Table 1: Summary of the included studies.

Study	Year	Country	Sex (M,F)	Age	Treatment Groups	Dose (mg)	Sample Size	Follow-up Period (h)	VAS Scale	Conclusion
Menke et al. [1]	1999	USA	14,22	>18	Etodolac	400 mg	12	0, 4, 8, 12, 24, 48, 72	100 mm	Prophylactic ibuprofen significantly reduced post-endodontic pain at four and eight hours after initiation of treatment, when compared to etodolac and a placebo
					Ibuprofen	600 mg	12
					Placebo		12
Gopikrishna and Parameswaran [2]	2003	India	29, 16	18–64	Ibuprofen	600 mg	15	4, 8, 12, 24, 48, 72	100 mm	Rofecoxib administration provides an effective reduction in post-endodontic pain
					Rofecoxib	50 mg	15
					Placebo		15
Attar et al. [3]	2008	USA	7, 7	44.9±4	Ibuprofen tablets	600 mg	15	0, 6, 12, 18, 24	100 mm	Single-dose pretreatment analgesia alone in endodontic pain patients did not significantly reduce postoperative pain below the level of reduction in pain from endodontic treatment of ibuprofen 600 mg and the placebo group
			7, 6	41.6±4.3	Ibuprofen liqui-gels	600 mg	15
			9, 3	45.8±5.1	Placebo		15
Saatchi et al. [4]	2009	Iran	NR	NR	Ibuprofen	400 mg	30	0, 2, 6, 10, 18, 36, 44, 54, 66, 72	0–10	Diclofenac sodium continuous-release single dose pre-treatment of root canals compared to ibuprofen can prolong pain relief after root canal treatment for a longer period of time.
					Diclofenac sodium	100 mg	30
					Placebo		30
Jalalzadeh et al. [5]	2010	Iran	14, 6	18–59	Prednisolone	30 mg	20	6, 12, 24	10 cm	Postendodontic pain was substantially reduced by preoperative administration of a single oral dose of prednisolone compared with placebo
			14, 6		Placebo		20
Arslan et al. [6]	2011	Turkey	16, 32	18–52	Tenoxicam	20 mg	16	6, 12, 24, 48, 72	100 mm	A prophylactic single dose of 20 mg tenoxicam or 200 mg Ibuprofen administration before RCT provides effective reduction of post-operative pain at 6 h
					Ibuprofen	200 mg	16
					Placebo		16
Ashraf et al. [7]	2013	Iran	7, 7	18-57	celecoxib	400mg	15	4, 8, 12, 24, 48	170mm	Prophylactic Celecoxib is not recommended for post-endodontic pain reduction especially in cases with gastrointestinal (GI) problems
			8, 6		Placebo		15
Atbaei et al. [8]	2010	Iran	36, 29	14-65	piroxicam	8mg	35	4, 8, 12, 24, 48	10mm	Piroxicam is highly effective for reducing post-endodontic pain in vital teeth with irreversible pulpitis during the first 48 h. It was found to be much more effective than a similar lidocaine injection in reducing postoperative endodontic pain
					Placebo		30
Baradaran et al. [9]	2014	Iran	26, 19	20-45	ibuprofen	400mg	15	4, 6, 12, 24, 48, 72	10mm	Alprazolam may enhance the analgesic efficacy of ibuprofen in post-endodontic pain
					Ibuprofen+alprazolam	400mg+0.5mg	15
					Placebo		15
Douglas [10]	2004	Portugal	3,17	16-61	Rofecoxib	50mg	20	4,8,10,12,24	10mm	Single dose of COX-2 inhibitors maybe sufficient to prevent post-endodontic pain
			4,16		Diclofenac sodium	50mg	20
			5,15		Placebo		20
Ehsani et al. [11]	2012	Iran	NA	NA	NAC	400mg	20	6, 8, 12, 24	10mm	The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand, it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain
					Ibuprofen	400mg	20
					NAC + Ibuprofen	400 + 200mg	20
					placebo		20
Elkhadem et al. [12]	2017	Egypt	78, 122	18-35	Prednisolone	40mg	200	6, 12, 24	100mm	A single dose of prednisolone was beneficial to control short-term post-obturation pain in patients with symptomatic irreversible pulpitis reducing pain incidence after 24 h by approximately 30% and postoperative analgesic intake by approximately 55%
			63, 137		placebo		200
Flath et al. [13]	1987	USA	116, 4	20-80	Placebo		29	3, 7, 24	100mm	Endodontic treatment significantly reduced post-operative pain in preoperatively symptomatic patients. Doses of 100 or 200 mg of flurbiprofen resulted in minimal side effects
					Flurbiprofen	100mg	87
Isik et al. [14]	2014	Turkey	7, 23	18-45	Gabapentin	600mg	30	4, 8, 12, 24	100mm	Prophylactic lornoxicam controlled post-endodontic treatment pain more effectively than did the placebo drugs, and gabapentin was more effective in controlling the pain than either lornoxicam or the placebo.
					lornoxicam	8mg	30
					placebo		30
Joshi et al. [15]	2016	India	11, 11	18-65	piroxicam	40mg	22	4, 8, 12, 24, 48	10 cm	Peroxicam group perceived less post-endodontic pain as compared to placebo at all the time intervals
			12, 10		Placebo		22
Kaviani et al. [16]	2011	Iran	NA	15-45	Ketamine	10mg	18	24	10mm	A low dose of ketamine might be beneficial for enhancing the effect of local anesthetics
					Placebo		18
Khorasani et al. [17]	2011	Iran	8, 8	25-50	ibuprofen	400mg	16	6, 12, 24, 48, 72	100mm	Prophylactic use of Ibuprofen and sulindac for reduction of post-endodontic pain is not suggested
			9, 7		sulindac	200mg	16
			6, 10		placebo		16
Mehrvarzfar et al. [18]	2016	Iran	9, 11	32+4.6	placebo		20	6, 12, 24	170mm	Pretreatment PDL injection of dexamethasone can significantly reduce the post-treatment endodontic pain in patients with symptomatic irreversible pulpitis.
			10, 10	26.1+9.8	lidocaine	0.2ml	20
			8, 12	30.3+4.2	dexamethasone	8 mg	20
Mehrvarzfar et al. [19]	2012	Iran	15, 9	31.4+10.7	placebo		24	6, 12, 24	10mm	A single oral dose of Naproxen, Novafen and Tramadol taken immediately after treatment reduced postoperative pain following pulpectomy and root canal preparation of teeth with irreversible pulpitis.
			13, 11	29.5+6.9	tramadol	100mg	24
			11, 12	29.6+8.1	Novafen	325 mg of paracetamol, 200 mg ibuprofen and 40 mg caffeine anhydrous)	23
			14, 10	28.4+7.6	naproxen	500mg	24
Menhinick et al. [20]	2004	USA	8, 11	24-80	placebo		19	4, 8	100mm	The results demonstrate that the combination of ibuprofen with acetaminophen may be more effective than ibuprofen alone for the management of postoperative endodontic pain.
			6, 14	21-61	ibuprofen	600	20
			2, 16	19-58	ibuprofen + paracetamol	600mg + 1000mg	18
Mirzaie et al. [21]	2011	Iran	56, 34	18-65	Celecoxib	200mg	30	4, 8, 12, 24, 48	100 mm	Use of Gelofen or Celecoxib before treatment reduces post-endodontic pain. These drugs can be prescribed before initiation of treatment as effective agents for the reduction of post-endodontic pain.
					Gelofen	400mg	30
					Placebo		30
Mokhtari et al. [22]	2016	Turkey	9, 13	19-0	Ibuprofen	400mg	22	8, 12, 24	100mm	Premedication with ibuprofen and indomethacin can effectively control short term post-operative pain; the lower incidence of side effects and greater analgesic power of ibuprofen make it a superior choice.
			7, 15		Indomethacin	25mg	22
			13, 9		Placebo		22
Negm 1st group [23]	1989	Egypt	NA	16-71	Piroxicam	20mg	48	2, 4, 8	1 to 4	Piroxicam was more effective than diclofenac or the placebo. Diclofenac required a longer time to reach maximum effectiveness. Piroxicam’s superiority was greater at the first and second days after the initial dose of medication was taken.
					Diclofenac sodium	50mg	52
					Placebo		43
Negm 2nd group [23]					Piroxicam	20mg	45
					diclofenac sodium	50mg	40
					placebo		40
Negm 1st group [24]	1994	Egypt	NA	18-78	diclofenac	75mg	65^	2, 4, 8, 12	1 to 4	Post-endodontic pain occurred with less frequency when the teeth were treated with diclofenac, but diclofenac-treated and ketoprofen-treated cases were not significantly different in controlling post-endodontic pain. An increase in the number of patients who reported a complete absence of pain was recorded when hyaluronidase was added to the study medications. However, the difference between the medications and medication-hyaluronidase was not of statistical significance.
					diclofenac-hyaluronidase	75mg + 1500 iu	63^
					Ketoprofen	100mg	60^
					Ketoprofen-hyaluronidase	100mg + 1500 iu	70^
					Placebo		58^
					Placebo-hyaluronidase	1500 iu	51^
Negm 2nd group [24]					diclofenac	75mg	73^
					diclofenac-hyaluronidase	75mg + 1500 iu	70^
					Ketoprofen	100mg	66^
					Ketoprofen-hyaluronidase	100mg + 1500 iu	60^
					Placebo		60^
					Placebo-hyaluronidase	1500 iu	64^
Nekoofar et al. [25]	2003	USA	NA	>15	meloxicam	15mg	17	8, 24	9cm	Based on the two-way repeated measures ANOVA, the reduction in pain with meloxicam, piroxicam, and placebo was not significantly different (p=0.058), although the mean change of pain was greater with meloxicam over piroxicam and greater with piroxicam than placebo.
					piroxicam	20mg	17
					placebo		17
Praveen et al. [26]	2017	India	15, 14	18-50	Ketorolac	20mg	31	0, 6, 12, 24, 48	10 cm	Single pre-treatment dose of prednisolone has a more sustained effect in reducing post-endodontic pain compared with placebo or ketorolac.
			16, 14		prednisolone	30mg	31
			13, 14		placebo		31
Ramazani et al. [27]	2013	Iran	15, 12	18-65	ibuprofen	400mg	30	4, 8, 12, 24, 48, 72	100mm	The obtained results of the trial revealed that prophylactic use of 2 g Zintoma is not an effective pain-relieving agent.
			13, 11		zintoma	2000mg	30
			10, 11		placebo		30
Rashka et al. [28]	2013	India	NA	NA	diclofenac sodium	30mg	26	4, 8, 12, 24, 48	10mm	Diclofenac Sodium was found to be highly effective in reducing post-endodontic pain of vital teeth with irreversible pulpitis during the first 48 h.
					placebo		26
Ryan et al. [29]	2008	USA	6, 8	NA	placebo		14	0, 6, 12, 18, 24	NA	Statistical analysis of the data showed that ibuprofen 600 mg provided statistically significantly greater analgesic effect than placebo at 6 and 12 hours (P=0.0014 and 0.0024), and pentazocine/naloxone provided statistically significantly greater analgesic effect than placebo at 12 hours (P =0.0084).
			8, 7		ibuprofen	600mg	15
			6, 8		talwin	50mg	14
Salarpoor et al. [30]	2013	Iran	6, 13	31.3	ibuprofen	400mg	19	6, 12, 24, 48	10mm	The results demonstrate that betamethasone and indomethacin may be more effective than ibuprofen for the management of post-operative pain after nonsurgical endodontic treatment when patients present with moderate to severe pain
			4, 17	24.5	betamethasone	2mg	21
			7, 15	28	indomethacin	75mg	22
			6, 14	29	placebo		20
Sethi et al. [31]	2014	India	12, 6	18-60	Tapentadol	100mg	20	0, 6, 12, 18, 24	10cm	Single oral dose of 10 mg of ketorolac and 100mg of tapentadol as a pretreatment analgesic significantly reduced postoperative endodontic pain in patients with symptomatic irreversible pulpitis when compared to 400 mg of etodolac
					Etodolac	400mg	20
					Ketorolac	10mg	20
Elzaki et al. [32]	2016	Sudan	66, 104	33+10.5	paracetamol	1000mg	34	1, 2, 3, 4, 6, 8	NA	The combination of ibuprofen/paracetamol, taken immediately after initial endodontic therapy and root canal preparation in teeth with irreversible pulpitis, reduced post-endodontic pain
					Ibuprofen + paracetamol	600 + 1000mg	33
					Mefenamic acid + paracetamol	500mg + 1000mg	34
					Diclofenac K + paracetamol	50mg + 1000mg	35
					Placebo		34
Jorge-Araújo et al. [33]	2018	Brazil	7, 12	18-66	Placebo		20	4, 8, 12, 24, 48	NA	Preoperative administration of Ibuprofen or dexamethasone reduces post-endodontic pain and discomfort in comparison with a placebo. Premedication with anti-inflammatory drugs could contribute to control of the post-endodontic pain, mainly in patients more sensitive towards pain
			7, 12		Ibuprofen	400mg	20
			7, 11		Dexamethasone	8mg	20
Jenarthanan et al. [34]	2018	India	7,3	30±6	Oral diclofenac sodium	75mg	10	6,12,24,48	10cm	In patients with low pain threshold, intra-ligamentary route of administration is effective in controlling pain of endodontic origin postoperatively.
			5,5	26±9	Intraligamentary route of diclofenac sodium	NA	10
			6,4	28±7	Placebo		10
Yavari et al. [35]	2019	Iran	NA	20-50	Placebo		64	6, 12, 24, 48, 72	0-10	Infiltration of long-acting betamethasone and dexamethasone resulted in decreased postoperative pain experience. Dexamethasone was more effective in alleviating pain within the first 24-hour period after treatment. Infiltration of long-acting betamethasone and dexamethasone exhibited the same efficacy in 48 hours. The efficacy of long-acting betamethasone in pain relief lasted for 7 days. The QOL in the 2 groups receiving corticosteroids was higher than that in the placebo group.
					Betamethasone	0.7 mL	66
					Dexamethasone	4mg	64
Makkar et al. [36]	2012	India	7,3	39.6 yrs	Ibuprofen and paracetamol	400 mg,325 mg	10	6,12,24	10 cm	A single oral dose of diclofenac sodium and paracetamol and ibuprofen and paracetamol combination reduced postoperative pain following pulpectomy and root canal preparation of teeth with irreversible pulpitis.
			6,4	41.3 yrs	Diclofenac sodium and paracetamol	50 mg, 500mg	10
			6,4	37.9 yrs	Placebo		10
Doroschak et al. [37]	1999	USA	NA	18-65	Tramadol	100 mg	12	1,2,3	100 mm	NSAID/opiate combination, together with endodontic therapy, may be useful in the management of endodontic pain.
					Flurbiprofen	100 mg	12
					Tramadol/Flurbiprofen	100 mg	13
					Placebo		12
Konagala et al. [38]	2019	India	62,70	18-50	Piroxicam	20 mg	30	6,12,24,48,72	100 mm	Preoperative single oral dose of piroxicam or dexamethasone or deflazacort is equally effective in controlling post-endodontic pain.
					dexamethasone	4 mg	30
					deflazacort	30 mg	30
					Placebo		30
Ashraf [39]	2002	Iran	NA	NA	Rofecoxib	NA	60	12	100mm	NA
					Ibuprofen
					Placebo
Chance et al. [40]	1987	USA	NA	NA	prednisolone	NA	158	NA	NA	The corticosteroid was effective in significantly reducing the incidence of postoperative pain in teeth where vital pulp was present.
					Placebo		142
Glassman et al. [41]	1989	USA	NA	NA	Dexamethasone	4 mg	19	NA	NA	oral dexamethasone is sufficient to significantly reduce endodontic interappointment pain for teeth with asymptomatic vital-inflamed pulps.
					Placebo		18
Kaufman et al. [42]	1994	Israel	16,29	19-71	Methylprednisolone	8 mg	18	24	NA	The tested drug significantly reduced the frequency and intensity of postoperative pain sequelae in the experimental set-up.
					Mepivacaine	NA	17
					Placebo	NA	10
Krasner et al. [43]	1986	USA	NA	NA	Dexamethasone	5.25mg	25	8,24	100 mm	Post-treatment endodontic pain was substantially reduced by administration of oral dexamethasone. The risks to the otherwise healthy patient seem to be minimal and acceptable
					Placebo		25
Liesinger et al. [44]	1993	USA	NA	NA	Dexamethasone	8 mg	106	1,4,8,24,48,72	9 cm	Patients who received dexamethasone took significantly fewer posttreatment pain medications than those who received the placebo
					Placebo
Marshall et al. [45]	1984	USA	NA	NA	Dexamethasone	4 mg	50	4,24	NA	Injection of the steroid (dexamethasone, 4 mg) significantly reduced both the incidence and severity of pain at 4 h post-treatment and reduced pain at 24 h post-treatment.
					Placebo
Mehrvarzfar et al. [46]	2008	Iran	34,66	21-58	Dexamethasone	4 mg	50	6,12,24,48	NA	Dexamethasone was considerably effective in controlling the severity of pain during the first 24 h; in contrast, there was no difference between dexamethasone and placebo groups 48 h after the first appointment.
					Placebo		50
Pochapski et al. [47]	2009	Brazil	26,24	18-67	Dexamethasone	4 mg	25	4,6,12,24	NA	Preoperative single oral dose of dexamethasone substantially reduced post-endodontic pain
					Placebo		23
Rogers et al. [48]	1999	USA	NA	NA	Dexamethasone	4mg	12	6,12,24,48	100 mm	At the 12-h period, both dexamethasone and ketorolac provided statistically significant better pain relief than placebo. At the 24-h period, only ketorolac demonstrated better pain relief than the placebo. There were no statistically significant differences among the groups at 6 and 48 h.
					Ketorolac tromethamine	30 mg	12
					Ibuprofen	600 mg	12
					placebo		12
Shantiaee et al. [49]	2012	Iran	30,60	18-42	Dexamethasone	4 mg	30	4,8,24,48	9cm	Periapical infiltration of dexamethasone and morphine led to a considerable decrease in postoperative endodontic pain during the first 24 h after operation. Dexamethasone was more effective than morphine in pain reduction.
					Morphine	1 mg	30
					Placebo		30
Zarrabi	2003	Iran	NA	NA	betamethasone	4 mg	50	6,12,24	NA	NA
					Placebo		50
Zarrabi et al. [50]	2007	Iran	NA	NA	betamethasone	2 mg	20	6,12,24	NA	NA
					Placebo		20
Sharma et al. [51]	2015	India	NA	NA	dexamethasone	4 mg	20	6,12,24	100 mm	NSAID resulted in significantly less post-operative endodontic pain at all time-intervals. Preoperative oral administration of Dexamethasone performed best in reducing pain post operatively.
					Placebo		20
Eftekhar et al. [52]	2013	NA	NA	NA	Triamcinolone	1 mg	40	NA	NA	NA
					Placebo		40
Moradi et al. [53]	2013	Iran	NA	NA	dexamethasone	4 mg	15	6,12,24,48	10 cm	Administration of dexamethasone did not reduce post-operative pain severity in the first 12hours after endodontic treatment
					Placebo		15
Ahangari	2009	Iran	NA	NA	dexamethasone	0.5 mg	20	6,12,24	10 cm	NA
					Placebo		20
Fava [54]	1998	NA	NA	28-64	Otosporin	NA	30	48 h/1 w	NA	No difference was observed in the incidence of post-operative pain between the two groups.
					Placebo		30
Ehrmann et al. [55]	2003	Australia	NA	NA	Triamcinolone acetonide		58	4,24,48,72	100 mm	Ledermix is an effective intracanal medicament for the control of postoperative pain associated with acute apical periodontitis, with a rapid onset of pain reduction.
					Placebo		71
Negm et al. [56]	2001	Egypt	NA	15-75	Kenacomb	NA	245	24	100 mm	intracanal use of corticosteroid-antibiotic combination for controlling posttreatment endodontic pain.
					Placebo		230
Wells et al. [57]	2011	USA	17,16	34.3±14.0	Ibuprofen/acetaminophen	600 mg/1000 mg	35	24,48,72	100 mm	There were decreases in pain levels and analgesic use over time in the ibuprofen and ibuprofen/acetaminophen groups.
			20,15	37.3± 14.7	Ibuprofen	600 mg	36
Battrum et al. [58]	1996	USA	NA	NA	Ketorolac	10 mg	10	6,24	100mm	There was no significant difference in pain relief between the two groups treated with different drug regimens
					Placebo		10
Torabinejad et al. [59]	1994	NA	NA	NA	Salicylic acid	650 mg	50	30, 36, 42, 48, 54, 60, 66, 72	90mm	Ibuprofen, ketoprofen, erythromycin base, penicillin, and methylprednisolone plus penicillin were more effective than placebo within the first 48 h following complete instrumentation.
					Acetaminophen	650 mg	57
					Ibuprofen	400 mg	57
					Ketoprofen 50 mg	50 mg	53
					Acetaminophen + codeine	325 mg/60 mg	48
Moskow et al. [60]	1984	NA	NA	NA	Dexamethasone	4 mg	26	24,48,72	100 mm	A statistically significant decreased incidence of pain was reported for the corticosteroid cases as compared to the control at the 24-hour time period (p<0.05)
					Placebo		24