimulated, which can cause the larynx to constrict. Additional side effects include hoarseness (the most common), coughing, and sore throat. Other nonspecific symptoms have been reported, including stomach upset, nausea and vomiting, shortness of breath, headache, and numbness. Finally, although the left vagus nerve has significantly fewer effects on the heart, there can still be cardiac-related adverse effects, such as reversible bradycardia (slowed pulse).

DBS

DBS is the most invasive procedure of the three described and is still not FDA approved. It is similar to VNS in that it uses a pacemaker that periodically stimulates an area of the brain, but instead of doing so indirectly by wrapping leads around the vagus nerve, the leads are placed directly in specific brain regions. DBS has shown clear benefits to patients with Parkinson’s disease and other movement disorders.

The FDA has approved it for these conditions. More recently, it has been used in treatment-resistant depression as well as chronic pain with some success. As in VNS, the pacemaker is placed under the clavicle. The leads then run up under the skin of the neck, behind the ear, and under the scalp. This is performed under general anes-thesia.

Then, under local anesthesia a small diameter hole is drilled in the skull, allowing the lead to enter the brain. For Parkinson’s disease, essential tremor, and other movement disorders, lead placement is fairly standardized. It is important that the patient be awake for this part of the procedure for the surgeon to receive feedback from the patient regarding the success of lead placement.

Currently, there is limited evidence for the FDA to grant approval for the use of DBS in depression. In 2005 research demonstrated its effectiveness when the leads were placed in the frontal cortex of the brains of six depressed patients, with four responding positively. The effects were immediate. Researchers are also investigating other brain regions.

As with any invasive procedure the potential side effects are significant but, in this instance, include any surgical procedures involving the brain, including bleeding, infection, and swelling. Lead placement can also inadvertently create new problems for the individual. There can be significant cognitive and emotional side effects associated with improper lead placement. These can include the very conditions one is attempting to treat, such as depression, but also compulsive behaviors and psycho-sis have been reported.