Summary Aims and methods:  In this double‐blind, double‐dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re‐dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results:  Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention‐to‐treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain‐free rates higher than 30% (95% CI of odds‐ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds‐ratio: 0.82–1.84) with both the drugs. The efficacy of re‐dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain‐free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re‐dosing to treat a recurrence/relapse was very high without differences between the drugs (pain‐free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well‐tolerated. Conclusion:  The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.

This study, analyzed according to the more recent guidelines for controlled trials in migraine, showed that a fixed combination of indomethacin, prochlorperazine, and caffeine is significantly more effective than sumatriptan in the acute treatment of migraine attacks. It is notable that the combination is less expensive than sumatriptan per unit dose.

In this double-blind, randomized, parallel group, multicentre study the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) and nimesulide were compared over an 8-h period in the treatment of two consecutive episodes of tension-type headache (TTH). Both drugs were administered orally. Of 54 randomized patients, 40 were compliant to the protocol. More patients on IndoProCaf than on nimesulide were pain-free at 2 h post-dose (45% vs. 10%; P<0.05), reached a pain reduction of at least 50% at 2 (75% vs. 30%; P<0.05) and 4 h post-dose (90% vs. 58%; P<0.05), and had a statistically significant lower mean time to a 50 and 100% pain reduction in the second TTH episode. A higher percentage of patients reached a 50 or 100% pain reduction at 2 h post-dose with IndoProCaf compared with nimesulide, in two of two treated TTH episodes. A clinically and statistically significant change within each treatment group over time was found for the severity of pain, the headache intensity difference (HID), the sum of headache intensity difference (SHID), the maximum headache intensity difference (MAXHID), the headache relief (HER), the sum of total headache relief (TOTHER) and the maximum headache relief (MAXHER). In conclusion, IndoProCaf showed to be superior, but globally not statistically different from nimesulide in the treatment of episodic TTH. Both drugs were very effective and well tolerated.

The combination of indomethacin, caffeine, and prochlorperazine (hereinafter IndoProCaf) represents an effective antimigraine drug available on the Italian market. The aim of this study was to test the efficacy of the three active principles alone and in combination in reverting hyperalgesia. Hyperalgesia was induced by morphine withdrawal in mice treated with morphine for 15 days and then made hyperalgic by morphine substitution with water. This study showed that indomethacin 0.3 mg kg −1 , i.p.; caffeine 0.1 and 0.3 mg kg −1 , i.p.; and prochlorperazine 0.1 mg kg −1 , i.p.; as well as the combination of the three active principles, were able to revert morphine withdrawal induced hyperalgesia, causing a statistically significant increase of pain threshold in hyperalgic mice. In a second model, hyperalgesia was induced by the i.p. injection of a 0.3% solution of acetic acid in mice and was evaluated counting the number of abdominal constrictions. Indomethacin (0.1 mg kg −1 , i.p.), caffeine (0.3 mg kg −1 , i.p.), and prochlorperazine (0.1 mg kg −1 , i.p.) reduced the number of abdominal constrictions, while the combination of the three active principles was able to abolish almost completely the abdominal constrictions, with a significantly higher efficacy compared to the single active principles. In both models, indomethacin, caffeine, and prochlorperazine reverted hyperalgesia at dosages 10 times lower than the corresponding analgesic ones. These data provide the pharmacologic evidence of the efficacy of IndoProCaf in reverting hyperalgesia, a condition of reduction of pain threshold similar to that occurring in migraine.

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