Brief Biofeedback Protocol Improves Stress and Mood Outcomes in Multiple Sclerosis

A decade-long study from Cleveland Clinic’s Mellen Center for Multiple Sclerosis (Mult Scler Relat Disord. 2026;107:106967) demonstrates that a condensed, four-session stress management protocol significantly improves both subjective mood and objective physiologic markers in people with multiple sclerosis (MS).

“Unlike traditional, lengthy interventions that often suffer from high attrition, this streamlined approach offers a feasible clinical model that can empower patients to regulate their autonomic responses in real-world settings,” says the study’s lead and corresponding author, Amy Sullivan, PsyD, Director of Behavioral Medicine and Research in the Mellen Center. “Our findings suggest that even brief, targeted behavioral interventions can yield measurable improvements in patient-reported outcomes and physiologic stability.”

Stress as a disease modifier in MS

In people with MS, stress can be more than a secondary symptom; it is a complex phenomenon that can trigger relapses and worsen the overall disease course. Stress initiates a cascade within the autonomic nervous system, often activating a sympathetic response that manifests as increased heart rate, elevated blood pressure and altered breathing. For people with MS, these physiologic changes are often accompanied by higher rates of depression and anxiety, which directly diminish quality of life.

Need for a more practical stress intervention

Previous research has shown that intensive stress management — sometimes involving up to 16 or more sessions — can reduce the development of new gadolinium-enhancing brain lesions in people with MS, but such long-term interventions can be a significant hurdle. Patients often cite time obligations such as employment, family obligations and MS-related fatigue as barriers to completing months of weekly therapy.

To overcome these barriers, Dr. Sullivan and her Mellen Center colleagues developed a shortened four-session stress management protocol adapted from the published Stress Management Therapy for MS (SMT-MS) protocol, which was designed to comprise 16 sessions over 20 to 24 weeks.

Their new, briefer approach, called the Stress Management Protocol (SMP), involves four one-hour individual sessions spaced four to six weeks apart. This spacing provides patients with time to practice self-regulation techniques in their daily environments rather than just in the clinic. A unique aspect of the SMP is its integration of a portable biofeedback tool, specifically a pulse oximeter, to enable patients to monitor their breathing rate, pulse and blood oxygen saturation in real time and in real-world environments.

The SMP’s four sessions are structured as follows:

• Session 1: Psychoeducation about the MS/stress connection and training in diaphragmatic breathing
• Session 2: Focus on “serial 3 breathing” to manage hyperventilation responses
• Session 3: Use of individualized guided imagery and visualization
• Session 4: Training in mindfulness, distress tolerance and progressive muscle relaxation

“We conducted the current study to determine whether participating in our short-term SMP with biofeedback monitoring yields improvements in objective and subjective metrics of stress and mood during and across each SMP session,” Dr. Sullivan explains.

Study design

She and colleagues retrospectively examined data from 195 patients with MS who underwent at least one SMP session at the Mellen Center between 2012 and 2022. The 164 patients with demographic and disease data available were largely female (71.9%) and white (81.1%), with an average disease duration of approximately 12 years.

Subjective mood data were tracked across SMP sessions, with depression assessed using the Patient Health Questionnaire-9 (PHQ-9) and anxiety assessed via the Generalized Anxiety Disorder-7 (GAD-7) instrument. Objective physiologic data — i.e., breathing rate, pulse and blood oxygen saturation — were collected using biofeedback before and after each SMP session by way of a pulse oximeter.

Results: Immediate and sustained gains

The data revealed that patients experienced significant physiologic improvements within a single session, beginning with session 1. Intrasession results showed meaningful reductions in breathing rates and pulse, along with increases in oxygen saturation, indicating a successful shift toward a parasympathetic relaxation response.

Across the duration of the protocol, the results were similarly compelling:

• Mood improvements. Symptoms of depression (PHQ-9) and anxiety (GAD-7) decreased to a statistically significant degree between the sessions overall and between most pairs of consecutive sessions. Patients with moderate baseline distress saw the most clinically meaningful improvements.
• Physiologic regulation. Significant overall improvements were noted in pre-session breathing rates and oxygen saturation from the start of the study to its conclusion. Improvements in pulse did not achieve statistical significance across the overall span of sessions.

Considerable voluntary dropout occurred across the sessions, with 192 patients completing session 1, 121 completing session 2, 79 completing session 3 and 49 completing session 4. “We encouraged patients to drop out of the sessions once they felt they mastered the material and their mood improved,” Dr. Sullivan explains. “The real-world applicability and respect of their time was one of our greatest accomplishments in this dataset.”

Interestingly, patients who completed three sessions showed the greatest average improvement in depression scores and respiratory measures. The researchers noted a plateau or slight decline in average improvement among those who continued through the fourth session. “This may reflect a selection bias in a real-world study like this,” Dr. Sullivan says, “as patients who achieve rapid mastery of the skills may discontinue the program early while those with more complex or treatment-resistant symptoms may be more apt to continue through the final session.”

Blueprint for feasible stress relief

The researchers conclude that brief, technology-assisted behavioral interventions can effectively manage stress in this setting. “This study demonstrates that people with MS can be taught to voluntarily modulate their autonomic nervous system functions using simple, accessible tools like pulse oximeters,” Dr. Sullivan notes. “This mastery of mind-body skills provides patients with a sense of agency over their symptoms, which is often lost in the face of a chronic, unpredictable neurologic condition like MS.”

The researchers note that levels of improvement differed somewhat by patient race and other demographic variables, which may argue for further individualization of the SMP to address unique stressors or barriers faced by specific patient subpopulations.

By shifting from a 16-session model to a more flexible and realistically applicable four-session protocol, the Mellen Center has demonstrated a way to integrate high-quality behavioral health into the busy flow of MS care. “This protocol prioritizes feasibility and real-world applicability to foster development of lifelong skills for physiologic homeostasis in people with MS,” Dr. Sullivan observes. “We hope it may serve as a blueprint for other centers looking to help patients address the burden of stress that MS can bring.”