Non-Cochrane · intervention · PM42265625
The effect of pregabalin for pain after third molar surgery: a systematic review and meta-analysis.
Li Jie, Wang Anli · BMC anesthesiology · 2026 · PubMed · doi:10.1186/s12871-026-04000-w
Findings
Population Patients undergoing third molar surgery
17 findings
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 2 h to 72 h, all assessments pooled · Third molar surgery, oral and maxillofacial surgery | MD -0.99 [-1.46, -0.52] Low Downgraded: imprecision, inconsistency 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 2 h to 24 h pooled · Third molar surgery, oral and maxillofacial surgery · Sensitivity: timepoint analysis excluding Diniz 2024 | Pooled effect not significant (p=0.60) and I2 reduced from 92% to 0% after excluding Diniz 2024; estimate not reported GRADE not reported 2 studies · 108 participants |
| Pregabalin | Placebo or no pregabalin control | Adverse events Postoperative · Third molar surgery, oral and maxillofacial surgery | OR 4.36 [2.52, 7.55] 272 [148, 408] more per 1,000 Low Downgraded: imprecision, inconsistency 3 studies · 321 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 24 h postoperatively · Third molar surgery, oral and maxillofacial surgery · Timepoint subgroup | MD -0.81 [-2.15, 0.52] GRADE not reported 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 6 h postoperatively · Third molar surgery, oral and maxillofacial surgery · Timepoint subgroup | MD -1.20 [-3.30, 0.90] GRADE not reported 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 2 h postoperatively · Third molar surgery, oral and maxillofacial surgery · Timepoint subgroup | MD -1.00 [-2.75, 0.75] GRADE not reported 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 8 h postoperatively · Third molar surgery, oral and maxillofacial surgery · Timepoint subgroup | MD -1.30 [-3.45, 0.84] GRADE not reported 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 4 h postoperatively · Third molar surgery, oral and maxillofacial surgery · Timepoint subgroup | MD -1.20 [-3.11, 0.70] GRADE not reported 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 2 h to 24 h pooled · Third molar surgery, oral and maxillofacial surgery · Timepoint analysis, all timepoints (2, 4, 6, 8, 12, 24 h) | MD -1.11 [-1.73, -0.49] GRADE not reported 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 12 h postoperatively · Third molar surgery, oral and maxillofacial surgery · Timepoint subgroup | MD -1.10 [-3.23, 1.04] GRADE not reported 3 studies · 170 participants |
| Pregabalin | Placebo, ibuprofen or no pregabalin control | Postoperative pain intensity (VAS 0-10) 2 h to 72 h, all assessments pooled · Third molar surgery, oral and maxillofacial surgery · Sensitivity: leave-one-out excluding Diniz 2024 | MD -0.03 [-0.21, 0.15] GRADE not reported 2 studies · 108 participants |
| Pregabalin | Placebo plus dexamethasone | Postoperative pain intensity (VAS 0-10) 2 h to 72 h, all assessments pooled · Third molar surgery, oral and maxillofacial surgery · Comparator type subgroup | MD -2.04 [-2.84, -1.24] GRADE not reported 1 study · 62 participants |
| Pregabalin | No pregabalin control | Postoperative pain intensity (VAS 0-10) 2 h to 72 h, all assessments pooled · Third molar surgery, oral and maxillofacial surgery · Comparator type subgroup | MD -0.42 [-0.96, 0.13] GRADE not reported 1 study · 60 participants |
| Pregabalin | Ibuprofen | Postoperative pain intensity (VAS 0-10) 2 h to 72 h, all assessments pooled · Third molar surgery, oral and maxillofacial surgery · Comparator type subgroup | MD 0.02 [-0.17, 0.20] GRADE not reported 1 study · 48 participants |
| Pregabalin 50 mg | Placebo or no pregabalin control | Adverse events Postoperative · Third molar surgery, oral and maxillofacial surgery · Pregabalin dose subgroup | OR 1.18 [0.41, 3.36] GRADE not reported 1 study · 99 participants |
| Pregabalin 75 mg | Placebo or no pregabalin control | Adverse events Postoperative · Third molar surgery, oral and maxillofacial surgery · Pregabalin dose subgroup | OR 5.19 [1.94, 13.88] GRADE not reported 2 studies · 122 participants |
| Pregabalin 300 mg | Placebo or no pregabalin control | Adverse events Postoperative · Third molar surgery, oral and maxillofacial surgery · Pregabalin dose subgroup | OR 11.16 [4.26, 29.18] GRADE not reported 1 study · 100 participants |
Included primary studies 6
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Cheung 2012 A double-blind randomized crossover study to evaluate the timing of pregabalin for third molar surgery under local anesthesia. PMID:21820233 | 2012 | this review only | not stated | not extracted yet |
| Diniz 2024 Evaluation of the effects of pregabalin and dexamethasone coadministration on preemptive multimodal analgesia and anxiety in third molar… PMID:38717697 | 2024 | this review only | Postoperative pain intensity (VAS 0-10); Adverse events | not extracted yet |
| Hill 2001 Pregabalin in patients with postoperative dental pain. PMID:11465977 | 2001 | this review only | Adverse events | not extracted yet |
| Hill 2009 ECG variations in patients pre- and post-local anaesthesia and analgesia. PMID:19893562 | 2009 | this review only | not stated | not extracted yet |
| Latifi 2023 Comparison of the analgesic effects of single-dose 75 mg oral pregabalin versus single-dose 400 mg oral ibuprofen after impacted third… PMID:37905456 | 2023 | this review only | Postoperative pain intensity (VAS 0-10) | not extracted yet |
| Olmedo-Gaya 2015 Oral pregabalin for postoperative pain relief after third molar extraction: a randomized controlled clinical trial. PMID:26578119 | 2016 | this review only | Postoperative pain intensity (VAS 0-10); Adverse events | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients undergoing surgical extraction of third molars | Patients undergoing third molar surgery (n=545 in 6 RCTs; 170 in pain meta-analysis) |
| Intervention | Pregabalin | Pregabalin 50 to 300 mg (n=6 RCTs) |
| Comparison | Placebo or active comparators | Placebo, ibuprofen, paracetamol, no pregabalin, placebo plus dexamethasone |
| Outcomes | Pain intensity within 72 h (VAS or NRS); frequency of adverse events | Pain VAS (3 RCTs), adverse events (3 RCTs) |
| Study designs | RCTs | RCTs (6; 4 parallel, 2 split-mouth) |
| Timing | Up to 72 h postoperatively | 0.5 to 72 h |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | No | No | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: No · NRSI: N/A | NRSI: N/A · RCT: No | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |