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Monitoring Internet postings for mentions of an extended-release hydrocodone formulation with abuse-deterrent properties
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Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Monitoring Internet postings for mentions of an extended-release hydrocodone formulation with abuse-deterrent properties Angela DeVeaugh-Geiss 1,∗ , Howard Chilcoat 1 , Paul Coplan 1 , Venkatesh Harikrishnan 1 , Andrea Carrig Besharat 2 , Jody L. Green 2 1
Purdue Pharma LP, Stamford, CT, United States Denver Health RADARS System, Denver, CO, United States 2
Aims: The first single-entity (SE) extended-release (ER) hydrocodone formulation with abuse deterrent characteristics, Hysingla® ER, was approved by FDA in November 2014 and launched in January, 2015. Because of the potential for abuse of opioids it is important to understand the interest of potential abusers. Therefore, Internet mentions of Hysingla were examined before (3-4Q2014) and after (1-3Q2015) launch. Methods: Over 150 million websites (e.g., public social media websites, forums, blogs) worldwide were searched using a commercially available web monitoring platform (operated by the RADARS® System Web Monitoring Program). All posts that mentioned Hysingla ER, regardless of content, were identified. Trained coders reviewed posts to characterize salient themes and identify posts related to misuse, abuse, addiction, overdose, death, route of administration, and source of drug acquisition. Additionally, because understanding availability during this time is important for context, monthly prescriptions dispensed were also examined using IMS Xponent data. Results: The highest number of posts about Hysingla occurred prior to launch, increasing from 70 in 3Q2014 (385 themes) to a peak of 1293 in 4Q2014 (4920 themes). After launch, the number of posts was low: 149 posts (319 themes) in 1Q2015, 120 posts (347 themes) in 2Q2015, and 49 posts (149 themes) in 3Q2015. After launch, the most common theme for posts (>90%) was opinion or sharing experience. Few posts mentioned abuse/misuse (3Q2014-1Q2015: 0%; 2Q2015:<1%; 3Q2015: 6.1%) and none mentioned addiction, overdose, death, or route of administration. During this time, dispensed prescriptions increased from approximately 8000 in 1Q15 to over 25,000 in 3Q2015. Conclusions: There was a peak in Internet discussion after FDA approval in anticipation of the launch, though overall discussion of Hysingla has been low with few posts mentioning abuse or misuse. Financial support: Purdue Pharma LP. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.159 Neural effects of treatment in a trial of behavioral therapies and disulfiram for cocaine dependence Elise Eva DeVito 1,∗ , Guangheng Dong 1,2 , Hedy Kober 1 , Jiansong Xu 1 , Kathleen Carroll 1 , Marc N. Potenza 1 1 Psychiatry, Yale University School of Medicine, New Haven, CT, United States 2 Psychology, Zhejiang Normal University, Jinhua, China
Aims: To investigate how changes in neural activity across treatment for cocaine dependence relate to engagement in treatment components, which purportedly act via distinct mechanisms of action. Methods: Cocaine-dependent participants (N = 35) in a randomized clinical trial received cognitive behavioral therapy (CBT)
plus, in a 2 × 2 design, contingency management (CM) or no-CM, and disulfiram or placebo. Participants performed an fMRI Stroop Task, a measure of cognitive-control (Stroop) before and after the 12-week treatment. Analyses assessed changes in Stroop-related neural activity overall, in relation to measures of treatmentengagement, and by treatment conditions. Results: Stroop-related neural activity was diminished at postversus pre-treatment in thalamus, cingulate, precentral, postcentral, and lingual gyri and culmen regions (pFWE < .05), consistent with prior work. Greater reductions in Stroop-related activity were associated with more treatment engagement: ‘days in treatment’ with precentral gyrus; ‘CBT sessions’ with cingulate, precentral and postcentral gyri; ‘CM prizes’ with thalamus and postcentral gyrus. ‘Disulfiram medication days’ were not associated with changes in Stroop-related activity in these clusters. Reductions in Strooprelated activity were more pronounced in the CM, versus no-CM, group in midbrain, medial frontal, cingulate, superior temporal, and lingual gyri; findings did not differ between disulfiram versus placebo groups. Conclusions: Findings suggest key process indicators of CBT and CM are associated with functional changes in cognitive-controlrelated neurocircuitry, possibly indicating increased efficiency of cognitive-control-related neurocircuitry as one treatment mechanism. Financial support: R01 DA019078, R01 DA020908, R01 DA035058, P50 DA09241 K12 DA00167, K01 DA027750 from NIDA; MIRECC; K12 DA031050 from NIDA, ORWH, NIAAA and NIH-OD; 31371023 from NSF of China. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.160 PPAR␥ agonism to treat white matter damage in cocaine use disorder Andrea Dimet 1,3,∗ , Larry Denner 1 , Ryan Miller 1,3 , Kathryn A. Cunningham 1,3 , Matt Huentelman 4 , Scott D. Lane 2 , Kelly Dineley 1,3 1
UTMB, Galveston, TX, United States Psychiatry & Behavioral Sciences, University of Texas Health Science Center Houston, Houston, TX, United States 3 Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States 4 Translational Genomics Research Institute, Phoenix, AZ, United States 2
Aims: Cocaine use disorder elicits behavioral and structural changes in human subjects and rodent models. One behavioral change is increased reactivity to cocaine-paired (CP) cues, and one structural change is damage to white matter (WM) tracts that interconnect gray matter (GM) structures thought to underlie drug-seeking behaviors. We discovered that the FDAapproved peroxisome proliferator-activated receptor ␥ (PPAR␥) agonist pioglitazone (PIO, ActosTM ) attenuated CP cue reactivity in rats after forced abstinence (FA) from self-administration (SA), and this was reversed by the PPAR␥ antagonist GW9662. Thus, we hypothesize that PPAR␥ agonism counteracts the cocainemediated damage to WM and GM underlying CP cue reactivity through induction of markers for functional and structural integrity in WM. Methods: Using previous research, Sequence SearcherTM gene analysis software, and the NCBI/ENCODE databases, we identified proteins which met the following criteria:1. Modulated by cocaine2. Modulated by PPAR␥/ERK3. Contain ERK or PPAR response element4. Important to WM integrityQuantitative immunoblot was used to measure the proteins’ expression.
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Monitoring Internet postings for mentions of an extended-release hydrocodone formulation with abuse-deterrent properties Angela DeVeaugh-Geiss 1,∗ , Howard Chilcoat 1 , Paul Coplan 1 , Venkatesh Harikrishnan 1 , Andrea Carrig Besharat 2 , Jody L. Green 2 1
Purdue Pharma LP, Stamford, CT, United States Denver Health RADARS System, Denver, CO, United States 2
Aims: The first single-entity (SE) extended-release (ER) hydrocodone formulation with abuse deterrent characteristics, Hysingla® ER, was approved by FDA in November 2014 and launched in January, 2015. Because of the potential for abuse of opioids it is important to understand the interest of potential abusers. Therefore, Internet mentions of Hysingla were examined before (3-4Q2014) and after (1-3Q2015) launch. Methods: Over 150 million websites (e.g., public social media websites, forums, blogs) worldwide were searched using a commercially available web monitoring platform (operated by the RADARS® System Web Monitoring Program). All posts that mentioned Hysingla ER, regardless of content, were identified. Trained coders reviewed posts to characterize salient themes and identify posts related to misuse, abuse, addiction, overdose, death, route of administration, and source of drug acquisition. Additionally, because understanding availability during this time is important for context, monthly prescriptions dispensed were also examined using IMS Xponent data. Results: The highest number of posts about Hysingla occurred prior to launch, increasing from 70 in 3Q2014 (385 themes) to a peak of 1293 in 4Q2014 (4920 themes). After launch, the number of posts was low: 149 posts (319 themes) in 1Q2015, 120 posts (347 themes) in 2Q2015, and 49 posts (149 themes) in 3Q2015. After launch, the most common theme for posts (>90%) was opinion or sharing experience. Few posts mentioned abuse/misuse (3Q2014-1Q2015: 0%; 2Q2015:<1%; 3Q2015: 6.1%) and none mentioned addiction, overdose, death, or route of administration. During this time, dispensed prescriptions increased from approximately 8000 in 1Q15 to over 25,000 in 3Q2015. Conclusions: There was a peak in Internet discussion after FDA approval in anticipation of the launch, though overall discussion of Hysingla has been low with few posts mentioning abuse or misuse. Financial support: Purdue Pharma LP. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.159 Neural effects of treatment in a trial of behavioral therapies and disulfiram for cocaine dependence Elise Eva DeVito 1,∗ , Guangheng Dong 1,2 , Hedy Kober 1 , Jiansong Xu 1 , Kathleen Carroll 1 , Marc N. Potenza 1 1 Psychiatry, Yale University School of Medicine, New Haven, CT, United States 2 Psychology, Zhejiang Normal University, Jinhua, China
Aims: To investigate how changes in neural activity across treatment for cocaine dependence relate to engagement in treatment components, which purportedly act via distinct mechanisms of action. Methods: Cocaine-dependent participants (N = 35) in a randomized clinical trial received cognitive behavioral therapy (CBT)
plus, in a 2 × 2 design, contingency management (CM) or no-CM, and disulfiram or placebo. Participants performed an fMRI Stroop Task, a measure of cognitive-control (Stroop) before and after the 12-week treatment. Analyses assessed changes in Stroop-related neural activity overall, in relation to measures of treatmentengagement, and by treatment conditions. Results: Stroop-related neural activity was diminished at postversus pre-treatment in thalamus, cingulate, precentral, postcentral, and lingual gyri and culmen regions (pFWE < .05), consistent with prior work. Greater reductions in Stroop-related activity were associated with more treatment engagement: ‘days in treatment’ with precentral gyrus; ‘CBT sessions’ with cingulate, precentral and postcentral gyri; ‘CM prizes’ with thalamus and postcentral gyrus. ‘Disulfiram medication days’ were not associated with changes in Stroop-related activity in these clusters. Reductions in Strooprelated activity were more pronounced in the CM, versus no-CM, group in midbrain, medial frontal, cingulate, superior temporal, and lingual gyri; findings did not differ between disulfiram versus placebo groups. Conclusions: Findings suggest key process indicators of CBT and CM are associated with functional changes in cognitive-controlrelated neurocircuitry, possibly indicating increased efficiency of cognitive-control-related neurocircuitry as one treatment mechanism. Financial support: R01 DA019078, R01 DA020908, R01 DA035058, P50 DA09241 K12 DA00167, K01 DA027750 from NIDA; MIRECC; K12 DA031050 from NIDA, ORWH, NIAAA and NIH-OD; 31371023 from NSF of China. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.160 PPAR␥ agonism to treat white matter damage in cocaine use disorder Andrea Dimet 1,3,∗ , Larry Denner 1 , Ryan Miller 1,3 , Kathryn A. Cunningham 1,3 , Matt Huentelman 4 , Scott D. Lane 2 , Kelly Dineley 1,3 1
UTMB, Galveston, TX, United States Psychiatry & Behavioral Sciences, University of Texas Health Science Center Houston, Houston, TX, United States 3 Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States 4 Translational Genomics Research Institute, Phoenix, AZ, United States 2
Aims: Cocaine use disorder elicits behavioral and structural changes in human subjects and rodent models. One behavioral change is increased reactivity to cocaine-paired (CP) cues, and one structural change is damage to white matter (WM) tracts that interconnect gray matter (GM) structures thought to underlie drug-seeking behaviors. We discovered that the FDAapproved peroxisome proliferator-activated receptor ␥ (PPAR␥) agonist pioglitazone (PIO, ActosTM ) attenuated CP cue reactivity in rats after forced abstinence (FA) from self-administration (SA), and this was reversed by the PPAR␥ antagonist GW9662. Thus, we hypothesize that PPAR␥ agonism counteracts the cocainemediated damage to WM and GM underlying CP cue reactivity through induction of markers for functional and structural integrity in WM. Methods: Using previous research, Sequence SearcherTM gene analysis software, and the NCBI/ENCODE databases, we identified proteins which met the following criteria:1. Modulated by cocaine2. Modulated by PPAR␥/ERK3. Contain ERK or PPAR response element4. Important to WM integrityQuantitative immunoblot was used to measure the proteins’ expression.