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Now, let’s look at an article on treatment of obsessive-compulsive disorder with deep TMS, transcranial magnetic stimulation. This is an article from the American Journal of Psychiatry in May 2019. If you’ve treated many people with OCD, you’ve likely experienced the frustration of not being able to help as much as you’d hoped when you began a treatment. According to this international team from Tel Aviv, San Diego, Toronto, Florida, and more, only 40% to 60% of patients with OCD get even a partial response from routine treatment. There’s a lot of partial response and nonresponse in the treatment of this illness. You might hope to hear that TMS produced a much better outcome than treatment as usual. It was better, but how much better? That may depend on how you think of “better.” Let’s take a look.
These 94 patients all had at least 1 serotonin reuptake inhibitor treatment before entering the study. Some of them also had exposure and response prevention psychotherapy. All of them had a Y-BOCS—the Yale-Brown Obsessive Compulsive Scale—over 20, which means at least moderate. We’ll get on more detail on what those scores mean in a minute. Deep TMS uses a different magnetic coil compared to regular TMS, one that’s been modeled to produce activation in deeper layers of the brain. What about regular TMS in the treatment of OCD? Well, a 2017 Dutch review concluded that the differences between TMS and placebo were often not statistically or clinically significant, and the effect frequently disappeared within weeks. Basically, they dismissed TMS. By contrast, the article I’m reviewing here from the American Journal of Psychiatry cites a 2016 meta-analysis of 15 randomized trials that found conventional TMS superior to sham treatment with an effect size of 0.45. So, we could say that the efficacy of conventional TMS is uncertain in the treatment of OCD, and what we’re doing here is comparing the idea of a different TMS coil that might better target the circuitry responsible for OCD.
Going back to the study in the American Journal of Psychiatry, in the design both for active and sham TMS, the subjects received a personalized OCD symptom provocation. So, they looked at what kinds of things were likely to do that and individualized this so that everybody was basically getting an exposure treatment at the beginning of each treatment session to “activate the pathological circuitry.” This is kind of a combination of exposure therapy plus TMS. Both sham and active got it. The result with deep TMS in multiple sessions is that even with these exposure exercises, the mean Y-BOCS reductions were 3 points for sham and around 6 points for deep TMS. In case you haven’t used the Y-BOCS lately, score ranges [of] 16 to 23 is moderate, 24 to 31 is severe, and 32 to 40 would be extreme. We’re looking at a 6-point reduction with deep TMS vs 3 with sham, which is pretty small.
But in a secondary outcome measure, the investigators found a big difference in the number of patients who got a full response. Here, full response means a 30% reduction in the Y-BOCS. It’s not remission. That means, let’s say symptoms were extreme before the study, like in the 32 to 40 range on the Y-BOCS, that means a 30% reduction will get you down to 22 to 28. You’re still in the severe range. If you started in severe as opposed to extreme, a 30% reduction will get you down to 17 to 21. That’s still moderate OCD. Even this full response they’re defining, which did show that more people got into that range than did with sham, is still not particularly impressive in terms of what we might hope for clinically.
Before we wrap up here, what about adverse effects? The sham in this study included a superficial electrical current; so, the blinding was pretty good. It’s wasn’t perfect per their after-study assessment. Headache was the main side effect, and 35% of the sham-treated subjects got it vs 37% of the active treatment. There was pretty good blinding in terms of at least the incidence of that common side effect. No other study-related major problems were described.
So, is it worth seeking deep TMS for treatment-resistant OCD? Where can you get deep TMS? Which leads to the usual questions: Who makes this device, and was this study supported by that company? The answer is the company did support the study. There weren’t company employees involved in this study, nor was there editorial support. But when I looked on the internet about where can you find deep TMS, everybody’s using that company’s coil, and it’s a small number of clinics that offer it.
In conclusion, deep TMS is better than sham for OCD. In this 1 study so far, compared with like 17 randomized trials for regular TMS, maybe there’s an advantage here over the old method. We will have to wait for some replications and ideally a head-to-head comparison with conventional TMS. Meanwhile, since exposure and response prevention has demonstrated efficacy and is much more widely available (although not ubiquitous), ERP should be sought out first before deep TMS if it’s not already underway for your patients with OCD.
Abstract
Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial
Lior Carmi, Aron Tendler, Alexander Bystritsky, Eric Hollander, Daniel M Blumberger, Jeff Daskalakis, Herbert Ward, Kyle Lapidus, Wayne Goodman, Leah Casuto, David Feifel, Noam Barnea-Ygael, Yiftach Roth, Abraham Zangen, Joseph Zohar
Objective: Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study.
Methods: At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of ≥30% in YBOCS score) at the posttreatment assessment and after another month of follow-up.
Results: Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up.
Conclusions: High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions.
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Reference
Carmi, L., Tendler, A., Bystritsky, A., Hollander, E., Blumberger, D. M., Daskalakis, J., Ward, H., Lapidus, K., Goodman, W., Casuto, L., Feifel, D., Barnea-Ygael, N., Roth, Y., Zangen, A., & Zohar, J. (2019). Efficacy and safety of deep Transcranial magnetic stimulation for obsessive-compulsive disorder: A prospective multicenter randomized double-blind placebo-controlled trial. American Journal of Psychiatry, 176(11), 931-938
