‘New Kid on the Block’ May Help Relieve PTSD, Panic Disorder

A digital intervention may offer a new and effective treatment option for panic disorder (PD) and posttraumatic stress disorder (PTSD), new research suggests.

The 28-day home-based treatment, known as the Capnometry Guided Respiratory Intervention (CGRI), uses an app-based feedback protocol to normalize respiration and increase patients’ ability to cope with symptoms of stress, anxiety, and panic by providing real time breath-to-breath feedback of respiratory rate and carbon dioxide (CO2) levels via a nasal cannula.

Results from the large real-world study showed that 55% of patients with PD and 53% of those with PTSD responded to the treatment. In addition, almost 75% of participants adhered to the study protocol, with low dropout rates.

“The brief duration of treatment, high adherence rates, and clinical benefit suggests that CGRI provides an important addition to treatment options for PD and PTSD,” the investigators write.

The study was published online November 17 in Frontiers in Digital Health.

‘New Kid on the Block’

The “respiratory dysregulation hypothesis” links CO2 sensitivity to panic attacks and PD, and similar reactivity has been identified in PTSD, but a “common limitation of psychotherapeutic and pharmacologic approaches to PD and PTSD is that neither address the role of respiratory physiology and breathing style,” the investigators note.

The most widely studied treatment for PTSD is trauma-focused psychotherapy, in which the patient reviews and revisits the trauma, but it has a high dropout rate, study investigator Michael Telch, PhD, director of the Laboratory for the Study of Anxiety Disorders, University of Texas, Austin, told Medscape Medical News.

He described CGRI for PTSD as a “relatively new kid on the block, so to speak.” The intervention received US Food and Drug Administration approval for treatment of PD and PTSD in 2013 and 2018, respectively, and is currently available through the Veterans Administration (VA) for veterans with PTSD. It is also covered by some commercial insurance plans.

“The underlying assumption [of CGRI] is that a person can learn to develop skills for controlling some of their physiological reactions that are triggered as a result of trauma,” said Telch.

The device uses a biofeedback approach to give patients “greater control over their physiological reactions, such as hyperventilation and increased respiration rate, and the focus is on providing a sense of mastery,” he said.

Participants with PTSD were assigned to a health coach. The device was delivered to the patient’s home, and patients met with the trained coach weekly and could check in between visits via text or e-mail. Twice-daily sessions were recommended.

“The coach gets feedback about what’s happening with the patient’s respiration and end-tidal CO2 levels [etCO2] and instructs participants how to keep their respiration rate and etCO2 at a more normal level,” said Telch.

The CGRI “teaches a specific breathing style via a system providing real-time feedback of respiratory rate (RR) and exhaled carbon dioxide levels facilitated by data capture,” the authors note.

Sense of Mastery

Of the 1569 participants, 1395 had PD and 174 had PTSD (mean [SD] age, 39.2 [13.9] years and 40.9 [14.9] years, respectively; 76% and 73% female, respectively). Those with PD completed the Panic Disorder Severity Scale (PDSS) and those with PTSD completed the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), before and after the intervention.

The treatment response rate for PD was defined as a ≥ 40% reduction in PDSS total scores, whereas treatment response rate for PTSD was defined as a ≥ 10-point reduction in PCL-5 scores.

At baseline, patients were classified either as normocapnic or hypocapnic (etCO2 ≥ 37 or < 37, respectively), with 65% classified as normocapnic and 35% classified as hypocapnic.

Among patients with PD, there was a 50.2% mean pre-to-post-treatment reduction in total PDSS scores (P < .001; d = 1.31), with a treatment response rate of 65.3% of patients.

Among patients with PTSD, there was a 41.1% pre-to post-treatment reduction in total PCL-5 scores (P < .001; d = 1.16), with a treatment response rate of 72.4%.

When investigators analyzed the response at the individual level, they found that 55.7% of patients with PD and 53.5% of those with PTSD were classified as treatment responders. This determination was based on a two-pronged approach that first calculated the Reliable Change Index (RCI) for each participant, and, in participants showing statistically reliable improvement, whether the posttreatment score was closer to the distribution of scores for patients without or with the given disorder.

“Patients with both normal and below-normal baseline exhaled CO2 levels experienced comparable benefit,” the authors report.


Baseline CO2

Effect Size: PD

Effect Size: PTSD








There were high levels of adherence across the full treatment period in both the PD and the PTSD groups (74.8% and 74.9%, respectively), with low dropout rates (10% and 11%, respectively).

“Not every single patient who undergoes any treatment has a perfect response, but the response rates to this treatment have, surprisingly, been quite positive and there have been no negative side effects,” Telch remarked.

He noted that one of the effects of PTSD is that the “patient has negative beliefs about their ability to control the world. ‘I can’t control my reactions. At any time, I could have a flashback.’ Helping the patient to develop any sense of mastery over some of their reactions can spill over and give them a greater sense of mastery and control, which can have a positive effect in reducing PTSD symptoms.”

‘A Viable Alternative’

Commenting for Medscape Medical News, Charles Marmar, MD, chair and Peter H. Schub Professor of Psychiatry, Department of Psychiatry, NYU Grossman School of Medicine, New York, said that the study has some limitations, probably the most significant of which is that most participants had normal baseline CO2 levels.

“The treatment is fundamentally designed for people who hyperventilate and blow off too much CO2 so they can breathe in a more calm, relaxed way, but most people in the trial had normal CO2 to begin with,” said Marmar, who was not involved with the study.

“It’s likely that the major benefits were the relaxation from doing the breathing exercises rather than the change in CO 2 levels,” he speculated.

The treatment is “probably a good thing for those patients who actually have abnormal CO2 levels. This treatment could be used in precision medicine, where you tailor treatments to those who actually need them rather than giving the same treatment to everyone,” he said.

“For patients who don’t respond to trauma-focused therapy or it’s too aversive for them to undergo, this new intervention provides a viable alternative,” Telch added.

The study was internally funded by Freespira, Inc. Telch is a scientific advisor at Freespira and receives compensation by way of stock options. The other authors’ disclosures are listed on the original paper. Marmar has declared no relevant financial relationships.

Front Digit Health. Published online November 17, 2022. Full text

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).

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