Impact of <scp>IV</scp> metoclopramide + diphenhydramine on post‐concussion symptoms. A secondary analysis of data from an <scp>ED</scp> ‐based randomized study

BACKGROUND: In a randomized, placebo-controlled study, intravenous metoclopramide 20 mg + diphenhydramine 25 mg (M+D) improved post-concussion symptoms 1 h later among patients seeking care in an emergency department (ED) following head trauma. We performed a secondary hypothesis-generating analysis of those data to determine whether M+D is effective against cognitive and affective symptoms in addition to somatic symptoms, and whether post-treatment symptomatology is associated with 1-week and 1-month outcomes. METHODS: We enrolled patients in two urban EDs in the Bronx, NY. Enrollment commenced in August 2017 and concluded in March 2020. Patients were included in the initial randomized controlled trial if they experienced head trauma and reported a new onset headache of at least moderate or severe intensity. We assessed post-concussion symptoms at 1 h, 1 week, and 1 month after treatment using the Post-Concussion Symptom Scale (PCSS), a 22-item instrument on which each symptom is graded as zero (none) through 6 (severe). We determined the impact of treatment, time, and their interaction on PCSS score. We repeated this analysis among the somatic, cognitive, and affective domains of the PCSS scale. Finally, we determined if post-treatment PCSS scores in the ED were associated with any severe symptom 1 week and 1 month later. RESULTS: Eighty-one participants received M+D; of those, 30 (37.0%) were female. Their mean age was 43.3 (standard deviation 16.1) years. All 81 provided 1-h data; 72 (89.9%) provided 1-week data; and 61 (75.3%) provided 1-month data. Seventy-nine received placebo; of those, 23 (29.1%) were female. Their mean age was 45.7 (SD 17.3) years. All 79 provided 1-h data; 67 (84.8%) provided 1-week data; and 54 (68.4%) 1-month data. At 1 h, the overall mean PCSS score was 20.8 (SD 20.2); at 1 week it was 17.4 (SD 23.0); and at 1 month it was 19.5 (SD 27.7). Participants who received M+D reported lower post-concussion symptom scores on the PCSS at 1 h (9.2 units lower, 95% confidence interval [CI]: 2.0, 16.4) but not at 1 week (7.2, 95% CI: -0.4, 14.9) or 1 month (2.4, 95% CI: -5.9, 10.8). In the main mixed-effects model, there was a significant effect of treatment (p = 0.008), indicating overall lower PCSS scores in the M+D group across follow-up, although not for time (p = 0.289) or treatment-by-time interaction (p = 0.175). The treatment effect remained significant in the affective (p = 0.002) and cognitive (0.010) domains. PCSS scores prior to ED discharge were associated with severe symptoms at 1 week (adjusted odds ratio [OR] 1.02, 95% CI: 1.01, 1.04), but not 1 month (adjusted OR 1.02, 95% CI: 1.00, 1.04). CONCLUSION: In this exploratory secondary analysis, M+D improved post-concussive symptoms 1 h after treatment, including affective and cognitive post-concussion symptoms. PCSS scores after treatment are associated with 1-week but not 1-month outcomes.