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Combination of Oral Tranexamic Acid with Topical 3% Tranexamic Acid versus Oral Tranexamic Acid with Topical 20% Azelaic Acid in the Treatment of Melasma

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Abstract

Objective: To compare the effect of combination therapies of topical 3% tranexamic acid versus topical 20% azelaic acid each combined with oral tranexamic acid in the treatment of melasma. Study design: Interventional comparative study. Place and duration of study: Department of Dermatology, Sheikh Zayed Hospital, Rahim Yar Khan, from July 2017 to June 2018. Methodology: Cases of melasma diagnosed clinically (based upon history and the clinical findings of symmetrically distributed hyperpigmented macules and patches on the face), aged 12 to 50 years, were selected. The cases were divided into two groups by simple random sampling method. The cases in group A were treated by oral tranexamic acid (250 mg twice daily) with topical 3% tranexamic acid (twice daily). In group B, cases had oral tranexamic acid (250 mg twice daily) with topical 20% azelaic acid (daily) for six months. They were followed every second month upto 6 months and the efficacy was assessed on the basis of scores on MASI scale. Results: In 100 patient, there was no significant difference in terms of mean MASI score at 2 and 4 months with p-value of 0.20 and 0.89, respectively. However, mean MASI score was significantly less in group A (6.06 ±5.06 vs. 10.62 ±7.43) in group B (p=0.001). In group A, 14 (28%) had excellent response, whereas in group B, 11 (22%) had excellent results. Conclusion: Combination of oral and topical 3% tranexamic acid is significantly better than oral tranexamic acid with 20% azelaic acid for treatment of melasma.
502 Journal of the College of Physicians and Surgeons Pakistan 2019, Vol. 29 (6): 502-504
INTRODUCTION
Melasma is an acquired hyperpigmentation of the skin
that typically affects the sun-exposed areas of the face.
It is most common in women with darker complexions,
who live in areas of intense ultraviolet (UV) radiation
exposure.1,2 Melasma causes considerable cosmetic
disfigurement and psychological distress; quality-of-life
studies have shown a significant negative effect of
melasma on emotional wellbeing, social life, and leisure
activities.3,4 The prevalence of melasma is reported
around the globe. In Brazil, it is about 5-9%, which
remains main cause of demand for dermatological care
in Saudia Arabia, Nepal and Brazil.3-5 The pathogenesis
of melasma is poorly understood. Contributing factors
include darker skin phototype (especially III and IV),
ultraviolet (UV) radiation, hormonal factors (eg, pregnancy,
oral contraceptives), genetic predisposition, cosmetic
use, thyroid dysfunction, and antiepileptic medications.5,6
The diagnosis of melasma is based upon history and the
clinical finding of symmetrically distributed hyper-
pigmented macules and patches on the face.7, 8
Examination under Wood's light may be helpful in
identifying the pattern of pigment deposition.9-11 The
melasma area and severity index (MASI) was created in
an attempt to standardise the subjective evaluation of
melasma in clinical trials.4,5
The treatment of melasma can be challenging because
of its chronic and relapsing nature.12-14 Treatments
include skin-lightening agents, chemical peels, and laser
and light-based therapy.15-18
These include hydroquinone used in strength of 2% and
4%, azelaic acid 15% and 20%, mequinol, kojic acid,
topical retionids 0.25%, 0.5% and 0.1%. All of these
treatment options result in excellent cure rate among
60% to 90%.19-22 Several types of lasers have been
used for the treatment of melasma with variable results.4
Oral and topical tranexamic acid has been used recently
in the treatment of melasma.4,5,11-13
Tranexamic acid is a plasmin inhibitor and lysine
analogue that has been shown to inhibit UV-induced
pigmentation in animal models while azelaic acid is a
naturally occurring, nonphenolic, nine-carbon dicarboxylic
acid that competitively inhibits tyrosinase. Both have
shown variable results for its efficacy in melasma.11,13
ORIGINAL ARTICLE
Combination of Oral Tranexamic Acid with Topical 3% Tranexamic Acid
versus Oral Tranexamic Acid with Topical 20% Azelaic Acid
in the Treatment of Melasma
Fahmida Malik1, Malik Muhammad Hanif1and Ghulam Mustafa2
ABSTRACT
Objective: To compare the effect of combination therapies of topical 3% tranexamic acid versus topical 20% azelaic acid
each combined with oral tranexamic acid in the treatment of melasma.
Study Design: Interventional comparative study.
Place and Duration of Study: Department of Dermatology, Sheikh Zayed Hospital, Rahim Yar Khan, from July 2017 to
June 2018.
Methodology: Cases of melasma diagnosed clinically (based upon history and the clinical findings of symmetrically
distributed hyperpigmented macules and patches on the face), aged 12 to 50 years, were selected. The cases were
divided into two groups by simple random sampling method. The cases in group A were treated by oral tranexamic acid
(250 mg twice daily) with topical 3% tranexamic acid (twice daily). In group B, cases had oral tranexamic acid (250 mg
twice daily) with topical 20% azelaic acid (daily) for six months. They were followed every second month upto 6 months
and the efficacy was assessed on the basis of scores on MASI scale.
Results: In 100 patient, there was no significant difference in terms of mean MASI score at 2 and 4 months with p-value
of 0.20 and 0.89, respectively. However, mean MASI score was significantly less in group A (6.06 ±5.06 vs. 10.62 ±7.43)
in group B (p=0.001). In group A, 14 (28%) had excellent response, whereas in group B, 11 (22%) had excellent results.
Conclusion: Combination of oral and topical 3% tranexamic acid is significantly better than oral tranexamic acid with 20%
azelaic acid for treatment of melasma.
Key Words: Melasma, Tranexamic acid, Azelaic acid.
Department of Dermatology1/ Community Medicine2,
Sheikh Zayed Medical College and Hospital, Rahim Yar Khan,
Pakistan
Correspondence: Dr. Fahmida Malik, Department of Dermatology,
Sheikh Zayed Medical College and Hospital, Rahim Yar Khan,
Pakistan
E-mail: fahmidamalik77@gmail.com
Received: July 13, 2018; Accepted: January 29, 2019
This study was planned to assess the effects of
combination therapy in melasma. The objective of this
study was to compare the effect of combination
therapies of oral tranexamic acid with topical 3%
tranexamic acid versus oral tranexamic acid with topical
20% azelaic acid in the treatment of melasma.
METHODOLOGY
This was an interventional comparative study, conducted
from July 2017 to June 2018 at Department of
Dermatology, Sheikh Zayed Hospital, Rahim Yar Khan.
Sample size was calculated by taking 95% confidence
interval power of study 80% and cure rate in azelaic acid
group taken as 65%; whereas, cure rate in Tranexamic
acid group taken as 90%.16,17
Cases were taken in the range of 12 to 50 years of either
gender of melasma diagnosed clinically based upon
history and the clinical findings of symmetrically
distributed hyperpigmented macules and patches on the
face. Examination under Wood's light was used when
differentiating the pattern of pigment deposition
(assessed by history and medical record) were selected.
The cases being pregnant or nursing women, taking
contraceptive pills at the time of study or past 12
months, any chronic illness, with allergy to any of the
agents used in the treatment and those taking any
topical and systemic treatment for melisma in the last
one month were excluded from this study.
The cases were divided into two groups by simple
random sampling method. MASI scoring done before
starting the treatment. The cases in group A were treated
by oral tranexamic acid (250 mg twice daily); with topical
3% tranexamic acid solution (twice daily) and in group B
with oral tranexamic acid (250 mg twice daily) with
topical 20% azelaic acid (daily at night) for 6 months.
Topical 3% tranexamic acid solution was 3 g tranexamic
acid dissolved in 10-cc ethanol 96o, 10-cc 1.3-butanediol
and distilled water up to 100-cc formulated by Green
Plus Pharma Lahore. Candidates were asked to apply
sunscreen with SPF 60 or more during day time. They
were followed every 2nd month at OPD of dermatology
and the final outcome was seen at 6 months where the
efficacy was assessed on the basis of score on MASI
scale. Follow-up done for 6 months after completion of
treatment by using MASI score.
The data was entered and analysed by using (SPSS)
version 23. Age was compared by using t-test.
Qualitative variables were presented as frequencies and
percentages, while quantitative variables as mean and
standard deviation. Both the groups [Group A oral
tranexamic acid (250mg twice daily) with topical 3%
tranexamic acid solution and Group B oral tranexamic
acid (250 mg twice daily) with topical 20% azelaic acid]
were compared in terms of efficacy by using Chi-square
test taking p-value less than 0.05 as significant.
RESULTS
In the present study, there were a total of 100 cases, 50
in each group. Group A contained 6 (12%) males and 44
(88%) females, in contrast to group B, where they had 7
(14%) males and 43 (86%) females (p=0.76). There was
no significant difference in terms of mean MASI score at
2 and 4 months with p-value of 0.20 and 0.89
respectively.
However, mean MASI score was significantly less in
group A where it was seen as 6.06 ±5.06 as compared
to 10.62 ±7.43 in group B with p-value of 0.001 as shown
in Table I. There was also no significant difference of
response of patients in terms of satisfaction (Table II)
with p-value of 0.74. Pre-treatment mean MASI score in
group A was 33.7 ±12 versus 34 ±13 in group B
(p=0.74). Mean age in group A was 24 ±6.02 and in
group B was 23.08 ±6.31 (p=0.45).
DISCUSSION
Melasma is defined as acquired macular hyper-pigmen-
tation, commonly seen in young population and majority of
them are females of child bearing age.14-18 Multiple factors
that influence its presence and precipitation include oral
contraceptive pills, pregnancy, genetics, endocrine
dysfunction, nutritional deficiency, medications, hepatic
dysfunction, and HIV etc. Sun exposure is common
factor for exacerbation of symptoms.19-22
In the present study, the efficacy in terms of MASI score
was significantly better in group A where it was seen as
6.06 ±5.06 as compared to 10.62 ±7.43 in group B with
p-value of 0.04. No such comparison of this combination
done before. However, significant difference in MASI score
was not found at 2 and 4 months follow-up in this study.
In a study of 100 cases of melasma done by Lee et al.
where they had used tranexamic acid intradermal every
week for 12 weeks, found significant improvement in
terms of MASI score at 8 and 12 weeks (p<0.05).15 The
efficacy seen in their study was even higher as compared
to the present one, where it was seen in 76.5% of
subjects. It may be due to the fact that they had longer
follow-up as compared to current study.
Combination therapies for melasma
Table I: Comparison of efficacy in both groups (independent t-test results).
MASI score Treatment group Significance
Group A Group B
At 2 months 21.68 ±10.93 24.32 ±9.82 0.20
At 4 months 14.02 ±9.07 17.04 ±8.47 0.89
At 6 months 6.06 ±5.06 10.62 ±7.43 0.001
Table II: Patient response to treatment in both groups (Chi-square test
results).
Response Treatment group Significance
Group A Group B
Excellent 14 (28%) 11 (22%) 0.74
Good 28 (56%) 29 (58%)
Fair 8 (16%) 10 (20%)
Total 50 50
Journal of the College of Physicians and Surgeons Pakistan 2019, Vol. 29 (6): 502-504 503
Fahmida Malik, Malik Muhammad Hanif and Ghulam Mustafa
504 Journal of the College of Physicians and Surgeons Pakistan 2019, Vol. 29 (6): 502-504
A study of 25 cases done by Fox et al., using tranexamic
acid in the topical emulsion form up to 18 weeks, showed
that the improvement was even better and was observed
in 80% subjects,may be due to long follow-up.16 In both
of these studies, no major side effects were observed.
Karn et al. compared the combination of oral tranexamic
acid with topical hydroquinone with that of topical hydro-
quinone alone.17 It was observed that there was
significant reduction in MASI score in tranexamic acid
group. The efficacy of this can be explained by the factor
that tranexamic acid is temperature-stable, not UV
sensitive, and does not get oxidised easily. Thus, it acts
as an ideal choice for composition in skin lightening
creams. The advantage of it is that it is present in both
oral as well as topical preparations.
Siddique et al. in their study used combination of 20%
azelaic acid with 0.05% tretinoin. Good efficacy was
seen in 38.66% of the cases only. Side effects were also
noted during therapy.18
Mazurek et al. also used different combinations of azelaic
acid for the treatment of melasma, and they showed
better efficacy but none was significantly better as
compared to each other. The best results were seen in a
combination of 20% azelaic acid and mandelic acid,
phytic acid, 4N-butyl resorcinol, and ferulic acid.19
Fatemi et al. used topical solution form of tranexamic
acid. That study introduced the topical TA as an effective
and safe medication for the treatment of melasma.20
CONCLUSION
Combination of oral and topic 3% tranexamic acid is
significantly better than oral tranexamic acid with 20%
azelaic acid for treatment of melasma.
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... As regards the criteria of evaluation, all the mentioned studies are based on a unique criterion: MASI score. There is a good homogeneity in the duration of treatment: 3 months for all trials except [40]. We can observe that the investigators used different concentrations of topical TA, ranging from 2 to 5 %. ...
... One study [40] is comparing 3 % TA with 20 % azelaic acid, both in combination with 250 mg oral TA daily and another trial is comparing 3 % TA with TA microneedling [17]. The total number of volunteers was 397 taking all the trials together. ...
... 50 The combination of oral 250 mg twice daily tranexamic acid with topical 3% tranexamic acid (twice daily) is significantly better than oral tranexamic acid (250 mg twice daily) with 20% azelaic acid for treatment of melasma. 51 ...
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... Eight studies 14-21 evaluated the efficacy and safety of oral TXA, four studies 22-25 evaluated the efficacy and safety of intradermal TXA, and twelve studies evaluated the efficacy and safety of topical TXA. 5,[26][27][28][29][30][31][32][33][34][35][36] In the study by Tawfic SO, 30 topical and intradermal TXA administration routes were adopted in the treatment arm; thus, the study was analysed separately. Table 2 summarizes the methodological quality and the risk of bias of the included studies. ...
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Background: Melasma is a common acquired macular hyperpigmentation which involves mostly the sun exposed areas of face and neck. Objective: To assess the efficacy of the combination of 20% azelaic acid with 0.05% tretinoin cream in the treatment of melasma. Patients and methods: 30 patients of melasma were treated with daily night application of 20% azelaic acid and 0.05% tretinoin. Patients were assessed at 4, 8 and 12 weeks of treatment using melasma area severity index. Side effects during therapy were also noted. Results: Majority i.e. 43% cases were between 26 to 30 years, 73.3% of patients were females and 56.7% were housewives, 70% were married and 86.7% were in middle class. Family history of melasma was positive in 66.7% cases. 93.3% patients had no history of systemic drug and 73.3% had no history of use of cosmetics. 93.3% of patients had malar area involvement and 6.7% had centrofacial area involvement. After treatment, the average MASI score decreased by 38.66% indicating moderate reduction of the severity of melasma. Burning sensation, itching and erythema developed in 50%, 30% and 16%, respectively. Conclusion: The combination of 20% azelaic acid and 0.05% tretinoin cream in the treatment of melasma has a moderate lightening effect with some remarkable side effects.
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Melasma is a chronic acquired hypermelanosis of the skin, characterized by irregular brown macules symmetrically distributed on sun-exposed areas of the body, particularly on the face. It is a common cause of demand for dermatological care that affects mainly women (especially during the menacme), and more pigmented phenotypes (Fitzpatrick skin types III-V). Due to its frequent facial involvement, the disease has an impact on the quality of life of patients. Its pathogeny is not yet completely understood, although there are some known triggering factors such as sun exposure, pregnancy, sexual hormones, inflammatory processes of the skin, use of cosmetics, steroids, and photosensitizing drugs. There is also a clear genetic predisposition, since over 40% of patients reported having relatives affected with the disease. In this manuscript, the authors discuss the main clinical and epidemiological aspects of melasma.
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Background: Melasma poses a great challenge as its treatment is unsatisfactory and recurrence is high. Treatment of melasma using tranexamic acid (oral, topical or intralesional) is a novel concept. Objective: To compare the efficacy of oral tranexamic acid with routine topical therapies for the treatment of melasma. Methods: It is a prospective, interventional, randomized controlled trial conducted among 260 melasma patients. Patients were divided into two groups consisting of 130 patients each. First group (Group A) was given routine treatment measures and oral Tranexamic Acid while second group (Group B) was treated only with routine topical measures. Capsule Tranexamic Acid was prescribed at a dose of 250 mg twice a day for three months and cases were followed for three months. Response was evaluated on the basis of Melasma Assessment Severity Index (MASI). Mean scores between the two groups were then compared. Results: Statistically significant decrease in the mean Melasma Assessment Severity Index from baseline to 8 and 12 weeks was observed among group A patients (11.08±2.91 vs 8.95±2.08 at week 8 and vs. 7.84±2.44 at week 12; p<0.05 for both). While among group B patients the decrease in mean score was significant at 8 weeks and insignificant at 12 weeks follow up (11.60±3.40 vs 9.9±2.61 at 8 weeks and vs. 9.26±3 at 12 weeks; p<0.05 for former but p>0.05 for later). Conclusion: Addition of oral tranexamic acid provides rapid and sustained improvement in the treatment of melasma.
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Tranexamic acid is a procoagulant agent that is approved by the US Food and Drug Administration for treatment of menorrhagia and to prevent hemorrhage in patients with hemophilia undergoing tooth extractions. Through its inhibitory effects on the plasminogen activation pathway, tranexamic acid also mitigates the UV radiation-induced pigmentation response. Systemic tranexamic acid has consistently been reported as an effective treatment of melasma, though its broad use may be limited by the risk for thromboembolism. Limited studies have investigated the efficacy of topical tranexamic acid, with or without the use of adjunctive therapies to increase uptake. This review summarizes the effects of tranexamic acid on the pathophysiology of melasma and the available evidence on the off-label treatment of melasma using systemic and topical tranexamic acid.
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Melasma is a common acquired condition of symmetric hyperpigmentation, typically occurring on the face, with higher prevalence in females and darker skin types. Multiple etiologies, including light exposure, hormonal influences, and family history, have been implicated in the pathogenesis of this disorder. Overall prevalence ranges widely at 1–50%, since values are typically calculated within a specific ethnic population within a geographic region. Histologically, melasma can display increased epidermal and/or dermal pigmentation, enlarged melanocytes, increased melanosomes, solar elastosis, dermal blood vessels, and, occasionally, perivascular lymphohistiocytic infiltrates. Various topical, oral, and procedural therapies have been successfully used to treat melasma. Traditional topical therapies including hydroquinone, tretinoin, corticosteroids, and triple combination creams; however, other synthetic and natural topical compounds have also shown varying efficacies. Promising oral therapies for melasma include tranexamic acid, Polypodium leucotomos, and glutathione. Procedures, including chemical peels, microneedling, radiofrequency, and lasers, are also often used as primary or adjunctive treatments for melasma. Notably, combination therapies within or across treatment modalities generally result in better efficacies than monotherapies. This review serves as a comprehensive update on the current understanding of the epidemiology, pathogenesis, clinical and histologic features of melasma, as well as treatments for this common, yet therapeutically challenging, condition.
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Background: Melasma is one of the most frequently diagnosed hyperpigmentation changes on the skin of women's faces. Nearly 30% of women using oral estrogen therapy struggle with this problem. A common way of reducing melasma is the application of azelaic acid products. Aim: Comparison of efficacy of three dermocosmetic products, containing azelaic acid, in the reduction in melasma for women aged 35-55. Material and methods: A group of 60 women diagnosed with melasma were divided into three even, twenty-person subgroups. Each subgroup was assigned one dermocosmetic product containing azelaic acid. For 24 weeks, the patients applied the assigned product twice a day. The level of the colorant within the hyperpigmentation was marked before the treatment, after 1 month, after 3 months, and after 6 months of therapy. The pigmentation was measured using Mexameter(®) (Courage + Khazaka electronic, Germany). In addition, during each inspection, the patients' level of hydration, elasticity, and intensity of erythema was checked using Corneometer(®) , Reviscometer(®) . Results: All dermocosmetics containing azelaic acid that were applied significantly contributed to the reduction in pigment in the pigmentary lesion. The largest decrease in the amount of pigment was observed in the first 3 months of use of the products. A combination containing 20% azelaic acid and mandelic acid, phytic acid, 4N-butyl resorcinol, and ferulic acid proved to be the most effective dermocosmetic III (Sesderma, Valencia, Spain). Conclusions: Dermocosmetics containing azelaic acid significantly contribute to the clearing of melasma. The effect depends on the treatment time, the acid concentration, and addition of other components.
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In recent times, tranexamic acid (TA) is claimed to have whitening effects especially for ultraviolet-induced hyperpigmentation including melasma. The aim of our study was to evaluate the efficacy and safety of topical solution of TA and compare it with combined solution of hydroquinone and dexamethasone as the gold standard treatment of melasma in Iranian women. This was a double-blind split-face trial of 12 weeks which was conducted in Isfahan, Iran. Fifty Iranian melasma patients applied topical solution of 3% TA on one side of the face, and topical solution of 3% hydroquinone + 0.01% dexamethasone on the other side two times a day. The Melasma Area and Severity Index (MASI) and the side effects were evaluated at baseline and every 4 weeks before and after photographs to be compared by a dermatologist were taken. The patient satisfaction was documented at week 12. A repeated measurement analysis was used to evaluate the changes in the MASI score before and after treatments. A significant decreasing trend was observed in the MASI score of both groups with no significant difference between them during the study (P < 0.05). No differences were seen in patients' and investigator's satisfaction of melasma improvement between two groups (P < 0.05). However, the side effects of hydroquinone + dexamethasone were significantly prominent compared with TA (P = 0.01). This study's results introduce the topical TA as an effective and safe medication for the treatment of melasma.
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Melasma is an acquired, symmetrical hypermelanosis of the face. The pathogenesis of melasma is complex and the treatment is often challenging with frequent relapses. Genetic background, exposure to ultraviolet radiation, and female sex hormones are classical influencing factors. To the light of the recent literature, other factors could promote melasma lesions. Moreover, there are increasing evidences showing that melanocytes are not the only cells involved, and that other players probably have a key role in the development and the relapses of melasma. Identifying those associated factors should provide new targets for a more efficient treatment of melasma and a better prevention of the relapses.
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Melasma is an acquired, irregularly patterned, light to dark-brown hypermelanosis, with symmetric distribution mostly over the face. The aim of this study was to evaluate clinical characteristics and factors related to melasma in Brazilian patients. This was a cross-sectional, multicenter study performed in Brazil. Investigators examined and questioned 953 patients over 18 years of age on clinical characteristics and other factors related to their melasma. Melasma was more prevalent in women (97.5%) and in Fitzpatrick skin phototypes II (12.8%), III (36.3%), and IV (39.7%). Skin phototypes II and III and family history of melasma had early onset of the disorder when compared with skin phototypes IV, V, and VI (P < 0.0001). Similar results were also observed when these same groups were compared with the absence of family history (P < 0.0001). Extra-facial melasma was more frequent in postmenopausal women compared with those who were not experiencing menopause (14.2% vs. 3.5%, P < 0.0001). Data suggested that the age of melasma onset are related to skin phototypes and family history. Additionally, extra-facial melasma was more common in menopausal women. This is the first study on the epidemiology of melasma in Brazil involving a large sample of the population. These data can be a source of new relevant research on the cause and development of melasma.
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Melasma is an acquired disorder of hyperpigmentation occurring on the face and predominantly affecting women of childbearing age. It is a chronic, often relapsing condition with a negative impact on quality of life. Current treatments for melasma are unsatisfactory. The aim of this article was to conduct an evidence-based review of interventions available for the treatment of melasma. A systematic literature search was performed using PubMed and the keywords 'melasma' or 'chloasma' in the title. The search was further refined by using a filter for 'controlled clinical trials' and 'randomized controlled trial'. The included studies were used to develop recommendations for treatment. The electronic search yielded a total of 80 citations. Forty studies were included in this review, which had a total of 2,912 participants. Three different therapeutic modalities were investigated-topical agents, chemical peels, and laser and light therapies. Topical depigmenting agents were found to be the most effective in treating moderate-to-severe melasma, with combination therapies, such as triple-combination therapy (hydroquinone, tretinoin, and fluocinolone acetonide), yielding the best results. Chemical peels as well as laser and light therapies were found to have moderate benefit but more studies are needed to determine their efficacy and long-term safety. Adverse events associated with treatment were mild and short-lasting and included skin irritation, dryness, burning, and erythema. The data could not be statistically pooled because of the heterogeneity of treatments and lack of consistency across study designs. Topical combination therapies were found to be more effective than monotherapy. Triple combination therapy was found to be the most effective, but approximately 40 % of patients develop erythema and peeling. Chemical peels and laser and light therapies produced mixed results, with increased risk of irritation and subsequent hyperpigmentation, particularly in darker-skinned individuals. Hence, current treatments available for melasma remain unsatisfactory. Many of the studies lacked long-term follow-up. Limitations of current literature include the heterogeneity of study designs, small sample sizes, and poor follow-up rates. Additional evidence for the effects and role of sunscreens is needed. Categorization or stratification of demographic data should also be included in future studies, such as age, melasma type, and duration of melasma prior to initiation of treatment. Patient's perception of improvement versus investigator's assessment of improvement should also be included in future studies and standardized methods of study design and assessment of outcomes are needed to form definitive conclusions on the efficacy of different treatment modalities.