New developments in interventional psychiatry: What primary care providers should know

In early September, the FDA granted Breakthrough Device Designation and cleared the SAINT Neuromodulation System for treatment-resistant depression, or TRD.

The SAINT system combines accelerated transcranial magnetic stimulation (TMS) treatment — the use of focal electromagnetic pulses to the brain — with a specific functional MRI navigation system. This approval, granted in response to a highly successful randomized sham-controlled trial, was a watershed in psychiatry. SAINT represented a rapid, safe and remarkably well-tolerated treatment for TRD, with a response rate potentially similar to electroconvulsive therapy (ECT), until now the most reliably effective treatment for severe depression.

SAINT treatment is not yet accessible to the larger public, and many questions remain about both its effectiveness and cost in real-world clinical settings. However, it’s recognition by the FDA has drawn attention to the larger field of interventional psychiatry and its growing role in the treatment of major depressive disorder and other mental health conditions. The use of interventional psychiatry approaches, particularly transcranial magnetic stimulation, intranasal esketamine and IV ketamine, have been expanding greatly in recent years, yet knowledge and utilization of these interventions by primary care providers remains low.

Nicholas T. Weiss

TRD is generally understood as a major depressive episode that fails to respond adequately to at least two trials of antidepressant medication. This definition is meaningful. If a patient has failed to respond to trials of two different antidepressant medications at adequate dose and duration, the likelihood of responding to a third antidepressant medication trial is only 14%. Although most commonly associated with major depressive disorder, TRD can also occur in the context of bipolar disorder. Whether in major depressive disorder or bipolar disorder, studies show that at least 30% of individuals with depression have TRD. Most are treated in the primary care setting, as access to specialized psychiatric care remains limited in the United States. TRD is highly impairing and chronic.

There are currently five interventional treatments for TRD that have at least some form of FDA recognition: ECT, TMS, nasal esketamine, vagus nerve stimulation and deep brain stimulation. In addition, IV ketamine, while not FDA approved as a treatment for depression, has accumulated an increasingly large evidence base. All of these interventions have substantial data supporting their superiority to traditional antidepressant medication trials in TRD. ECT is likely the most reliably effective treatment for TRD, though the evidence of efficacy for TMS and esketamine are also robust, and these latter two treatments are far more accessible and acceptable to most patients compared to ECT.

Until recently, TMS and nasal esketamine were difficult to access because there were relatively few centers offering the procedures and many did not accept insurance. This has changed rapidly as treatment centers expand throughout the U.S. and insurance payers have clarified their prior authorization requirements. These treatments are now covered by all major payers, including Medicare and Medicaid. Given this, one could now argue that all patients with TRD should be referred for consideration of an interventional psychiatry approach, and that it has become a minimum standard of care.

So what should every primary care provider know about these interventions? Each of these interventions has its own profile of strengths and weaknesses. TMS, for instance, has an excellent response rate and safety profile. It is a simple outpatient procedure that requires minimal preparation and causes no cognitive impairment or sedation. Patients can resume all typical activities immediately after a treatment session, including driving. The only absolute contraindications to TMS are relatively uncommon: the presence of ferromagnetic metals and implantable devices in the head of the patient. Among those who respond to TMS, the response is often very durable, with 50% maintaining that response for at least 1 year. The major disadvantage of TMS is that it typically requires multiple consecutive weeks of daily treatment in order to be most effective. Though each daily treatment may take less than 15 minutes, the daily schedule remains challenging for many patients, particularly if they need to travel long distances to a treatment center.

Nasal esketamine, on the other hand, typically requires just twice weekly treatment for the first month and then just once weekly treatment for the following month. When effective, the response is typically much faster than TMS and may rapidly reduce suicidal ideation, which is common in this population. But treatment sessions are lengthy — at least 2 hours each — and the overall response rate compared to TMS is lower. Also, patients cannot do typical activities immediately following appointments because of the lingering sedating effects of the medication, and the benefits of treatment typically fade quickly after a course is completed.

ECT, while highly effective, is perhaps the most underutilized of all the interventional approaches. It does require general anesthesia, which carries an inherent degree of risk. But as protocols have evolved, it has become far safer and better tolerated than ever before. Lasting cognitive side-effects are now rare, and cognition often improves in those patients who had already been experiencing cognitive symptoms from the depression itself. Nonetheless, the stigma still associated with the procedure and the fear many have of a deliberately induced seizure makes many patients reluctant to consider this intervention, even if they have failed all other typical interventions.

Vagus nerve stimulation and deep brain stimulation remain the province of highly specialized services primarily organized as research programs, though hopefully will become more accessible over time.

Primary care providers who become knowledgeable about these interventions have a tremendous opportunity, an opportunity to improve the lives of the many patients in their care suffering from TRD who will otherwise go on to round after round of ineffective antidepressant medication trials.

References:

• Daly EJ, et al. JAMA Psychiatry. 2019;doi:10.1001/jamapsychiatry.2019.1189.
• Dunner DL, et al. J Clin Psychiatry. 2014;doi:10.4088/JCP.13m08977.
• Li H, et al. J Affect Disord. 2021;doi:10.1016/j.jad.2021.03.019.
• Magnus Medical receives FDA clearance for the SAINT Neuromodulation System for non-invasive, individualized and precise treatment of depression. https://www.magnusmed.com/press-releases/magnus-medical-receives-fda-clearance-for-the-saint-neuromodulation-system/. Accessed Dec. 1, 2022.
• Zhdanava M, et al. J Clin Psychiatry. 2021;doi:10.4088/JCP.20m13699.