by Joan A. Camprodon-Gimenez
Joan A. Camprodon-Gimenez, MD, MPH, PhD, is the director of the Transcranial Magnetic Stimulation (TMS) clinical service; director of the Laboratory for Neuropsychiatry and Neuromodulation; and the director of Translational Research in the Department of Psychiatry at Massachusetts General Hospital, Harvard Medical School in Boston, MA.
This article was initially published in the Fall 2015 edition of the OCD Newsletter.
“I’ve tried several different kinds of medication. Nothing helps.”
We regularly receive inquiries about Transcranial Magnetic Stimulation (TMS), Deep Brain Stimulation, and other newer treatments to help those individuals who have not responded to medication or cognitive behavioral therapy (CBT). A lot of research in the past few decades has been conducted to better understand what exactly isn’t working right in the brains of individuals with OCD. One approach has been to target brain chemistry. The thinking is that OCD symptoms result from an imbalance in brain chemicals (or neurotransmitters), which medications such as SRIs can address. And for many individuals, adjusting the brain’s chemistry has been successful in significantly reducing OCD symptoms. But for some, adjusting the brain’s chemistry with medication has not worked (or has not worked all that well).
Recently, psychiatric research has become increasingly focused on the idea that the structure and function of the brain’s “neural networks” might play a part in OCD. Consider your brain from this perspective. Your brain is made up of cells called “neurons” which communicate with each other. When several neurons work together, they are referred to as a circuit or network. If you’ve ever taken apart a computer or other electronic device, you’ve likely seen a green plastic board covered in gold circuits. Much in the way electricity travels through this circuit board to convey information from one part of the computer to another, your brain uses neural networks to convey information from one part of the brain to the other.
So, instead of targeting neurotransmitters (the chemicals used to communicate between individual neurons) researchers are now looking at how neural networks function to communicate from the parts of the brain that regulate, say, emotions to the part of the brain that regulates movement. It is our hope that new treatment methods that focus on neural networks, rather than neurotransmitters, may offer help to those individuals who have not had success with other treatment methods.
-Jeff Szymanski, PhD, Executive Director of the IOCDF
Welcome to the “circuit revolution.” Revolution is a strong word, but this new trend in psychiatric research focused on neural circuits and networks has the power to change how we think about and treat OCD by providing a framework for the development of new treatments such as Brain Stimulation therapies.1 The focus of this article is to review the evidence to date about the effectiveness of one of these therapies, Transcranial Magnetic Stimulation (TMS).
Brain Stimulation therapies are also called Neuromodulation, Somatic Therapies, or Psychiatric Neurotherapeutics. All of these labels refer to a group of treatments that use devices (rather than medication or psychotherapy) capable of changing electrical activity in a targeted area of the brain and changing the flow of information through those networks. The goal of these electrical and biological changes is to alter the way the brain is functioning; to change patterns in the brain that are leading to disease, and instead, force these circuits to operate in a healthy state that allows for better functioning and well-being.
Neuromodulation therapies fall into three general groups. The first group is referred to as “invasive” because it requires surgery to put electrodes directly into the brain. Deep Brain Stimulation (DBS) or Vagal Nerve Stimulation (VNS) are examples. DBS is used for disorders such as Parkinson’s disease and OCD,1 while VNS is used for epilepsy and depression. The second group is called “convulsive,” with Electroconvulsive Therapy or ECT being the most relevant example. This strategy does not require surgery, but patients still need to be put under general anesthesia. The goal of ECT is to send strong electrical currents through the skull capable of inducing a controlled seizure under general anesthesia and with the supervision of a team of physicians and nurses in an environment similar to an operating room. This seizure is capable of rewiring the brain, and for some individuals, is an effective treatment for depression, mania, and psychotic disorders (such as schizophrenia). Finally, “noninvasive” strategies like Transcranial Magnetic Stimulation (TMS) can change brain activity without the need for surgery or inducing seizures. This technique involves applying electromagnetic currents on the skull and directing them to specific brain regions.
In a typical TMS session, patients are awake and sit in a comfortable treatment chair, while the operator places a coil measuring about 5×2 inches over a given region of the head. Then, electromagnetic pulses are applied that travel through hair, skin, muscle, and bone until they reach the brain. When magnetic pulses reach the targeted brain region, they turn into electricity and force neurons (brain cells) to fire, which then affects the interconnected brain networks. The amount of stimulation and target of stimulation is always specific for each patient according to an initial assessment of the person’s brain “excitability.” A typical TMS session lasts from 20 to 40 minutes (although newer protocols lasting one to six minutes have recently been shown to be effective), and most treatments require daily sessions Monday to Friday for a few weeks (the current standard for depression is 6 weeks, then treatments decrease in frequency for a two or three week-period afterward). Because there aren’t any side effects, TMS is a treatment where patients travel to the clinic on their own, receive the treatment, and then continue with regular daily activities.
TMS is painless and non-invasive and has been shown to be safe and very well tolerated by patients.2 Since its development in the mid 1980s3, TMS has become widely used for neuroscience research and clinical applications. In 2008 the FDA approved the use of TMS for the treatment of depression, 4, 5 and in 2013, approved the use of “deep TMS” (using as device called TMS H-coils) also for depression.6 In 2015, two additional devices have also been cleared by the FDA for use in treating depression.
A series of studies have recently been done to determine how safe and effective TMS might be as a treatment for patients with obsessive compulsive disorder (OCD). These studies have focused on three different TMS approaches, each of which will be discussed below. The focus of the rest of this article is to review the effectiveness of TMS as a promising new treatment for OCD.
TMS Strategy #1: Target the Dorsolateral Prefrontal Cortex
The Dorsolateral Prefrontal Cortex (DLPFC) is a region located in the lateral surface of the frontal lobes (the front part of the brain that controls important cognitive skills). This is also the TMS target the FDA has approved for the treatment of depression. The first study to explore the use of TMS for OCD examined how effective one single session of repetitive TMS targeting the DLPFC would be for 12 patients. The researchers found a noticeable reduction in compulsions, but not obsessions, that lasted up to 8 hours, and patients showed an improvement in mood as well. While these results were promising, a number of smaller studies followed using repeated TMS treatment sessions over the course of one or two weeks, but showed little to no benefit. However, these studies were conducted early in the development of TMS, and we know now the treatment strategies used then were too weak to have an effect (for example, early studies used one or two weeks instead of six weeks of treatment, or TMS intensities of 80% as opposed to 120%). It is therefore not surprising that they were unable to observe benefit. Two recent studies have reported improvement in OCD symptoms using newer TMS techniques targeting the DLPFC. Bottom line: while the DLPFC may not be the most promising target for OCD, it has still not been tested sufficiently and it may be too early to say that it doesn’t work.
TMS Strategy #2: Target the Orbitofrontal cortex (OFC)
The part of the brain called the Orbitofrontal cortex or OFC has consistently been identified as one of the primary regions affected by OCD, generally showing significant overactivity. Three studies targeting the OFC with TMS found positive results. The first study used a standard TMS coil. A later study used a different coil with a bent shape that reaches deeper structures because the OFC is deep in the brain and the penetration of standard TMS is relatively superficial. All three studies showed improvements in OCD symptoms, although benefits lasted only a month.
Similar to the examples with DLPFC though, studies of TMS to the OFC for OCD only used 1–3 weeks of treatment, which is not enough. We know from research on the treatment of depression with TMS that it generally requires 6 weeks of treatment to be fully effective. In addition, treatment of OCD generally requires higher doses with a longer duration than treatment of depression. Future studies should assess the effectiveness of longer treatments targeting the OFC.
The other important findings from these studies, however, is that in addition to looking at whether patients improved, researchers also used neuroimaging (technology that takes pictures of the brain) to understand how TMS affects the OFC. Specifically, they used neuroimaging scans that measure how much energy brain regions are using. Information gathered from the scans showed changes in brain activity in the OFC (on the right side in particular) as patients improved in their symptoms. This knowledge may lead to future therapeutic advances.
TMS Strategy #3: Target Pre-Supplementary Motor Area (pre-SMA)
Studies targeting an area of the brain called the “pre-Supplementary Motor Area” or pre-SMA with TMS have so far shown the best outcomes for OCD. This area of the brain, like the OFC, has been observed to be consistently overactive in patients with OCD.
The first studies targeting the pre-SMA examined the use of TMS for patients with OCD and Tourette’s syndrome. At the end of treatment, patients showed general reduction in OCD symptoms in addition to improvement in functioning, as well as reductions in depression and anxiety. Importantly, the improvements held for at least three months. This study was followed by a second study with 21 OCD patients and a more careful study design. At end of four weeks of TMS treatment, patients showed notable decreases in OCD symptoms in addition to depression and anxiety, and again, three months later, benefits were still present for most patients.
Although TMS targeting the pre-SMA has been shown to be the most effective so far, it isn’t clear whether this is indeed the only or best area of the brain to target because pre-SMA studies are the only ones thus far that use doses and treatment protocols similar to the standard of care for depression. That said, these positive results are very encouraging and are helping us move forward.
While a significant number of patients with OCD respond to traditional treatments, including medication, cognitive behavioral therapy, or a combination of both, many still remain symptomatic with very minimal benefit and are therefore considered “treatment-resistant.” For these patients, we must continue to develop new treatments capable of reducing symptoms and increasing well-being. Research has shown that noninvasive neuromodulation like TMS is a safe and well-tolerated treatment option appropriate for many patients with varying degrees of severity and treatment resistance with no significant negative side effects when used appropriately.
In addition, research shows that TMS strategies that suppress (not increase) the activity of the overactive OFC or pre-SMA seem to be effective treatments for OCD. This benefit is especially apparent when one looks and quantifies the results from all TMS OCD studies together as a group.7 While these results are promising, more research using larger samples and higher doses of TMS is still needed. Of note: early results of TMS for depression research were mixed and also used lower doses of TMS. Later depression studies used higher (yet still very safe) doses of TMS, leading to greater, more consistent, and longer-lasting benefits. More research is certainly needed to determine the best “dose” of TMS for OCD and to identify the most effective brain targets. Importantly, we are at a point when we can start developing strategies to choose the optimal brain region and TMS treatment parameters for each patient on an individual basis.
While TMS for OCD is in the early stages of development, it holds great promise for patients and families, and we are certain to see an increasing number of studies published in the next years.
- Cusin C, Dougherty DD. Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS. Biol Mood Anxiety Disord. 2012;2(1):14.
- Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009;120(12):2008-39.
- Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet. 1985;1(8437):1106-7.
- O’Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007;62(11):1208-16.
- Carpenter LL, Janicak PG, Aaronson ST, Boyadjis T, Brock DG, Cook IA, et al. Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and anxiety. 2012;29(7):587-96.
- Levkovitz Y, Isserles M, Padberg F, Lisanby SH, Bystritsky A, Xia G, et al. Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World Psychiatry. 2015;14(1):64-73.
- Berlim MT, Neufeld NH, Van den Eynde F. Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials. Journal of psychiatric research. 2013;47(8):999-1006.