Integrating Deep Transcranial Magnetic Stimulation Into the OCD Treatment Algorithm

Apr 07, 2020

As our understanding of the neurobiology of OCD grows, additional treatment options become available and should be thoughtfully integrated into the treatment algorithm. One such option is dTMS.

NEUROPSYCHIATRY

In the US, OCD affects about 4 million people.1 Compared with schizophrenia, which is notoriously disabling, OCD causes similar degrees of serious impairment in social relationships and daily living, but we often do not consider OCD in this light because effective treatments are available. However, up to half of patients do not respond to first-line treatments and traditional pharmacological approaches are often associated with difficult adverse effects. In fact, even when patients do “respond,” it is rare to see true symptom remission.

Unlike depression studies, which often measure the percentage of “responders” and “remitters,” many OCD studies only measure “responders” and “partial responders.” For these reasons, it is essential to develop a more effective treatment algorithm that can help patients who do not respond to first-line options.

Current OCD treatment

OCD is characterized by uncontrollable, recurring thoughts or images (obsessions) accompanied by the urge to repeat specific behaviors (compulsions) to alleviate these intrusive thoughts. Effective treatments reduce symptoms and help patients cope with the anxiety surrounding these obsessions and compulsions. The American Psychiatric Association implemented an OCD treatment algorithm that designates a specific type of cognitive behavioral therapy (CBT)-exposure-response prevention (ERP)-and SSRIs as first-line treatments [PDF].

ERP involves patients working with their therapist to actively expose themselves in increasing degrees to the very things that elicit their fears. The process reduces anxiety surrounding the various triggers that induce the obsessive thoughts and compulsions. This form of CBT is effective in patients who complete a full course of treatment; however, some patients may have difficulty fully committing to the therapy as it can be extremely anxiety inducing. Ultimately, 45% of OCD patients either quit ERP because of the difficult treatment process or fail to respond to this treatment to a satisfactory degree.2 One option is to introduce a pharmacological treatment in parallel with ERP.

The first pharmacological option for patients with OCD is an SSRI. SSRIs are effective in about 50% to 70% of patients.3,4 However, because their effects are not localized only to OCD brain regions, they can have significant negative adverse effects in other parts of the body. Further exacerbating this issue is the fact that patients with OCD often require higher doses of SSRIs than those effective in treating depression. Research has shown that increasing the dose of  SSRIs in this manner can lead to increased adverse effects, which can often be severe enough that patients choose to stop their medications.5,6 Moreover, because we do not fully understand how SSRIs work in the brain to reduce OCD symptoms, we have not yet found methods for predicting who will respond to the treatment in any reliable, affordable, or clinically feasible way.

Options after first-line

After non-response to ERP and/or initial doses of SSRIs, psychiatrists have only a few validated options. Clinicians will often escalate the dose of SSRIs, try multiple different SSRIs, or switch to or add clomipramine, an older, but sometimes more effective SRI, but which unfortunately can often have more serious adverse effects. Next, atypical antipsychotics such as risperidone or aripiprazole are added to the patients’ treatment regimen. Again, the adverse effects associated with adding an antipsychotic are often worse than those associated with treatment with an SSRI alone. This process of escalating doses and testing different medications and combinations can often take several months to years.

When these options are exhausted, the next option in the treatment algorithm is surgical implantation of a deep brain stimulator (DBS) or a procedure known as a ventral capsulotomy, which creates a lesion in part of the brain implicated in OCD.7 While surgery has been proven effective in treatment-resistant patients, there are risks, costs, and complications associated with the procedures.8

Furthermore, brain surgery can be particularly anxiety-provoking for patients with severe OCD, and many are not willing to proceed with surgery. This leaves clinicians in a difficult position, and other non-invasive treatment options are needed. Fortunately, a non-invasive treatment was cleared by the FDA, offering psychiatrists another neurocircuitry-based tool with far fewer risks compared with surgical options.

dTMS as an option

The FDA approved deep transcranial magnetic stimulation (dTMS); dTMS works by directing electromagnetic fields that generate excitation or inhibition of neurons deep inside the brain. It is completely noninvasive and performed in an outpatient setting, with no need for hospital gowns or anesthesia. Patients receive stimulation through a helmet with a built-in
magnetic coil (Figure 1).

Treatment is well tolerated, usually with only mild discomfort due to sensations on the scalp sometimes described as feeling like a woodpecker tapping on the head; however, with increasing treatments, the scalp desensitizes to this sensation, and most patients report it to be less bothersome with each treatment.

Unlike SSRIs, this treatment is localized, more precisely targeting specific brain regions-the medial prefrontal cortex and the anterior cingulate cortex (Figure 2)-that play an essential role in regulating OCD symptoms.9 This localized specificity means that the rest of the body is spared adverse effects.

Clinical trial results show that daily dTMS treatment for a 6-week period results in a statistically significant 30% reduction in symptom severity as measured by the Yale-Brown Obsessive-Compulsive Scale.10 This magnitude of response is on par with responses seen in SSRI treatment; however, dTMS may achieve these results faster. Many SSRI studies demonstrate similar responses but only after 8 to 12 weeks.11

At the 10-week follow up, the response rate to dTMS increased further. This increase demonstrated a positive treatment effect over time, even once the stimulation had ceased. Overall, 38.1% of patients in the dTMS group showed a response, compared with 11.1% of patients in the sham treatment group.21 Adverse effects were limited; the most frequent adverse reaction was headache, which resolved shortly after treatment.

This clinical trial was especially unique, because prior to each treatment session, OCD symptoms were provoked in each patient. This provocation of symptoms was personalized, based on a fear hierarchy created between patients and their clinician before the start of treatment. For example, immediately before undergoing dTMS treatment, patients with obsessions related to contamination fears may have been presented with a dirty sponge to touch, or perhaps they brought triggering items from home.

This idea of provoking symptoms and activating trigger-specific circuity stems from earlier studies in posttraumatic stress disorder, addiction, and smoking cessation that have shown greater improvement in groups that had provocation protocols.12,13 The sham group also received the brief exposure or provocation protocol but did not see the same results.10

Integrating dTMS into clinical practice>

Integrating dTMS into clinical practice

Many patients who have experienced minimal relief from their symptoms with pharmacological treatment and/or therapy are able to function at a significantly higher level following dTMS treatment. This comes without adverse effects, and the benefits are sometimes quicker than pharmacologic approaches. These results are promising; however, it remains to be seen how this treatment is integrated into clinical practices more broadly: dTMS may not work in some patients and do wonders in others. We do not yet know how to predict patient response.

Patients who respond often describe feeling that they have more choice over their behaviors, that obsessions are more muted, and that they feel they can resist the compulsions more successfully. Patients who previously struggled to progress in ERP sometimes report feeling they are now able to make new progress or progress at a faster pace. This anecdotal evidence is exciting, especially to those who believe in ERP as the cornerstone of OCD treatment.

In a population that often struggles with treatment resistance, any additional treatment that is complementary to ERP and SSRIs without increasing the adverse effect burden and decreasing the quality of life is worth incorporating into the OCD treatment algorithm. It makes sense to place dTMS into the algorithm between pharmacological approaches and surgery (Figure 3).

Moving forward, after a specific time at which pharmacological and therapy approaches have failed to help patients to a sufficient degree, dTMS approaches should be considered and potentially integrated into the treatment plan. For particularly severe patients, it might even be considered sooner, in conjunction with both medications and therapy.

Are there downsides to TMS?

Deep TMS is quite safe, with minimal overall risk and few significant or persistent adverse effects. Risk of seizure is often discussed with patients. However, this is rare, with less than 1% of patients in depression studies from the past 10 years who experience seizures.14 In the trial that achieved FDA clearance for OCD, no patients had seizures.10

The biggest downside to TMS is that it is usually administered as a daily treatment, 5 days per week, for about 4 to 6 weeks. Treatment itself, depending on the parameters used, is only about 15 to 20 minutes. Without anesthesia and cognitive adverse effects, patients are often able to come in for treatment early in the morning, on a lunch break, or between classes. Nonetheless, it is a daily commitment. This could change in the future: data for accelerated TMS, which involves treating patients multiple times a day for fewer overall days, are showing that it may be similarly effective for
depression as traditional TMS.15

Conclusion

While OCD is considered treatable, not all patients respond to therapy or medication. Even when patients do respond, it is rare to see full remission of symptoms. Fortunately, new research is ongoing, and as there is more understanding of the neurobiology underlying OCD, additional treatment options become available and should be thoughtfully integrated into the treatment algorithm. One such option is dTMS.

As a noninvasive treatment with few adverse effects, dTMS may be a good option for patients who have not responded to first- or second-line therapies. Additional data are needed, but the potential of dTMS to enhance or augment other modalities is exciting. Similarly, as dTMS is integrated into clinical practice, clinicians will be better able to identify the variables in OCD that are more receptive to dTMS treatment and in which patients it will be most successful. It will be interesting to see how this option works in clinical practice and in the broader population outside of clinical trials.

A further point of note: this treatment offers greater possibility for collaboration between behavioral therapists and psychiatrists. Together we should brainstorm new protocols and study designs, utilizing dTMS to further enhance each of our own already validated treatments.

This article was originally posted on September 13, 2019, and has since been updated. -Ed

Disclosures:

Dr Vidrine is Assistant Clinical Professor, Department of Psychiatry, UCSF School of Medicine, and Director, OCD Program, TMS Health Solutions, San Francisco, CA. He reports that he is employed by TMS Health Solutons, an insurance-based, group psychiatric private practice that offers rTMS and dTMS as one of many various treatment modalities.

References:

1. Hollander E, Doernberg E, Shavitt R, et al. The cost and impact of compulsivity: a research perspective. Eur Neuropsychopharmacol. 2016;26:800-809. 2. Whittal ML, Thordarson DS, McLean PD. Treatment of obsessive–compulsive disorder: cognitive behavior therapy vs exposure and response prevention. Behav Res Ther. 2005;43:1559-1576.

3. Jenike MA. Obsessive-compulsive disorder. New Eng J Med. 2004;350:259-265.

4. Pallanti S, Hollander E, Bienstock C, et al. Treatment non-response in OCD: methodological issues and operational definitions. Int J Neuropsychopharmacol. 2002;5:181-191.

5. Bloch MH, McGuire J, Landeros-Weisenberger A, et al. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mole Psychiatry. 2010;15:850-855.

6. Pittenger C, Bloch MH. Pharmacological treatment of obsessive-compulsive disorder. Psychiatr Clin N Am. 2014;37:375-391.

7. Janardhan Reddy YC, Sundar AS, Narayanaswamy JC, Math SB. Clinical practice guidelines for obsessive- compulsive disorder. Indian J Psychiatry. 2017;59(Suppl 1):S74-S90.

8. Jung HH, Kim SJ, Roh D, et al. Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mole Psychiatry. 2015;20:1205-1211.

9. Dougherty DD, Brennan BP, Stewart SE, et al. Neuroscientifically informed formulation and treatment planning for patients with obsessive-compulsive disorder: a review. JAMA Psychiatry. 2018;75:1081-1087.

10. Tendler A, Zohar J, Carmi L, et al. Deep TMS of the medial prefrontal and anterior cingulate cortices for OCD: a double-blinded multi-center study. Biol Psychiatry. 2018;83(Supple 9):S113-S114.

11. Soomro GM, Altman DG, Rajagopal S, Browne MO. Selective serotonin reuptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder. Cochrane Database Syst Rev. 2008;1: CD001765.

12. Dinur-Klein L, Dannon P, Hadar A, et al. Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial. Biol Psychiatry. 2014;76:742-749.

13. Isserles M, Shalev AY, Roth Y, et al. Effectiveness of deep transcranial magnetic stimulation combined with a brief exposure procedure in post-traumatic stress disorder: a pilot study. Brain Stimul. 2013;6:377-383.

14. Perera T, George MS, Grammer G, et al. The clinical TMS society consensus review and treatment recommendations for TMS therapy for major depressive disorder. Brain Stimul. 2016;9:336–346.

15. Sonmez AI, Camsari DD, Nandakumar AL, et al. Accelerated TMS for depression: a systematic review and meta-analysis. Psychiatry Res. 2018;273:778-781.

16. Hirschtritt ME, Bloch MH, Mathews CA. Obsessive- compulsive disorder: advances in diagnosis and treatment. JAMA. 2017;317:1358-1367.

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