Information provided in the “Ask the Doctors” column is not meant to take the place of individual consultation with a qualified health care provider. See your health care provider to discuss specific questions about your health, medication and treatment plan.

chatmaster
Welcome to DBSA’s “Ask the Doctor” chat session on TMS and VNS. We’re so happy you could join us! Please remember that the doctors will not answer questions pertaining to specific treatments, because those can be addressed only by your doctor. It is now my pleasure to introduce Drs. Gilmer and McDonald.

Dr. McDonald is the JB Chair for Late-Life Depression and Director of the Fuqua Center for Late-Life Depression at Emory University’s Wesley Woods Geriatric Hospital in Atlanta. Dr. McDonald has published extensively in treatment-resistant depression and the overlap of neurological disease and psychopathology. He is the Principal Investigator (PI) of a recently completed NIMH study in treatment resistant depression in the elderly and an ongoing NIMH study in transcranial magnetic stimulation (TMS) for resistant depression. He is the co-PI of a recently submitted multicenter trial investigating the efficacy of serotonergic selective reuptake inhibitors (SSRI’s) in the treatment of Parkinson’s disease (PD) with comorbid depression and an investigator on NIH-funded studies investigating deep brain surgery and TMS on the motor and nonmotor symptoms of PD.

Dr. McDonald has received active grants or research support from Neuronetics (the maker of the TMS device) and Cyberonics (the maker of the VNS device). He is a consultant to both Neuronetics and Cyberonics.

Dr. William Gilmer is an Associate Professor in the Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine in Chicago. He is also Medical Director of the Asher Depression Center Clinical Program and Director of Northwestern Behavioral Pharmacology Program. Dr. Gilmer is the Director of the Northwestern University Regional Center for the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, a national, multi-site study designed to systematically evaluate various treatment options in patients with major depressive disorders. His other clinical and research interests include the investigation of new pharmacological agents, mood disorder phenomenology, predictors of bipolar spectrum disorders, and various factors influencing the course of mood disorders.

Dr. Gilmer has received active grants or research support from Neuronetics (the maker of the TMS device.)

Thank you for joining us this evening, Dr. McDonald and Dr. Gilmer.

manicpanic
What are TMS and VNS? How do they work?

Dr. Gilmer
TMS stands for Transcranial Magnetic Stimulation. (rTMS is repetitive TMS.) TMS uses magnetic fields to create focal stimulation in specific areas of the brain. The TMS energy is directed at areas of the brain thought to be involved in regulation of mood. It is thought that TMS may restore function of these brain areas to more normal patterns of activity.

Dr. McDonald
Vagal nerve stimulation or VNS works by attaching a pacemaker like device to the vagus nerve which is located in your neck (so it requires surgery). It paces the vagal nerve with electrical impulses that stimulate the mood centers of the brain and can result in a decrease in depressive symptoms.

Hopeful
Are these new treatments effective for mania as well as depression?

Dr. Gilmer
Presently, we don't have adequate information regarding bipolar illness. If rTMS is approved, I hope we will see future studies to address that important question.

BP1
Is TMS FDA approved?

Dr. McDonald
At this time, TMS is under investigation and is not yet approved for use by the FDA.

mtntopmajesty
Could the VNS cause a switch to mania in people with bipolar?

Dr. McDonald
Any treatment for depression could cause a switch.

JWill
What kind of side effects occur?

Dr. Gilmer
The most common side effects seen in studies of rTMS include some local tingling or mild pain on the scalp under the site of the magnet. Headaches after the treatment are also seen. These generally can be relieved by over the counter pain medication - and are time limited.

Sipzener
How is TMS different from ECT (which I have had.)?

Dr. McDonald
TMS is a subconvulsive stimulus (you don’t have a seizure) unlike ECT- so you are awake during TMS.

Robert
Can you give us an idea of what the preliminary data indicates for TMS?

Dr. Gilmer
Pooling together all the research studies to date, it appears that rTMS can have a beneficial effect on depression for some patients.

Moet
How long does the pacemaker-like device stay in? What maintenance is required?

Dr. McDonald
Excellent question. The VNS device is implanted and usually the wires around the vagal nerve are left in even when the pacemaker with the batteries in it is removed (it is placed in the chest). Clinical studies showed that to get a true effect from VNS you had to use it for a year. A doctor programs the device every month or so just to make sure it is working optimally. Doctors can do that with a computer in their office and it takes about 15- 20 minutes.

Moby
What’s so special about the vagus nerve? Is it just a convenient path to the brain?

Dr. McDonald
There is something special- in fact the left vagus nerve has mostly fibers which go up to the brain mood centers whereas the right vagal nerve goes down to the heart and controls heart rate and to the stomach to control acid secretion. So the stimulator is placed on...you guessed it! the left vagal nerve. It is as you hypothesized a "convenient path" (that is a great way to put it and I may use that in the future). It is accessible because it is in the neck. Another very new procedure (deep brain stimulation) actually inserts the pacer in the brain but that of course is much more challenging surgery.

kardelune
Are these treatments only for those with acute depression, or is there any hope for those of us who hate taking the meds for our moderate depression?

Dr. Gilmer
The large trial sponsored by Neuronetics, in which Dr. McDonald and I have both participated, has studied individuals who have had inadequate responses to past medication trials. In the future, it is possible that the use of TMS may extend beyond that usage. However, as with all recurrent depressive illnesses, maintenance treatment is critical and we do not yet know the best way to maintain response to TMS – whether it is through periodic maintenance TMS treatments, medication, or both. Hence, it is possible that medication may still play a role for some individuals for whom TMS was necessary to help treat their depression acutely.

smurfette
Is TMS available in Canada?

Dr. Gilmer
Yes

smurfette
In TMS, is the magnetic field applied on the skin or does an opening need to be made?

Dr. Gilmer
The procedure is entirely non-invasive. The magnetic is simply placed on top of the scalp. Generally doesn't even mess up a person's hair.

Amy
Can VNS be tested on an individual prior to actual insertion of the device to determine the likelihood of success?

Dr. McDonald
Amy, that would be a great idea. However the answer is no. It may take at least a year to work so a simple one- or two-day test would not do much. I would really like to see published data at least on who is likely to respond but so far there do not appear to be a lot of clues in this area. For example I am very interested in whether people who do not respond to ECT would respond.

kardelune
Does TMS have other undesirable effects on the brain?

Dr. Gilmer
Before current guidelines were put in place several years ago, there was a small risk of seizures with TMS. Since the new guidelines regarding dosing and proper screening techniques have been in place (e.g. eliminating individuals with a history of previous seizures), there have been no reported seizures in any of the studies following these guidelines.

bj
Which technology acts faster, TMS or VNS?

Dr. McDonald
TMS is much faster. Although the longest TMS trials are only a few weeks and the VNS device has been tested for years. The issue is that in TMS you have to come into the clinic every day, with VNS it is implanted so it is left in and on for a years or more. The initial VNS trial showed really no short term effects and it was only after a year (in an open trial in which medications were also adjusted) that VNS had an effect. TMS trials have shown an effect in a matter of week(s).

biker
Does TMS take the place of medications or will a person still need to take them?

Dr. Gilmer
The current trial conducted by the Neuronetics company is studying rTMS without medication, but previous studies have looked at TMS with medication. If approved, it is likely be used both ways in practice, similar to the way ECT is used - however, we will need further studies to determine the best way to combine the treatments.

Sipzener
Is VNS approved by the FDA?

Dr. McDonald
VNS is approved by the FDA with the caveat that they will monitor response and adverse events closely in patients. As I stated the initial placebo-controlled trial (1/2 got active VNS and 1/2 got no stimulus - the VNS pacemaker was turned off) did not show a benefit for VNS. It was only in an "open" trial in which all patients had the stimulator on, their medications were also being adjusted, and their progress was charted for a year that a benefit was seen. In this open trial, about 1/3 of the patients had a 50% drop in their depression, when tested. Many of these patients were quite ill and the FDA felt they should approve the treatment but monitor it closely.

robertw
How would you describe the patients who can benefit from rTMS?

Dr. Gilmer
I'm not able to describe a specific type of depression that is more likely to respond. We hope to determine that from current and future trials. Obviously, it could be an important option for individuals who don't respond well to or tolerate current antidepressant medications. In a smaller study by Dr. Janicak and colleagues, it appeared that rTMS may be less useful for people with psychotic depression (depression that includes delusions, e.g., false beliefs, paranoia, or hallucinations, e.g., hearing voices or seeing things).

mike
What if depression symptoms return after TMS treatment?

Dr. Gilmer
We're asking that very question in the current Neuronetics sponsored trial. We're investigating the reinitiation of TMS treatments to determine their efficacy for relapse.

Charles-Colo_Spgs
I read in one article that studies on the effectiveness of TMS would be performed last year in not less than 15 U.S. research hospitals. Have their findings been published yet?

Dr. McDonald
They have not been published yet, but the multicenter trial you refer to has closed enrollment and is now looking at the data. I was part of the study and it was very well conducted. I think we are going to have an answer to whether TMS works and for whom around the first of next year. We are presently conducting a study sponsored by the National Institute of Health on TMS and for more information use the contacts below:

TMS Contacts

• Emory University in Atlanta 404-728-6470 toll free 877-498-0096

• MUSC in Charleston 843-792-9222

• Columbia in NY 212-543-5825

• Univ of Washington in Seattle 206-731-2436

Sipzener
Who shouldn't use TMS?

Dr. Gilmer
Individuals with seizure disorders, metal plates in their head, or cardiac pacemakers are individuals for whom TNS would not be as readily considered.

smurfette
Is there any indication as to when TMS might be FDA approved in the US?

Dr. Gilmer
Late 2006 at the earliest.

gtb
How successful has VNS been

Dr. McDonald
The initial placebo controlled trial was negative. However, in an open trial of patients who had failed an average of 4 good medication trials, about 1/3 of patients had a 50% decline in their depression scores. We would like to see published data on this and it should be coming out around the first part of next year.

Charles-Colo_Spgs
Does TMS have any effect on the memory, like ECT does?

Dr. Gilmer
Thus far, there does not appear to be any effect upon memory - which is a major advantage over ECT. Our patients go to work, school, etc. immediately after their treatments and notice no adverse effect upon their cognitive functioning.

stp
What are the side effects to VNS?

Dr. McDonald
The main side effects of VNS are that it can cause hoarseness when turned on, a tingling feeling in the skin, shortness of breath, difficulty swallowing, sore throat, neck pain and increased coughing.

Amy
What part of the brain does TMS affect?

Dr. Gilmer
Most studies have administered the treatment over an area on the left side of the brain called the dorsolateral prefrontal cortex - which is an area thought to modulate mood.

smurfette
Are there any precautions one should take prior to TMS treatment?

Dr. Gilmer
It is advised not to take medications or substances that significantly increase the risk of seizure. This is little preparation necessary - no anesthesia is required. A few of our patients will take something like aspirin or ibuprofen beforehand if they experience headaches with the treatment.

Amy
Is there any evidence of memory loss with TMS?

Dr. Gilmer
No.

Chad
Which treatment is better for people with treatment resistant depression, TMS or VNS?

Dr. McDonald
Tough question, Chad and again we should wait to see the published data. TMS does not require surgery and is easier to administer in that sense. VNS is a much bigger commitment. The published data will tell us what factors predict response in which groups but it would seem that the more treatment resistant you are the harder it is to get a good response. The other side of the coin is that these treatments clearly work differently from medication and there may be a subgroup of patients who respond to these treatments. Again, published data will be important in making that decision with your doctor.

bj
Are these treatments better than ECT?

Dr. McDonald
We need published data but...ECT is clearly the most efficacious treatment in depression- no question. However it has side effects, is expensive, requires anesthesia etc. TMS is relatively easy to administer and appears to have no associated memory problems and no clear risks except for a seizure risk which is dose-related and can therefore be controlled in a clinical setting. VNS will require surgery. So let’s wait for the data and decide if either has an effect as good as ECT or shows a response in particular patient type. It may be that a trial of TMS will make sense prior to ECT in a particular patient type- that is not clear right now.

kardelune
I'm wondering how often one would have to go in for another treatment of TMS. Would the patient feel the effect "wearing off" after a time?

Dr. Gilmer
We do not yet know what the most optimal treatment schedule is for treatments beyond acute response. We hope to get information regarding that from our current Neuronetics trial.

bj
When TMS is FDA approved, where can a patient get a treatment? Hospital, psychiatrist’s office?

Dr. Gilmer
It will likely be available in hospital-based clinics, university medical centers, and private psychiatry clinics.

Sipzener
Do you have to plug TMS in to an electrical outlet?

Dr. Gilmer
The device does require being plugged into an electrical outlet.

Asher
Why does magnetism affect the nervous system?

Dr. Gilmer
The magnetic fields induce a focal electrical current that can be directed to the specific location desired. That causes stimulation of the brain area that is being targeted.

Jay
How long has TMS been studied?

Dr. McDonald
TMS has been in trials at Emory since 1996 and the technology has been around for at least twenty-five years.

Moet
Can the general public do anything to assist in getting FDA approval for TMS?

Dr. Gilmer
Interesting question that I'm not sure how best to respond. If patient groups feel strongly about this - or any treatment - it may be something the organization could pursue.

gtb
How long has VNS been in use?

Dr. McDonald
VNS has been used in epilepsy for perhaps 8 years and in depression for the last 2-3 years.

gtb
Is TMS something only a doctor will be able to administer?

Dr. Gilmer
It almost certainly will require a doctor's recommendation and supervision.

Asher
Are TMS and VNS available only for patients in research studies?

Dr. McDonald
TMS is available in research studies at the following institutions:

• Emory University in Atlanta 404-728-6470 toll free 877-498-0096

• MUSC in Charleston 843-792-9222 Columbia in NY 212-543-5825

• Univ of Washington in Seattle 206-731-2436

VNS is FDA-approved and the main research trials has ended.  The company is monitoring how people are doing with VNS in a registry (i.e., patients who have the VNS device are monitored).

robertw
If it takes a year for VNS to begin to show effect, how do we know that it is the VNS rather than a person biologically cycling out of depression?

Dr. McDonald
Good point - although most of the patients in the trial had chronic depression- the current episodes were on the order of 16 months. In that study, the patients' medication could be changed so it could have been due to that. In talking with a company spokesperson they said the responders actually had fewer medication changes although that could be due to the fact that they were responding (as well as the possibility that medication did not make a difference). Again the published data will hopefully make that clear.

Sam
Please explain how long you have to wear the magnet and be plugged into it.

Dr. Gilmer
The magnet is not worn. It's only about the size of a man's hand - and it's placed over the scalp, supported by the device. The lengths of treatments have varied among studies -- in the current trial, it takes about 37 minutes total and patients are generally in and out of the office in about an hour on treatment days. On days when the localization of magnetic placement is determined, it takes about another 20 minutes or so.

wheels63
Are their any web links that you may be able to supply so we all could follow the progress?

Dr. McDonald
http://fuqua.emoryhealthcare.org is our website and we are trying to update it with new information as we get it. I also think the FDA website is pretty good and impartial if you just Google it.

Arobix
I’ve heard magnetic fields cause brain tumors. Is this true?

Dr. Gilmer
I am not aware of any brain tumors as a result of TMS. TMS field strengths are similar to those of MRI scanners. MRI's have been used since the early 1980's - and to the best of my knowledge, there are no reports of brain tumors that have resulted from the use of MRI devices or TMS.

manicpanic
What type of improvement should a person expect with TMS?

Dr. Gilmer
As with antidepressant medications, amount of improvement will likely vary by individual and we do not know how best to predict the degree of response to any of our treatments.

manicpanic
Will I set off airport metal detectors if I have a VNS implant - if so, how should I explain it?

Dr. McDonald
I think you would set them off and I would tell them you have a pacemaker and show it to them. Actually it may get you through airports more quickly as they would not send you through the sensors (just as they would if you had a heart pacemaker- both are clearly visible on your chest under the skin).

Arobix
How strong is the TMS magnet, compared to your usual magnet?

Dr. Gilmer (Aug 24, 2005 7:58:38 PM)
Since magnet strengths vary significantly, it's probably best to compare it to the field strength of MRI scanners. It is much stronger than the type of magnetic wrist bands one sometimes sees sold in stores.

Sam
When will VNS be widely available for depression? Does insurance or Medicaid pay for it?

Dr. McDonald
It should be available soon. The company is Cyberonics and they have a website which will list places doing VNS implants. There is not a billing code for it yet and that needs to be established first but I think that is coming soon. This is the type of treatment (i.e., surgery) that I would consider carefully by talking with your doctor, reviewing published studies with your doctor. Also, DBSA is always a good source for unbiased opinions on new medical research so I would check their web site. VNS is available now for the treatment of epilepsy and Emory University in Atlanta is one site that will be doing the implants- we were part of the clinical trial. 1-877-498-0096

chatmaster
We’re about out of time, so I want to thank you all for coming tonight and thank Dr. Gilmer and Dr. McDonald for being with us and answering so many great questions!

Dr. McDonald
This has really been a great group with excellent questions. I hope we have been of help. The bottom line is that we are all working on the same goal- effective treatment of depression. We can do it together with groups like the DBSA.

Dr. Gilmer
I second Dr. McDonald's comments. I commend DBSA for sponsoring this type of program - and thanks to everyone for the excellent questions.