Australasian Journal of Dermatology

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background/Obectives</jats:title><jats:p>Oral retinoids are teratogenic, and pregnancy avoidance is an important part of retinoid prescribing. Australia does not have a standardised pregnancy prevention programme for women using oral retinoids, and the contraception strategies for women who use oral retinoids are not well understood.</jats:p><jats:p>The objectives were to determine trends in the use of prescription retinoids among Australian reproductive‐aged women and whether women dispensed oral retinoids used contraception concomitantly.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This was a population‐based study using Australian Pharmaceutical Benefits (PBS) dispensing claims for a random 10% sample of 15‐44‐year‐old Australian women, 2013 ‐ 2021. We described rates and annual trends in dispensing claims for PBS‐listed retinoids and contraceptives. We also estimated concomitant oral retinoid and contraceptive use on the day of each retinoid dispensing and determined if there was a period of contraceptive treatment that overlapped. Estimates were then extrapolated to the national level.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>There were 1,545,800 retinoid dispensings to reproductive‐aged women; 57.1% were oral retinoids. The rate of retinoid dispensing to reproductive‐aged women increased annually, from 28 dispensings per 1000 population in 2013 to 41 per 1000 in 2021. The rate of oral retinoid dispensing doubled over the study period, from 14 dispensings per 1000 population in 2013 to 28 per 1000 in 2021, while topical retinoid dispensing did not change. Only 25% of oral retinoid dispensings had evidence of concomitant contraceptive use in 2021.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Rates of oral retinoid dispensing have doubled among reproductive‐aged women over the past decade. A large percentage of oral retinoid use does not appear to have concomitant contraception use, posing a risk of teratogenic effects in pregnancies.</jats:p></jats:sec>

publication_history

received

accepted

published

National Health and Medical Research Council

Financial Markets Foundation for Children

Isotretinoin: the mothersafe experience 2010 to 2014. A need to revisit education and prescribing practices

Birth Defects Res A Clin Mol Teratol

Terminations of pregnancy associated with isotretinoin use in New Zealand

New Zealand Med J

iPLEDGE must abstain from abstinence

J Clin Aesthet Dermatol

Oral retinoids are teratogenic, and pregnancy avoidance is an important part of retinoid prescribing. Australia does not have a standardised pregnancy prevention programme for women using oral retinoids, and the contraception strategies for women who use oral retinoids are not well understood. The objectives were to determine trends in the use of prescription retinoids among Australian reproductive-aged women and whether women dispensed oral retinoids used contraception concomitantly.
This was a population-based study using Australian Pharmaceutical Benefits (PBS) dispensing claims for a random 10% sample of 15-44-year-old Australian women, 2013 - 2021. We described rates and annual trends in dispensing claims for PBS-listed retinoids and contraceptives. We also estimated concomitant oral retinoid and contraceptive use on the day of each retinoid dispensing and determined if there was a period of contraceptive treatment that overlapped. Estimates were then extrapolated to the national level.
There were 1,545,800 retinoid dispensings to reproductive-aged women; 57.1% were oral retinoids. The rate of retinoid dispensing to reproductive-aged women increased annually, from 28 dispensings per 1000 population in 2013 to 41 per 1000 in 2021. The rate of oral retinoid dispensing doubled over the study period, from 14 dispensings per 1000 population in 2013 to 28 per 1000 in 2021, while topical retinoid dispensing did not change. Only 25% of oral retinoid dispensings had evidence of concomitant contraceptive use in 2021.
Rates of oral retinoid dispensing have doubled among reproductive-aged women over the past decade. A large percentage of oral retinoid use does not appear to have concomitant contraception use, posing a risk of teratogenic effects in pregnancies.

Prescription retinoid and contraception use in women in Australia: A population-based study.

Prescription retinoid and contraception use in women in Australia: A population‐based study

JAMA Dermatology

<jats:sec id="ab-doi230057-4"><jats:title>Importance</jats:title><jats:p>Isotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear.</jats:p></jats:sec><jats:sec id="ab-doi230057-5"><jats:title>Objective</jats:title><jats:p>To clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users.</jats:p></jats:sec><jats:sec id="ab-doi230057-6"><jats:title>Data Sources</jats:title><jats:p>PubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023.</jats:p></jats:sec><jats:sec id="ab-doi230057-7"><jats:title>Study Selection</jats:title><jats:p>Randomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users.</jats:p></jats:sec><jats:sec id="ab-doi230057-8"><jats:title>Data Extraction and Synthesis</jats:title><jats:p>Relevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the <jats:italic>I</jats:italic><jats:sup>2</jats:sup> statistic, and meta-regression analyses were performed.</jats:p></jats:sec><jats:sec id="ab-doi230057-9"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Absolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users.</jats:p></jats:sec><jats:sec id="ab-doi230057-10"><jats:title>Results</jats:title><jats:p>A total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants’ average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide.</jats:p></jats:sec><jats:sec id="ab-doi230057-11"><jats:title>Conclusions and Relevance</jats:title><jats:p>The findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.</jats:p></jats:sec>

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Ann Gen Psychiatry

Undue reliance on I(2) in assessing heterogeneity may mislead.

BMC Med Res Methodol

Isotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear.
To clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users.
PubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023.
Randomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users.
Relevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the I2 statistic, and meta-regression analyses were performed.
Absolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users.
A total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants' average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; I2 = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; I2 = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide.
The findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.

Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis.

Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users

Papers