BackgroundIsotretinoin is an effective treatment for severe acne; no alternative treatment has an equal therapeutic effect. The teratogenic effects of isotretinoin can be avoided, and numerous recommendations and regulations are in force to minimize the risk of pregnancy during treatment.ObjectivesTo describe isotretinoin prescription patterns for women aged 15–45 years, assess the concomitancy of isotretinoin and contraceptive use, and determine the rate of potential isotretinoin-exposed pregnancies in Estonia.MethodsThis retrospective, nationwide, population-based, cohort study derived data from national health insurance databases and included female patients aged 15–45 years in Estonia for whom one or more prescriptions for isotretinoin were dispensed between 2012 and 2016. The main outcome was the proportion of women who used systemic isotretinoin and had a concomitant record of (hormonal or intrauterine) contraception use covering the isotretinoin treatment period when pregnancy is contraindicated.ResultsOf the 2792 women aged 15–45 years filling an isotretinoin prescription, 15.7% (95% CI 14.4–17.1) had full and 13.9% (95% CI 12.7–15.3) partial (not covering the whole period during which pregnancy is contraindicated) contraceptive coverage. The risk for potential isotretinoin-exposed pregnancy was 3.6 (95% CI 2.0–7.0) per 1000 treated women over the 5-year observation period. The odds for full coverage with effective contraception increased with the age of the patient, with the duration of isotretinoin treatment and over the period of observation.ConclusionOur study adds to the existing literature documenting limited compliance with pregnancy prevention programs for isotretinoin-containing products, and calls for program assessment to identify whether new measures should be taken or whether weaknesses in policy or implementation can be corrected.

Valproic acid (VPA) is a widely used anticonvulsant that is effective against most seizure types. Due to its teratogenic effects, its use should be avoided among females of childbearing age, unless other treatments are ineffective or not tolerated. This study aimed to determine the prevalence of VPA use in 2005-2018 in Estonia, with special attention to females of childbearing age. Methods: In this retrospective nationwide population-based cohort study, outpatient prescription data from the national health insurance provider were used. Annual sex-and age-specific prevalence rates were calculated, and changes therein during the study period were evaluated. Results: The annual rates of VPA use among females of childbearing age increased significantly in 2005-2014. After 2014, the increasing trend stopped; in 2014-2018, the prevalence rates declined slightly [prevalence rate ratio (PRR), 0.94; P = 0.136]. In males of the same age, the increasing trend continued (PRR, 1.08: P = 0.028). Among neurologists, the rate of VPA prescription to females aged < 15 and 15-44 years decreased during 2014-2018 (PRR, 0.74; P < 0.001 and PRR 0.72; P < 0.001, respectively); no change in prescription frequency was seen among psychiatrists during this period. Conclusions: The increasing trend in VPA usage among females of childbearing age in Estonia stopped after 2014, when the European Medicines Agency's strengthened restrictions on VPA use in females were communicated extensively in Estonia. The level of awareness of VPA's harmful effects during pregnancy is lower in the psychiatric community.

Our objective was to examine the trends and variation in opioid prescribing in Estonia from 2011 to 2017. This retrospective cross‐sectional study is based on a nationwide prescription medicines database. We stratified the analysis by treatment indication (cancer vs noncancer pain). Between 2011 and 2017, annual opioid prescribing rates increased by 67% (from 82.9 to 138.6 prescriptions per 1000 population). The annual number of prescriptions per patient did not change substantially (from 2.94 in 2011 to 2.87 in 2017), and was higher among cancer patients (5.07 vs 2.67 annual prescriptions per cancer and noncancer patients, respectively, in 2017). The use of the most potent opioids (morphine, fentanyl) was higher in noncancer than in cancer patients. The use of prescription opioids is low, and raises concern about the potential undertreatment of cancer pain, in parallel with misuse of opioids for either noncancer pain or diversion.

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