TMS Breakthrough: New Hope for Treating Severe Depression With Few Side Effects

A new treatment for major depression – and possibly other maladies, including pain and post-traumatic stress disorder – seems as effective as the alternatives, with lower cost and fewer side effects. Psychiatrists say TMS is showing much promise in preliminary studies.

Until four years ago, psychiatrists had only two options for treating major depression: drugs and electroconvulsive therapy (ETC), formerly known as electroshock.

Antidepressant drugs can take as long as four to six weeks to kick in, and they have many side effects: cardiac toxicity, urinary retention, impotence, loss of libido, blurred vision, dry mouth, somnolence, overstimulation and assorted other complications that vary from drug to drug.

Surprisingly, ECT, which passes an electric current through the brain, is considered to be safer than drugs for patients with many physical illnesses, but it also has a steep downside of its own: A course of ECT can wipe out crucial memories like Ajax scouring out a sink.

Most psychiatry textbooks write that a first trial of an antidepressant is effective only 60 percent of the time. ECT is generally said to be effective 70 percent to 80 percent of the time.

In 2008, the US Food and Drug Administration approved a new device for treating major depression: Transcranial Magnetic Stimulation, or TMS. TMS has its roots in the research of Michael Faraday, the giant of 19th century physics. He could scarcely have dreamed that his law of induction would one day be used to treat mental illness.

Faraday’s Law is simple: It states that an oscillating magnetic coil – that is, a coil moving back and forth – generates an electric field. Now if a magnetic coil sets up an electric field inside the brain, the electric field will stimulate the neurons to release brain chemicals called neurotransmitters, of which the three most familiar are serotonin, dopamine, and noradrenaline (although there are dozens more under varying degrees of investigation).

Serotonin is a sedating neurotransmitter; dopamine is energizing; noradrenaline resides somewhere in between. The increased availability of one or more of these neurotransmitters is believed to lift the depression.

The instrument that was approved by the FDA is called “NeuroStar.” It is manufactured by Neuronetics for “major depression that does not respond to a trial of an antidepressant drug.”

This is very generous labeling by the FDA, and in reality the labeling doesn’t amount to much, because once a drug or medical device has been approved for marketing, it can be used by the physician for any indication he sees fit.

Already NeuroStar is being used to treat chronic anxiety, bipolar depression (the depressive swing of manic-depressive illness) and chronic pain. I’ve also been told the military has bought several TMS instruments for treating post-traumatic stress disorder.

As for “major depression,” it is an entity that has paraded through the psychiatric literature under a variety of names, among them: “unipolar depression” (to signify that it is not the depressed phase of manic-depressive – bipolar – disorder), “and “endogenous depression (which is intended to signify that it is a biologically, and probably a genetically driven, disorder).”

The condition is marked by mental symptoms such as low mood and morbid or outright suicidal thoughts, as well as physical symptoms like sleep disturbance, loss of appetite and anxiety.

According to Sue McMonigle, vice president for marketing at Neuronetics, there are currently 424 facilities in the US, ranging from hospitals to private offices that use the device. So far, McMonigle said, about 9,000 people have undergone treatment with TMS.

Small-scale studies indicate it is effective about 70 percent or more of the time – in the same range as ECT, but definitive studies are needed to nail this figure down.

The potential for TMS is enormous. According to the Centers for Disease Control, one American adult in ten suffers from depression, by which the CDC means major depression or the milder condition, dysthymia.

This number does not include manic-depressive (bipolar) patients in the depressed phase. Nor does it factor in all the other psychiatric and neurological disorders for which TMS is already being used.

Truthout spoke with two practitioners of TMS – Dr. Alan Manevitz, clinical associate professor of psychiatry at Weill Cornell Medical School, and Dr. James Halper, MD, clinical associate professor of psychiatry at New York University School of Medicine, who set up the first TMS facility in New York City.

The doctors said that, second to depression, the best-established indication for TMS is pain. They called TMS a “new pathway of treatment” without the problems of antidepressant drugs or ECT.

So exactly what is NeuroStar? Manevitz and Halper invited me to visit their private clinic on New York’s chic Sutton Place, where their clinical coordinator, Yoko Kanamori, demonstrated the workings of the Neurostar for me.

The treatment room looks like a dentist’s office, with a comfortable recliner and the magnet mounted in an armature, rather like the dentist’s drill, that is connected up to a box that allows the operator to adjust the number of magnetic oscillations per second and, applying Faraday’s Law of Induction, the strength of the electrical field inside the brain.

The magnetic field is weak – it would take 30 treatments with the NeuroStar to equal the degree of magnetic exposure of a single scan with a magnetic resonance imager (MRI), Kanamori told me.

The business end is the magnetic coil under a padded headpiece that covers the prefrontal cortex, a region of the brain associated with depressive mood and morbid, sometimes suicidal, thoughts. The prefrontal cortex sends and receives bundles of nerve fibers to and from a region of the brain, the limbic system, that is responsible for what are called the somatic or “vegetative” symptoms of depression like disordered sleep, loss of appetite, anxiety and other symptoms not ordinarily amenable to will power (which is one good reason why it is stupid and cruel to tell someone suffering from depression to “snap out of it”).

Kanamori switched on the NeuroStar and held the back of my hand against the cushion. I felt a mildly annoying rat-tat-tat of the magnet oscillating back and forth, then a longish respite, followed by another burst of magnetic activity. Not surprisingly, headache is a rather frequent complaint from TMS, but it can be easily treated with Tylenol or aspirin. Otherwise, TMS is largely free of side effects.

The definitive study on the indications and side effects of TMS was conducted last year by a “blue ribbon” panel of experts chosen by French medical societies. After reviewing the literature on TMS, the authors concluded that the only significant side effect was the rare occurrence of seizures, and these occurred as a rule when the practitioner departed from the instructions for using the instrument, or rarely when the patient was taking an antidepressant that lowers the seizure threshold.

In TMS, the patient is fully awake, sitting comfortably in the recliner, and reading or watching a video. There are five sessions a week, and each session lasts for one hour. A complete course of treatment lasts four to six weeks. Since this is about the same as the time it usually takes for antidepressant medication to go to work, what’s the advantage of TMS?

First, far fewer side effects. Secondly, some studies show that it works when drugs fail. When the magnet is lifted off the patient’s head, out she walks.

The same cannot be said of ECT. Practitioners vary in their methods, but ECT is usually given every couple of days for a total of seven to 10 treatments. The patient is wheeled into the ECT suite on a gurney, where a minimum team of a psychiatrist, an anesthesiologist, and an ECT nurse await him.

The anesthesiologist promptly administers a short-acting anesthetic such as brevital. Next comes succinylcholine, an agent that paralyzes all the skeletal muscles of the body – including the muscles involved in breathing. An ECT nurse at once begins to “bag” the patient, that is, force oxygen into his lungs or else he would soon die.

With the patient all “prepped,” the psychiatrist positions electrodes on the temples (or on just one side, if he opts for the unilateral procedure) and hits the “on” button, which sends a jolt of 225-450 volts of electricity through the brain.

Were it not for the muscle-paralytic effects of succinylcholine, the patient would experience violent convulsions that often shattered bones in the past. As it is practiced today, just about all there is to see that suggests a convulsion is a brief bending of the feet.

The ECT nurse continues to bag the patient until he starts breathing on his own; then he is wheeled into the recovery room where he is observed by a nurse until the anesthetic progressively wears off, and he emerges from his experience disoriented and confused.

Today, ECT is almost always administered to hospitalized patients, but there are “buzz shops” to be found that give ECT on an out-patient basis. Usually it takes the patient a couple of hours before she’s steady enough to leave, but the patient is usually warned not to drive herself home.

It will probably have occurred to the reader that TMS and ECT have a common denominator: Both set up an electric field within the brain, although TMS delivers the electricity gradually and moderately over a period of weeks, while ECT serves it up in seven to ten flashes of current.

In fact, one of many theories of ECT efficacy is that the electric field releases a torrent of neurotransmitters.

An important consideration in treating depression, and all the more important when the depression is severe, is a feature called the durability – the length of time from the termination of treatment to the return of depressive symptoms.

For antidepressant drugs, the durability is six months to relapse. Skilled psycho-pharmacologists usually maintain their seriously ill patients on medication for two years, then taper the dose very gradually and kick it right back up again at the first hint of a relapse.

Some depressed patients require lifelong medication. I have been using the word “antidepressant” in the singular, but in fact the art of psychopharmacology is often to use drug combinations skillfully.

The most popular and effective adjunct is to add lithium to an antidepressant. This combination is so effective that results are often seen in a matter of days. Another safe and effective adjunct is thyroxine (T3), and the addition of lithium and thyroxine is more effective that either adjunct alone.

Many other drug combinations are used, such as two different categories of antidepressants – for example, a tricyclic like Elavil, and a monoamine oxidase inhibitor like Phenelzine – or the addition of a stimulant, like Ritalin, to an antidepressant.

In recent years, the addition of “second-generation antipsychotics” – Abilify, Seroquel, Zyprexa and other agents that are more than just antipsychotics; they possess antidepressant and anxiolytic properties in their own right – are gaining in popularity as adjuncts.

This far from exhausts the cornucopia of adjuncts that are used in modern psychopharmacology.

Clinical experience over a period of decades has found that ECT has a durability of six months. Most psychiatrists find it prudent to discontinue antidepressant medications before embarking on a course of ECT; once the patient has completed seven to ten treatments, the psychiatrist starts a regimen of antidepressant medication to prolong the durability of the recovery; some psychiatrists, rather than administering medication, give periodic “booster” doses of ECT. Similarly, two or three booster treatments of TMS will usually effect a remission in patients who have experienced a course of TMS and, after a variable period of time, show signs of a depressive relapse.

One advantage of TSM over ECT is that the patient can safely take antidepressants during TSM therapy, a consideration that strengthens its durability.

Memory loss and, sometimes, confusion are the major side effects of ECT – and they can be major, according to Dr. Maria A. Sullivan, a psychiatrist and psychologist at New York State Psychiatric Institute, who uses ECT so infrequently that she couldn’t recall when she last employed it. Her view is that ECT should only be administered to the most severely ill patients – those with catatonia and severe, life-threatening depression that does not respond to aggressive pharmacotherapy and psychotherapy.

Other psychiatrists intervene earlier. Thus, Dr. Gabriella Centurion – a psychiatrist in private practice who is a TMS provider – calls ECT the “gold standard” for treating severe depression. Virtually since its introduction, ECT has stirred controversy between therapeutic “doves” and “hawks.” An ongoing study at Columbia University, which compares TMS to ECT and which is large enough to overcome the objections to the small, existing pilot studies, may provide definitive information.

So long as they are interpreted cautiously, the existing pilot studies show that TMS and ECT are comparable. If confirmed, these data will have a major impact on the way that we treat severe depression.

What about the bottom line? Fees vary for the treatment. According to Manevitz and Halper, the usual cost for TMS runs from $10,000-$11,000. ECT costs generally run higher, because the treatment requires a three-person team: a course of 12 ECTs comes to about $24,000, according to the Carrier Clinic in New Jersey.

Pills may be the most expensive of all, though, especially if someone has to take a combination of drugs for two years. According to Mark Bausinger, a vice president at Neuronetics, the insurance industry is slow to pick up the tab for TMS, but one by one they are coming on board as they come to appreciate the cost-effectiveness of TMS. This is often the case with new medical instrumentation.

Inexplicably, but not surprisingly, Medicare is divided on the issue. The New England district picks up the tab for a course of treatment. Other districts won’t pay a cent. Still others remunerate at such a miserly rate that few psychiatrists are willing to learn how to use TSM and invest in the apparatus.

The failure of Medicare to pay for TMS is yet one more burden on the elderly, who have an even higher prevalence of depression than younger people. With their multiple illnesses and failing memories, our senior citizens are often poor candidates for medication or ECT, but as Kanamori told me, old people tolerate TMS well.

Neuronetics has a special program for TMS patients that helps them to fill out insurance forms to receive remuneration from insurance carriers. Manevitz and Halper reported that, at least in their practice, 75 percent of patients receive some reimbursement from their insurance carriers after taking their case to appeal – but the remuneration often is not adequate, and depressed people may have a hard time coping with the complex appeals procedures of public and private carriers. It will be interesting to see how much – if anything – the Affordable Care Act allows for TMS.

At this point, Manevitz and Halper told me in our three-way phone conversation, major depression and chronic pain are two indications for which TMS therapy is well-supported by the evidence from clinical trials and psychiatric practice.

It is being looked at closely for other indications; some will hold up under the weight of rigorous clinical trials and others will turn out to be disappointing. But right now, hopes are high in the psychiatric community.