Table 2.

Characteristics of the included studies

Study	Country	Design	Age (years)	Sex (% female)	Orthodontic treatment	Interventions	Evaluation intervals	Outcome measures
Bernhardt 2001 [11]	America	RCT	Mean12	51%	separator placement	Ibuprofen(400 mg),placebo	2 h, 6 h, at night, 24 h, 2 d, 3 d, 7 d	VAS
Farzanegan 2012 [12]	Iran	RCT	13–18	100%	archwire placement	Ibuprofen(400 mg),placebo, chewing gum,soft viscoelastic wafer, and hard viscoelastic wafer	2 h, 6 h, at night, 24 h, 2 d, 3 d, 7 d	VAS
Kohli 2011 [13]	India	RCT	13–20	50%	separator placement	Ibuprofen(400 mg), placebo	2 h, 6 h, at night, 24 h, 2 d, 3 d, 7 d	VAS
Minor 2009 [14]	America	RCT	13–30	25%	separator placement	Ibuprofen(400 mg),placebo	2 h, 6 h, bedtime,awakening,24 h	VAS
Patel 2011 [15]	America	RCT	18–30	46%	separator placement	Ibuprofen, naproxen sodium, acetaminophen, placebo (OTC)	2 h, 6 h, bedtime,awakening,24 h	VAS
Polat 2005 [16]	Turkey	RCT	10–24	38%	archwire placement	Ibuprofen(400 mg),placebo, naproxen sodium	2 h, 6 h, at night, 24 h, 2 d, 3 d, 7 d	VAS
Salmassian 2009 [17]	America	RCT	12–18	48%	separator placement	Ibuprofen(400 mg),acetaminophen(600 mg),placebo	0 h,3 h, 7 h, 19 h,24 h, 31 h,48 h, 3 d,4d, 7 d	VAS
Sudhakar 2014 [18]	India	RCT	14–21	50%	separator placement	Ibuprofen(400 mg),acetaminophen(650 mg),aspirin(300 mg),placebo	2 h, 6 h, bedtime,24 h,2 d, 3 d, 7 d	VAS
Gupta 2014 [19]	India	RCT	15–22	49%	archwire placement	Acetaminophen(500 mg), etoricoxib(60 mg), placebo	2 h, 6 h, at night, 24 h,2d,3d	VAS
Eslamian 2017 [20]	Iran	RCT	14–20	68%	separator placement	Naproxen, placebo	2 h, 6 h, 24 h,2d,3d,7d	VAS
Nik 2016 [21]	Iran	RCT	Mean15	56%	separator placement	Acetaminophen(650 mg), ibuprofen(400 mg), and placebo	0 h, 2 h, 6 h, bedtime, 24 h	VAS
Kaur 2019 [22]	India	RCT	Mean15	70%	separator placement	Acetaminophen(500 mg), verbal behavior modification, placebo	6 h, 24 h,2d,3d,4d,5d,6d,7d	VAS