Table 4. Pharmacological Intervention .

Study ID	Authors & Year of Publication	Study Design	Sample Size & Groups	Drug & Dose	Duration of Intervention	Tools	Results & Conclusion	Difference in Percentage/ Mean/Median Between Groups at the Final Measurement
6	Tvedsko et al26	Double-Blind, Randomized, Placebo-Controlled, Crossover Study	Sample Size: n = 13	10 mg Olcegepant or Placebo (5% Xylitol)	Day 1: Initial infusion of 0.5 mg/kg/min NTG for 20 minutes, followed by a 10 mg infusion of Olcegepant 40 minutes later over 10 minutes Day 2: Initial infusion of 0.5 mg/kg/min NTG for 20 minutes, followed by a placebo infusion (5% xylitol) for 10 minutes	The 0-to-10 Verbal NRS	Peak headache scores ranged from 0 to 10 (median of 5) in patients receiving NTG plus placebo and from 0 to 9 (median of 4) in those receiving NTG plus Olcegepant (P = 0.69). Olcegepant, a CGRP receptor antagonist (BIBN4096BS), does not have a preventive effect on NTG-induced migraines.	Difference in the median peak headache scores between the intervention and placebo groups after 12 hours: 1
7	Tfelt‐Hansen et al17	Double-Blind, Randomized, Placebo-Controlled, Crossover Study	Intervention Group: n = 15 Placebo Group: n = 15	150 mg Prednisolone	Intervention Group: Administration of prednisolone at 12-hour intervals prior to NTG infusion (0.5 µg/kg/min for 20 minutes). Placebo Group: Administration of placebo Washout Period: 3 weeks	The 0-to-10 Verbal NRS	Findings showed significantly lower peak headache scores over 12 hours after the use of prednisolone (P < 0.01), but peak headache and headache response did not significantly change (P < 0.07). Pretreatment with prednisolone did not reduce immediate NTG-induced headaches and did not prevent delayed headache frequency, but significantly reduced the severity of delayed NTG-induced headaches.	Difference in the mean peak headache scores between the two groups after 12 hours: 2
8	Tvedskov et al24	Double-Blind, Randomized, Placebo-Controlled, Multicenter Crossover Study	Sample Size: n = 35 (19 Patients with Migraine, 16 Controls)	160 mg Propranolol or Placebo	Intervention Group: Administration of 160 mg propranolol daily for 13 days prior to the date of NTG infusion Placebo Group: Administration of placebo daily for 13 days prior to the date of NTG infusion Washout Period: 14 days	The 0-to-10 Verbal NRS	NTG-induced headaches were more pronounced in migraine patients compared to healthy individuals, both with (P = 0.003) and without (P = 0.017) pretreatment with propranolol. Propranolol was not effective in treating NTG-induced headaches and migraines.	Difference in the median peak headache scores between the two groups after 12 hours: 1
9	Tvedskov et al16	Randomized, Double-Blind, Crossover Study	Sample Size: n = 12 Intervention Group: n = 6 Placebo Group: n = 6	1000 mg Sodium Valproate or Placebo Tablets	Intervention Group: Administration of sodium valproate for at least 13 days Placebo Group: Administration of placebo for at least 13 days Washout Period: 14 days at least	The 0-to-10 Verbal NRS	The mean peak headache intensity was 1 (range of 0–9) after the use of valproate compared to 4.5 (range of 0–8) after the use of placebo (P = 0.12). Valproate was effective in managing NTG-induced headaches and migraines.	Difference in the median headache intensity scores between the two groups after 12 hours: 3.5
10	Tvedskov, Iversen& Olesen27	Randomized, Double-Blind, Crossover Study	Sample Size: n = 15 Day 1: n = 9 Day 2: n = 9	40 mg Oral Dose of SB-220453 (Tonerbasat) or Placebo Tablets	Intervention Group: Administration of a Tonerbasat tablet before Intravenous infusion NTG Placebo Group: Administration of a placebo tablet Washout Period: 11 days at least	The 0-to-10 Verbal NRS	No significant reduction was observed in headache scores. There was no decrease in the number of individuals with delayed headaches or migraine attacks.	Difference in the mean headache intensity scores between the two groups after 12 hours: 1.2
11	Schmetterer et al20	Double-Blind, Randomized, Placebo-Controlled, Crossover Study	Sample Size: n = 10 (Healthy Male Participants)	Subcutaneous Injection of 6 mg Sumatriptan (0.5 mL) or Placebo (0.5 mL Physiological Saline Solution)	Intervention Group: Subcutaneous administration of sumatriptan Placebo Group: Subcutaneous administration of placebo Washout Period: 2-6 days	Participants were asked twice whether they experienced pain or discomfort (20 minutes after the administration of sumatriptan or placebo and 10 minutes after the start of NTG infusion).	Following the NTG infusion, the velocity of the middle cerebral blood flow decreased by 13.3% from baseline after placebo treatment, compared to 2.2% after the consumption of sumatriptan (treatment effect, + 10.8%; P < 0.05).	Not reported
12	Iversen & Olesen19	Randomized, Double-Blind Crossover Study	Sample Size: n = 10	Subcutaneous Injection of 6 mg Sumatriptan or Placebo (Isotonic Saline)	Intervention Group: Subcutaneous administration of 6 mg sumatriptan in the deltoid region Placebo Group: Subcutaneous administration of placebo (isotonic saline) in the deltoid region	The 0-to-10 Verbal NRS	Sumatriptan reduced NTG-induced headache (mean score of 1.5 vs. 4 after placebo; P < 0.01). Whether sumatriptan acts on preventive receptors cannot be determined based on the results of this study	Difference in the median headache scores at the time of NTG infusion between the two groups: 2.5
13	Iversen28	Randomized, Placebo-Controlled, Crossover Study	Sample Size: n = 11	100 mg/kg N- Acetylcysteine diluted in 100 mL isotonic dextrose solution or Placebo (Saline Solution)	Day 1: Intravenous injection of N-acetylcysteine over 15 minutes, followed by an infusion of NTG for 20 minutes Day 2: Intravenous injection of saline over 15 minutes, followed by an infusion of NTG for 20 minutes Washout Period: 6 days at least	The 0-to-10 Verbal NRS	Headaches during both NTG infusion sessions lasted longer after the administration of N-acetylcysteine compared to after that of placebo.	Difference in the median peak headache scores between the intervention and placebo groups after 3 hours: 2