Isotretinoin has revolutionised treatment of acne, with new studies showing evidence of excellent clinical outcomes in treating rosacea. After decades of clinical experience, new insights are still being gained into dosing strategies, prevention of recurrence and dose-related side effects.
Some of the major concerns during treatment with isotretinoin include hypertriglyceridaemia, liver enzyme elevation, leukopenia and thrombocytopenia; in brief, recent studies do not support monthly testing.
According to the most recent recommendations, complete blood counts should be eliminated and a lipid panel and liver function should be assessed at baseline and after achieving peak dose.
No further monitoring is warranted if these parameters are normal. 
This guidance is confirmed by the results of a recent study in over 1800 patients in routine practice in which grade 3 or greater triglyceride and liver function testing abnormalities were noted in fewer than 1% and 0.5% of patients screened, respectively, and no grade 3 or greater cholesterol or complete blood count abnormalities were observed. 
Moreover, there were no meaningful changes in the frequency of laboratory monitoring over time.
A decrease in testing is also highly relevant in an era of high-value, cost-conscious care.
Although no causal link between isotretinoin and psychiatric adverse effects has been established, widespread media reporting of depression and suicidality with use of isotretinoin have raised concerns in both patients and clinicians and generated numerous cases of costly litigation.
Between 1997 and 2017, 17,829 psychiatric adverse events with isotretinoin use were submitted to the US FDA, with depressive disorders, emotional lability and anxiety disorders reported most frequently. 
However, these reports must be considered in the context of elevated rates of depression and suicide among patients with acne at large.
In fact, recent data suggest that the rate of completed suicide in patients taking isotretinoin may be lower than that of the general US population.
Many psychiatric adverse events unrelated to depression and suicidality were also reported, but it is unclear if they were a result of isotretinoin therapy.
At present, no causal link between isotretinoin and psychiatric risk has been established, even if patients taking the drug appear vulnerable to psychiatric concerns.
Similar results were reported in a nationwide cohort study involving over 440,000 patients taking isotretinoin in France where, compared with the general population, a lower risk of suicide attempt was observed among patients exposed to isotretinoin and there was no evidence for a triggering effect of isotretinoin initiation on suicide attempt. 
Regarding depression, in a systematic review and meta-analysis, isotretinoin was associated with significantly improved depressive symptoms. 
The conflicting results may be explained as isotretinoin was associated with an increased risk for depression on pooling retrospective studies, while this significant difference was not observed upon pooling prospective studies.
In fact, isotretinoin has been shown to improve quality of life, social anxiety and obsessive-compulsive disorder symptoms in acne patients. 
There is a widespread notion that systemic isotretinoin taken within 6 to 12 months of cutaneous surgery contributes to abnormal scarring or delayed wound healing.
However, this idea is recently being challenged.
In a systematic review on 32 relevant publications and 1485 procedures, there was insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and non-ablative laser procedures for patients currently receiving or having recently completed isotretinoin therapy. 
The American Society for Dermatologic Surgery recently issued consensus recommendations regarding the safety of lasers, dermabrasion, chemical peels, energy devices and skin surgery during and after isotretinoin use, stating that there is insufficient evidence to justify delaying treatment with superficial chemical peels and nonablative lasers, including hair removal lasers and lights, vascular lasers, and nonablative fractional devices for patients currently or recently exposed to isotretinoin. 
Oral isotretinoin has been associated with somewhat conflicting evidence in the treatment of papulopustular rosacea.
New data from randomised trials is now indicating that isotretinoin is associated with significant reduction in papules and pustules (in one study by 90%), although relapse is seen in about 50% of patients. 
Considering this, further studies are needed on the value of a minimal effective isotretinoin dose to maintain these remissions.
A small retrospective review of 52 patients reported that very low-dose isotretinoin (e.g., 10-20 mg once to five times a week, equivalent to 5 mg/day) is an effective treatment for mild to moderate papulopustular rosacea and is well tolerated. 
Greater personalisation of laboratory monitoring is needed during therapy with isotretinoin.
The psychological risks previously reported with isotretinoin may be related to acne per se, and not to isotretinoin.
There is no evidence to support poor outcomes of surgical/cosmetic procedures during isotretinoin therapy except for mechanical dermabrasion and ablative lasers.
There is likely no impact of isotretinoin on the onset of IBD.
New evidence suggests that low-dose isotretinoin is effective in difficult to treat papulopustular rosacea.
Key messages/Clinical perspectives
Some of the common notions about isotretinoin in the treatment of acne are being revisited, and some of the limitations previously perceived about the drug are being contested in the light of recent evidence.
Droitcourt C, Nowak E, Rault C, et al. Risk of suicide attempt associated with isotretinoin: a nationwide cohort and nested case-time-control study. Int J Epidemiol. 2019 May 16. pii: dyz093. doi: 10.1093/ije/dyz093.
Erdoğan Y, Erturan İ, Aktepe E, et al. Comparison of quality of life, depression, anxiety, suicide, social anxiety and obsessive-compulsive symptoms between adolescents with acne receiving isotretinoin and antibiotics: A prospective, non-randomised, open-label study. Paediatr Drugs. 2019 Jun;21(3):195-202.
Waldman A, Bolotin D, Arndt KA, et al. ASDS Guidelines Task Force: consensus recommendations regarding the safety of lasers, dermabrasion, chemical peels, energy devices, and skin surgery during and after isotretinoin use. Dermatol Surg. 2017 Oct;43(10):1249-62.
Etminan M1, Bird ST, Delaney JA, et al. Isotretinoin and risk for inflammatory bowel disease: a nested case-control study and meta-analysis of published and unpublished data. JAMA Dermatol. 2013 Feb;149(2):216-20.
Presented by: Prof. Kristian Reich, Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany