NSAID chronotherapy after impacted third molar extraction: a randomized controlled trial

Z. Tamimi, M. Abusamak, H. Al-Waeli, M. Al-Tamimi, R. Al Habashneh, M. Ghanim, M. Al-Nusair, Q. Gao, B. Nicolau, F. Tamimi

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Objectives: Postoperative pain management impacts patients’ quality of life and morbidity. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are widely used for this following a 3-doses-per-day regime. However, pain and inflammation follow a circadian rhythm, and animal models assessing the scheduling of NSAID administration (e.g., chronotherapy) have shown that while their use during the active phase of the day enhances postoperative recovery, their administration during the resting phase could have detrimental effects. This observation has led us to hypothesize that night administration of NSAID might be unnecessary in post-surgical scenarios. Therefore, a randomized clinical trial was conducted to test this hypothesis in surgical third molar extractions. Materials and methods: Seventy (18–35 years) healthy participants requiring surgical removal of impacted lower third molars were recruited and randomized into a double-blind placebo-controlled study. For three days postoperatively, the treatment group (n = 33) received ibuprofen (400 mg) at 8 AM, 1 PM, and a placebo at 8 PM, while the control group (n = 37) received ibuprofen (400 mg) at 8 AM, 1 PM, and 8 PM. Pain severity was assessed by visual analog scale (VAS) and healing indicators including facial swelling, mouth opening, and C-reactive protein blood levels were also measured. Results: Pain VAS measures showed a circadian variation peaking at night. Also, no significant differences were observed between the two groups of the study in terms of postoperative pain scores (estimate: 0.50, 95% CI = [− 0.38, 1.39]) or any other healing indicator. Conclusions: Postoperative pain follows a circadian rhythm. Moreover, night administration of ibuprofen might not provide any significant benefits in terms of pain management and control of inflammation, and two doses during the day only could be sufficient for pain management after surgical interventions. Knowledge transfer statement: Even though this study cannot rule out the possibility that a reduced regime is different than a standard regime, nocturnal doses of ibuprofen seem to have no clinical significance in the short term, and the results of this study provide evidence in favor of reducing ibuprofen administration from three doses to two doses only after third molar surgery.

Original languageEnglish
Pages (from-to)663-672
Number of pages10
JournalOral and Maxillofacial Surgery
Issue number4
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This study was funded by Jordan University of Science and Technology in Irbid, Jordan (funding number: 20170307).

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.


  • Chronotherapy
  • Drug chronotherapy
  • Molar
  • NSAIDs
  • Pain management
  • Third
  • Tooth extraction

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial


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