TNX-102 SL 5.6 mg improved sleep quality by CAPS-5 “sleep disturbance” item.

TNX-102 SL was associated with clinically significant early symptom improvement.

TNX-102 SL improved patient-rated global PTSD symptoms at week 12.

TNX-102 SL was well tolerated by patients with military-related PTSD.

It is proposed that TNX-102 SL facilitates a sleep-dependent recovery mechanism.

Sleep disturbances in posttraumatic stress disorder (PTSD) are a potential target for improving PTSD severity with pharmacotherapy. TNX-102 SL is a bedtime sublingual formulation of cyclobenzaprine with potent binding and antagonist activity at 5-HT2A, α1-adrenergic, H1 histaminergic, and M1 muscarinic receptors, which play roles in the pharmacological management of sleep disturbances. This Phase 3 trial evaluated the efficacy and safety of TNX-102 SL in patients with military-related PTSD. Early and sustained improvements in sleep were associated with TNX-102 SL treatment by PROMIS Sleep Disturbance scale and Clinician Administered PTSD Scale (CAPS-5) “sleep disturbance” item, establishing a sleep quality benefit. Primary analysis comparing change from baseline in CAPS-5 total severity between TNX-102 SL and placebo at week 12 was not significant; however, week 4 was associated with an improvement. Secondary analyses showed TNX-102 SL treatment was associated with benefits on the Clinician Global Impression of Improvement at week 4 and the Patient Global Impression of Change at week 12. Time since trauma exposure was a discriminator of CAPS-5 treatment response in the subgroup ≤ 9 years since the index event. This study provides preliminary evidence that TNX-102 SL is well-tolerated and may promote recovery from PTSD by addressing sleep-related symptoms.

Pharmacotherapy

Sleep quality

Hyperarousal

Memory consolidation

Military trauma

Time since trauma

© 2024 The Author(s). Published by Elsevier B.V.