Original article
Isotretinoin treatment for acne and risk of depression: A systematic review and meta-analysis

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Background

The relationship between isotretinoin treatment for acne and depression is controversial. Quantitative analysis has not yet been conducted.

Objective

To conduct a meta-analysis, evidence-based examination of the relationship between isotretinoin and depression.

Method

A systematic review and meta-analysis of the literature published from inception to September 30, 2016, was conducted. Controlled or prospective non-controlled trials on ≥15 acne patients receiving isotretinoin treatment were included. The prevalence of depression and change in depression scores were calculated.

Result

Thirty-one studies met the inclusion criteria. In the controlled studies, the change in depression scores from baseline was not significantly different between patients receiving isotretinoin treatment and those receiving an alternative treatment (standardized mean difference [SMD] −0.334, 95% confidence interval [CI] −0.680 to 0.011). The prevalence of depression after isotretinoin treatment significantly declined (relative risk [RR] 0.588, 95% CI 0.382–0.904). The mean depression scores significantly decreased from baseline (SMD −0.335, 95% CI −0.498 to −0.172).

Limitations

No randomized controlled trials were reviewed; a large inter-study variation was observed.

Conclusions

Isotretinoin treatment for acne does not appear to be associated with an increased risk for depression. Moreover, the treatment of acne appears to ameliorate depressive symptoms.

Section snippets

Methods

This meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (http://www.prisma-statement.org/).

Search results and trial characteristics

Of the 172 studies screened, the inclusion criteria were met in 31 studies (Fig 1): 3 population-based studies, 8 controlled studies, and 20 prospective open-label studies, of which 4 provided only the prevalence of depression without before and after depression scores. A summary of the trial characteristics is presented in Table I.

Of the 31 studies, 1 population-based study found that isotretinoin significantly increased the risk of depression, while 2 open-label studies found increased

Discussion

The relationship between isotretinoin treatment for acne and depression remains controversial both clinically and scientifically. Because isotretinoin is a fat-soluble compound, it can easily cross the blood–brain barrier and interact with brain tissue wherever intracellular retinoid receptors are present. It can affect the dopaminergic36 and serotonergic systems,37 hippocampal neurogenesis,38 and frontal orbital activity.8 The chronic administration of 1-mg/kg dose of isotretinoin has been

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    Funding sources: None.

    Conflicts of interest: None declared.

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    © 2016 by the American Academy of Dermatology, Inc.