Nie and colleagues answer critics of isotretinoin suicidality study

The Journal of the American Academy of Dermatology has published a formal author response in its November 2026 issue (Volume 95, Issue 5), with Wenjia Nie, Liyun Zheng, Juhua Liu, Lifang Cheng and Xiaoyi Wen replying to a comment letter concerning their 2026 paper on suicidality reports in acne patients treated with isotretinoin and concomitant antidepressants.

The original study, which the response defends, was a descriptive analysis of FDA Adverse Event Reporting System (FAERS) data. That design point matters more than it might first appear. Descriptive pharmacovigilance work sits in an awkward spot in dermatology: it generates signals, not causal verdicts. Commenters know this, and the exchange published here turns on exactly that tension.

What is actually being debated?

The comment letter targeted the Nie et al analysis of suicidality reports among isotretinoin users who were also taking antidepressants. Isotretinoin and psychiatric risk is one of the longest-running controversies in acne care, and every new data source gets scrutinized hard. FAERS, as a spontaneous reporting system, carries known limitations — reporting bias, missing denominators, duplicate entries, channeling of high-risk patients into monitoring. Any descriptive analysis built on it will draw methodological fire, and did.

The authors' response, appearing in this issue, is their published rebuttal to that critique. The back-and-forth format — original paper, comment, response — is how JAAD and comparable journals referee disputes short of retraction or correction. A published response means the editors judged the reply worth the record, not that either side has won.

What does this change for prescribers?

In practical terms, very little right now — and that is the honest read. The exchange concerns interpretation of spontaneous-report data, not new trial findings or a changed label. Prescribers writing isotretinoin today work under the same psychiatric-risk counseling and monitoring framework they worked under before this correspondence appeared.

What the exchange does change is the interpretive frame. When a FAERS-based paper on isotretinoin and suicidality draws a comment serious enough to warrant a published response, practitioners should read both documents together before citing the original study's conclusions. Author responses often clarify cohort definitions, outcome ascertainment and confounding handling in ways abstracts don't capture. For clinicians who cite this literature in consent discussions or institutional protocols, the paired letters are the citation, not the original paper alone.

Why the antidepressant angle matters

The concomitant-antidepressant cohort is the distinctive element of the original analysis. Patients on antidepressants while receiving isotretinoin are, by selection, a group with documented psychiatric history or active illness — exactly the population where disentangling drug effect from underlying disease is hardest. Any descriptive signal in that group is riddled with confounding by indication, which is presumably one axis of the comment, and one axis of the defense.

This is not a new problem in dermatology. The iPLEDGE-era debates, the European regulatory reviews of isotretinoin, and decades of cohort studies have all circled the same question: does the drug add psychiatric risk, or does severe acne and its psychiatric comorbidity explain the association? Descriptive FAERS data cannot settle it. The comment-response exchange makes clear the authors and their critics agree on at least that boundary condition, even as they dispute what falls inside it.

How to read correspondence sections

For the Derm Field reader, a few ground rules for consuming this kind of publication:

• A response to a comment is not new evidence. It is argument about existing evidence.
• Published correspondence signals that the journal considered the critique substantive enough, and the reply adequate enough, to appear in the record.
• Where the original study was descriptive, no amount of rebuttal converts its findings into causal estimates. The design ceiling holds.

Where this goes next

The November 2026 exchange will likely feed the next round of isotretinoin safety research rather than close the question. Larger linked database studies — with denominators, prescription records and psychiatric history — remain the evidentiary step that FAERS cannot provide, and until those speak, the Nie group's descriptive signal and its critics' caveats will travel together through the literature.