High Levels of Serotonin Found in People with Social Anxiety Disorder
JAMA Psychiatry
Abstract
Serotonin is involved in negative affect, but whether anxiety syndromes, such as social anxiety disorder (SAD), are characterized by an overactive or underactive serotonin system has not been established. Serotonin 1A autoreceptors, which inhibit serotonin synthesis and release, are downregulated in SAD, and serotonin transporter availability might be increased; however, presynaptic serotonin activity has not been evaluated extensively.
Objective
To examine the serotonin synthesis rate and serotonin transporter availability in patients with SAD and healthy control individuals using positron emission tomography (PET) with the radioligands 5-hydroxytryptophan labeled with carbon 11 ([11C]5-HTP) and 11C-labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile [11C]DASB.
Design, Setting, and Participants
We performed a cross-sectional study at an academic clinical research center. Eighteen patients with SAD (9 men and 9 women; mean [SD] age, 32.6 [8.2] years) and 18 sex- and age-matched healthy controls (9 men and 9 women; mean [SD] age, 34.7 [9.2] years) underwent [11C]5-HTP PET imaging. We acquired [11C]DASB PET images for 26 additional patients with SAD (14 men and 12 women; mean [SD] age, 35.2 [10.7] years) and the same 18 sex- and age-matched healthy controls. Participants were recruited through newspaper advertisements. Data were acquired from March 12, 2002, through March 5, 2012, and analyzed from March 28, 2013, through August 29, 2014.
Main Outcomes and Measures
The influx rate of [11C]5-HTP as a measure of serotonin synthesis rate capacity and [11C]DASB binding potential as an index of serotonin transporter availability were acquired during rest. We used the Liebowitz Social Anxiety Scale to measure severity of social anxiety symptoms.
Results
The PET data were not available for analysis in 1 control for each scan. Increased [11C]5-HTP influx rate was observed in the amygdala, raphe nuclei region, caudate nucleus, putamen, hippocampus, and anterior cingulate cortex of patients with SAD compared with healthy controls (P < .05 corrected), supporting an enhanced serotonin synthesis rate. Increased serotonin transporter availability in the patients with SAD relative to healthy controls was reflected by elevated [11C]DASB binding potential in the raphe nuclei region, caudate nucleus, putamen, thalamus, and insula cortex (P < .05 corrected).
Conclusions and Relevance
Neurotransmission in SAD is characterized by an overactive presynaptic serotonin system, with increased serotonin synthesis and transporter availability. Our findings could provide important new insights into the etiology of anxiety disorders.
Link: http://jamanetwork.com/
Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study
The American Journal of Psychiatry
Abstract
The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.
Method:
This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures.
Results:
Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (–6.4 [SD=6.4] compared with –3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group.
Conclusions:
Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.
Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study
The BMJ
Abstract
Objective
To evaluate maternal medical and perinatal outcomes associated with antipsychotic drug use in pregnancy.
Design
High dimensional propensity score (HDPS) matched cohort study.
Setting
Multiple linked population health administrative databases in the entire province of Ontario, Canada.
Participants
Among women who delivered a singleton infant between 2003 and 2012, and who were eligible for provincially funded drug coverage, those with ≥2 consecutive prescriptions for an antipsychotic medication during pregnancy, at least one of which was filled in the first or second trimester, were selected. Of these antipsychotic drug users, 1021 were matched 1:1 with 1021 non-users by means of a HDPS algorithm.
Main outcome measures
The main maternal medical outcomes were gestational diabetes, hypertensive disorders of pregnancy, and venous thromboembolism. The main perinatal outcomes were preterm birth (<37 weeks), and a birth weight <3rd or >97th centile. Conditional Poisson regression analysis was used to generate rate ratios and 95% confidence intervals, adjusting for additionally prescribed non-antipsychotic psychotropic medications.
Results
Compared with non-users, women prescribed an antipsychotic medication in pregnancy did not seem to be at higher risk of gestational diabetes (rate ratio 1.10 (95% CI 0.77 to 1.57)), hypertensive disorders of pregnancy (1.12 (0.70 to 1.78)), or venous thromboembolism (0.95 (0.40 to 2.27)). The preterm birth rate, though high among antipsychotic users (14.5%) and matched non-users (14.3%), was not relatively different (rate ratio 0.99 (0.78 to 1.26)). Neither birth weight <3rd centile or >97th centile was associated with antipsychotic drug use in pregnancy (rate ratios 1.21 (0.81 to 1.82) and 1.26 (0.69 to 2.29) respectively).
Conclusions
Antipsychotic drug use in pregnancy had minimal evident impact on important maternal medical and short term perinatal outcomes. However, the rate of adverse outcomes is high enough to warrant careful assessment of maternal and fetal wellbeing among women prescribed an antipsychotic drug in pregnancy.
To evaluate maternal medical and perinatal outcomes associated with antipsychotic drug use in pregnancy.
Design
High dimensional propensity score (HDPS) matched cohort study.
Setting
Multiple linked population health administrative databases in the entire province of Ontario, Canada.
Participants
Among women who delivered a singleton infant between 2003 and 2012, and who were eligible for provincially funded drug coverage, those with ≥2 consecutive prescriptions for an antipsychotic medication during pregnancy, at least one of which was filled in the first or second trimester, were selected. Of these antipsychotic drug users, 1021 were matched 1:1 with 1021 non-users by means of a HDPS algorithm.
Main outcome measures
The main maternal medical outcomes were gestational diabetes, hypertensive disorders of pregnancy, and venous thromboembolism. The main perinatal outcomes were preterm birth (<37 weeks), and a birth weight <3rd or >97th centile. Conditional Poisson regression analysis was used to generate rate ratios and 95% confidence intervals, adjusting for additionally prescribed non-antipsychotic psychotropic medications.
Results
Compared with non-users, women prescribed an antipsychotic medication in pregnancy did not seem to be at higher risk of gestational diabetes (rate ratio 1.10 (95% CI 0.77 to 1.57)), hypertensive disorders of pregnancy (1.12 (0.70 to 1.78)), or venous thromboembolism (0.95 (0.40 to 2.27)). The preterm birth rate, though high among antipsychotic users (14.5%) and matched non-users (14.3%), was not relatively different (rate ratio 0.99 (0.78 to 1.26)). Neither birth weight <3rd centile or >97th centile was associated with antipsychotic drug use in pregnancy (rate ratios 1.21 (0.81 to 1.82) and 1.26 (0.69 to 2.29) respectively).
Conclusions
Antipsychotic drug use in pregnancy had minimal evident impact on important maternal medical and short term perinatal outcomes. However, the rate of adverse outcomes is high enough to warrant careful assessment of maternal and fetal wellbeing among women prescribed an antipsychotic drug in pregnancy.
Link: http://www.bmj.com/
Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four-Decade Longitudinal Cohort Study
The American Journal of Psychiatry
Abstract
Objective:
Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective longitudinal study has described the childhoods of the adult ADHD population. The authors report follow-back analyses of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD cases diagnosed in childhood, in one cohort.Method:
Participants belonged to a representative birth cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed to age 38, with 95% retention. Symptoms of ADHD, associated clinical features, comorbid disorders, neuropsychological deficits, genome-wide association study-derived polygenic risk, and life impairment indicators were assessed. Data sources were participants, parents, teachers, informants, neuropsychological test results, and administrative records. Adult ADHD diagnoses used DSM-5 criteria, apart from onset age and cross-setting corroboration, which were study outcome measures.
Results:
As expected, childhood ADHD had a prevalence of 6% (predominantly male) and was associated with childhood comorbid disorders, neurocognitive deficits, polygenic risk, and residual adult life impairment. Also as expected, adult ADHD had a prevalence of 3% (gender balanced) and was associated with adult substance dependence, adult life impairment, and treatment contact. Unexpectedly, the childhood ADHD and adult ADHD groups comprised virtually nonoverlapping sets; 90% of adult ADHD cases lacked a history of childhood ADHD. Also unexpectedly, the adult ADHD group did not show tested neuropsychological deficits in childhood or adulthood, nor did they show polygenic risk for childhood ADHD.
Conclusions:
The findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder. If this finding is replicated, then the disorder’s place in the classification system must be reconsidered, and research must investigate the etiology of adult ADHD.
Estradiol Withdrawal and Mood in Women With Past Perimenopausal Depression
JAMA Psychiatry
Abstract
Importance
Perimenopause is accompanied by an increased risk of new and recurrent depression. The coincidence of declining ovarian function with the onset of depression led to the inference that “withdrawal” from physiologic estradiol levels underpinned depression in perimenopause. To our knowledge, this is the first controlled systematic study to directly test the estrogen withdrawal theory of perimenopausal depression (PMD).
Objective
To examine the role of estradiol withdrawal in PMD.
Design, Setting, and Participants
Initial open-label treatment with estradiol followed by randomized, double-blind, placebo-controlled, parallel-design evaluation of continued estradiol treatment was evaluated at an outpatient research facility at the National Institutes of Health Clinical Center. An intent-to-treat analysis was performed between October 2003 and July 2012. Participants included asymptomatic postmenopausal women with past PMD responsive to hormone therapy (n = 26) and asymptomatic postmenopausal women with no history of depression (n = 30) matched for age, body mass index, and reproductive status who served as controls. Data were analyzed between November 2012 and October 2013 by repeated-measures analysis of variance.
Interventions
After 3 weeks of open-label administration of transdermal estradiol (100 µg/d), participants were randomized to a parallel design to receive either estradiol (100 µg/d; 27 participants) or matched placebo skin patches (29 participants) for 3 additional weeks under double-blind conditions.
Main Outcomes and Measures
Center for Epidemiologic Studies–Depression Scale and 17-item Hamilton Depression Rating Scale (completed by raters blind to diagnosis and randomization status), self-administered visual analog symptom ratings, and blood hormone levels obtained at weekly clinic visits.
Results
None of the women reported depressive symptoms during open-label use of estradiol. Women with past PMD who were crossed over from estradiol to placebo experienced a significant increase in depression symptom severity demonstrated using the Center for Epidemiologic Studies–Depression Scale and 17-item Hamilton Depression Rating Scale, with mean (SD) scores increasing from estradiol (ie, 2.4 [2.0] and 3.0 [2.5]) to placebo (8.8 [4.9] and 6.6 [4.5], respectively [P = .0004 for both]). Women with past PMD who continued estradiol therapy and all women in the control group remained asymptomatic. Women in both groups had similar hot-flush severity and plasma estradiol levels during use of placebo.
Conclusions and Relevance
In women with past PMD that was previously responsive to hormone therapy, the recurrence of depressive symptoms during blinded hormone withdrawal suggests that normal changes in ovarian estradiol secretion can trigger an abnormal behavioral state in these susceptible women. Women with a history of PMD should be alert to the risk of recurrent depression when discontinuing hormone therapy.
Abstract
Importance
Perimenopause is accompanied by an increased risk of new and recurrent depression. The coincidence of declining ovarian function with the onset of depression led to the inference that “withdrawal” from physiologic estradiol levels underpinned depression in perimenopause. To our knowledge, this is the first controlled systematic study to directly test the estrogen withdrawal theory of perimenopausal depression (PMD).
Objective
To examine the role of estradiol withdrawal in PMD.
Design, Setting, and Participants
Initial open-label treatment with estradiol followed by randomized, double-blind, placebo-controlled, parallel-design evaluation of continued estradiol treatment was evaluated at an outpatient research facility at the National Institutes of Health Clinical Center. An intent-to-treat analysis was performed between October 2003 and July 2012. Participants included asymptomatic postmenopausal women with past PMD responsive to hormone therapy (n = 26) and asymptomatic postmenopausal women with no history of depression (n = 30) matched for age, body mass index, and reproductive status who served as controls. Data were analyzed between November 2012 and October 2013 by repeated-measures analysis of variance.
Interventions
After 3 weeks of open-label administration of transdermal estradiol (100 µg/d), participants were randomized to a parallel design to receive either estradiol (100 µg/d; 27 participants) or matched placebo skin patches (29 participants) for 3 additional weeks under double-blind conditions.
Main Outcomes and Measures
Center for Epidemiologic Studies–Depression Scale and 17-item Hamilton Depression Rating Scale (completed by raters blind to diagnosis and randomization status), self-administered visual analog symptom ratings, and blood hormone levels obtained at weekly clinic visits.
Results
None of the women reported depressive symptoms during open-label use of estradiol. Women with past PMD who were crossed over from estradiol to placebo experienced a significant increase in depression symptom severity demonstrated using the Center for Epidemiologic Studies–Depression Scale and 17-item Hamilton Depression Rating Scale, with mean (SD) scores increasing from estradiol (ie, 2.4 [2.0] and 3.0 [2.5]) to placebo (8.8 [4.9] and 6.6 [4.5], respectively [P = .0004 for both]). Women with past PMD who continued estradiol therapy and all women in the control group remained asymptomatic. Women in both groups had similar hot-flush severity and plasma estradiol levels during use of placebo.
Conclusions and Relevance
In women with past PMD that was previously responsive to hormone therapy, the recurrence of depressive symptoms during blinded hormone withdrawal suggests that normal changes in ovarian estradiol secretion can trigger an abnormal behavioral state in these susceptible women. Women with a history of PMD should be alert to the risk of recurrent depression when discontinuing hormone therapy.
Link: http://jamanetwork.com/
SSRI Antidepressant Use Late in Pregnancy and Risk of Persistent Pulmonary Hypertension of the Newborn
JAMA
Abstract
Importance
The association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006.
Objective
To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy.
Design and Setting
Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010.
Participants
A total of 3 789 330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders.
Exposures for Observational Studies
SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use.
Main Outcomes and Measures
Recorded diagnosis of PPHN during the first 30 days after delivery.
Results
A total of 128 950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102 179 (2.7%) used an SSRI and 26 771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10 000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10 000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10 000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74).
Conclusions and Relevance
Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.
The association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006.
Objective
To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy.
Design and Setting
Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010.
Participants
A total of 3 789 330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders.
Exposures for Observational Studies
SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use.
Main Outcomes and Measures
Recorded diagnosis of PPHN during the first 30 days after delivery.
Results
A total of 128 950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102 179 (2.7%) used an SSRI and 26 771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10 000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10 000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10 000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74).
Conclusions and Relevance
Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.
Link: http://jamanetwork.com/
FDA takes action to protect consumers from potentially dangerous counterfeit medicines and devices sold online
International Operation Pangea VIII combats the unlawful sale and distribution of illegal prescription medicines and medical devices on the Internet
The action occurred as part of the Eighth Annual International Internet Week of Action (IIWA), a global cooperative effort, led by INTERPOL, to combat the unlawful sale and distribution of illegal and potentially counterfeit medical products on the Internet.
As part of this year’s international effort – Operation Pangea VIII – the FDA sent Warning Letters to the operators of nearly 400 websites offering unapproved or misbranded prescription medicines to U.S. patients and to nine firms distributing unapproved or uncleared medical devices online. FDA inspectors, in collaboration with other federal agencies, screened and seized illegal drug products and medical devices received through International Mail Facilities (IMFs) in Chicago, Miami and New York during the IIWA. These screenings resulted in 814 parcels being detained and referred to appropriate FDA offices for follow up. Parcels found in violation of the Federal Food, Drug and Cosmetic Act will be refused entry into the country.
Multiple centers and offices within the FDA participated in the enforcement action, which ran from June 9 to June 16, 2015.
The goal of Pangea VIII – which involves law enforcement, customs and regulatory authorities from 115 countries – was to identify the makers and distributors of illegal prescription drug products and medical devices and to remove these products from the supply chain.
“Our efforts to protect the health of American patients by preventing the online sale of potentially dangerous illegal medical products will not cease,” said George Karavetsos, director of the FDA’s Office of Criminal Investigations. “Operation Pangea VIII provides yet another avenue for the FDA to engage with our international law enforcement partners on these critical issues. We are not only pleased to be a part of this strong international enforcement effort, but resolved to do everything we can to ensure that the global problem of illegal Internet drug and device sales is deterred as a result.”
Some of the unapproved prescription drugs targeted during Operation Pangea VIII that purport to be FDA-approved generic versions of brand name drugs and are sold illegally by the websites included: “Generic Nolvadex,” “Generic Meridia,” “Generic Valium,” “Generic Truvada” and “Generic Advair Diskus.”
Some of the devices sold illegally online and targeted during Operation Pangea VIII included “The Ondamed System” and “Colon Care Products of PA Open System Colon Hydrotherapy Device (Grace)” as well as illegal dermal fillers such as “Interfall Hydrogel polyacrylamide dermal filler,” “Dermafil hyaluronic acid dermal filler” and “Teosyal hyaluronic acid dermal filler.”
Preliminary findings from drug products screened at IMFs show that certain drug products from abroad, such as antidepressants, hormone replacement therapies, sleep aids and other drugs to treat erectile dysfunction, high cholesterol and seizures were en route to U.S. consumers..
Link: http://www.fda.gov/
Fermented foods, neuroticism, and social anxiety: An interaction model
Psychiatry Research
Abstract
Animal models and clinical trials in humans suggest that probiotics can have an anxiolytic effect. However, no studies have examined the relationship between probiotics and social anxiety. Here we employ a cross-sectional approach to determine whether consumption of fermented foods likely to contain probiotics interacts with neuroticism to predict social anxiety symptoms. A sample of young adults (N=710, 445 female) completed self-report measures of fermented food consumption, neuroticism, and social anxiety. An interaction model, controlling for demographics, general consumption of healthful foods, and exercise frequency, showed that exercise frequency, neuroticism, and fermented food consumption significantly and independently predicted social anxiety. Moreover, fermented food consumption also interacted with neuroticism in predicting social anxiety. Specifically, for those high in neuroticism, higher frequency of fermented food consumption was associated with fewer symptoms of social anxiety. Taken together with previous studies, the results suggest that fermented foods that contain probiotics may have a protective effect against social anxiety symptoms for those at higher genetic risk, as indexed by trait neuroticism. While additional research is necessary to determine the direction of causality, these results suggest that consumption of fermented foods that contain probiotics may serve as a low-risk intervention for reducing social anxiety.
POtiga (ezogabine): FDA Determines 2013 Labeling Adequate to Manage Risks of Retinal Abnormalities, Potential Vision Loss, and Skin Discoloration
ISSUE: Based on reviews of additional safety reports from patients treated with the anti-seizure drug Potiga (ezogabine), the FDA has determined that the potential risks of vision loss due to pigment changes in the retina and of skin discoloration can be adequately managed by following the current recommendations in the Potiga labeling. To further explore any potential long-term consequences of these pigment changes, FDA has required the Potiga manufacturer, GlaxoSmithKline, to conduct a long-term observational study.
FDA review of additional safety reports does not indicate that the pigment changes in the retina observed in some patients affect vision. Skin discoloration associated with the use of Potiga appears to be a cosmetic effect and does not appear to be associated with more serious adverse effects. Therefore, a modification of the Risk Evaluation and Mitigation Strategy (REMS) is not needed at this time to ensure that the benefits of Potiga outweigh the risks of retinal and skin pigment changes. FDA expects that the required long-term observational study will provide further information on whether pigment changes in the retina caused by Potiga can lead to vision loss or other long-term side effects. In addition, the study should provide more information on the relationship between pigment changes in the retina and skin discoloration.
BACKGROUND: Potiga is approved for use in combination with other anti-seizure drugs to treat partial-onset seizures in adult patients who have had an inadequate response to several alternative therapies and for whom the benefits of treatment outweigh the risks.
RECOMMENDATION: Health care professionals should continue to follow the recommendations provided in the Boxed Warning, FDA’s most serious type of warning, and the Warnings and Precautions and Indications and Usage sections of the labeling.
FDA review of additional safety reports does not indicate that the pigment changes in the retina observed in some patients affect vision. Skin discoloration associated with the use of Potiga appears to be a cosmetic effect and does not appear to be associated with more serious adverse effects. Therefore, a modification of the Risk Evaluation and Mitigation Strategy (REMS) is not needed at this time to ensure that the benefits of Potiga outweigh the risks of retinal and skin pigment changes. FDA expects that the required long-term observational study will provide further information on whether pigment changes in the retina caused by Potiga can lead to vision loss or other long-term side effects. In addition, the study should provide more information on the relationship between pigment changes in the retina and skin discoloration.
BACKGROUND: Potiga is approved for use in combination with other anti-seizure drugs to treat partial-onset seizures in adult patients who have had an inadequate response to several alternative therapies and for whom the benefits of treatment outweigh the risks.
RECOMMENDATION: Health care professionals should continue to follow the recommendations provided in the Boxed Warning, FDA’s most serious type of warning, and the Warnings and Precautions and Indications and Usage sections of the labeling.
Link: http://www.fda.gov/
"Female Viagra": FDA panel backs Flibanserin with safety restriction
Government health experts are backing an experimental drug intended to boost the female sex drive, but stress that it must carry safety restrictions to manage side effects including fatigue, low blood pressure and fainting.
The Food and Drug Administration panel voted 18-6 in favor of approving Sprout Pharmaceutical’s daily pill flibanserin, on the condition that its manufacturer develops a plan to limit safety risks.
The positive recommendation is a major victory for a drug sometimes hailed as “female Viagra”, but which has been plagued by for years by concerns about its lackluster effectiveness and safety issues. The FDA has twice rejected the drug since 2010.
The vote was preceded by testimony from women urged the agency to approve the drug and told about their fears of never being able to have sex again.
A coalition of women’s groups and the drug’s manufacturer advocated for approval of the pill, Flibanserin. Other women’s health advocates advised that the agency remain cautious.
The Food and Drug Administration panel voted 18-6 in favor of approving Sprout Pharmaceutical’s daily pill flibanserin, on the condition that its manufacturer develops a plan to limit safety risks.
The positive recommendation is a major victory for a drug sometimes hailed as “female Viagra”, but which has been plagued by for years by concerns about its lackluster effectiveness and safety issues. The FDA has twice rejected the drug since 2010.
The vote was preceded by testimony from women urged the agency to approve the drug and told about their fears of never being able to have sex again.
A coalition of women’s groups and the drug’s manufacturer advocated for approval of the pill, Flibanserin. Other women’s health advocates advised that the agency remain cautious.
Online Journals:
Biological Psychiatry - Volume 78, Issue 2, July 2015
