Hypnosis versus relaxation for anxiety in COPD pulmonary rehabilitation: a cluster-randomized trial

Abstract Rationale Anxiety affects 22–56% of patients with chronic obstructive pulmonary disease and predicts exacerbations, readmissions, and mortality. Mind-body adjuncts to pulmonary rehabilitation are recommended, but trials have lacked comparators isolating technique-specific effects and left determinants of individual benefit unexamined. Objectives Testing whether adjunctive medical hypnosis reduces anxiety more than matched structured relaxation. Methods Cluster-randomized, active-comparator trial with patients undergoing pulmonary rehabilitation for chronic obstructive pulmonary disease. Consecutive 4-week inpatient cohorts were randomized 1:1 to adjunctive hypnosis or structured relaxation matched on session length, practitioner pool, and framing. Primary outcome was the six-item State-Trait Anxiety Inventory at week 4 (intention to treat). Complementary multidimensional metrics of anxiety were obtained for robustness. Exploratory analyses tested outcome moderation by baseline sensory-affective dyspnea burden. Measurements and Main Results Of 80 participants (24 clusters), 79 were analyzed (hypnosis 36, relaxation 43). Hypnosis did not differ from relaxation on the primary outcome (+0.95 points; 95% credible interval −5.85 to 7.42; posterior probability of clinically important hypnosis advantage 0.12) or its complementary metrics. Anxiety improved in both arms (pooled −5.72 points; −9.35 to −2.00). Exploratory analyses showed that the hypnosis advantage rose with baseline sensory and fell with affective burden, reaching −9.26 points at a high-sensory, low-affective profile (−23.37 to 4.71; posterior probability of clinically important hypnosis advantage 0.81). No deaths or serious adverse events occurred. Conclusions Anxiety improved with no advantage of hypnosis over matched relaxation. Exploratory analysis suggests greater hypnosis benefit in patients with predominantly sensory dyspnea, proposing a candidate phenotype for stratified trials. Clinical trial registered with www.clinicaltrials.gov ( NCT04868357 ). Impact statement Anxiety affects 22–56% of patients with chronic obstructive pulmonary disease and independently predicts exacerbations, readmissions, and death; current guidance recommends mind-body adjuncts to pulmonary rehabilitation for anxiety, yet their pooled benefit is heterogeneous, and no demographic or disease-severity variable explains who responds. By randomizing medical hypnosis against a structured-relaxation comparator matched on everything but hypnotic suggestion, this trial found no hypnosis benefit over relaxation for the pooled population, yet a post hoc multilevel moderator analysis revealed a clinically important hypnosis benefit that scaled with baseline sensory dyspnea burden. This hypothesis-generating responder profile is identifiable at screening with instruments already in routine respiratory practice, and points to the sensory–affective architecture of dyspnea as a plausible discriminant for matching adjunct to patient. At a Glance Commentary Scientific Knowledge on the Subject Pulmonary rehabilitation has a moderate anxiolytic effect in chronic obstructive pulmonary disease, with marked between-patient heterogeneity that demographic and disease-severity variables do not predict. Mind-body adjuncts have been tested almost exclusively against waitlist or usual care, designs that cannot separate technique-specific effects from the nonspecific benefits of structured psychological contact. Hypnosis attenuates both the sensory and affective dimensions of experimentally induced dyspnea, but whether this translates into a reliable anxiolytic benefit during rehabilitation, and for whom, is unknown. What This Study Adds to the Field This cluster-randomized trial compared medical hypnosis with structured relaxation matched on session number, length, format, and self-management framing, delivered from verbatim scripts by the same certified practitioners, leaving hypnotic suggestion the only intended difference. In unselected patients, hypnosis conferred no advantage over relaxation on primary or confirmatory anxiety outcomes. An exploratory moderation analysis, however, suggested that hypnotic advantage grew with baseline sensory dyspnea burden, reaching three times the minimal clinically important difference at a high-sensory, low-affective profile. This potential candidate responder phenotype, pending stratified confirmation, is identifiable at screening with routine instruments in respiratory practice, and underscores the sensory–affective dyspnea profile’s potential as a discriminant for matching adjunct to patient.