Abstract
BACKGROUND: Although treatment-resistant depression (TRD) is a major public health problem that increases mortality due to suicides, a considerable percentage of patients do not respond adequately to variable treatments. Patients with TRD sometimes have comorbid cervical stiffness. This observational study aims to examine the association of local modulation of cervical muscles with TRD and to learn the involvement of the parasympathetic nervous system in the underlying mechanism. METHODS: A total of 1103 hospitalized patients with TRD who were resistant to outpatient care were enrolled between May 2006 and October 2021. All patients underwent local modulation of the cervical muscles by physical therapy during hospitalization. The presence or absence of TRD and whole-body disorders, such as headache, dazzling, cervical stiffness, and cardiovascular and gastrointestinal disorders, was determined by the patient's subjectivity using the self-rated medical interview sheet at admission and discharge. Pupil light reflex parameters were also measured at admission and discharge using a binocular infrared pupilometer. RESULTS: The improvement rate of TRD during hospitalization was 72.1%, and did not differ significantly by sex, age, and hospitalization period. The improvement of TRD showed a strong association with those of cervical stiffness and dazzling, a pupil light reflex disorder (p < 0.001: odds ratios = 12.76 and 6.39, respectively), but not with those of headache or cardiovascular and gastrointestinal disorders (p > 0.05). In the TRD-improved patients, the pupil light reflex parameters representative of the parasympathetic nervous system function ameliorated: pupil diameter decreased, while constriction rate and velocity increased during hospitalization. In contrast, little amelioration of the parameters was seen in the TRD-unimproved patients. CONCLUSIONS: Cervical muscle stiffness may be associated with TRD, possibly through dysfunction of the parasympathetic nervous system. TRIAL REGISTRATION: ID: UMIN000040590. First registration date: 30/05/2020.