Additional Table 3.

Clinical trials of minocycline or N-acetylcysteine

Author	Compound	TBI severity	Design	Enrolled	Dose, duration	Time of first dose	Findings
Hofer, 2013	N-acetylcysteine	Mild TBI (Balance dysfunction, confusion, headache, hearing loss, impaired memory, sleep disturbances)	Randomized, double blind, placebo controlled clinical trial	81	8g loading dose, 1.3g PO three time daily for 3 d, 1g three times daily for 4 d	Within 3 d post-blast exposure	Significantly greater number of patients with no residual symptoms
Meythalar, 2019	Minocycline	Moderate-severe TBI (Glasgow Coma Score 3–9)	Dose escalation	15	800 mg IV loading followed by 200 mg or 400 mg twice daily for 7 d	Within 6 h post-injury	Safe in TBI population; higher doses trended towards improved disability rating score. No statistical significance
Scott, 2018	Minocycline	Moderate-severe TBI (Mayo classification)	Randomized clinical trial	15	100 mg PO twice daily for 12 weeks	At least 6 months post-injury	Lowered chronic microglial activation Increased serum neurofilament light protein
Koulaeinejad, 2019	Minocycline	Moderate-severe TBI (Glasgow Coma Score <12)	Randomized, double blind, placebo. Includes both	34	100 mg twice daily for7d	Within 24 h post-injury	Lowered Serum S100B, trending (P< 0.1 ) Lowered Serum Neuronal Specific Enolase (P = 0.01) No effect, Glasgow OutcomeScale-Extended

Clinical trial design is provided followed by the number of subjects enrolled, dose and duration and the most salient findings. TBI: Traumatic brain injury.