Non-Cochrane · intervention · PM42936803

Efficacy and safety of internal bleaching agents for discolored endodontically treated teeth: A systematic review and network meta-analysis of in vitro and ex vivo studies.

Drouri Sofia, Essanhajy Zohair, Jabri Mouna · Journal of conservative dentistry and endodontics · 2026 · PubMed · doi:10.4103/jcde.jcde_776_26

Findings

96 findings

Population
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Santos (2020) omitted
SMD 3.60 [2.37, 4.83]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, El Zayat (2025) omitted
SMD 2.92 [1.49, 4.34]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Feiz (2014) omitted
SMD 2.70 [1.10, 4.30]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Majidinia (2025) omitted
SMD 2.89 [1.50, 4.28]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Arslan (2025) omitted
SMD 2.66 [1.22, 4.10]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethCPControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD 2.66 [1.31, 4.01]
GRADE not reported
3 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 2.90 [1.61, 4.20]
Low
Downgraded: risk of bias, imprecision, inconsistency
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: no-outlier network
SMD 2.91 [1.57, 4.26]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethCPControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD 5.83 [1.11, 10.54]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Yogha-Padhma (2018) omitted
SMD 2.90 [1.61, 4.20]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Papadopoulos (2021) omitted
SMD 2.91 [1.57, 4.26]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethCPControlImmediate color change
End of active bleaching · Laboratory · Human teeth only
SMD 3.50 [1.96, 5.04]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 3.05 [1.94, 4.17]
GRADE not reported
9 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, de Almeida b (2023) omitted
SMD 2.61 [1.24, 3.98]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethHP + activationControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD 1.88 [-0.07, 3.82]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Santos (2020) omitted
SMD 3.48 [2.21, 4.74]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 2.74 [1.46, 4.01]
GRADE not reported
9 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: no-outlier network
SMD 2.55 [0.93, 4.17]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Feiz (2014) omitted
SMD 2.52 [0.93, 4.11]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Papadopoulos (2021) omitted
SMD 2.55 [0.93, 4.17]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Yogha-Padhma (2018) omitted
SMD 2.64 [1.14, 4.13]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethHP + activationControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD 3.72 [1.40, 6.04]
GRADE not reported
1 study
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, El Zayat (2025) omitted
SMD 2.61 [0.86, 4.35]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 2.64 [1.14, 4.13]
Very low
Downgraded: risk of bias, imprecision, inconsistency, indirectness
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Majidinia (2025) omitted
SMD 2.85 [1.16, 4.55]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, de Almeida b (2023) omitted
SMD 1.85 [-0.13, 3.84]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethHP + activationControlImmediate color change
End of active bleaching · Laboratory · Human teeth only
SMD 3.57 [1.24, 5.90]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Arslan (2025) omitted
SMD 2.40 [0.92, 3.89]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Papadopoulos (2021) omitted
SMD 2.07 [0.75, 3.39]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Santos (2020) omitted
SMD 2.01 [0.84, 3.17]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethSP/perborateControlImmediate color change
End of active bleaching · Laboratory · Human teeth only
SMD 1.91 [0.44, 3.38]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Arslan (2025) omitted
SMD 2.71 [1.29, 4.13]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 2.06 [0.79, 3.33]
Low
Downgraded: risk of bias, imprecision, inconsistency
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Majidinia (2025) omitted
SMD 2.05 [0.68, 3.42]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, El Zayat (2025) omitted
SMD 2.07 [0.67, 3.48]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Yogha-Padhma (2018) omitted
SMD 2.06 [0.79, 3.33]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Feiz (2014) omitted
SMD 1.71 [0.12, 3.29]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: no-outlier network
SMD 2.07 [0.75, 3.39]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethSP/perborateControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD 5.74 [0.99, 10.50]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 1.27 [0.06, 2.48]
GRADE not reported
9 studies
Discolored endodontically treated or simulated teethSP/perborateControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD 1.78 [0.46, 3.09]
GRADE not reported
3 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate (SP/perborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, de Almeida b (2023) omitted
SMD 1.78 [0.44, 3.12]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: no-outlier network
SMD 2.06 [0.78, 3.35]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethHPControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD 3.16 [-0.28, 6.60]
GRADE not reported
Studies not reported
Discolored endodontically treated or simulated teethHPControlImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD 1.87 [0.56, 3.19]
GRADE not reported
3 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Yogha-Padhma (2018) omitted
SMD 2.04 [0.81, 3.27]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Papadopoulos (2021) omitted
SMD 2.06 [0.78, 3.35]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Arslan (2025) omitted
SMD 1.79 [0.45, 3.13]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Feiz (2014) omitted
SMD 1.90 [0.57, 3.24]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 2.10 [1.04, 3.15]
GRADE not reported
9 studies
Discolored endodontically treated or simulated teethHPControlImmediate color change
End of active bleaching · Laboratory · Human teeth only
SMD 2.70 [0.84, 4.56]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Santos (2020) omitted
SMD 3.02 [1.89, 4.16]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 2.04 [0.81, 3.27]
Low
Downgraded: risk of bias, imprecision, inconsistency
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, de Almeida b (2023) omitted
SMD 1.34 [-0.20, 2.88]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, El Zayat (2025) omitted
SMD 2.06 [0.69, 3.42]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Majidinia (2025) omitted
SMD 2.00 [0.67, 3.33]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Santos (2020) omitted
SMD 1.72 [-0.33, 3.76]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: no-outlier network
SMD 1.78 [-0.88, 4.44]
GRADE not reported
7 studies
Discolored endodontically treated or simulated teethOther agentControlImmediate color change
End of active bleaching · Laboratory · Human teeth only
SMD 1.62 [-0.90, 4.14]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 0.98 [-1.25, 3.21]
GRADE not reported
9 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Feiz (2014) omitted
SMD 1.42 [-1.40, 4.23]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Papadopoulos (2021) omitted
SMD 1.78 [-0.88, 4.44]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, de Almeida b (2023) omitted
SMD 1.49 [-1.14, 4.13]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Majidinia (2025) omitted
SMD 1.76 [-1.00, 4.52]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, Arslan (2025) omitted
SMD 2.42 [0.00, 4.84]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 1.77 [-0.79, 4.33]
Very low
Downgraded: risk of bias, imprecision, indirectness
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Sensitivity: leave-one-out, El Zayat (2025) omitted
SMD 1.78 [-1.06, 4.62]
GRADE not reported
7 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Hydrogen peroxide (HP)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 0.86 [-0.52, 2.25]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Hydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 0.27 [-1.40, 1.94]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Other agent (sodium tetraborate)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 1.13 [-1.43, 3.69]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationCarbamide peroxide (CP)Sodium perborate (SP/perborate)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 0.84 [-0.43, 2.11]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Hydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD -0.60 [-1.64, 0.45]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Other agent (sodium tetraborate)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 0.27 [-2.35, 2.88]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide (HP)Sodium perborate (SP/perborate)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD -0.02 [-1.40, 1.36]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Other agent (sodium tetraborate)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 0.86 [-1.91, 3.64]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide with physical activation (laser/LED/ultrasonic) (HP + activation)Sodium perborate (SP/perborate)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD 0.58 [-1.09, 2.24]
GRADE not reported
8 studies · 354 participants
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationOther agent (sodium tetraborate)Sodium perborate (SP/perborate)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory
SMD -0.29 [-2.51, 1.93]
GRADE not reported
8 studies · 354 participants
Discolored endodontically treated or simulated teethCPHPImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD 1.24 [-0.32, 2.80]
GRADE not reported
2 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate + carbamide peroxide (SP + CP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 3.35 [1.83, 4.87]
GRADE not reported
9 studies
Discolored endodontically treated or simulated teethCPHPImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD -0.57 [-3.59, 2.45]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationSodium perborate + hydrogen peroxide (SP + HP)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 3.22 [1.52, 4.92]
GRADE not reported
9 studies
Discolored endodontically treated or simulated teethCPSP/perborateImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD -8.72 [-52.27, 34.83]
GRADE not reported
Studies not reported
Discolored endodontically treated or simulated teethCPSP/perborateImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD 0.85 [-0.42, 2.12]
GRADE not reported
3 studies
Discolored endodontically treated or simulated teethHPHP + activationImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD -4.51 [-9.46, 0.45]
GRADE not reported
Studies not reported
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide + calcium oxalate (HP + Ca-oxalate)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 3.07 [1.19, 4.95]
GRADE not reported
9 studies
Discolored endodontically treated or simulated teethHPHP + activationImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD -0.41 [-1.48, 0.66]
GRADE not reported
4 studies
Discolored endodontically treated or simulated teethHPSP/perborateImmediate color change
End of active bleaching · Laboratory · Node splitting: Indirect estimate
SMD 0.56 [-2.37, 3.49]
GRADE not reported
Studies not reported
Discolored endodontically treated or simulated teethHPSP/perborateImmediate color change
End of active bleaching · Laboratory · Node splitting: Direct estimate
SMD -0.19 [-1.75, 1.38]
GRADE not reported
2 studies
Extracted permanent teeth, endodontically treated or simulated, with intrinsic or experimentally induced discolorationHydrogen peroxide + calcium oxalate + activation (HP + Ca-oxalate + activation)Untreated control (no bleaching)Immediate color change (standardized across ΔEab/ΔE00 metrics)
Immediate (end of active bleaching) · In vitro / ex vivo laboratory · Exploratory fine (disaggregated) network, 10 nodes
SMD 2.85 [0.98, 4.73]
GRADE not reported
9 studies
Discolored endodontically treated or simulated teethControlBaseline colorColor change ΔEab
End of active bleaching · Laboratory · Random-effects pooled arm mean
MEAN 3.34 [2.89, 3.80]
GRADE not reported
3 studies
Discolored endodontically treated or simulated teethCPBaseline colorColor change ΔEab
End of active bleaching · Laboratory · Random-effects pooled arm mean
MEAN 11.38 [9.77, 13.00]
GRADE not reported
2 studies
Discolored endodontically treated or simulated teethHPBaseline colorColor change ΔEab
End of active bleaching · Laboratory · Random-effects pooled arm mean
MEAN 15.79 [1.50, 30.07]
GRADE not reported
4 studies
Discolored endodontically treated or simulated teethHPBaseline colorColor change ΔE00
End of active bleaching · Laboratory · Random-effects pooled arm mean
MEAN 17.25 [6.58, 27.92]
GRADE not reported
2 studies
Discolored endodontically treated or simulated teethHP + activationBaseline colorColor change ΔEab
End of active bleaching · Laboratory · Random-effects pooled arm mean
MEAN 21.28 [-0.60, 43.16]
GRADE not reported
3 studies
Discolored endodontically treated or simulated teethSP/perborateBaseline colorColor change ΔEab
End of active bleaching · Laboratory · Random-effects pooled arm mean
MEAN 16.46 [8.79, 24.14]
GRADE not reported
3 studies
Discolored endodontically treated or simulated teethInternal bleaching agentsAlternative agents or no bleachingExternal cervical root resorption
Laboratory
no estimate extracted
No studies found
0 studies

Included primary studies 26

Open in Studies
StudyYearAlso included byOutcomes it informs hereTrial data
Arslan 2025
Comparative study of the effectiveness of different bleaching agents on blood-colored extracted teeth and investigation of recoloring…
PMID:40660936
2025this review onlynot statednot extracted yet
Cardoso 2013
Ultrasonic activation of internal bleaching agents.
PMID:22788541
2013this review onlynot statednot extracted yet
Celik 2019
Deionized water can substitute common bleaching agents for nonvital tooth bleaching when treated with non-thermal atmospheric plasma.
PMID:30713266
2019this review onlynot statednot extracted yet
Coppola 2023
Chemical, morphological and microhardness analysis of coronary dentin submitted to internal bleaching with hydrogen peroxide and violet LED.
PMID:37890812
2023this review onlynot statednot extracted yet
Daneshpooy 2024
Investigating the Effect of Internal Bleaching With 10% Carbamide Peroxide on the Color Change of Three Types of Common Endodontic Sealers.
PMID:38420069
2024this review onlynot statednot extracted yet
de Almeida 2023a
Effectiveness and color stability of non-vital dental bleaching photoactivated by violet LED on blood-stained teeth.
PMID:36758735
2023this review onlynot statednot extracted yet
de Almeida 2023b
Effect of non-vital tooth bleaching photoactivated with blue or violet LED on color and microhardness.
PMID:37037401
2023this review onlynot statednot extracted yet
de Almeida 2023c
Fracture strength and hybrid layer formation of endodontically-treated teeth after dental bleaching photoactivated with violet LED.
PMID:37748699
2023this review onlynot statednot extracted yet
El Zayat 2025
The Effect of Novel Laser-Activated Bleaching Protocols on the Color Change of Non-Vital Anterior Teeth: An In Vitro Study.
PMID:39750516
2025this review onlynot statednot extracted yet
Feiz 2014
Effect of several bleaching agents on teeth stained with a resin-based sealer.
PMID:23647234
2014this review onlynot statednot extracted yet
Gaidarji 2022
Effectiveness and color stability of bleaching techniques on blood-stained teeth: An in vitro study.
PMID:34859941
2022this review onlynot statednot extracted yet
Jang 2013
Tooth discoloration after the use of new pozzolan cement (Endocem) and mineral trioxide aggregate and the effects of internal bleaching.
PMID:24238455
2013this review onlynot statednot extracted yet
Kaneko 2000
Bleaching effect of sodium percarbonate on discolored pulpless teeth in vitro.
PMID:11194360
2000this review onlynot statednot extracted yet
Majidinia 2025
Internal bleaching with calcium oxalate and laser irradiation for managing discolorations induced by mineral trioxide aggregate.
PMID:40055702
2025this review onlynot statednot extracted yet
Marchesan 2018
Effect of access design on intracoronal bleaching of endodontically treated teeth: An ex vivo study.
PMID:28858418
2018this review onlynot statednot extracted yet
Martin-Biedma 2010
Colorimeter and scanning electron microscopy analysis of teeth submitted to internal bleaching.
PMID:20113803
2010this review onlynot statednot extracted yet
Papadopoulos 2021
Spectrophotometric evaluation of the effectiveness of Er,Cr:YSGG laser-assisted intracoronal tooth bleaching treatment using different…
PMID:33798751
2021this review onlynot statednot extracted yet
Salem 2022
matched by author and year (probable)
NRthis review onlynot statednot extracted yet
Santos 2020
[Hip pain in children].
PMID:2020816
1991this review onlynot statednot extracted yet
Tavsan 2025
Effects of non-vital bleaching agents and resin composites on the color stability, translucency, and whiteness index of stained teeth at…
PMID:40611161
2025this review onlynot statednot extracted yet
Teodosio 2022
Bleaching effect of violet LED of 405-410 nm on stained endodontically treated teeth.
PMID:35644346
2022this review onlynot statednot extracted yet
Wang 2018
A colourimetric evaluation of the effect of bacterial contamination on teeth stained with blood in vitro: Evaluation of the efficacy of…
PMID:29485695
2018this review onlynot statednot extracted yet
Wei 2016
Spectroradiometric and Chemical Analysis of Severely Discolored Endodontically Treated Teeth.
PMID:26919085
2016this review onlynot statednot extracted yet
Yang 2021
Tooth discoloration and the effects of internal bleaching on the novel endodontic filling material SavDen® MTA.
PMID:32600866
2021this review onlynot statednot extracted yet
Yogha-Padhma 2018
Tooth discoloration and internal bleaching after the use of ledermix paste with various bleaching agents - An in vitro study.
PMID:30607221
2018this review onlynot statednot extracted yet
Yui 2008
Ex vivo evaluation of the effectiveness of bleaching agents on the shade alteration of blood-stained teeth.
PMID:18422585
2008this review onlynot statednot extracted yet

Review question

ElementPlanned (methods)Found (results)
PopulationExtracted permanent teeth, endodontically treated or experimentally prepared to simulate endodontically treated teeth, with intrinsic or experimentally induced discoloration relevant to nonvital teethExtracted human anterior teeth (most), bovine specimens (4), one intact human tooth; discoloration mostly blood-induced, also sealer, tetracycline, tea, coffee, red wine, MTA/restorative materials (n=26 reports, 24 studies)
InterventionInternal bleaching: walking-bleach, in-office intracoronal, inside-outside, and chemically or physically activated protocols (agent nodes defined a priori by bleaching agent and activation)SP, HP, CP at various concentrations alone or combined; activation with diode or Er,Cr:YSGG lasers, blue/violet LEDs, nonthermal plasma, ultrasonic; calcium oxalate; sodium tetraborate; sodium percarbonate (primary network: CP, HP, HP + activation, SP/perborate, other agent; n=8 studies)
ComparisonBaseline color, no bleaching, placebo or distilled/deionized water, or an alternative agent, concentration, technique, activation method, or time pointUntreated control and alternative agents/activation (primary network reference: untreated control)
OutcomesPrimary: immediate color change (ΔEab, ΔE00, WID, CIELAB coordinates; visual shade guide separately). Secondary: color stability/relapse/recoloration; dentine or enamel microhardness; fracture resistance; surface morphology, tubule exposure, chemical change or roughness; bond strength and resin-dentine interface integrity; cervical sealing or leakageImmediate color change pooled in NMA (n=8 studies, 354 specimen observations); color stability narrative (n=7 reports); structural, chemical, mechanical, restorative effects narrative (n=8 datasets); external cervical resorption not measured (n=0)
Study designsIn vitro and ex vivo laboratory studies onlyIn vitro and ex vivo laboratory studies (n=26 reports)
TimingImmediate efficacy at end of active bleaching; longest available time point for stabilityFollow-up from a single measurement to 9 months

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.

ItemExtractor AExtractor BAgree
1Research question includes PICO componentsYesYesyes
2Protocol established before the reviewcriticalYesPartial Yesno
3Choice of study designs explainedYesYesyes
4Comprehensive literature searchcriticalNoPartial Yesno
5Study selection in duplicateYesYesyes
6Data extraction in duplicateYesYesyes
7List of excluded studies with reasonscriticalNoNoyes
8Included studies described in detailYesYesyes
9Risk of bias assessed satisfactorilycriticalRCT: N/A · NRSI: Partial YesNRSI: N/A · RCT: N/Ano
10Funding of included studies reportedNoNoyes
11Appropriate meta-analysis methodscriticalRCT: N/A · NRSI: YesNRSI: N/A · RCT: N/Ano
12Impact of risk of bias on the pooled resultsYesYesyes
13Risk of bias accounted for in interpretationcriticalYesYesyes
14Heterogeneity explainedYesYesyes
15Publication bias investigatedcriticalYesYesyes
16Conflicts of interest reportedYesPartial Yesno
OverallCritically LowLowno