Melasma is a common, acquired hyperpigmentation disorder that presents a significant clinical challenge due to its chronic nature, high relapse rates, and pronounced impact on patients' quality of life (1, 2). This condition disproportionately affects women and individuals with darker skin phototypes (Fitzpatrick III–VI) (3, 4). The pathophysiology of melasma is multifactorial and complex, involving not only the hyperactivity of melanocytes but also the influence of ultraviolet radiation, hormonal factors, underlying vascular and inflammatory components, and disruption of the basement membrane (3, 4). These intertwined mechanisms contribute to its resistance to treatment and high recurrence rates. Current first-line therapies, including topical agents (e.g., triple-combination creams) and systemic treatments (e.g., tranexamic acid), are often limited by their efficacy, adverse effects, and propensity for high recurrence rates (3, 5).

Laser and light-based modalities, such as Q-switched (QS) lasers and intense pulsed light (IPL), have emerged as valuable options for refractory cases. Their complementary mechanisms—with QS lasers targeting melanin via selective photothermolysis and IPL targeting both pigmentary and vascular components—provide a rationale for combination therapy aimed at simultaneously addressing multiple pathogenic pathways (4, 6, 7). This potential synergy suggests that combining QS lasers, which target melanin via selective photothermolysis, with IPL, which targets both pigmentary and vascular components, may improve outcomes and reduce relapse rates by simultaneously targeting epidermal and dermal pigments (4, 6–8). However, monotherapy with these modalities can be problematic due to inconsistent response rates, a significant risk of post-inflammatory hyperpigmentation (PIH) especially in patients with darker skin types (Fitzpatrick III–VI), and the requirement for multiple treatment sessions (9, 10).

Critically, there is a distinct gap in the current evidence base. While narrative reviews discuss combination therapies, there is a lack of comprehensive quantitative synthesis specifically comparing the combined efficacy and safety of QS laser and IPL against each modality alone. Existing meta-analyses have typically focused on single modalities, leaving the relative benefit of this specific combination unclear. Furthermore, available comparative studies are limited by methodological heterogeneity, small sample sizes, and often insufficient follow-up to assess relapse rates. Therefore, a rigorous synthesis of efficacy and safety data is urgently needed to guide clinical decision-making.

It is also crucial to consider the study population's context. The risk of PIH and treatment response varies significantly with skin phototype (9). Notably, the majority of the existing primary research on laser and light-based therapies for melasma, and consequently the evidence base for this meta-analysis, has been conducted in populations with Fitzpatrick skin types III–V, predominantly comprising individuals of East Asian descent (4, 9, 10). This demographic focus must be acknowledged upfront as it directly impacts the safety profile and generalizability of the findings to other ethnic groups and skin phototypes.

Therefore, this study employs a systematic review and meta-analysis to quantitatively evaluate the efficacy—measured by reduction in the Melasma Area and Severity Index (MASI) score, a tool assessing the extent and severity of melasma—and safety of combining QS laser with IPL vs. either modality alone. To address the identified gaps, this research provides the first focused meta-analysis comparing this specific combination against monotherapies, synthesizing data from both randomized controlled trials and non-randomized controlled trials to offer a comprehensive, quantitative evaluation. Through this comprehensive evidence synthesis, our study aims to optimize therapeutic strategies and improve care for patients suffering from this challenging condition.

Publication bias was evaluated for the primary outcomes (MASI score and adverse reaction rates). Visual inspection of the funnel plots suggested approximate symmetry, which was supported by non-significant results from both Begg's test (all p > 0.05) and Egger's test (all p > 0.05). The funnel plots are presented in Figures 9–12.

The GRADE evaluation showed moderate-quality evidence (⊕⊕⊕○) for most outcomes—MASI improvement, effectiveness, adverse reactions, and satisfaction—but low-quality evidence (⊕⊕○○) for recurrence rates. The limited number of studies reporting recurrence rates is a key reason for the downgrading of the evidence quality for this outcome. The complete evidence profile is provided in Table 3.

Melasma is a disfiguring facial dermatosis that causes substantial psychological distress and economic burdens for affected individuals. This highlights the persistent need for more effective and durable treatment options. While numerous therapeutic modalities exist, each demonstrates distinct limitations that complicate long-term management. In recent years, laser and light-based interventions—particularly Q-switched (QS) lasers and intense pulsed light (IPL)—have gained increasing clinical interest.

This systematic review and meta-analysis provides the first quantitative evaluation of the efficacy and safety of combined QS laser and IPL therapy compared to monotherapy for melasma. The results indicate that compared to the monotherapy groups, participants receiving combination therapy achieved significantly greater improvement in the Melasma Area and Severity Index (MASI) scores and a higher clinical response rate, along with a reduction in recurrence. Furthermore, no significant differences were observed between the two groups in terms of adverse event rates or patient satisfaction. This discussion will analyze the clinical implications, explore the potential mechanisms underlying the enhanced efficacy of this combined approach, and consider its clinical significance in the management of this complex dermatological condition.

Building on the observed effectiveness of combination therapy in lowering MASI scores, further investigation into the underlying mechanisms was conducted. The improved outcomes may result from the combined effects of QS lasers and IPL, which work through heat and sound-based mechanisms. In the included studies, QS lasers were mainly Q-switched Nd:YAG lasers (1,064 nm), with the fluence ranging from 0.8 to 4.0 J/cm², pulse duration of 5–20 ns, spot size of 6–10 mm, 3–6 treatment sessions and 2–4 weeks interval between sessions. IPL was usually set at the wavelength of 560–1,200 nm with cut-off filters, fluence of 15–30 J/cm², pulse duration of 3–10 ms (mostly double or triple pulses), spot size of 8–15 mm, 4–8 treatment sessions and 2–4 weeks interval. Most combination therapy protocols applied alternating regimens, and all included studies adopted contact cooling during treatment and recommended daily use of broad-spectrum sunscreen (SPF ≥30, PA + + + ) post-treatment to minimize photodamage. Notably, the included studies showed low heterogeneity, supporting the reliability of the pooled results; however, a parameter-level meta-analysis was not feasible due to incomplete reporting of treatment parameters in individual studies (4, 8, 42, 43). The Q-switched Nd:YAG laser, especially when applied at low fluence, effectively disrupts melanosomes and selectively targets melanin-rich cells through a process known as photothermolysis (42). Meanwhile, IPL works by targeting both epidermal and superficial dermal pigmentation, utilizing selective absorption by melanin and hemoglobin chromophores (43, 44). Beyond pigment-targeting, IPL can modulate inflammatory mediators, reduce mast cell infiltration, downregulate pro-angiogenic pathways, remodel dermal extracellular matrix, and restore basement membrane integrity—key effects to counteract the chronic persistence and recurrence of melasma, as well as improve vascular abnormalities and dermal photoaging-related changes (8, 45–47). In contrast, QS laser monotherapy only focuses on melanin clearance, lacking regulatory effects on dermal stroma, vascular structures and inflammatory responses associated with melasma, which accounts for its limited efficacy and relatively high recurrence rate (4, 10, 48). This complementary mechanism of the two modalities not only achieves synergistic therapeutic efficacy but also provides a mechanistic basis for its anti-recurrence potential (8, 46, 47), which is verified by reflectance confocal microscopy and neural network evaluations showing significant and sustained MASI score reductions (8, 46). Unlike monotherapies (QS laser or IPL) with moderate efficacy (usually below 60%), combined therapy targets multiple pathological pathways (pigment metabolism, vascular dysregulation and inflammatory cascades) simultaneously to achieve higher treatment response rates, which is consistent with existing academic consensus (4, 6, 8, 10, 49). Molecular and imaging data further confirm that this combined strategy reduces pigmentation while optimizing the local skin microenvironment, with its superior efficacy rooted in enhanced pigment clearance and blocked chronic inflammatory and vascular cycles involved in melasma pathogenesis (45, 47, 48).

Notably, variations in therapeutic efficacy among the included studies may be attributed to differences in device settings, patient characteristics, and lesion duration. It should be emphasized that melasma is a chronic and recurrent cutaneous disorder, and at least 12 months of long-term follow-up is indispensable to confirm the durability of treatment effects. However, current evidence has clear limitations: the number of studies specifically evaluating recurrence rates is limited, and all studies only provided short-term follow-up data. Based on these short-term data, it is important to avoid overstating the long-term anti-recurrence benefits of combination therapy. Whether combination therapy possesses a definitive long-term anti-recurrence advantage still requires verification through future high-quality prospective studies with extended follow-up (2, 4, 47). Collectively, existing findings support that simultaneous intervention of both pigment-related and non-pigment-related pathogenic pathways is key to achieving remission (4, 6, 47), although the certainty of its long-term effects needs further confirmation.

This study found that combination and monotherapy regimens have comparable safety profiles regarding adverse reaction rates. This finding is significant, especially given concerns about cumulative photothermal damage and post-inflammatory hyperpigmentation (PIH). However, our results regarding safety contrast with the findings of Guan et al. (13), who observe a higher rate of PIH. This discrepancy may result from differences in treatment parameters, patient characteristics—including Fitzpatrick skin type—and operator experience. Previous studies show that using QS lasers and IPL at appropriate fluences and intervals causes minimal adverse effects—mainly transient erythema or mild irritation—and rarely leads to serious complications (49, 50). Notably, the risk of adverse events seems to be more closely associated with the operator's technique, energy settings, and the patient's skin phototype rather than the use of combination therapies themselves (8). Because combined treatment protocols do not increase complication rates, this supports the idea that carefully adjusting treatment parameters can maintain safety while improving efficacy. Moreover, IPL's anti-inflammatory properties may help reduce irritation caused by laser treatments (51). Overall, these findings confirm that combination therapy can be implemented without a corresponding rise in safety risks.

Although the combined therapy group showed superior objective outcomes, such as a significant reduction in MASI scores and higher clinical efficacy, patient satisfaction did not differ significantly between the combined and monotherapy groups. This clinically meaningful discrepancy between objective efficacy and subjective satisfaction is closely related to the clinical value and patient compliance of combined therapy, warranting further in-depth discussion. Firstly, psychosocial factors play a core role: melasma patients often experience long-term psychological distress, including anxiety and social avoidance, which can reduce their recognition of objective treatment improvements despite significant MASI score reductions (1, 2). Secondly, baseline treatment expectations are critical: patients with unrealistic high expectations for complete depigmentation have low satisfaction with partial efficacy, while those who establish reasonable expectations through standardized pre-treatment counseling have higher subjective recognition of the same curative effect (2, 5). Thirdly, limitations of assessment tools further aggravate this discrepancy. Most included studies used simple single-item scales (e.g., satisfied, general, dissatisfied) without multidimensional evaluation of transient skin discomfort (redness, dryness, itching) during treatment and recovery, thus failing to fully capture the comprehensive treatment experience. Additionally, the beneficial improvements of combined therapy on dermal vascular abnormalities and inflammatory microenvironment are invisible to patients, which cannot be reflected in subjective satisfaction scores and lead to a disconnection between objective and subjective perceptions (4, 7). In summary, patient satisfaction depends not only on clinical indicators like MASI reduction and efficacy rate, but also on factors such as psychosocial status, disease severity at baseline, and treatment expectations (1, 2, 5). Even with significant pigment clearance, patients' worries about recurrence, recovery duration and mild transient adverse reactions will negatively affect overall satisfaction (4, 49), which highlights the necessity of thorough pre-treatment counseling, effective expectation management, and the importance of developing validated multidimensional patient-reported outcome metrics in future clinical trials (2, 5).

This study confirms that combined QS laser and IPL therapy is more effective than monotherapies for melasma. It provides better clinical outcomes, a lower short-term recurrence rate, and an acceptable safety profile. Nevertheless, since the findings are based on short follow-up data from a limited geographic region, their long-term applicability and generalizability are limited. This combined regimen is a promising method to improve melasma treatment; however, its long-term therapeutic value requires further verification.