Citation

Kridin K, Ludwig RJ. J. Am. Acad. Dermatol. 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Elsevier Publishing)

DOI

10.1016/j.jaad.2023.01.038

PMID

36841334

Abstract

We read with great interest the commentary of Loh et al. about our paper entitled: "Isotretinoin33 and the risk of psychiatric disturbances - A global study shedding new light on a debatable story". As its name indicates, our study explores a highly debatable topic that has not been studied in a methodologically sufficient way in the past. The sparse literature left the dermatologic society struggling with significant uncertainty regarding the safety of one of the most frequently prescribed dermatologic drugs. Loh et al. claim that the comparable risk of depression and suicidal attempts among isotretinoin-prescribed patients might mirror indication bias as physicians render from prescribing isotretinoin for patients with preexisting psychiatric comorbidities. While we cannot thoroughly refute this hypothesis, we made substantial efforts to optimize between-group comparability by applying a comprehensive propensity-score matching that guaranteed a good balance between the two study groups. Both study groups were balanced in accordance with socioeconomic determinants of health and a wide array of organic comorbidities. Another measure that was taken to minimize selection bias was the elimination of patients with a preexisting diagnosis of psychiatric conditions. For instance, a patient with a history of depression was excluded from the analysis investigating the risk of depression following isotretinoin. This accounts for the different numbers of eligible patients in each one of the analyses. We are convinced that these methodological measures considerably reduced the risk of selection bias and is likely to substantiate the validity of our observations.

To refute the concerns that the extended follow-up might have 'diluted' the risk of study outcomes, we performed a time-stratified analysis that is confined to the initial three months following drug initiation. When investigating the risk of psychiatric outcomes only within the first three months of treatment, isotretinoin was associated with a comparable risk of major depressive disorder (HR, 0.94; 95% CI, 0.78-1.13; P=0.496) and suicidal attempts (HR, 1.35; 95% CI, 0.93-56 1.88; P=0.073). Intriguingly, isotretinoin was associated with a decreased risk of post-traumatic stress disorder (HR, 0.58; 95% CI, 0.43-0.79; P<0.001), anxiety (HR, 0.83; 95% CI, 0.76-0.91;58 P<0.001), bipolar disorder (HR, 0.65; 95% CI, 0.49-0.86; P=0.002), and adjustment disorder (HR,59 0.48; 95% CI, 0.38-0.60; P<0.001) within this period. These findings authenticate the conclusions...

Language: en

Keywords

depression; suicidal ideation; Acne; isotretinoin; oral antibiotics; psychiatric disturbances; suicidal attempt