PCORI Biweekly COVID-19 Scan: Low-Dose Naltrexone, Treatment-Resistant Depression (October 13-26, 2022)

ECRI Horizon Scanning has selected the topics below as those with potential for impact relative to COVID-19 in the United States within the next 12 months. All views presented are preliminary and based on readily available information at the time of writing.

Because these topics are rapidly developing, we cannot guarantee the accuracy of this information after the date listed on this publication. In addition, all views expressed in the commentary section are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders. Topics are listed in alphabetical order.

Description

Naltrexone is an opioid receptor antagonist approved by the FDA to treat alcohol and opioid use disorders. It is currently being investigated at a low dose to treat post-COVID conditions (PCC).

PCC encompass a broad range of new and worsening symptoms, including fatigue, headaches, difficulty concentrating, joint and muscle pain, and breathing problems that might persist for months after SARS-CoV-2 infection.

Low-dose naltrexone (doses below 5.0 mg), used off-label, has shown promise in pilot studies for treating PCC. It has also demonstrated efficacy in regulating immune function and reducing pain and inflammation in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia, which share prevalent features of, and might be related to PCC.

Based on these data, two phase 2 studies of low-dose naltrexone are ongoing to treat PCC (AgelessRx, Ann Arbor, Michigan) and postviral fatigue syndrome associated with PCC (University of British Columbia, Vancouver, Canada), with primary completion dates before the end of the year. Additionally, according to trial advisors, naltrexone is on the short list of treatments to be investigated as part of the National Institute of Health’s RECOVER initiative.

The cost of naltrexone to treat substance use disorders varies from $25 to $60 per month. However, because the FDA has not approved low-dose naltrexone for any condition it is only available from compounding pharmacies.

Commentary

Roughly 1 in 3 adults treated for COVID-19 experience PCC, and effective treatments are needed to improve outcomes of this large patient population. Repurposing drugs approved for other indications, like naltrexone, might speed this process.

Early feedback from ECRI internal stakeholders suggests that naltrexone might reduce common PCC symptoms, including fatigue, malaise, and pain. This might improve a patient’s overall health and quality of life. If effective, naltrexone might reduce the need for pain medication, including over-the-counter pain relievers and opioid medications. Side effects of the low-dose formulation are likely to be negligible. However, its use might be contraindicated for patients taking opioid medications.

Due to its low cost, naltrexone might reduce disparities in access to health. However, the low-dose formulation is currently only available from compounding pharmacies. Additional data are needed to determine whether naltrexone might meaningfully improve PCC symptoms, particularly over longer time periods.

• Category: Treatment
• Areas of potential impact: Patient outcomes, health care disparities, health care costs

Description

The SAINT neuromodulation system developed by Stanford University (Stanford, California) and Magnus Medical, Inc (Burlingame, California) is a non–invasive neurostimulation technology recently FDA-cleared to treat adults with treatment-resistant depression, which affects about 1 in 3 people with depression and constitutes a highly vulnerable group during the COVID-19 pandemic.

The system is designed to deliver an accelerated, high-pulse dose form of transcranial magnetic stimulation (TMS) to restore healthy neural activity in the left dorsolateral prefrontal cortex (DLPFC), a brain region linked to depression. Dose targeting with the SAINT protocol is individually optimized using baseline functional imaging, and is only administered for 5 days, compared with traditional TMS treatment, which typically requires 4 to 6 weeks. Consistent with an earlier open-label study, a sham-controlled, double-blind trial found that 79 percent of people treated with the SAINT protocol experienced remission of their depression, compared with 13 percent of people treated with sham therapy. The SAINT neuromodulation system has not been compared to traditional TMS systems in terms of efficacy.

Magnus Medical, Inc, announced on September 6, 2022, the SAINT neuromodulation system received 510(k) clearance from the FDA for treatment-resistant depression in adults. The developer expects a limited commercial launch in late 2023.

Accelerated TMS, like the SAINT protocol, has been offered at a cost to patients of $10,00 a day, or $5,000 total. Traditional TMS costs between $6,000 and $12,000 for a course of therapy and is often covered by health insurance. We were unable to find potential pricing information for SAINT neuromodulation system to treat treatment-resistant depression.

Commentary

The SAINT neuromodulation system is an individualized, accelerated TMS protocol that might expedite and improve the convenience of treatment for adults with treatment-resistant depression.

Early feedback from ECRI internal stakeholders suggested that the SAINT neuromodulation system, with its quicker response rates, is likely to be a welcome and preferable treatment for patients rather than traditional TMS, particularly if patients have undergone numerous rounds of pharmacotherapy without sufficient relief. It might not be accessible to all patients, however, due to its potential cost and requirement of baseline functional imaging for targeting.

Stakeholders thought health insurers are likely to look favorably upon the treatment and to cover its cost. However, insurers might first require longer-term data and comparative studies of the system versus traditional TMS. The treatment has potential to result in overall cost savings if it is effective and helps reduce the need for accompanying antidepressant treatments.

• Category: Treatment
• Areas of potential impact: Patient outcomes, health care delivery and process, health care disparities, health care costs

Horizon scanning is a systematic process that serves as an early warning system to inform decision makers about possible future opportunities and threats. Health care horizon scanning identifies technologies, innovations, and trends with potential to cause future shifts or disruptions—positive or negative—in areas such as access to care, care delivery processes, care setting, costs of care, current treatment models or paradigms, health disparities, health care infrastructure, public health, and patient health outcomes.

The PCORI Health Care Horizon Scanning System (HCHSS) conducts horizon scanning to better inform its patient-centered outcomes research investments. Initially, PCORI defined the HCHSS project scope to focus on interventions with high potential for disruption in the United States in 5 priority areas: Alzheimer’s disease and other dementias, cancer, cardiovascular diseases, mental and behavioral health conditions, and rare diseases. In addition, the system captures high-level disruptive trends across all clinical areas, which may lead PCORI to expand the project scope to include other priority areas in the future.

In early 2020, the COVID-19 pandemic created a fast-moving, widespread public health crisis. In May 2020, PCORI expanded its HCHSS to elucidate the landscape of potentially impactful applications for COVID-19. The HCHSS COVID-19 supplement scans for, identifies, monitors, and reports on emerging and available COVID-19-related treatments, diagnostics, preventive measures, management strategies, and systems changes with potential for high impact to patient outcomes—for individuals and populations—in the United States in the next 12 months.

The HCHSS COVID-19 supplement produces 3 main outputs:

• Biweekly COVID-19 Scans (eg, this document) provide ECRI Horizon Scanning with a vehicle to inform PCORI and the public in a timely manner of important topics of interest identified during ongoing scanning and topic identification or through the ECRI stakeholder survey process.
• Status Reports (quarterly) briefly list and describe all COVID-19-related topics identified, monitored, and recently archived.
• High Impact Reports (every 4 months) highlight those topics that ECRI internal stakeholders (eg, physicians, nurses, allied health professionals, public health professionals, first responders, health systems experts, clinical engineers, researchers, business and finance professionals, and information technology professionals) have identified as having potential for high impact relative to COVID-19 in the United States.

In May 2021, the COVID-19 supplement was modified and merged with the HCHSS. The Biweekly COVID-19 Scans continue, while the Status Reports and High Impact Reports were folded into the PCORI Horizon Scanning Database and High Potential Disruption Reports.