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Arash Mostaghimi - One of the best experts on this subject based on the ideXlab platform.
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psychiatric adverse events in patients taking Isotretinoin as reported in a food and drug administration database from 1997 to 2017
JAMA Dermatology, 2019Co-Authors: Elizabeth Tkachenko, Sean Singer, Priyank Sharma, John S Barbieri, Arash MostaghimiAbstract:Importance Isotretinoin is a highly effective medication for severe acne. 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. Objective To evaluate reports of psychiatric adverse events associated with Isotretinoin use submitted to the US Food and Drug Administration from January 1, 1997, through December 31, 2017. Design, Setting, and Participants This retrospective study evaluated reports of psychiatric adverse events with Isotretinoin as the primary suspect drug in the US Food and Drug Administration’s Adverse Event Reporting System from 1997 through 2017. Publicly available data on number of patients enrolled in the iPLEDGE program were used to calculate rates of completed suicide per 100 000 patients enrolled in iPLEDGE in 2009 and 2010. All data were analyzed between July 1, 2018, and January 31, 2019. Main Outcomes and Measures The main outcomes were frequency and type of psychiatric adverse events in patients taking Isotretinoin. Secondary analyses were stratification by age and sex and evaluation of completed suicide rates. Results Between 1997 and 2017, 17 829 psychiatric adverse events with Isotretinoin use were reported to the US Food and Drug Administration, with depressive disorders, emotional lability, and anxiety disorders reported most frequently. Of these events, 8936 (50.1%) were reported among men and 8362 (46.9%) among women; the sex of the individual was not reported for 531 events (3.0%). Of the 13 553 reports that included patient age, the mean (SD) age was 22.1 (8.6) years. More than half (52.5%) of all events occurred in 10- to 19-year-old individuals. Whereas depression and anxiety were reported equally between sexes, eating disorders were more common in females (58 of 85 [68.2%]), while attention-deficit/hyperactivity disorder (55 of 83 events [66.3%]) and completed suicides (290 of 368 [78.8%]) were more common in males. The rates of completed suicide were 8.4 and 5.6 suicides per 100 000 patients enrolled in iPLEDGE in 2009 and 2010, respectively. Conclusions and Relevance Although depressive disorders and suicidality were frequently reported with Isotretinoin use, these reports must be considered in the context of elevated rates of depression and suicide among patients with acne at large. These 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. Although no causal link between Isotretinoin and psychiatric risk has been established, patients taking the drug appear vulnerable to psychiatric concerns. Mandated monthly iPLEDGE visits may provide an opportunity to screen patients for psychiatric conditions and improve outcomes.
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us food and drug administration reports of pregnancy and pregnancy related adverse events associated with Isotretinoin
JAMA Dermatology, 2019Co-Authors: Elizabeth Tkachenko, Sean Singer, Priyank Sharma, John S Barbieri, Arash MostaghimiAbstract:Importance iPLEDGE is a rigorous program initiated in 2006 to reduce fetal exposure to Isotretinoin, a disease-modifying medication for acne that carries a risk of teratogenesis. Despite the imposition of iPLEDGE requirements on patients and clinicians, the scope of Isotretinoin-related adverse events is unknown. Objective To determine the frequency and rate of pregnancy and pregnancy-related adverse events among women taking Isotretinoin reported to the US Food and Drug Administration (FDA). Design, Setting, and Participants Pregnancy reports from the FDA Adverse Event Reporting System, a public database of medication adverse event reports filed by prescribers, consumers, and manufacturers, were used to perform a retrospective analysis of pregnancy-related adverse events associated with Isotretinoin from January 1, 1997, to December 31, 2017. Each individual reporting any pregnancy-related adverse event signified 1 pregnancy. Abortions, pregnancies that occurred while contraception was used, and fetal defects were counted as subgroups of total pregnancy events. Main Outcomes and Measures The frequency of pregnancy and of pregnancy-related events (abortions, pregnancies that occurred while using contraception, and fetal defects) were stratified by year that the FDA was notified of the event and by age. The rates of adverse events were calculated using Isotretinoin prescribing data. Results There was a total of 6740 pregnancies among women taking Isotretinoin reported to the FDA from 1997 to 2017, peaking in 2006 (768 pregnancies) before settling into a range of 218 to 310 annual reports of pregnancy after 2011. The mean (SD) age of the women was 24.6 (7.1) years. The rate of pregnancy for females of childbearing potential was between 0.33% (388 of 115 925) and 0.65% (768 of 117 784), with a peak in 2006. Although pregnancies, abortions, and fetal defects among women taking Isotretinoin have decreased since the initiation of iPLEDGE in 2006, all 3 persist. Conclusions and Relevance The number of reports of pregnancies, abortions, and fetal defects among women taking Isotretinoin has decreased since peaking around the initiation of iPLEDGE in 2006. Explanations for this trend include a broader national decrease in teenage pregnancies and abortion rates, improvements in access to effective long-term and emergency contraception, stringent iPLEDGE requirements, and reporting fatigue over time. Despite the decrease, persistent reporting of pregnancy-related events in the last decade warrants investigation into the efficacy of iPLEDGE and exploration of new approaches for lowering fetal exposure to Isotretinoin.
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differences in Isotretinoin start interruption and early termination across race and sex in the ipledge era
PLOS ONE, 2019Co-Authors: Alexandra Charrow, Fan Di Xia, Michael Waul, Cara Joyce, Arash MostaghimiAbstract:Background iPLEDGE is the mandatory regulatory program for Isotretinoin in the United States, aimed to prevent Isotretinoin-related teratogenicity. However, little is known about potential unintended impact of the program, including delay in Isotretinoin initiation, course interruption, and premature termination, which may vary across sex and racial domains. Objective To determine whether differences in Isotretinoin start, interruption, and completion exist across sex and racial domains and whether iPLEDGE regulations contribute to such differences. Methods Retrospective review of Isotretinoin courses of patients prescribed Isotretinoin for acne at the Brigham & Women’s Hospital and Massachusetts General Hospital from 2008–2016. Results 418 patients were included in analysis after being tightly matched across age and gender. 43.5% of non-white patients ended their course early compared to 30.1% of white patients (p = 0.010). iPLEDGE -related barriers were the most commonly specified reasons for delayed starting and interruption. Conclusion iPLEDGE may disproportionately contribute to access barriers for non-white patients. Continued evaluation of iPLEDGE is needed to minimize unintended barriers to access.
Sean Singer - One of the best experts on this subject based on the ideXlab platform.
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psychiatric adverse events in patients taking Isotretinoin as reported in a food and drug administration database from 1997 to 2017
JAMA Dermatology, 2019Co-Authors: Elizabeth Tkachenko, Sean Singer, Priyank Sharma, John S Barbieri, Arash MostaghimiAbstract:Importance Isotretinoin is a highly effective medication for severe acne. 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. Objective To evaluate reports of psychiatric adverse events associated with Isotretinoin use submitted to the US Food and Drug Administration from January 1, 1997, through December 31, 2017. Design, Setting, and Participants This retrospective study evaluated reports of psychiatric adverse events with Isotretinoin as the primary suspect drug in the US Food and Drug Administration’s Adverse Event Reporting System from 1997 through 2017. Publicly available data on number of patients enrolled in the iPLEDGE program were used to calculate rates of completed suicide per 100 000 patients enrolled in iPLEDGE in 2009 and 2010. All data were analyzed between July 1, 2018, and January 31, 2019. Main Outcomes and Measures The main outcomes were frequency and type of psychiatric adverse events in patients taking Isotretinoin. Secondary analyses were stratification by age and sex and evaluation of completed suicide rates. Results Between 1997 and 2017, 17 829 psychiatric adverse events with Isotretinoin use were reported to the US Food and Drug Administration, with depressive disorders, emotional lability, and anxiety disorders reported most frequently. Of these events, 8936 (50.1%) were reported among men and 8362 (46.9%) among women; the sex of the individual was not reported for 531 events (3.0%). Of the 13 553 reports that included patient age, the mean (SD) age was 22.1 (8.6) years. More than half (52.5%) of all events occurred in 10- to 19-year-old individuals. Whereas depression and anxiety were reported equally between sexes, eating disorders were more common in females (58 of 85 [68.2%]), while attention-deficit/hyperactivity disorder (55 of 83 events [66.3%]) and completed suicides (290 of 368 [78.8%]) were more common in males. The rates of completed suicide were 8.4 and 5.6 suicides per 100 000 patients enrolled in iPLEDGE in 2009 and 2010, respectively. Conclusions and Relevance Although depressive disorders and suicidality were frequently reported with Isotretinoin use, these reports must be considered in the context of elevated rates of depression and suicide among patients with acne at large. These 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. Although no causal link between Isotretinoin and psychiatric risk has been established, patients taking the drug appear vulnerable to psychiatric concerns. Mandated monthly iPLEDGE visits may provide an opportunity to screen patients for psychiatric conditions and improve outcomes.
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us food and drug administration reports of pregnancy and pregnancy related adverse events associated with Isotretinoin
JAMA Dermatology, 2019Co-Authors: Elizabeth Tkachenko, Sean Singer, Priyank Sharma, John S Barbieri, Arash MostaghimiAbstract:Importance iPLEDGE is a rigorous program initiated in 2006 to reduce fetal exposure to Isotretinoin, a disease-modifying medication for acne that carries a risk of teratogenesis. Despite the imposition of iPLEDGE requirements on patients and clinicians, the scope of Isotretinoin-related adverse events is unknown. Objective To determine the frequency and rate of pregnancy and pregnancy-related adverse events among women taking Isotretinoin reported to the US Food and Drug Administration (FDA). Design, Setting, and Participants Pregnancy reports from the FDA Adverse Event Reporting System, a public database of medication adverse event reports filed by prescribers, consumers, and manufacturers, were used to perform a retrospective analysis of pregnancy-related adverse events associated with Isotretinoin from January 1, 1997, to December 31, 2017. Each individual reporting any pregnancy-related adverse event signified 1 pregnancy. Abortions, pregnancies that occurred while contraception was used, and fetal defects were counted as subgroups of total pregnancy events. Main Outcomes and Measures The frequency of pregnancy and of pregnancy-related events (abortions, pregnancies that occurred while using contraception, and fetal defects) were stratified by year that the FDA was notified of the event and by age. The rates of adverse events were calculated using Isotretinoin prescribing data. Results There was a total of 6740 pregnancies among women taking Isotretinoin reported to the FDA from 1997 to 2017, peaking in 2006 (768 pregnancies) before settling into a range of 218 to 310 annual reports of pregnancy after 2011. The mean (SD) age of the women was 24.6 (7.1) years. The rate of pregnancy for females of childbearing potential was between 0.33% (388 of 115 925) and 0.65% (768 of 117 784), with a peak in 2006. Although pregnancies, abortions, and fetal defects among women taking Isotretinoin have decreased since the initiation of iPLEDGE in 2006, all 3 persist. Conclusions and Relevance The number of reports of pregnancies, abortions, and fetal defects among women taking Isotretinoin has decreased since peaking around the initiation of iPLEDGE in 2006. Explanations for this trend include a broader national decrease in teenage pregnancies and abortion rates, improvements in access to effective long-term and emergency contraception, stringent iPLEDGE requirements, and reporting fatigue over time. Despite the decrease, persistent reporting of pregnancy-related events in the last decade warrants investigation into the efficacy of iPLEDGE and exploration of new approaches for lowering fetal exposure to Isotretinoin.
Elizabeth Tkachenko - One of the best experts on this subject based on the ideXlab platform.
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psychiatric adverse events in patients taking Isotretinoin as reported in a food and drug administration database from 1997 to 2017
JAMA Dermatology, 2019Co-Authors: Elizabeth Tkachenko, Sean Singer, Priyank Sharma, John S Barbieri, Arash MostaghimiAbstract:Importance Isotretinoin is a highly effective medication for severe acne. 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. Objective To evaluate reports of psychiatric adverse events associated with Isotretinoin use submitted to the US Food and Drug Administration from January 1, 1997, through December 31, 2017. Design, Setting, and Participants This retrospective study evaluated reports of psychiatric adverse events with Isotretinoin as the primary suspect drug in the US Food and Drug Administration’s Adverse Event Reporting System from 1997 through 2017. Publicly available data on number of patients enrolled in the iPLEDGE program were used to calculate rates of completed suicide per 100 000 patients enrolled in iPLEDGE in 2009 and 2010. All data were analyzed between July 1, 2018, and January 31, 2019. Main Outcomes and Measures The main outcomes were frequency and type of psychiatric adverse events in patients taking Isotretinoin. Secondary analyses were stratification by age and sex and evaluation of completed suicide rates. Results Between 1997 and 2017, 17 829 psychiatric adverse events with Isotretinoin use were reported to the US Food and Drug Administration, with depressive disorders, emotional lability, and anxiety disorders reported most frequently. Of these events, 8936 (50.1%) were reported among men and 8362 (46.9%) among women; the sex of the individual was not reported for 531 events (3.0%). Of the 13 553 reports that included patient age, the mean (SD) age was 22.1 (8.6) years. More than half (52.5%) of all events occurred in 10- to 19-year-old individuals. Whereas depression and anxiety were reported equally between sexes, eating disorders were more common in females (58 of 85 [68.2%]), while attention-deficit/hyperactivity disorder (55 of 83 events [66.3%]) and completed suicides (290 of 368 [78.8%]) were more common in males. The rates of completed suicide were 8.4 and 5.6 suicides per 100 000 patients enrolled in iPLEDGE in 2009 and 2010, respectively. Conclusions and Relevance Although depressive disorders and suicidality were frequently reported with Isotretinoin use, these reports must be considered in the context of elevated rates of depression and suicide among patients with acne at large. These 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. Although no causal link between Isotretinoin and psychiatric risk has been established, patients taking the drug appear vulnerable to psychiatric concerns. Mandated monthly iPLEDGE visits may provide an opportunity to screen patients for psychiatric conditions and improve outcomes.
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us food and drug administration reports of pregnancy and pregnancy related adverse events associated with Isotretinoin
JAMA Dermatology, 2019Co-Authors: Elizabeth Tkachenko, Sean Singer, Priyank Sharma, John S Barbieri, Arash MostaghimiAbstract:Importance iPLEDGE is a rigorous program initiated in 2006 to reduce fetal exposure to Isotretinoin, a disease-modifying medication for acne that carries a risk of teratogenesis. Despite the imposition of iPLEDGE requirements on patients and clinicians, the scope of Isotretinoin-related adverse events is unknown. Objective To determine the frequency and rate of pregnancy and pregnancy-related adverse events among women taking Isotretinoin reported to the US Food and Drug Administration (FDA). Design, Setting, and Participants Pregnancy reports from the FDA Adverse Event Reporting System, a public database of medication adverse event reports filed by prescribers, consumers, and manufacturers, were used to perform a retrospective analysis of pregnancy-related adverse events associated with Isotretinoin from January 1, 1997, to December 31, 2017. Each individual reporting any pregnancy-related adverse event signified 1 pregnancy. Abortions, pregnancies that occurred while contraception was used, and fetal defects were counted as subgroups of total pregnancy events. Main Outcomes and Measures The frequency of pregnancy and of pregnancy-related events (abortions, pregnancies that occurred while using contraception, and fetal defects) were stratified by year that the FDA was notified of the event and by age. The rates of adverse events were calculated using Isotretinoin prescribing data. Results There was a total of 6740 pregnancies among women taking Isotretinoin reported to the FDA from 1997 to 2017, peaking in 2006 (768 pregnancies) before settling into a range of 218 to 310 annual reports of pregnancy after 2011. The mean (SD) age of the women was 24.6 (7.1) years. The rate of pregnancy for females of childbearing potential was between 0.33% (388 of 115 925) and 0.65% (768 of 117 784), with a peak in 2006. Although pregnancies, abortions, and fetal defects among women taking Isotretinoin have decreased since the initiation of iPLEDGE in 2006, all 3 persist. Conclusions and Relevance The number of reports of pregnancies, abortions, and fetal defects among women taking Isotretinoin has decreased since peaking around the initiation of iPLEDGE in 2006. Explanations for this trend include a broader national decrease in teenage pregnancies and abortion rates, improvements in access to effective long-term and emergency contraception, stringent iPLEDGE requirements, and reporting fatigue over time. Despite the decrease, persistent reporting of pregnancy-related events in the last decade warrants investigation into the efficacy of iPLEDGE and exploration of new approaches for lowering fetal exposure to Isotretinoin.
Diane K Wysowski - One of the best experts on this subject based on the ideXlab platform.
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use of Isotretinoin accutane in the united states rapid increase from 1992 through 2000
Journal of The American Academy of Dermatology, 2002Co-Authors: Diane K Wysowski, Joslyn Swann, Amarilys VegaAbstract:Abstract Background: Isotretinoin, a drug approved to treat severe recalcitrant nodular acne, has been marketed in the United States since 1982. The drug is an effective treatment for acne that is refractory to other therapies, but it is a teratogen and can cause serious side effects. Objective: Our purpose was to describe trends in the use of Isotretinoin in the United States from marketing through year 2000 and summarize characteristics of patients and prescribers. Methods: Data from 2 pharmaceutical marketing research databases, the National Prescription Audit Plus and the National Disease and Therapeutic Index, and from 2 health plan networks were obtained and analyzed. Results: Retail pharmacies dispensed 19.8 million outpatient prescriptions for Isotretinoin from marketing in 1982 through 2000. From 1983 through 1993, the median annual number of prescriptions was just over 800,000; between 1992 and 2000, the number of prescriptions increased 2.5-fold (250%) to nearly 2 million in year 2000. The increases registered in the health plans were somewhat larger: about 275% increases from 1995 through 1999. There is no ICD-9 code for nodulocystic acne; consequently, the type of acne treated with Isotretinoin is not determinable from these data. However, between 1993 and 2000, the proportion of Isotretinoin treatment for severe acne declined from 63% to 46%, whereas the proportion of treatment for mild and moderate acne increased from 31% to 49%. Data also indicated that the sex distribution of patients was nearly even, and that 63% of male patients prescribed Isotretinoin were 15 to 19 years old, whereas 51% of female patients were 15 to 24 years old. Conclusion: In the last 8 years, there has been a 2.5-fold (250%) increase in the number of dispensed prescriptions for Isotretinoin in the United States. Data also reveal an increasing proportion of Isotretinoin use for mild and moderate acne. (J Am Acad Dermatol 2002;46:505-9.)
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an analysis of reports of depression and suicide in patients treated with Isotretinoin
Journal of The American Academy of Dermatology, 2001Co-Authors: Diane K Wysowski, Marilyn Pitts, Julie BeitzAbstract:Abstract Background: The Food and Drug Administration (FDA) has received reports of depression and suicide in patients treated with Isotretinoin. Objective: Our purpose was to provide the number and describe the cases of depression and suicide reported to the FDA in US patients treated with Isotretinoin and to consider the nature of a possible association between Isotretinoin and depression. Methods: An analysis was made of reports of depression, suicidal ideation, suicide attempt, and suicide in US Isotretinoin users voluntarily submitted to the manufacturer and the FDA from 1982 to May 2000 and entered in the FDA's Adverse Event Reporting System database. Results: From marketing of Isotretinoin in 1982 to May 2000, the FDA received reports of 37 US patients treated with Isotretinoin who committed suicide; 110 who were hospitalized for depression, suicidal ideation, or suicide attempt; and 284 with nonhospitalized depression, for a total of 431 patients. Factors suggesting a possible association between Isotretinoin and depression include a temporal association between use of the drug and depression, positive dechallenges (often with psychiatric treatment), positive rechallenges, and possible biologic plausibility. Compared with all drugs in the FDA's Adverse Event Reporting System database to June 2000, Isotretinoin ranked within the top 10 for number of reports of depression and suicide attempt. Conclusion: The FDA has received reports of depression, suicidal ideation, suicide attempt, and suicide in patients treated with Isotretinoin. Additional studies are needed to determine whether Isotretinoin causes depression and to identify susceptible persons. In the meantime, physicians are advised to inform patients prescribed Isotretinoin (and parents, if appropriate) of the possibility of development or worsening of depression. They should advise patients (and parents) to immediately report mood swings and symptoms suggestive of depression such as sadness, crying, loss of appetite, unusual fatigue, withdrawal, and inability to concentrate so that patients can be promptly evaluated for appropriate treatment, including consideration of drug discontinuation and referral for psychiatric care. (J Am Acad Dermatol 2001;45:515-9.)
Lorraine J. Gudas - One of the best experts on this subject based on the ideXlab platform.
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NCI 6896: a phase I trial of vorinostat (SAHA) and Isotretinoin (13-cis retinoic acid) in the treatment of patients with advanced renal cell carcinoma
Investigational New Drugs, 2020Co-Authors: Ana M. Molina, Johannes C. Mijn, Paul Christos, John Wright, Charlene Thomas, Janice P. Dutcher, David M. Nanus, Scott T. Tagawa, Lorraine J. GudasAbstract:Preclinical studies suggest that histone deacetylase (HDAC) inhibitors may restore tumor sensitivity to retinoids and have synergistic anti-tumor activity when combined. We performed a Phase I clinical trial to evaluate the safety and preliminary efficacy of combining the oral HDAC inhibitor vorinostat and Isotretinoin in patients with advanced renal cell carcinoma (RCC). Vorinostat was administered at 300 mg orally twice daily in combination with escalating doses of Isotretinoin for 3 consecutive days per week. A standard 3 + 3 dose escalation design was used. Dose limiting toxicities (DLT) were assess during the first cycle to determine the maximum tolerated dose (MTD). Fourteen patients enrolled on the trial of which 12 were evaluable for toxicity (6 cohort 1; 3 cohort 2; 3 cohort 3) and 11 for tumor response. One patient in cohort 1 experienced a DLT (grade 3 depression). Common grade 1–2 toxicities included fatigue and GI effects (nausea, diarrhea, anorexia). MTD was established as vorinostat 300 mg with isoretinoin 0.5 mg/kg twice daily 3 days per week. Best responses in evaluable patients included 1 partial response and 9 stable disease, lasting a median of 3.7 months (range 1.8–10.4 months). The combination of vorinostat and Isotretinoin is safe, tolerable and associated with responses in patients with refractory metastatic RCC.