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The 2022 APA Annual Meeting highlights the latest guidelines for these treatments, plus recommendations for updates and improvements.
“We have clinical guidelines for the treatment of some disorders, and we have clinical guidelines that motivate the way we use certain treatments. But, for new and emerging treatments, we often don’t have guidelines on how best to use them, who to recommend for a particular intervention, and who not to do so,” said Eric Achtyes, MD, MS, in a presentation at the 2022 American Psychiatric Association (APA) Annual Meeting.
The presentation, chaired by Achtyes—a staff psychiatrist and researcher at Michigan State University with appointments at Pine Rest Christian Mental Health Services, Cherry Street Health Services, and Network180—focused on assessing current gaps and opportunities in the guidelines for electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS).
Although ECT has been used in the treatment of severe mental and medical conditions for more than 80 years, it is one of the few medical procedures that is regulated by state laws not based on medical guidelines, according to Georgios Petrides, MD, associate professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. “These laws are not based on medical guidelines—they’re mostly based on politics,” Petrides said. “Powerful antipsychiatry groups target ECT nationwide.” Today, 44 US states have specific ECT regulations, 21 states have specific regulations for ECT in minors, and 9 states mandate ECT reporting.
Petrides explained that, in 1975, the US Food and Drug Administration (FDA) gave ECT class III classification—for “unknown efficacy and risk”—with cleared indications for use in the treatment of unipolar and bipolar depression, schizophrenia, bipolar mania and mixed states, schizoaffective disorder, schizophreniform disorder, and catatonia. Although the FDA’s original aim was to reevaluate ECT and reclassify it as class II (“known efficacy”), reevaluation did not occur until 2018. In response to some scandals in the 2000s, the FDA reclassified ECT class II in 2018, but only for the treatment of severe depressive episodes and catatonia.
“This means that, according to the FDA, there is evidence of efficacy, but only for depression and catatonia,” Petrides said. “The rationale for these restrictions is a lack of double-blind, placebo-controlled trials in the other diagnoses. Scientific literature and the global clinical experience of more than 80 years has been completely disregarded.”
The ramifications of these restrictions are that treatment will remain off-label for a significant number of patients, and there is a need for investigational device exemption for research in diagnoses other than depression and catatonia. However, these restrictions have also drawn attention to informed consent processes, documentation, and database creation, presenting opportunities to reduce/eliminate the stigma associated with ECT; conduct efficacy and outcomes research in disorders considered “unproven”; and create comprehensive databases.
The most recent consensus guidelines for rTMS were developed by the APA Council on Research Task Force and the National Network of Depression Centers (NNDC) rTMS Task Force in 2018, according to Tracy Barbour, MD.
“These guidelines were based on literature published from 1990 to 2016. Given that TMS is a rapidly evolving field, and we have a lot of research in this field, these guidelines likely have some updating that needs to occur,” said Barbour, who is medical director of Massachusetts General Hospital, instructor at Harvard Medical School, and program director of the Interventional Neuropsychiatry and Neuromodulation Fellowship. These guidelines focus on rTMS as a treatment for patients with major depressive disorder (MDD), including patients who are medication-resistant and those who have significant comorbid anxiety. “Patients with significant comorbid psychotic disorders or acute suicidal ideation should consider other antidepressant treatments with established efficacy, such as ECT,” Barbour said.
Barbour discussed the 2018 consensus guideline recommendations for location and frequency, coil positioning, pulsing, motor threshold determination, treatment planning, and number of sessions, comparing the recommendations for each area to findings from more recent research. In regard to location and frequency, for example, most evidence supports high-frequency stimulation (10Hz) to the left DLPFC; however, there is also evidence that using the H1 coil is effective for bilateral PFC stimulation, and that right DLPFC low-frequency stimulation is also safe and effective for patients who are at risk of seizure, or who do not tolerate/respond to high-frequency left DLPFC stimulation. More recent studies have shown that theta burst stimulation (iTBS) can be applied for a shorter period of time, allow for more sessions per day, and have longer-lasting physiological and cognitive effects compared to high-frequency alternatives.
In 1 study, “the FDA-cleared protocol took 27 minutes, compared to iTBS, which took only 3 minutes,” Barbour said. “I think updated guidelines would definitely comment on iTBS.” And, when compared to a new type of rTMS called Stanford neuromodulation therapy (SNT), the FDA-cleared iTBS protocol involves 1 session per day for 36 days at 600 pulses iTBS per session, versus the SNT protocol of 10 sessions per day, with 50-minute intersession intervals for 5 days, at 1800 pulses iTBS per session. “If patients can get better that quickly and it has the efficacy,” Barbour said, “I think it is something to be excited about.”
Because DBS is not yet FDA-approved, it remains a thoroughly investigational, off-label treatment, and there are no official guidelines for its usage, according to Alik Widge, MD, PhD, assistant professor in the University of Minnesota Department of Psychiatry. However, some research has suggested its efficacy for the treatment of depression. “Open-label data showed an average of 50% loss of depressive symptom burden and then retention—back in 2009,” Widge said. “So, why is DBS still not FDA-approved and available at an academic medical center near you? Because we’ve had a devil of a time getting it through randomized clinical trials.” Widge explained that, because depression is heterogenous—and doubly so in patients who are treatment-resistant—this leads to difficulty passing the randomized controlled trials necessary for FDA approval.
Because there are some promising recent and ongoing clinical trials on the efficacy of DBS, Widge recommended that clinicians connect their patients who may be good candidates with clinical trials so those patients can receive advanced care while also helping develop the necessary data for FDA approval. A good candidate typically is at least 30 years old; has had multiple either bipolar or unilateral depressive episodes that are severe/disabling; has responded to treatment in prior episodes but experiences consistent/faster relapse; is resistant to evidence-based, guideline-adherent therapies; and is able to handle the burden of participating in a clinical trial. Widge also made some recommendations for how to get these patients involved, when and how to screen trials and their investigators, and how to warn patients of the study burden.
Widge emphasized that managing patients with DBS would not be an added burden on clinicians, as the device does not cause any cognitive impairment or prevent any specific medications and is stable for years once it is programmed. “A patient with a neurostimulator is just like anybody else who’s in your office for regular management, except they now tend to be more responsive to other interventions,” Widge said.
Achtyes closed the presentation by discussing some national surveys gauging perceptions and opinions of these treatment modalities and the most important ethical considerations relating to them. Among the 505 participating psychiatrists who have referred or administered these interventions to patients within the past 5 years, the top 3 most important ethical considerations when developing practical guidelines for these treatments were (1) providing evidence of the safety and efficacy of the interventions (nearly 50%); (2) selecting patients who would be good candidates for the interventions (20%); and (3) having a standard accreditation system to assure and improve the quality of administration of the interventions (around 12%).
The presentation was organized by Laura Y. Cabrera, PhD, associate professor of engineering science and mechanics and philosophy, and Dorothy Foehr Huck and J. Lloyd Huck Career Chair in Neuroethics at Penn State University.