October 2012 | Sarah Hollingsworth Lisanby
Dr. Lisanby: ECT is alive and well. It is still the most effective psychiatric treatment that we have for medication-resistant major depression. Utilization figures are hard to track because it is not centrally reported in the United States, but my impression is that use remains steady. The number of psychiatrists doing ECT has been fairly constant. In another way, despite the periodic availability of novel antidepressant medications and, in more recent years, novel devices, the utilization of ECT remains robust because it continues to fill a need that is not being filled by other available treatments.
Is that also reflected in insurance coverage? Is it as likely to be covered today as it was 10 or 20 years ago?
Dr. Lisanby: Yes, and I believe that is because of its efficacy. Insurers look at healthcare utilization and efficacy when they are making those decisions, and ECT is helpful in shortening length of stay and in achieving remission and preventing relapse; these are things that are important both for patient outcomes, and, from the payers’ perspective, controlling health care costs. Private and public payers have consistently been covering ECT because it is not only effectively clinically but cost-effective.
What about changes in the field and how ECT is being used differently?
Dr. Lisanby: ECT is not one-size-fits-all. There are different choices in dosing, electrode placement, and the parameters of the electrical stimulus. So taking those in order:
• Individualizing the dosage is important for ensuring the efficacy and also the safety of ECT. In the early days of ECT, it was a maximal dose, enough to get a seizure. Later, other methods were introduced, like basing the dose on the age of the patient, and then more recent innovations to titrate the dosage for each patient. Several strategies exist for individualizing the dosage, which often results in better outcomes.
• Electrode placement is critical for cognitive safety. Amnesia is the major side effect that dissuades people from getting ECT and dissuades clinicians from referring patients for ECT. Options in electrode placement like unilateral and bifrontal (compared to the standard, which is bilateral) provide opportunities to lower the cognitive risk of the treatment, so that patients can get effective treatment with a lower risk of amnesia.
• Alteration in the stimulus parameters, specifically ultra-brief pulse ECT, which refers to the length of each pulse. With standard pulse ECT, the electrical pulse lasts 1 to 2 milliseconds. With ultra-brief pulse ECT, it is about a quarter of a millisecond. Ultra-brief unilateral ECT, when it is personalized to the individual seizure threshold (combining all three of those innovations), has dramatically improved cognitive outcomes so that we can effectively use ECT with a substantially lowered risk of memory loss. As the use of this form of ECT increases, the overall utilization of ECT should begin to climb because this ameliorates a significant barrier to utilization.
Dr. Lisanby: We divide the course of ECT into different phases. The acute phase—during which we are giving three times a week treatment—ideally ends when the patient achieves remission. We recommend measurement-based care using a rating scale like the Hamilton Depression Rating Scale or Montgomery Asberg Depression Rating Scale. And we use the standard format to really get a full sense of how the patient is doing, including sleep, appetite, and neurovegetative symptoms. A remission is essentially an absence of symptoms, not just a 50% drop in the rating scale score. We advocate treating until remission because when you stop early the chance of relapse is higher. A recommended practice for the acute phase of ECT is three treatments a week until remission. After that, we want to prevent relapse. A course of ECT for the purpose of preventing relapse may involve two treatments per week, then one per week for a couple of weeks, while adjusting antidepressant medication and a mood stabilizer. Another approach is to transition to a maintenance course of ECT, where you space out the treatments once a week and then once every other week, every three weeks, and so on. Maintenance courses can last six months or more.
What happens after a course of ECT?
Dr. Lisanby: Although ECT remains most effective in acute treatment, the problem is we stop it as soon as it works. When you stop ECT once you achieve remission, the chance of relapse is 80% within six months if the patient receives no treatment afterwards. The standard relapse-prevention strategies have been combination pharmacotherapy, which is an antidepressant medication plus lithium, or maintenance ECT. Recent results of the consortium for research on ECT (CORE) found that regardless of which of those strategies you use, 50% of patients will still relapse within six months. I am a coprinciple investigator on an NIMH-sponsored study called PRIDE (Prolonging Remission in Depressed Elders). The study is a multicenter trial in the geriatric population. We are systematically evaluating whether maintenance ECT can provide additional benefit to combination pharmacotherapy, but with an attempt to titrate the frequency of ECT treatments based on the symptoms of the patient. It is called a System-Titrated Algorithm-Based Longitudinal ECT, or STABLE. We hope to personalize the maintenance schedule based on clinical need, while also preventing the overtreatment of patients in remission.
What other seizure-based treatments are on the horizon?
Dr. Lisanby: We are doing research in other groups on reducing the amplitude or how much amperage is actually being given in ECT. When you lower the amperage, this makes the seizure more focal. We also have an NIMH R01 grant for the rational design of electrical and magnetic seizure therapies, evaluating these innovations in a preclinical model and also a computational model prior to human use. Another experimental approach is using magnetic fields to induce seizures, which leads in to the area of transcranial magnetic stimulation (TMS). The form of TMS that is FDA-approved today is subconvulsive, or below the level for inducing seizures. However, magnetic stimulation can be used to induce seizures, and that is called magnetic seizure therapy. Magnetic fields pass through the scalp and skull without impedance, giving you better control over the site of stimulation. This makes it easier to localize the treatment, and opens the door to inducing focal seizures on just the parts of the brain that are important for effective antidepressant response. It has been developed in preclinical models and also clinical trials and international clinical trials but is not FDA approved.
How effective is subconvulsive TMS?
Dr. Lisanby: If you look at individual trials or metaanalyses, what we can say about efficacy is related to a very small subset of a very large terrain of possible doses, and we have only scratched the surface of how to optimize the efficacy of these devices. That is where I feel preclinical studies play a very important role, because we can rapidly and systematically examine this multifactorial dosage space to improve efficacy. There are many avenues to potentially enhance the potency of TMS that are currently being explored. With the present FDA-approved dosage, TMS has a modest effect, but that is the effect of 10 Hz given at 120% above the motor threshold to the left prefrontal cortex for three to six weeks of daily treatments. Other options to investigate include increasing the number of pulses per day, giving bilateral treatment, changing treatment location, or individualizing it based on an MRI scan.
The idea of doing office-based TMS or investing in some of these devices is pretty daunting. Is it a worthwhile investment for a practicing psychiatrist?
Dr. Lisanby: As with any technology, the costs come down over time and we have already seen that to some degree in new models. When I started working in the field of TMS, physicians administered every treatment. Now with increased knowledge about the safety of the protocols and ways to establish reliability in the training and supervision of the operators, more programs are using allied health professionals or others to do the treatment under supervision. That certainly brings down costs. TMS has some benefits over ECT. The costs of ECT are significant. You have the anesthesia; in some cases an inpatient admission—though increasingly it is done on an outpatient basis. ECT has remained robust and strong because it works. The future of TMS is going to hinge on its efficacy.
Do you think the narrowing pipeline of psychiatric drugs might open the space for greater use and acceptance of devices to treat depression and other conditions?
Dr. Lisanby: It may. These are orthogonal approaches. As we are seeking to discover novel effective treatments for depression and other conditions we have to look beyond the synapse. Brain stimulation is definitely beyond the synapse. It is a fundamentally different way of delivering therapy. The treatments of the future are probably going to combine pharmacotherapy with device-based interventions in intelligent ways—not just putting together two things that seem to work and seeing if they are additive, but rather looking for the synergistic interactions between stimulating neurons and then using pharmacotherapy to augment what happens after that. Using those two together may ultimately be the most effective.