Randomized clinical trial of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related PTSD and the role of sleep quality in treatment response.

Effective posttraumatic stress disorder (PTSD) pharmacotherapy is needed. This 12-week randomized multicenter trial evaluated efficacy and safety of TNX-102 SL, a bedtime sublingual formulation of cyclobenzaprine, in patients with military-related PTSD randomized to TNX-102 SL 2.8 mg or 5.6 mg, or placebo. Primary analysis comparing change from baseline in Clinician-Administered PTSD Scale-5 score between 2.8 mg (n=90) and placebo (n=92) was not significant. Secondary analysis of 5.6 mg (n=49) vs placebo demonstrated a mean difference of -4.5 units, p=.05, or, accounting for missing data by multiple imputation, -5.0 units, p=.03. Clinician Global Impression - Improvement responder rate was greater in 5.6 mg than placebo (p=0.04), as was mean functional improvement in Sheehan Disability Scale social domain (p=.03) and trended in work domain (p=.05). Post-hoc analyses showed early sleep improvement predicted improvement in PTSD after 12 weeks for TNX-102 SL (p<.01), not for placebo. Most common administration site reaction in TNX-102 SL groups was oral hypoaesthesia (5.6 mg, 36%; 2.8 mg, 39%; placebo, 2%), while most common systemic adverse event was somnolence (5.6 mg, 16%; 2.8 mg, 12%; placebo, 6%). This provides preliminary evidence that TNX-102 SL 5.6 mg reduces PTSD symptoms, improves sleep and psychosocial function, and is well tolerated. Clinicaltrials.gov Identifier: NCT02277704.