Research letter

Risk of depression among patients with acne
in the U.K.: a population-based cohort study
DOI: 10.1111/bjd.16099
DEAR EDITOR, Acne has been associated with adverse psychiatric
symptoms.1 In dermatology outpatient clinics, approximately
25.2% of patients with acne experience some psychiatric
morbidity.2 However, few studies have evaluated the clini-
cally significant diagnostic category of major depressive disor-
der (MDD) among people with acne. Here, we investigated
whether patients with acne are at an increased risk of devel-
oping MDD compared to the general population, using one
of the largest electronic medical records databases in the
world.
A retrospective cohort study was conducted using data from
The Health Improvement Network (THIN) (1986–2012), a
large primary care database in the U.K. that also includes data
from specialists. All individuals between 7 and 50 years of age
with ≥ 1 Read codes (diagnostic codes linked to International
Classification of Diseases codes) for acne were identified. A
general population cohort without acne was also identified.
The study was approved by the Conjoint Health Research
Ethics Board at the University of Calgary (ID 24423) and from
the Scientific Review Committee in the U.K. (ID 16THIN036),
authorizing access to extract relevant data from THIN. A com-
plete list of codes used to identify exposures, outcomes and
covariates is available from the authors.
All patients were followed from their start date for
≥ 2 years in THIN until the earliest of either their first MDD
Read code (main outcome),3,4 transfer out of practice, death
or end of data collection. Observations were censored at the
end of follow-up in patients where MDD was not observed
during the study period. To identify only incident cases,
patients with an acne or MDD Read code prior to the start of
follow-up were excluded. Baseline covariates at the start of
follow-up included age (young ≤ 19; adult > 19 years),5 sex,
obesity (BMI ≥ 30 kg m 2), smoking status (never, former,
current), alcohol use (yes or no), medical comorbidities using
the Charlson Comorbidity Index (0 or ≥ 1 comorbidity) and
socioeconomic status using the Townsend Deprivation Index
(quintiles 1–5, with 1 least and 5 most deprivation).

Fig 1. Hazard ratios (HR) for the development of depression among patients with acne over time. The HRs shown indicate the risk of depression
in patients with acne relative to the general population at various time points post-acne diagnosis. These HRs were determined from fully adjusted
models (aHR) including age, sex, socioeconomic deprivation, Charlson Comorbidity Index, smoking, alcohol use and obesity. These results were
unchanged after excluding patients who received isotretinoin (< 1-year HR 1.63, 95% CI 1.33–2.00; 5-year HR 1.02, 95% CI 0.88–1.17; 10-year
HR 1.06, 95% CI 0.86–1.31; 15-year HR 1.15, 95% CI 0.76–1.74). CI, Confidence interval. *Statistical significance, P < 0.05.

© 2018 British Association of Dermatologists British Journal of Dermatology (2018) 1

2 Research letter
Cox proportional hazards models stratified by time were
constructed with estimates reported as hazard ratios (HR) with
95% confidence intervals (95% CIs). A likelihood-ratio test
was used to assess statistical interactions. Confounding was
assessed by whether a substantial change (≥ 10%) to the esti-
mated HR resulted with removal of each covariate. Sensitivity
analyses were conducted whereby patients prescribed isotreti-
noin were removed from analyses.
A total of 134 437 patients with incident acne and
1 731 608 patients without acne were identified in THIN.
Patients with acne were more frequently younger (67.6% vs.
22.8%), female (58.6% vs. 48.6%), of higher socioeconomic
status (24.4% vs. 22.1%), never smokers (58.4% vs. 48.6%)
and had a comorbidity (17.2% vs. 13.8%), but less frequently
were alcohol users (17.0% vs. 39.0%) or obese (2.3% vs.
6.6%) (all P < 0.001).
Over the 15-year follow-up, the probability of developing
MDD was 18.5% among patients with acne and 12.0% in the
general population without acne. Patients with acne had a sig-
nificantly increased risk of developing MDD after adjustment
for all covariates but only in the first 5 years after being diag-
nosed with acne. This risk was highest within 1 year of acne
diagnosis (adjusted HR 1.63, 95% CI 1.33–2.00) and
decreased thereafter (Fig. 1). No statistical interactions were
observed at any time point. In the first 5 years following an
acne diagnosis, sex was the only covariate producing a con-
founding effect. At 10 and 15 years, both sex and obesity
demonstrated confounding effects. The increased risk of MDD
among patients with acne remained unchanged after excluding
patients who were prescribed isotretinoin (n = 900), who
may have the most severe acne.
Our results indicate that the onset of acne, when patients
present for treatment because of active disease, is associated
with a greater risk of developing depression. Although the
severity of acne was not assessed directly in the current study,
this finding suggests a potential dose–response relationship
such that more active disease may lead to a greater risk of
depression. In this study, female patients were more likely to
have acne (or to present to a physician) and were also more
likely to develop MDD, which is consistent with existing liter-
ature.6,7 At 10 and 15 years, both sex and obesity demon-
strated confounding effects, so future research on the disease
course of acne should account for these variables.
A potential limitation of this study is that cases of acne or
MDD may have been misclassified if patients with either con-
dition did not present to a physician for treatment. Addition-
ally, treatment for acne other than isotretinoin was not
considered; however, as treatment has been shown to improve
British Journal of Dermatology (2018)
depressive symptoms,8 we believe that the estimates reported
here are conservative. Lastly, significant results should be
interpreted based on clinical relevance given the large sample
size.
In conclusion, given the tremendous burden of MDD and
its temporal association with active acne, it is critical that
physicians monitor mood symptoms in patients with acne and
initiate prompt MDD management or seek consultation from a
psychiatrist when needed.
1
Department of Community Health Sciences; I . A . V A L L E R A N D 1,2 iD
2
Leaders in Medicine Program; 3Division of R . T . L E W I N S O N 2 iD
Dermatology; 4Department of Medicine; L.M. PARSONS3,4
5
Department of Physiology and M.W. LOWERISON1
Pharmacology; and 6Department of A.D. FROLKIS4
Psychiatry, University of Calgary, Calgary, G.G. KAPLAN1,4
Canada C. BARNABE1,4
E-mail: ivall@ucalgary.ca A.G.M. BULLOCH1,5,6
S.B. PATTEN1,6
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Funding sources: I.A.V. received funding for this project from an
Alberta Innovates Health Solutions MD-PhD Studentship and from the
Mach-Gaensslen Foundation of Canada.
Conflicts of interest: none declared.
© 2018 British Association of Dermatologists