Friday, 3 October 2008
Senator Says Emory Psychiatrist Didn't Disclose $500,000 in Payments from GSK !!
Senator Says Emory Psychiatrist Didn't Disclose $500,000 in Payments
http://online.wsj.com/article/SB122304669813202429.html?mod=googlenews_wsj
A prominent Emory University psychiatrist failed to tell the school about $500,000 in payments from drug maker GlaxoSmithKline while he was serving as the primary investigator for a government-funded research project studying Glaxo drugs, Sen. Charles Grassley alleged.
The payments to Charles Nemeroff, the chair of the Atlanta university's psychiatry department, were mainly for his work speaking to other doctors across the country about Glaxo drugs, including its big-selling anti-depressant Paxil, according to records Sen. Grassley obtained from Emory and Glaxo. The senator made the allegations in a letter to Emory President James W. Wagner dated Thursday.
In correspondence with Emory officials who police conflict of interest issues, Dr. Nemeroff repeatedly denied having a significant financial relationship with Glaxo, according to the records cited by Sen. Grassley. The Iowa Republican is the ranking minority member of the Senate Finance Committee, which is responsible for federal outlays for government health insurance programs.
A financial relationship is considered significant by Emory and other schools if the researcher is paid more than $10,000 a year, and Emory instructed Dr. Nemeroff not to exceed that amount, the records cited by Sen. Grassley indicate.
Dr. Nemeroff has been put in the spotlight before over his financial ties to the medical industry. In 2006, he stepped down as editor of the journal Neuropsychopharmacology after The Wall Street Journal reported he wrote a favorable review in the journal of a new device for treating depression but didn't disclose his financial ties to the device's maker. The review concerned a small device from Cyberonics Inc. that is implanted in the chest and delivers mild electrical pulses to the vagus nerve in the neck.
Dr. Nemeroff served from 2003 until this past summer as the primary investigator on a collaborative grant between Emory, Glaxo and the National Institute of Mental Health, a government agency that is part of the National Institutes of Health. Sen. Grassley wrote that the NIH budgeted $3.95 million for the project with about $1.35 million paid directly to Emory for overhead costs. He said that Dr. Nemeroff apparently received some payment for his salary from the grant, although the specific amount is unknown.
The research effort, called the Emory-GSK-NIMH Collaborative Mood Disorders Initiative, examined five Glaxo drugs considered for use as possible antidepressants. GSK stands for GlaxoSmithKline. The NIH requires that universities police their academics to avoid financial conflicts of interest.
Emory, in a statement, said the allegations made by Sen. Grassley are "serious" and that the university is "working diligently to determine whether our policies have been observed consistently with regard to the matters cited" by the senator. Dr. Nemeroff did not return a call to his office. But the university said it had spoken to Dr. Nemeroff, who told the school that "to the best of my knowledge, I have followed the appropriate university regulations concerning financial disclosures."
Glaxo, in a statement, said it has "rigorous guidelines governing our interaction with healthcare professionals who participate in GSK-supported speaking events," and that it requires them to "proactively disclose" these relationships.
Getty Images
The senator alleges Dr. Nemeroff did not report that he was giving promotional talks for Glaxo on the anti-depressant Paxil.
When questioned by Emory officials, Dr. Nemeroff apparently failed to report all of his ties with Glaxo's speaker's bureau, the Sen. Grassley said, citing an Oct. 1, 2003 email in which Dr. Nemeroff described his outside activities to the school:
"I have to dig up the agreement and send it to you, GSK no standing contract, I chair their ad board 2-3 times per year and I am paid per board meeting at a standard rate of $5K per weekend."
In 2003, however, Sen. Grassley said records show Dr. Nemeroff was an active member of Glaxo's speaker board and was paid $119,000 in fees and expenses. The senator alleges Dr. Nemeroff did not report that he was giving promotional talks for Glaxo on Paxil, and another drug, Lamictal, a medication often used to treat bipolar disorder.
On March 19, 2004, the senator said Dr. Nemeroff addressed questions from Emory's Conflicts of Interest Committee in a letter, in which he wrote: "Apart from speaking at national symposia, such as the American Psychiatric Association, for which GSK might serve as a sponsor, my consultation to the company is limited to chairing their Paroxetine Advisory board and for that, I am remunerated $15,000 per year." Paroxetine is the chemical name for Paxil.
Just three days earlier, however, Glaxo paid Dr. Nemeroff $3,500 for a talk he gave on Paxil in Orlando, Fla., Sen. Grassley alleges. The next day, March 17, he gave another $3,500 talk about Paxil in Kissimmee, Fla. In the week after writing to the conflict of interest committee, Dr. Nemeroff gave three talks on Paxil, for $3,500 each, at various locations in New York, according to the senator.
On July 6, 2004, Dr. Nemeroff promised the university he would limit his consulting work to Glaxo to under $10,000 a year, according to records cited by Sen. Grassley.
A week later, in two days of work, he exceeded that limit, according to records provided the senator. He saif that on July 12, 2004, GSK paid Dr. Nemeroff $3,500 in fees and $505.40 in expenses for a talk he gave on Paxil at the Larkspur Restaurant and Grill in Las Vegas; and that on the next day, hje was paid $7,000 for two talks he gave for Glaxo.
The university required annual payments from Glaxo had to be limited to $10,000 as long as he was involved in the government collaborative studying Glaxo drugs, according to university records cited by Sen. Grassley.
In an Aug. 4, 2004 letter to a university dean, Dr. Nemeroff said he had "taken the necessary steps to be in compliance with the recommendations" of the Emory conflicts-of- interest committee, "namely my consulting fees from GSK will be less than $10,000 per year throughout the period of this NIH grant, its renewals and final collections of data. GSK has been informed of this change and certainly understand the reasons for this decision and is supportive of my compliance with the university recommendations."
But according to Glaxo records, Dr. Nemeroff exceeded the $10,000 limit that month. The payments included a $3,500 fee for a teleconference with the Louisiana State University Psychiatry Department; talks on Paxil at two restaurants in New York —the Passion Fish Restaurant in Woodbury and Burton and Doyles in Great Neck – that paid a total of $7,000; and a $3,500 payment for another teleconference.
The Paxil talks for Glaxo continued until at least January 2006. It appears the university questioned Dr. Nemeroff's Glaxo relationship later that year, in November. In response to that questioning, Sen. Grassely says Dr. Nemeroff wrote that any suggestion he had a financial relationship with Glaxo is "absolutely untrue." In all, Sen. Grassley said Dr. Nemeroff apparently failed to report about a half million dollars in fees and expenses from Glaxo for dozens of talks he gave to promote the company's drugs.
Emory said it has asked Sen. Grassley for copies of the records he cited and promised a "fair, thorough, and evenhanded investigation of these claims."
http://online.wsj.com/article/SB122304669813202429.html?mod=googlenews_wsj
A prominent Emory University psychiatrist failed to tell the school about $500,000 in payments from drug maker GlaxoSmithKline while he was serving as the primary investigator for a government-funded research project studying Glaxo drugs, Sen. Charles Grassley alleged.
The payments to Charles Nemeroff, the chair of the Atlanta university's psychiatry department, were mainly for his work speaking to other doctors across the country about Glaxo drugs, including its big-selling anti-depressant Paxil, according to records Sen. Grassley obtained from Emory and Glaxo. The senator made the allegations in a letter to Emory President James W. Wagner dated Thursday.
In correspondence with Emory officials who police conflict of interest issues, Dr. Nemeroff repeatedly denied having a significant financial relationship with Glaxo, according to the records cited by Sen. Grassley. The Iowa Republican is the ranking minority member of the Senate Finance Committee, which is responsible for federal outlays for government health insurance programs.
A financial relationship is considered significant by Emory and other schools if the researcher is paid more than $10,000 a year, and Emory instructed Dr. Nemeroff not to exceed that amount, the records cited by Sen. Grassley indicate.
Dr. Nemeroff has been put in the spotlight before over his financial ties to the medical industry. In 2006, he stepped down as editor of the journal Neuropsychopharmacology after The Wall Street Journal reported he wrote a favorable review in the journal of a new device for treating depression but didn't disclose his financial ties to the device's maker. The review concerned a small device from Cyberonics Inc. that is implanted in the chest and delivers mild electrical pulses to the vagus nerve in the neck.
Dr. Nemeroff served from 2003 until this past summer as the primary investigator on a collaborative grant between Emory, Glaxo and the National Institute of Mental Health, a government agency that is part of the National Institutes of Health. Sen. Grassley wrote that the NIH budgeted $3.95 million for the project with about $1.35 million paid directly to Emory for overhead costs. He said that Dr. Nemeroff apparently received some payment for his salary from the grant, although the specific amount is unknown.
The research effort, called the Emory-GSK-NIMH Collaborative Mood Disorders Initiative, examined five Glaxo drugs considered for use as possible antidepressants. GSK stands for GlaxoSmithKline. The NIH requires that universities police their academics to avoid financial conflicts of interest.
Emory, in a statement, said the allegations made by Sen. Grassley are "serious" and that the university is "working diligently to determine whether our policies have been observed consistently with regard to the matters cited" by the senator. Dr. Nemeroff did not return a call to his office. But the university said it had spoken to Dr. Nemeroff, who told the school that "to the best of my knowledge, I have followed the appropriate university regulations concerning financial disclosures."
Glaxo, in a statement, said it has "rigorous guidelines governing our interaction with healthcare professionals who participate in GSK-supported speaking events," and that it requires them to "proactively disclose" these relationships.
Getty Images
The senator alleges Dr. Nemeroff did not report that he was giving promotional talks for Glaxo on the anti-depressant Paxil.
When questioned by Emory officials, Dr. Nemeroff apparently failed to report all of his ties with Glaxo's speaker's bureau, the Sen. Grassley said, citing an Oct. 1, 2003 email in which Dr. Nemeroff described his outside activities to the school:
"I have to dig up the agreement and send it to you, GSK no standing contract, I chair their ad board 2-3 times per year and I am paid per board meeting at a standard rate of $5K per weekend."
In 2003, however, Sen. Grassley said records show Dr. Nemeroff was an active member of Glaxo's speaker board and was paid $119,000 in fees and expenses. The senator alleges Dr. Nemeroff did not report that he was giving promotional talks for Glaxo on Paxil, and another drug, Lamictal, a medication often used to treat bipolar disorder.
On March 19, 2004, the senator said Dr. Nemeroff addressed questions from Emory's Conflicts of Interest Committee in a letter, in which he wrote: "Apart from speaking at national symposia, such as the American Psychiatric Association, for which GSK might serve as a sponsor, my consultation to the company is limited to chairing their Paroxetine Advisory board and for that, I am remunerated $15,000 per year." Paroxetine is the chemical name for Paxil.
Just three days earlier, however, Glaxo paid Dr. Nemeroff $3,500 for a talk he gave on Paxil in Orlando, Fla., Sen. Grassley alleges. The next day, March 17, he gave another $3,500 talk about Paxil in Kissimmee, Fla. In the week after writing to the conflict of interest committee, Dr. Nemeroff gave three talks on Paxil, for $3,500 each, at various locations in New York, according to the senator.
On July 6, 2004, Dr. Nemeroff promised the university he would limit his consulting work to Glaxo to under $10,000 a year, according to records cited by Sen. Grassley.
A week later, in two days of work, he exceeded that limit, according to records provided the senator. He saif that on July 12, 2004, GSK paid Dr. Nemeroff $3,500 in fees and $505.40 in expenses for a talk he gave on Paxil at the Larkspur Restaurant and Grill in Las Vegas; and that on the next day, hje was paid $7,000 for two talks he gave for Glaxo.
The university required annual payments from Glaxo had to be limited to $10,000 as long as he was involved in the government collaborative studying Glaxo drugs, according to university records cited by Sen. Grassley.
In an Aug. 4, 2004 letter to a university dean, Dr. Nemeroff said he had "taken the necessary steps to be in compliance with the recommendations" of the Emory conflicts-of- interest committee, "namely my consulting fees from GSK will be less than $10,000 per year throughout the period of this NIH grant, its renewals and final collections of data. GSK has been informed of this change and certainly understand the reasons for this decision and is supportive of my compliance with the university recommendations."
But according to Glaxo records, Dr. Nemeroff exceeded the $10,000 limit that month. The payments included a $3,500 fee for a teleconference with the Louisiana State University Psychiatry Department; talks on Paxil at two restaurants in New York —the Passion Fish Restaurant in Woodbury and Burton and Doyles in Great Neck – that paid a total of $7,000; and a $3,500 payment for another teleconference.
The Paxil talks for Glaxo continued until at least January 2006. It appears the university questioned Dr. Nemeroff's Glaxo relationship later that year, in November. In response to that questioning, Sen. Grassely says Dr. Nemeroff wrote that any suggestion he had a financial relationship with Glaxo is "absolutely untrue." In all, Sen. Grassley said Dr. Nemeroff apparently failed to report about a half million dollars in fees and expenses from Glaxo for dozens of talks he gave to promote the company's drugs.
Emory said it has asked Sen. Grassley for copies of the records he cited and promised a "fair, thorough, and evenhanded investigation of these claims."
don't feel too bad about being hoodwinked by them tho' - your in good company
UKsurvivors post 34907
But don't feel too bad about being hoodwinked by them tho' -- the
BBC, Paul Flynn, journalist and several other notable people have been succoured to ... although they probably just saw a quick and easy way to get some publicity whilst seeming to support those who have been affected!!
http://groups.yahoo.com/group/uksurvivors/message/34907
Perhaps you overlooked this article …..
http://www.guardian.co.uk/theobserver/2002/apr/28/features.magazine37
Simon Garfield
The Observer,
Sunday April 28 2002
Article history
"Mark Harvey says he is still 'shaking the tree' to see how many
people are suffering from the sort of severe withdrawal symptoms
afflicting Jenny Stanaway. People are learning of his interest at the
rate of about two a week."
September 2002 Hugh James set up
http://www.seroxatusergroup.org.uk/Documents/newsletterissue1.pdf
along with a second SeroxatUserGroup (SUG) on network 54 - which
Sarah Venn headed because Derek was too self obsessed to let his
group be used and shared with other committee members – he wouldn't
relinquish total control!
Supposedly a `support' group but to gain access to it you were
directed through the Hugh James Web site and had to fill out a
questionnaire about your drug experiences before being allowed to
join.
Derek on his Yahoo SeroatUserGroup did his bit to ALL new members
were directed to Hugh James web site instead of being given answers
to questions and advice.
Mark Harvey's "Shaking the tree" with the help of Goodrelations – the
additional publicity of the Panorama programs worked really well -- 2
years after the Observer article when he stated "People are learning
of his interest at the rate of about two a week finding 2 people a
fortnight" - it was reported by the SeroxatUserGroup and Dereks group
renamed the OnlineSeroxatSupportGroup (OSSG) (with early archives
removed to get rid of indiscreet posts) at a meeting with the EMEA,
that they were representing 10,000 people.
http://www.seroxatusergroup.org.uk/EMEA%20minutes%20April%202004.pdf
Meeting with EMEA on Monday 19th April 2004
"Janice Simmons then introduced everyone present from the. SUG/OSSG
and their guests. ... Janice said the group represents over 10000
people all of ..."
Bob which ever way you look at this it's definitely trawling for
clients – that makes them ambulance chasers!
So as you're still out there with the 'Single Issue Seroxat Tub
Thump' that was instigated in the UK by Mark Harvey after he liaised
with Baum/Hedlund in the USA – I guess Hugh James are still pulling
your strings!! By keep highlighting the Seroxat furore and
litigation your working for them paid or not …… and if that is true
…… ?
But don't feel too bad about being hoodwinked by them tho' -- the
BBC, Paul Flynn, journalist and several other notable people have
been succoured to ... although they probably just saw a quick and
easy way to get some publicity whilst seeming to support those who
have been affected!!
As Cyndi says the people behind this ALL have their own agendas -
even those who set up 'supposed' support groups ……… and it's not
helping the worthy litigants!!
Now you can answer my question.
But don't feel too bad about being hoodwinked by them tho' -- the
BBC, Paul Flynn, journalist and several other notable people have been succoured to ... although they probably just saw a quick and easy way to get some publicity whilst seeming to support those who have been affected!!
http://groups.yahoo.com/group/uksurvivors/message/34907
Perhaps you overlooked this article …..
http://www.guardian.co.uk/theobserver/2002/apr/28/features.magazine37
Simon Garfield
The Observer,
Sunday April 28 2002
Article history
"Mark Harvey says he is still 'shaking the tree' to see how many
people are suffering from the sort of severe withdrawal symptoms
afflicting Jenny Stanaway. People are learning of his interest at the
rate of about two a week."
September 2002 Hugh James set up
http://www.seroxatusergroup.org.uk/Documents/newsletterissue1.pdf
along with a second SeroxatUserGroup (SUG) on network 54 - which
Sarah Venn headed because Derek was too self obsessed to let his
group be used and shared with other committee members – he wouldn't
relinquish total control!
Supposedly a `support' group but to gain access to it you were
directed through the Hugh James Web site and had to fill out a
questionnaire about your drug experiences before being allowed to
join.
Derek on his Yahoo SeroatUserGroup did his bit to ALL new members
were directed to Hugh James web site instead of being given answers
to questions and advice.
Mark Harvey's "Shaking the tree" with the help of Goodrelations – the
additional publicity of the Panorama programs worked really well -- 2
years after the Observer article when he stated "People are learning
of his interest at the rate of about two a week finding 2 people a
fortnight" - it was reported by the SeroxatUserGroup and Dereks group
renamed the OnlineSeroxatSupportGroup (OSSG) (with early archives
removed to get rid of indiscreet posts) at a meeting with the EMEA,
that they were representing 10,000 people.
http://www.seroxatusergroup.org.uk/EMEA%20minutes%20April%202004.pdf
Meeting with EMEA on Monday 19th April 2004
"Janice Simmons then introduced everyone present from the. SUG/OSSG
and their guests. ... Janice said the group represents over 10000
people all of ..."
Bob which ever way you look at this it's definitely trawling for
clients – that makes them ambulance chasers!
So as you're still out there with the 'Single Issue Seroxat Tub
Thump' that was instigated in the UK by Mark Harvey after he liaised
with Baum/Hedlund in the USA – I guess Hugh James are still pulling
your strings!! By keep highlighting the Seroxat furore and
litigation your working for them paid or not …… and if that is true
…… ?
But don't feel too bad about being hoodwinked by them tho' -- the
BBC, Paul Flynn, journalist and several other notable people have
been succoured to ... although they probably just saw a quick and
easy way to get some publicity whilst seeming to support those who
have been affected!!
As Cyndi says the people behind this ALL have their own agendas -
even those who set up 'supposed' support groups ……… and it's not
helping the worthy litigants!!
Now you can answer my question.
My recent meeting with the MHRA appeared to be fruitful, had I known at the time that they were planning to team up with Pharma to dispel information about their drugs on websites and blogs then I would have taken what was said at the meeting with a pinch of salt.
I am hugely disappointed, more so because my attention has now been drawn once again to the conflict of interests between the MHRA and pharmaceutical companies when I should really be focused on GSK and withdrawal victims.
http://fiddaman.blogspot.com/
Thursday, 2 October 2008
mind you they failed before & no doubt will fail again - what ever happened to the Seroxat withdrawal centres ?
http://groups.yahoo.com/group/uksurvivors/message/36104
"We're going to ask GlaxoSmithKline to set up centres all over the US to help them." Hundreds of thousands are believed to be suffering. said Scientology lawyer Skip Murgatroyd
http://www.guardian.co.uk/world/2001/sep/06/medicalscience.businessofresearch
"We're going to ask GlaxoSmithKline to set up centres all over the US to help them." Hundreds of thousands are believed to be suffering. said Scientology lawyer Skip Murgatroyd
http://www.guardian.co.uk/world/2001/sep/06/medicalscience.businessofresearch
Scientologist Lawyers Baum Hedlund state up to $1 mill donated to charity !! - will that be a Hubbard charity ??
Judge Approves $40 Million Settlement in Second Phase of National Pediatric Paxil Class Action
http://www.expertclick.com/NewsReleaseWire/default.cfm?Action=ReleaseDetail&ID=23377
Minneapolis, MN October 1 2008
U.S. Judge Michael J. Davis of the District of Minnesota has approved the final settlement of $40M to reimburse insurance companies, as third-party payers, for their costs in insuring Paxil purchases paid for by the parents of minors prescribed Paxil or Paxil CR.
Baum, Hedlund, Aristei & Goldman originated the class actions and litigated the heart of the case based on internal GSK (GlaxoSmithKline) documents showing that GSK promoted Paxil as an effective medication for children and adolescents despite internal communications acknowledging that Paxil's pediatric depression clinical trials failed to out-perform sugar pills, yet had higher suicidality rates than sugar pills. Notwithstanding, GSK promoted Paxil as being "remarkably safe and effective" for depressed children.
Paxil was never approved for children, so there were no explicit warnings for pediatric use on Paxil's warning label. Thus, the prescription and sale of Paxil to children was all "off label", which is permitted, but with severe restrictions on such "off-label" promotion and marketing.
"Off-label marketing of drugs is prohibited, with limited exceptions that allow scientific trial results to be presented as long as they are truthful and accurate," stated Michael Baum, senior partner at Baum, Hedlund, Aristei & Goldman. "Here GSK should not have promoted Paxil for kids' use when GSK's own pediatric clinical trials showed Paxil was no more effective than sugar pills and, in fact, caused pediatric Paxil patients to experience increased suicidality. Litigation like this helps remove the incentive for drug companies to take advantage of the off-label marketing loophole."
Similar class actions were filed in several courts seeking restitution of money paid by insurance companies that paid for minors' Paxil, which were ultimately consolidated as a national class action before Judge Davis in Minneapolis. The first phase of these cases, the class action for the individual Paxil payments, were resolved in April, 2007 when GSK agreed to reimburse parents for the money they paid out-of-pocket for their children's Paxil prescriptions.
The class representatives in the insurance company phase are Universal Care Inc., the Carpenters and Joiners Welfare Fund, and Philadelphia Firefighters Local 22 Health and Welfare Fund (Carpenters and Joiners Welfare Fund, et al. v. SmithKline Beecham Corp., doing business as GlaxoSmithKline, No. CV 04-3500, D. Minn.). Each were class representatives of four individual class actions in California, Minnesota and Pennsylvania that sought a refund of monies paid by third-party payers who purchased Paxil for patients under 18 from Jan. 1, 1998, to Dec. 31, 2004.
In addition to Baum Hedlund, the team of law firms representing the insurance company class representatives are Brian Strange of Strange & Carpenter in Los Angeles; J.D. Horton of Quinn, Emanuel in Los Angeles; Christopher Coffin of Pendley, Baudin & Coffin in Plaquemine, LA; Shawn Raiter of Larson King in St. Paul; Stephen Swedlow of Swedlow & Associates in Chicago; Paul Dahlberg of Meshbesher & Spence in Rochester, MN; Michael Perrin of Bailey Perrin Bailey in Houston; and William Marvin of Cohen, Placitella & Roth in Philadelphia. GSK is represented by Dwight Davis and Meghan Magruder of King & Spalding.
Through the team's skillful negotiating, especially Steve Swedlow's, all objections to the class were handled and withdrawn. The settlement team also handled, with King & Spalding's assistance, nearly all of the companies that had considered opting out of the class, addressing their concerns and shepherding them back into the settlement, as well.
These lawyers coordinated a unique settlement that has the entire proceeds being paid out by GSK, not just the amount claimed.
Judge Davis pointed out that the case was "heavily litigated" and noted that the amount of opposition to the settlement was de minimis. Davis ruled that if the aggregate amount of claimed benefits does not exceed the $40 million settlement amount, up to $1 million will be donated to one or more charitable organizations whose primary purpose includes mental health affecting children and the rest will be distributed pro rata among the claimants.
Under the settlement terms, class members would be refunded up to 40 percent of their actual cost for Paxil if they provide proof that a patient under 18 with diagnosis of a major depressive disorder was prescribed Paxil or Paxil CR. Class members would receive 15 percent of their actual cost if the diagnosis is not included.
Each of the insurance companies were class representatives of four class actions in California, Minnesota and Pennsylvania. The class consists of "[a]ll third-party payors in the United States and its territories, including administrators and benefits managers, who reimbursed, purchased, or paid for Paxil or Paxil CR prescribed for consumption by any person under the age of 18, between Jan. 1, 1998, and Dec. 31, 2004."
About Baum, Hedlund:
Baum, Hedlund, Aristei & Goldman has the longest and most successful track-record handling SSRI (selective serotonin reuptake inhibitor antidepressants such as Prozac, Paxil and Zoloft) cases, having litigated more antidepressant cases, over 3,000, in the past 18 years than any other law firm in the country.
Robin McCall
Media Relations Director
Baum, Hedlund, Aristei & Goldman, PC
Los Angeles, CA
Phone : 310-207-3233
Fax : 310-820-7444
http://www.expertclick.com/NewsReleaseWire/default.cfm?Action=ReleaseDetail&ID=23377
Minneapolis, MN October 1 2008
U.S. Judge Michael J. Davis of the District of Minnesota has approved the final settlement of $40M to reimburse insurance companies, as third-party payers, for their costs in insuring Paxil purchases paid for by the parents of minors prescribed Paxil or Paxil CR.
Baum, Hedlund, Aristei & Goldman originated the class actions and litigated the heart of the case based on internal GSK (GlaxoSmithKline) documents showing that GSK promoted Paxil as an effective medication for children and adolescents despite internal communications acknowledging that Paxil's pediatric depression clinical trials failed to out-perform sugar pills, yet had higher suicidality rates than sugar pills. Notwithstanding, GSK promoted Paxil as being "remarkably safe and effective" for depressed children.
Paxil was never approved for children, so there were no explicit warnings for pediatric use on Paxil's warning label. Thus, the prescription and sale of Paxil to children was all "off label", which is permitted, but with severe restrictions on such "off-label" promotion and marketing.
"Off-label marketing of drugs is prohibited, with limited exceptions that allow scientific trial results to be presented as long as they are truthful and accurate," stated Michael Baum, senior partner at Baum, Hedlund, Aristei & Goldman. "Here GSK should not have promoted Paxil for kids' use when GSK's own pediatric clinical trials showed Paxil was no more effective than sugar pills and, in fact, caused pediatric Paxil patients to experience increased suicidality. Litigation like this helps remove the incentive for drug companies to take advantage of the off-label marketing loophole."
Similar class actions were filed in several courts seeking restitution of money paid by insurance companies that paid for minors' Paxil, which were ultimately consolidated as a national class action before Judge Davis in Minneapolis. The first phase of these cases, the class action for the individual Paxil payments, were resolved in April, 2007 when GSK agreed to reimburse parents for the money they paid out-of-pocket for their children's Paxil prescriptions.
The class representatives in the insurance company phase are Universal Care Inc., the Carpenters and Joiners Welfare Fund, and Philadelphia Firefighters Local 22 Health and Welfare Fund (Carpenters and Joiners Welfare Fund, et al. v. SmithKline Beecham Corp., doing business as GlaxoSmithKline, No. CV 04-3500, D. Minn.). Each were class representatives of four individual class actions in California, Minnesota and Pennsylvania that sought a refund of monies paid by third-party payers who purchased Paxil for patients under 18 from Jan. 1, 1998, to Dec. 31, 2004.
In addition to Baum Hedlund, the team of law firms representing the insurance company class representatives are Brian Strange of Strange & Carpenter in Los Angeles; J.D. Horton of Quinn, Emanuel in Los Angeles; Christopher Coffin of Pendley, Baudin & Coffin in Plaquemine, LA; Shawn Raiter of Larson King in St. Paul; Stephen Swedlow of Swedlow & Associates in Chicago; Paul Dahlberg of Meshbesher & Spence in Rochester, MN; Michael Perrin of Bailey Perrin Bailey in Houston; and William Marvin of Cohen, Placitella & Roth in Philadelphia. GSK is represented by Dwight Davis and Meghan Magruder of King & Spalding.
Through the team's skillful negotiating, especially Steve Swedlow's, all objections to the class were handled and withdrawn. The settlement team also handled, with King & Spalding's assistance, nearly all of the companies that had considered opting out of the class, addressing their concerns and shepherding them back into the settlement, as well.
These lawyers coordinated a unique settlement that has the entire proceeds being paid out by GSK, not just the amount claimed.
Judge Davis pointed out that the case was "heavily litigated" and noted that the amount of opposition to the settlement was de minimis. Davis ruled that if the aggregate amount of claimed benefits does not exceed the $40 million settlement amount, up to $1 million will be donated to one or more charitable organizations whose primary purpose includes mental health affecting children and the rest will be distributed pro rata among the claimants.
Under the settlement terms, class members would be refunded up to 40 percent of their actual cost for Paxil if they provide proof that a patient under 18 with diagnosis of a major depressive disorder was prescribed Paxil or Paxil CR. Class members would receive 15 percent of their actual cost if the diagnosis is not included.
Each of the insurance companies were class representatives of four class actions in California, Minnesota and Pennsylvania. The class consists of "[a]ll third-party payors in the United States and its territories, including administrators and benefits managers, who reimbursed, purchased, or paid for Paxil or Paxil CR prescribed for consumption by any person under the age of 18, between Jan. 1, 1998, and Dec. 31, 2004."
About Baum, Hedlund:
Baum, Hedlund, Aristei & Goldman has the longest and most successful track-record handling SSRI (selective serotonin reuptake inhibitor antidepressants such as Prozac, Paxil and Zoloft) cases, having litigated more antidepressant cases, over 3,000, in the past 18 years than any other law firm in the country.
Robin McCall
Media Relations Director
Baum, Hedlund, Aristei & Goldman, PC
Los Angeles, CA
Phone : 310-207-3233
Fax : 310-820-7444
" A third of the settlement will be paid to the law firms. "
The settlement this week resolves the case on behalf of some 42,000 health plans across the country that paid for the drug, said Paul Dahlberg, an attorney with Meshbesher & Spence, one of nine law firms involved in the case. A third of the settlement will be paid to the law firms.
http://www.startribune.com/lifestyle/health/30071004.html?elr=KArksLckD8EQDUoaEyqyP4O:DW3ckUiD3aPc:_Yyc:aULPQL7PQLanchO7DiUI
http://www.startribune.com/lifestyle/health/30071004.html?elr=KArksLckD8EQDUoaEyqyP4O:DW3ckUiD3aPc:_Yyc:aULPQL7PQLanchO7DiUI
Sreoxat (Paxil) suit settled by Glaxo for $40 million - naturally the children get nothing but don't expect Fiddaman to tell you this
Health plans that paid for kids and adolescents to get the antidepressant had sued the drugmaker.
By JOSEPHINE MARCOTTY, Star Tribune
Last update: October 1, 2008 - 9:37 PM
Featured comment
Amazing how we can see a settlement like this when Paxil is still actively being prescribed to children....and lawsuits filed on behalf of … read more a child are lost in the preemption battle. Yes, the children are paying the price for the lack of disclosure of potentially fatal/life altering adverse reactions by GSK. Yeah, lets give the "balance of the fund" non profits who continue to advocate for Paxil's use and deny those adverse reactions. Our children deserve better.
http://www.startribune.com/lifestyle/health/30071004.html?elr=KArksLckD8EQDUoaEyqyP4O:DW3ckUiD3aPc:_Yyc:aULPQL7PQLanchO7DiUI
In a settlement approved Tuesday in U.S. District Court in Minneapolis, British drugmaker GlaxoSmithKline agreed to pay $40 million to reimburse health plans that paid for children and adolescents to receive the antidepressant Paxil.
The agreement brings to a close the long-standing class-action litigation against Glaxo, which was sued for allegedly withholding negative information about the safety and efficacy of Paxil for teenagers and children. In 2007, Glaxo agreed to pay $63.9 million to consumers in another class-action settlement. In both cases Glaxo did not admit wrongdoing.
The settlement this week resolves the case on behalf of some 42,000 health plans across the country that paid for the drug, said Paul Dahlberg, an attorney with Meshbesher & Spence, one of nine law firms involved in the case. A third of the settlement will be paid to the law firms.
Although Paxil is not approved by the Food and Drug Administration (FDA) for use by children, doctors may prescribe it for them. Studies have shown that Paxil and other antidepressants in some instances lead to increased thoughts of suicide in adolescents. Last year the FDA ordered drugmakers to add a "black box" warning of the drug's risks after parents and other consumer advocates raised questions about the safety of antidepressants for those under age 18.
Under the settlement, GSK will pay insurers who paid for a Paxil prescription for use by a minor between January 1998 and December 2004. They may claim a refund of 40 percent of their actual costs of the drugs prescribed to children and adolescents diagnosed with a major depression, or 15 percent of the cost if the diagnosis was unknown.
If the settlement account is not exhausted, the unclaimed balance will be donated to nonprofits involved in mental health causes.
http://groups.yahoo.com/group/uksurvivors/message/36779
By JOSEPHINE MARCOTTY, Star Tribune
Last update: October 1, 2008 - 9:37 PM
Featured comment
Amazing how we can see a settlement like this when Paxil is still actively being prescribed to children....and lawsuits filed on behalf of … read more a child are lost in the preemption battle. Yes, the children are paying the price for the lack of disclosure of potentially fatal/life altering adverse reactions by GSK. Yeah, lets give the "balance of the fund" non profits who continue to advocate for Paxil's use and deny those adverse reactions. Our children deserve better.
http://www.startribune.com/lifestyle/health/30071004.html?elr=KArksLckD8EQDUoaEyqyP4O:DW3ckUiD3aPc:_Yyc:aULPQL7PQLanchO7DiUI
In a settlement approved Tuesday in U.S. District Court in Minneapolis, British drugmaker GlaxoSmithKline agreed to pay $40 million to reimburse health plans that paid for children and adolescents to receive the antidepressant Paxil.
The agreement brings to a close the long-standing class-action litigation against Glaxo, which was sued for allegedly withholding negative information about the safety and efficacy of Paxil for teenagers and children. In 2007, Glaxo agreed to pay $63.9 million to consumers in another class-action settlement. In both cases Glaxo did not admit wrongdoing.
The settlement this week resolves the case on behalf of some 42,000 health plans across the country that paid for the drug, said Paul Dahlberg, an attorney with Meshbesher & Spence, one of nine law firms involved in the case. A third of the settlement will be paid to the law firms.
Although Paxil is not approved by the Food and Drug Administration (FDA) for use by children, doctors may prescribe it for them. Studies have shown that Paxil and other antidepressants in some instances lead to increased thoughts of suicide in adolescents. Last year the FDA ordered drugmakers to add a "black box" warning of the drug's risks after parents and other consumer advocates raised questions about the safety of antidepressants for those under age 18.
Under the settlement, GSK will pay insurers who paid for a Paxil prescription for use by a minor between January 1998 and December 2004. They may claim a refund of 40 percent of their actual costs of the drugs prescribed to children and adolescents diagnosed with a major depression, or 15 percent of the cost if the diagnosis was unknown.
If the settlement account is not exhausted, the unclaimed balance will be donated to nonprofits involved in mental health causes.
http://groups.yahoo.com/group/uksurvivors/message/36779
Wednesday, 1 October 2008
Selective Serotonin Reuptake Inhibitor Induced Neonatal Abstinence Syndrome
Selective Serotonin Reuptake Inhibitor Induced Neonatal Abstinence Syndrome
http://www.redorbit.com/news/health/1551180/selective_serotonin_reuptake_inhibitor_induced_neonatal_abstinence_syndrome/
Posted on: Thursday, 11 September 2008, 03:00 CDT
By Klinger, Gil Merlob, Paul
Abstract: Depression is common in women of childbearing age and especially during pregnancy and the postpartum period. Selective serotonin reuptake inhibitors (SSRIs) are increasingly being used to treat depression prior to and throughout pregnancy. Up to 30% of the newborn infants exposed to SSRIs may present with clinical signs during the first days after birth. Neonatal abstinence syndrome (NAS) describes this clinical syndrome resulting from prior prolonged exposure to SSRI induced by cessation of the drug. NAS includes a wide spectrum from mild to severe non-specific symptoms which were categorized into four groups of effects: central nervous system (depression followed by excitation), gastrointestinal, autonomie and respiratory. A protocol for observation of SSRI- exposed newborns is presented including an objective method (Finnegan score) to monitor onset, progression and improvement of NAS symptoms. Introduction
Depression is common in women of childbearing age (1). During pregnancy increased stress may aggravate depression resulting in a prevalence of up to 12.9% of this disorder (2, 3). The prevalence of depression during the postpartum period continues to be high with 19.2% of women experiencing a major depressive episode within the first three months after delivery (2). Because many women experience depression during the postpartum period, it is often dismissed as part of the "normal" physiological changes that are associated with childbirth (4). However, if untreated, perinatal depression can have severe consequences for the fetus and newborn, as well as for the mother. Although psychotherapy is the first-line treatment for depression during pregnancy or after birth, antidepressant treatment is warranted in some patients. Because selective serotonin reuptake inhibitors (SSRIs) are perceived as safer than alternative medications, they are increasingly being used to treat depression prior to and throughout pregnancy. A recent survey has shown that 2.8% of women use SSRIs for the entire duration of pregnancy (5). This figure translates to 92,000 of approximately 4 million annual live births in the United States. Prolonged fetal exposure to SSRIs may be associated with a neonatal abstinence syndrome (NAS) affecting 30% of newborns (6). The widespread use of SSRIs during pregnancy and the resulting occurrence of NAS warrant a thorough review.
Pharmacokinetics
SSRIs are a group of psychotropic drugs that is chemically unrelated to tricyclics, tetracyclics, monoamine oxidase inhibitors or other antidepressants. They are used to treat depression, but also for obsessive-compulsive and other disorders. The action of SSRIs is thought to be linked to their inhibition of prejunctional reuptake of serotonin, but they do not have receptor-blocking effects. The side-effects of tricyclic and tetracyclic antidepressants may be worrisome in pregnancy and their narrow therapeutic range increases the risk of overdose. SSRIs have a safer therapeutic profile because of their relatively benign side-effects and their safety in overdose (4). The SSRI group is comprised of the following drugs:
1. Fluoxetine (Prozac, Prizma, Flutine, Affectine)
2. Paroxetine (Seroxat, Paxet, Paxol, Paroxetine)
3. Sertraline (Lustral, Zoloft)
4. Fluvoxamine (Favoxil, Luvox)
5. Citalopram (Cipramil, Recital)
6. Escitalopram (Ciprodex, Cipralex)
Venlafaxine (Efexor, Venla, Viepax) is a selective norepinephrine- serotonin reuptake inhibitor (SNSRI) that is closely related to the SSRIs.
The pharmacokinetic properties of SSRIs (7) are presented in Table 1. This table lists the most commonly recorded adult drug half- life of SSRIs because there is little or no information regarding the newborn. It is of note that during the newborn period, drug half- life is prolonged for most medications, but this is also dependent on drug metabolism. Of the SSRI half-lives, fluoxetine, sertraline and citalopram have a long one with fluoxetine having the longest, paroxetine and fluvoxamine have an intermediate one and venlafaxine has the shortest. A relatively short or intermediate drug half-life has been implicated with an increased risk of NAS after third- trimester exposure.
Transplacental passage determines fetal drug exposure. For drugs with no placental metabolism, transplacental passage is inversely related to molecular weight. SSRIs have a low molecular weight (around 300) with the exception of citalopram (405) and theoretically are able to cross the placental barrier. Placental drug transfer is also determined by duration of drug exposure, liposolubility, protein binding, volume of distribution and other pharmacokinetic factors. Placental transfer of SSRIs has been demonstrated experimentally both in animals and in humans. Pohland et al. (8) demonstrated in the rat that C14 labeled fluoxetine and norfluoxetine traversed the placenta during the periods of organogenesis and postorganogenesis and were distributed within the embryonic/fetal tissue, preferentially to the brain and thymus. Stowe et al. (9) studied the passage of SSRIs across the human placenta by measuring their concentrations in maternal serum and umbilical cord blood at delivery. No evidence of accumulation of fluoxetine, paroxetine, or sertraline in the fetal circulation was found. The fetal : maternal drug ratios for fluoxetine, sertraline and paroxetine were 0.94, 0.43 and 0.67, respectively. Hendrick et al. (10) studied transplacental transfer in paired maternal and umbilical serum samples at delivery showing that umbilical cord SSRI concentrations were invariably lower than corresponding maternal concentrations (the mean ratios of umbilical cord to maternal serum concentrations ranged from 0.29 to 0.89). Sertraline and paroxetine had the lowest ratios while citalopram and fluoxetine had the highest. These data suggest fetal drug exposure near delivery may be decreased for sertraline and paroxetine compared to fluoxetine. As fetal drug clearance at term is decreased and approximates only one- third that of adults, it is reassuring to know that third trimester maternal SSRI use does not result in fetal drug accumulation.
Drug protein binding is inversely related to transplacental passage because a protein bound drug cannot cross the placenta. The protein binding of SSRIs is variable (Table 1). This variation in protein binding may explain differences in the ratios for cord-to- maternal-serum concentrations (10). Sertraline is the most highly protein-bound (98%) of the SSRIs, and thus it can traverse the placenta only in minute quantities. Citalopram (80%) and especially Venlafaxine (27%) have the lowest protein binding allowing for increased transplacental drug passage to the fetus.
Definition of SSRI-induced Neonatal Abstinence Syndrome
Some controversy exists regarding the definition of the syndrome seen in newborns following prolonged in-utero exposure to SSRIs. The general terms "neonatal complications" (11), "transient neonatal symptoms" (12) or "neonatal effects" (13) have been used by some authors with no attempt at characterization of a specific syndrome. Moses-Kolko et al. (14) and Zeskind and Stephens (15) have used the terms "neonatal behavioral syndrome" or "behavioral symptoms" to describe the transient symptoms seen in the newborn after a minimum of third trimester exposure to SSRIs. "Serotonin syndrome" assumes a direct SSRI drug effect of serotonin or its metabolites. This terminology has been suggested by Isbister et al. (16) and by Laine et al. (17). "Withdrawal syndrome" or "discontinuation syndrome" are used to denote a causal relationship between discontinued exposure to a drug and moderate to severe symptoms (18). These terms have been used in SSRI exposed newborns by Sanz et al. (19), Costei et al. (20) and others (21, 22). Overlap between symptoms caused by drug withdrawal or direct serotonin effects likely exists. Correlation in some infants between symptom severity and cord blood (16) and infant serum levels (23) suggest the possible causative role of serotonin in the clinical syndrome. Conversely, withdrawal syndrome can be proved in symptomatic infants with very low or undetectable levels of drug or active metabolites. This has been shown repeatedly (24-26). Withdrawal can also be demonstrated by showing that timing of peak symptoms does not correspond with peak exposure but appears after a delay of days, which is compatible with drug withdrawal but not with a direct drug effect (6, 27). Also a prolonged duration of symptoms without continued drug exposure is suggestive of drug withdrawal (6, 26).
NAS describes the clinical syndrome resulting from prior prolonged exposure followed by cessation of a causative drug (28). NAS includes a wide spectrum from mild to severe symptoms. Although many of the symptoms are non-specific, the combination of symptoms together with prior exposure to a drug known to cause NAS suggests its possibility. Moderate to severe NAS symptoms are compatible with the definition of a withdrawal syndrome. As NAS includes both mild and severely affected newborns, it is preferable to alternative characterizations of SSRI exposed newborns that do not include all symptomatic newborns.
Clinical Presentation of SSRI-induced Neonatal Abstinence Syndrome
The clinical spectrum of NAS is variable. Factors that increase drug exposure prior to delivery aggravate the clinical syndrome. Specific factors that increase symptom severity include: increased transplacental transfer, decreased drug metabolism and elimination, type of medication (variable effect), increased duration of use during pregnancy (mainly third trimester use), increased dose, decreased time elapsed from last drug use until birth and term delivery (prematurity possibly decreases symptoms). The onset of symptoms often occurs shortly after birth or within the first few days of life. Infants who do not exhibit symptoms within the first 48 hours of life are unlikely to become symptomatic (6). Shorter drug half-life and a longer elapsed time since last maternal drug dose are associated with earlier onset of symptoms in the newborn infant.
Clinical symptoms are common and seen in 30% of newborns (6, 12). NAS symptoms can be categorized into four groups of effects: central nervous system (CNS), gastrointestinal, autonomie and respiratory effects. The various symptoms are described in Table 2. Symptoms may vary with time. In our experience, initial CNS effects are often those of depression with hypoactivity, hypotonia, lethargy and a weak cry. These symptoms rapidly evolve to those of CNS excitation (23). Commonly seen symptoms are irritability (14, 17, 19), jitteriness (14, 29), abnormal crying (14, 19, 29), altered behavior (14, 15), sleep abnormalities (14, 15), poor feeding (14, 19), vomiting (19), hypotonia (12, 29), hypertonia (14), respiratory distress (12, 14, 20, 29) and increased reflexes (14, 17). Less common symptoms are lethargy, a weak cry or seizures (6, 19). Although most symptoms are non-specific, some symptoms such as transient aphonia (30) have only been reported as a result of SSRI exposure. A previous association of hemorrhage with SSRI exposure (31) has not been recently substantiated (32). Some neonatal outcomes or symptoms seen in SSRI-exposed newborns are not part of the NAS. One such outcome associated with SSRI exposure is persistent pulmonary hypertension (5, 33). Newborns should be screened for all neonatal outcomes including those that are not part of the NAS (Table 3). Duration of symptoms is variable. For most infants symptoms peak up to 96 hours after birth and then spontaneously subside within a few days (6). Occasionally infants may remain symptomatic for weeks (34).
Protocol for Observation of an SSRI-Exposed Newborn
The various effects of SSRIs should all be considered when following an infant with prolonged in-utero SSRI exposure. Table 3 summarizes a protocol (6) that has been in use since 1998. The Finnegan score (6, 35, 36) may be used to follow signs of NAS. This score is an objective method used to monitor onset, progression, and improvement of NAS symptoms in passively exposed neonates. The score rates 21 symptoms most commonly seen in drug-exposed neonates, and is also used to assess the need for pharmacological intervention and the response to treatment. The total score is determined by adding the score assigned to each symptom group. Higher scores represent more severe abstinence symptoms. A score of 8 or higher in three consecutive measurements is considered an indication for pharmacotherapy. The score should be performed at intervals of 8 hours, unless severe symptoms are noted (Finnegan score >/= 8), in which case the intervals should be shortened. The newborn should be placed in an incubator and followed closely until signs of NAS normalize (Finnegan score
Unresolved Issues
The long-term effects of in-utero exposure to SSRIs have not been sufficiently studied. Oberlander et al. (37) have shown altered biobehavioral pain reactivity of exposed infants at 2 months suggesting the possibility of sustained neurobehavioral effect beyond the newborn period. Nulman et al. (38) studied 55 preschool children exposed to fluoxetine and also found no effect on global IQ, language development or behavioral development. Oberlander et al. (12) and Casper et al. (39) assessed exposed infants by the Bayley Scale of Infant Development at the ages of 8 months and 6-40 months, respectively. Both studies found the mental development index to be unaffected but showed a subtle effect on motor development. Although a single study has shown no difference between non-symptomatic and symptomatic infants (12), the long-term effects on the select group of SSRI-exposed infants who develop severe symptoms suggestive of a withdrawal syndrome have not been evaluated.
Treatment of SSRI-induced NAS is controversial. For most infants with NAS, "physiological" reversal of NAS is most readily achieved by reintroduction of the causative drug. For example, when narcotics cause a NAS, giving a similar narcotic allows control of abstinence symptoms. After symptom control, the drug can then be gradually tapered. In SSRI-induced NAS, this approach is not feasible because drug safety has not been established in infants. Therefore, the only currently available therapy is symptomatic treatment. For infants with severe NAS or for infants who develop seizures, phenobarbital is a possible treatment.
Breast-feeding has been shown to decrease the duration and severity of NAS (35). Currently breast feeding is not contraindicated for infants with SSRI-induced NAS, but no randomized controlled trials have been performed in breast-fed infants. Long- term follow-up studies on breast-fed infants are lacking.
Recommendations
* The risk benefit ratio of maternal treatment during pregnancy should be evaluated. If the indication for treatment is unchanged, then treatment should be continued.
* Tapering of SSRIs during the last month of pregnancy should theoretically prevent both NAS and direct drug effects. However, it is not known if tapering of medications reduces the risk of NAS.
* Infants born following third trimester exposure to SSRIs should be monitored for NAS symptoms for a minimum period of 48-72 hours with a standardized protocol including the Finnegan score. Infants who develop a NAS should remain under observation until symptom resolution. Neonatal Intensive Care Unit observation is recommended for severely effected infants.
* Breast-feeding is allowed but infants should be observed for any abnormal behavior.
* Treatment of infants with SSRI-induced NAS is symptomatic.
* Therapeutic drug monitoring may be indicated to differentiate between NAS and direct drug affect.
References
1. Campagne DM. The obstetricians and depression during pregnancy. Eur J Obstet Gynecol Reprod Biol 2004; 116:125-130.
2. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T. Perinatal depression. A systematic review of prevalence and incidence. Obstet Gynecol 2005;106:1071-1083.
3. Bennet HA, Einarson A, Taddio A, Koren G, Einarson TR. Prevalence of depression during pregnancy: Systematic Review. Obstet Gynecol 2004;103:698-709.
4. Gupta S, Masand PS, Rangwani S. Selective serotonin reuptake inhibitors in pregnancy and lactation. Obstet Gynecol Survey 1998;53:733-736.
5. Reefhuis J, Friedman JM. Selective serotonin-reuptake inhibitors and persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354:2188-2189.
6. Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 2006; 160:173-176.
7. Hale TW. Medications and mothers milk. 11th ed. Amarillo, Texas: Pharmasoft, 2004.
8. Pohland RC, Byrd TK, Hamilton M, Koons JR. Placental transfer and fetal distribution of fluoxetine in the rat. Toxicol Appl Pharmacol 1989;98:198-205.
9. Stowe ZN, Llewellyn AM, Strader JR, Kitts CD, Ritchie JC, Nemeroff CB. Placental passage of antidepressants. Amer Psychiatr Assoc, San Diego, May 1997.
10. Hendrick V, Stowe ZN, Altshuler LL, Hwang S, Lee E, Haynes D. Placental passage of antidepressant medications. Am J Psychiatry 2003;160:993-996.
11. Hendrick V, Smith LM, Suri R, Hwang S, Haynes D, Altshuler L. Birth outcomes after prenatal exposure to antidepressant medication. Am J Obstet Gynecol 2003; 188:812-815.
12. Oberlander TF, Misri S, Fitzgerald CE, Kostaras X, Rurak D, Riggs W. Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry 2004;65:230-237.
13. Kallen B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med 2004;158:312-316.
14. Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors. Literature review and implications for clinical applications. JAMA 2005;293:2372-2383.
15. Zeskind PS, Stephens LE. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 2004;113:368-375.
16. Isbister GK, Dawson A, Whyte IM, Prior FH, Clancy C, Smith AJ. Neonatal paroxetine withdrawal syndrome or actually serotonin syndrome? Arch Dis Child Fetal Neonatal Ed 2001;85:F147-148.
17. Laine K, Heikkinen T, Ekblad U, Kero P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry 2003;60:720-726. 18. American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics 1998;101: 1079-1088.
19. Sanz EJ, De-las-Cuevas C, Kiuru A, Bate A, Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: A database analysis. Lancet 2005;365:482-487.
20. Costei AM, Kozer E, Ho T, Ito S, Koren G. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med 2002;156:1129-1132.
21. Nordeng H, Lindemann R, Perminov KV, Reikvam A. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr 2001;90:288-291.
22. Nijhuis IJ, Kok-Van Rooij GW, Bosschaart AN. Withdrawal reactions of a premature neonate after maternal use of paroxetine. Arch Dis Child Fetal Neonatal Ed 2001;84:F77.
23. Knoppert D, Nimkar R, Principi T, Yuen D. Paroxetine toxicity in a newborn after in utero exposure. Clinical symptoms correlate with serum levels. Ther Drug Monitor 2006;28:5-7.
24. Jaiswal S, Coombs RC, Isbister GK. Paroxetine withdrawal in a neonate with historical and laboratory confirmation. Eur J Pediatr 2003;62:723-724.
25. Santos RP, Pergolizzi JJ. Transient neonatal jitteriness due to maternal use of sertraline (Zoloft). J Perinatol 2004;24:392- 394.
26. Stiskal JA, Kulin N, Koren G, Ho T, Ito S. Neonatal paroxetine withdrawal syndrome. Arch Dis Child Fetal Neonatal Ed 2001;84:F134-135.
27. Bot P, Semmekrot BA, van der Stappen J. Neonatal effects of exposure to selective serotonin reuptake inhibitors during pregnancy. Arch Dis Child Fetal Neonatal Ed 2006;91:F153.
28. Johnson K, Gerada C, Greenough A. Treatment of neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed 2003;88:F2-5.
29. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996;335:1010-1015.
30. Morag I, Batish D, Keidar R, Bulkenstein M, Heyman E. Paroxetine use throughout pregnancy: Does it pose any risk to the neonate? J Toxicol Clin Toxicol 2004;42: 97-100.
31. Nelva A, Guy C, Tardy-Poncet B, Bevens MN, Ratrema M, Benedetti C, Ollajnier M. Hemorrhagic syndromes related to selective serotonin reuptake inhibitor (SSRI) antidepressants. Seven case reports and review of the literature. Rev Med Interne 2000;21:152- 160.
32. Maayan-Metzger A, Kuint J, Lubetsky A, Shenkman B, Mazkereth R, Kenet G. Maternal selective serotonin reuptake inhibitor intake does not seem to affect neonatal platelet function tests. Acta Haematol 2006;115: 157-161.
33. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Louik C, Jones KL, Mitchell AA. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354: 579-587.
34. Franssen EJF, Meijs V, Ettahar F, Valeric PG, Keesen M, Lameijer W. Citalopram serum and milk levels in mother and infant during lactation. Ther Drug Monitor 2006;28:2-4.
35. Abdel-Latif ME, Pinner J, Clews S, Cooke F, Lui K, Oei J. Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers. Pediatrics 2006;117:e1163-e1169.
36. Finnegan LP. Neonatal abstinence syndrome. In: Nelson N, editor. Current Therapy in Neonatal Perinatal Medicine-2. Toronto: BC Decker, 1990; pp. 314-320.
37. Oberlander TF, Grunau RE, Fitzgerald C, Papsdorf M, Rurak D, Riggs W. Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 2005;115: 411-425.
38. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, Kulin N, Koren G. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258-262.
39. Casper RC, Fleisher BE, Lee-Ancajas JC, Gilles A, Gaylor E, DeBattista A, Hoyme HE. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003; 142:402-408.
Gil Klinger, MD, and Paul Merlob, MD
Neonatal Intensive Care Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel, and the Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
Address for Correspondence: Gil Klinger, MD, Neonatal Intensive Care Unit, Schneider Children's Medical Center of Israel, 14 Kaplan Street, Petah Tikva 49202, Israel. E-mail: gilkl@post.tau.ac.il
Copyright Gefen Publishing House Ltd. 2008
(c) 2008 Israel Journal of Psychiatry and Related Sciences, The. Provided by ProQuest LLC. All rights Reserved.
Source: Israel Journal of Psychiatry and Related Sciences, The
More News in this Category
http://www.redorbit.com/news/health/1551180/selective_serotonin_reuptake_inhibitor_induced_neonatal_abstinence_syndrome/
Posted on: Thursday, 11 September 2008, 03:00 CDT
By Klinger, Gil Merlob, Paul
Abstract: Depression is common in women of childbearing age and especially during pregnancy and the postpartum period. Selective serotonin reuptake inhibitors (SSRIs) are increasingly being used to treat depression prior to and throughout pregnancy. Up to 30% of the newborn infants exposed to SSRIs may present with clinical signs during the first days after birth. Neonatal abstinence syndrome (NAS) describes this clinical syndrome resulting from prior prolonged exposure to SSRI induced by cessation of the drug. NAS includes a wide spectrum from mild to severe non-specific symptoms which were categorized into four groups of effects: central nervous system (depression followed by excitation), gastrointestinal, autonomie and respiratory. A protocol for observation of SSRI- exposed newborns is presented including an objective method (Finnegan score) to monitor onset, progression and improvement of NAS symptoms. Introduction
Depression is common in women of childbearing age (1). During pregnancy increased stress may aggravate depression resulting in a prevalence of up to 12.9% of this disorder (2, 3). The prevalence of depression during the postpartum period continues to be high with 19.2% of women experiencing a major depressive episode within the first three months after delivery (2). Because many women experience depression during the postpartum period, it is often dismissed as part of the "normal" physiological changes that are associated with childbirth (4). However, if untreated, perinatal depression can have severe consequences for the fetus and newborn, as well as for the mother. Although psychotherapy is the first-line treatment for depression during pregnancy or after birth, antidepressant treatment is warranted in some patients. Because selective serotonin reuptake inhibitors (SSRIs) are perceived as safer than alternative medications, they are increasingly being used to treat depression prior to and throughout pregnancy. A recent survey has shown that 2.8% of women use SSRIs for the entire duration of pregnancy (5). This figure translates to 92,000 of approximately 4 million annual live births in the United States. Prolonged fetal exposure to SSRIs may be associated with a neonatal abstinence syndrome (NAS) affecting 30% of newborns (6). The widespread use of SSRIs during pregnancy and the resulting occurrence of NAS warrant a thorough review.
Pharmacokinetics
SSRIs are a group of psychotropic drugs that is chemically unrelated to tricyclics, tetracyclics, monoamine oxidase inhibitors or other antidepressants. They are used to treat depression, but also for obsessive-compulsive and other disorders. The action of SSRIs is thought to be linked to their inhibition of prejunctional reuptake of serotonin, but they do not have receptor-blocking effects. The side-effects of tricyclic and tetracyclic antidepressants may be worrisome in pregnancy and their narrow therapeutic range increases the risk of overdose. SSRIs have a safer therapeutic profile because of their relatively benign side-effects and their safety in overdose (4). The SSRI group is comprised of the following drugs:
1. Fluoxetine (Prozac, Prizma, Flutine, Affectine)
2. Paroxetine (Seroxat, Paxet, Paxol, Paroxetine)
3. Sertraline (Lustral, Zoloft)
4. Fluvoxamine (Favoxil, Luvox)
5. Citalopram (Cipramil, Recital)
6. Escitalopram (Ciprodex, Cipralex)
Venlafaxine (Efexor, Venla, Viepax) is a selective norepinephrine- serotonin reuptake inhibitor (SNSRI) that is closely related to the SSRIs.
The pharmacokinetic properties of SSRIs (7) are presented in Table 1. This table lists the most commonly recorded adult drug half- life of SSRIs because there is little or no information regarding the newborn. It is of note that during the newborn period, drug half- life is prolonged for most medications, but this is also dependent on drug metabolism. Of the SSRI half-lives, fluoxetine, sertraline and citalopram have a long one with fluoxetine having the longest, paroxetine and fluvoxamine have an intermediate one and venlafaxine has the shortest. A relatively short or intermediate drug half-life has been implicated with an increased risk of NAS after third- trimester exposure.
Transplacental passage determines fetal drug exposure. For drugs with no placental metabolism, transplacental passage is inversely related to molecular weight. SSRIs have a low molecular weight (around 300) with the exception of citalopram (405) and theoretically are able to cross the placental barrier. Placental drug transfer is also determined by duration of drug exposure, liposolubility, protein binding, volume of distribution and other pharmacokinetic factors. Placental transfer of SSRIs has been demonstrated experimentally both in animals and in humans. Pohland et al. (8) demonstrated in the rat that C14 labeled fluoxetine and norfluoxetine traversed the placenta during the periods of organogenesis and postorganogenesis and were distributed within the embryonic/fetal tissue, preferentially to the brain and thymus. Stowe et al. (9) studied the passage of SSRIs across the human placenta by measuring their concentrations in maternal serum and umbilical cord blood at delivery. No evidence of accumulation of fluoxetine, paroxetine, or sertraline in the fetal circulation was found. The fetal : maternal drug ratios for fluoxetine, sertraline and paroxetine were 0.94, 0.43 and 0.67, respectively. Hendrick et al. (10) studied transplacental transfer in paired maternal and umbilical serum samples at delivery showing that umbilical cord SSRI concentrations were invariably lower than corresponding maternal concentrations (the mean ratios of umbilical cord to maternal serum concentrations ranged from 0.29 to 0.89). Sertraline and paroxetine had the lowest ratios while citalopram and fluoxetine had the highest. These data suggest fetal drug exposure near delivery may be decreased for sertraline and paroxetine compared to fluoxetine. As fetal drug clearance at term is decreased and approximates only one- third that of adults, it is reassuring to know that third trimester maternal SSRI use does not result in fetal drug accumulation.
Drug protein binding is inversely related to transplacental passage because a protein bound drug cannot cross the placenta. The protein binding of SSRIs is variable (Table 1). This variation in protein binding may explain differences in the ratios for cord-to- maternal-serum concentrations (10). Sertraline is the most highly protein-bound (98%) of the SSRIs, and thus it can traverse the placenta only in minute quantities. Citalopram (80%) and especially Venlafaxine (27%) have the lowest protein binding allowing for increased transplacental drug passage to the fetus.
Definition of SSRI-induced Neonatal Abstinence Syndrome
Some controversy exists regarding the definition of the syndrome seen in newborns following prolonged in-utero exposure to SSRIs. The general terms "neonatal complications" (11), "transient neonatal symptoms" (12) or "neonatal effects" (13) have been used by some authors with no attempt at characterization of a specific syndrome. Moses-Kolko et al. (14) and Zeskind and Stephens (15) have used the terms "neonatal behavioral syndrome" or "behavioral symptoms" to describe the transient symptoms seen in the newborn after a minimum of third trimester exposure to SSRIs. "Serotonin syndrome" assumes a direct SSRI drug effect of serotonin or its metabolites. This terminology has been suggested by Isbister et al. (16) and by Laine et al. (17). "Withdrawal syndrome" or "discontinuation syndrome" are used to denote a causal relationship between discontinued exposure to a drug and moderate to severe symptoms (18). These terms have been used in SSRI exposed newborns by Sanz et al. (19), Costei et al. (20) and others (21, 22). Overlap between symptoms caused by drug withdrawal or direct serotonin effects likely exists. Correlation in some infants between symptom severity and cord blood (16) and infant serum levels (23) suggest the possible causative role of serotonin in the clinical syndrome. Conversely, withdrawal syndrome can be proved in symptomatic infants with very low or undetectable levels of drug or active metabolites. This has been shown repeatedly (24-26). Withdrawal can also be demonstrated by showing that timing of peak symptoms does not correspond with peak exposure but appears after a delay of days, which is compatible with drug withdrawal but not with a direct drug effect (6, 27). Also a prolonged duration of symptoms without continued drug exposure is suggestive of drug withdrawal (6, 26).
NAS describes the clinical syndrome resulting from prior prolonged exposure followed by cessation of a causative drug (28). NAS includes a wide spectrum from mild to severe symptoms. Although many of the symptoms are non-specific, the combination of symptoms together with prior exposure to a drug known to cause NAS suggests its possibility. Moderate to severe NAS symptoms are compatible with the definition of a withdrawal syndrome. As NAS includes both mild and severely affected newborns, it is preferable to alternative characterizations of SSRI exposed newborns that do not include all symptomatic newborns.
Clinical Presentation of SSRI-induced Neonatal Abstinence Syndrome
The clinical spectrum of NAS is variable. Factors that increase drug exposure prior to delivery aggravate the clinical syndrome. Specific factors that increase symptom severity include: increased transplacental transfer, decreased drug metabolism and elimination, type of medication (variable effect), increased duration of use during pregnancy (mainly third trimester use), increased dose, decreased time elapsed from last drug use until birth and term delivery (prematurity possibly decreases symptoms). The onset of symptoms often occurs shortly after birth or within the first few days of life. Infants who do not exhibit symptoms within the first 48 hours of life are unlikely to become symptomatic (6). Shorter drug half-life and a longer elapsed time since last maternal drug dose are associated with earlier onset of symptoms in the newborn infant.
Clinical symptoms are common and seen in 30% of newborns (6, 12). NAS symptoms can be categorized into four groups of effects: central nervous system (CNS), gastrointestinal, autonomie and respiratory effects. The various symptoms are described in Table 2. Symptoms may vary with time. In our experience, initial CNS effects are often those of depression with hypoactivity, hypotonia, lethargy and a weak cry. These symptoms rapidly evolve to those of CNS excitation (23). Commonly seen symptoms are irritability (14, 17, 19), jitteriness (14, 29), abnormal crying (14, 19, 29), altered behavior (14, 15), sleep abnormalities (14, 15), poor feeding (14, 19), vomiting (19), hypotonia (12, 29), hypertonia (14), respiratory distress (12, 14, 20, 29) and increased reflexes (14, 17). Less common symptoms are lethargy, a weak cry or seizures (6, 19). Although most symptoms are non-specific, some symptoms such as transient aphonia (30) have only been reported as a result of SSRI exposure. A previous association of hemorrhage with SSRI exposure (31) has not been recently substantiated (32). Some neonatal outcomes or symptoms seen in SSRI-exposed newborns are not part of the NAS. One such outcome associated with SSRI exposure is persistent pulmonary hypertension (5, 33). Newborns should be screened for all neonatal outcomes including those that are not part of the NAS (Table 3). Duration of symptoms is variable. For most infants symptoms peak up to 96 hours after birth and then spontaneously subside within a few days (6). Occasionally infants may remain symptomatic for weeks (34).
Protocol for Observation of an SSRI-Exposed Newborn
The various effects of SSRIs should all be considered when following an infant with prolonged in-utero SSRI exposure. Table 3 summarizes a protocol (6) that has been in use since 1998. The Finnegan score (6, 35, 36) may be used to follow signs of NAS. This score is an objective method used to monitor onset, progression, and improvement of NAS symptoms in passively exposed neonates. The score rates 21 symptoms most commonly seen in drug-exposed neonates, and is also used to assess the need for pharmacological intervention and the response to treatment. The total score is determined by adding the score assigned to each symptom group. Higher scores represent more severe abstinence symptoms. A score of 8 or higher in three consecutive measurements is considered an indication for pharmacotherapy. The score should be performed at intervals of 8 hours, unless severe symptoms are noted (Finnegan score >/= 8), in which case the intervals should be shortened. The newborn should be placed in an incubator and followed closely until signs of NAS normalize (Finnegan score
Unresolved Issues
The long-term effects of in-utero exposure to SSRIs have not been sufficiently studied. Oberlander et al. (37) have shown altered biobehavioral pain reactivity of exposed infants at 2 months suggesting the possibility of sustained neurobehavioral effect beyond the newborn period. Nulman et al. (38) studied 55 preschool children exposed to fluoxetine and also found no effect on global IQ, language development or behavioral development. Oberlander et al. (12) and Casper et al. (39) assessed exposed infants by the Bayley Scale of Infant Development at the ages of 8 months and 6-40 months, respectively. Both studies found the mental development index to be unaffected but showed a subtle effect on motor development. Although a single study has shown no difference between non-symptomatic and symptomatic infants (12), the long-term effects on the select group of SSRI-exposed infants who develop severe symptoms suggestive of a withdrawal syndrome have not been evaluated.
Treatment of SSRI-induced NAS is controversial. For most infants with NAS, "physiological" reversal of NAS is most readily achieved by reintroduction of the causative drug. For example, when narcotics cause a NAS, giving a similar narcotic allows control of abstinence symptoms. After symptom control, the drug can then be gradually tapered. In SSRI-induced NAS, this approach is not feasible because drug safety has not been established in infants. Therefore, the only currently available therapy is symptomatic treatment. For infants with severe NAS or for infants who develop seizures, phenobarbital is a possible treatment.
Breast-feeding has been shown to decrease the duration and severity of NAS (35). Currently breast feeding is not contraindicated for infants with SSRI-induced NAS, but no randomized controlled trials have been performed in breast-fed infants. Long- term follow-up studies on breast-fed infants are lacking.
Recommendations
* The risk benefit ratio of maternal treatment during pregnancy should be evaluated. If the indication for treatment is unchanged, then treatment should be continued.
* Tapering of SSRIs during the last month of pregnancy should theoretically prevent both NAS and direct drug effects. However, it is not known if tapering of medications reduces the risk of NAS.
* Infants born following third trimester exposure to SSRIs should be monitored for NAS symptoms for a minimum period of 48-72 hours with a standardized protocol including the Finnegan score. Infants who develop a NAS should remain under observation until symptom resolution. Neonatal Intensive Care Unit observation is recommended for severely effected infants.
* Breast-feeding is allowed but infants should be observed for any abnormal behavior.
* Treatment of infants with SSRI-induced NAS is symptomatic.
* Therapeutic drug monitoring may be indicated to differentiate between NAS and direct drug affect.
References
1. Campagne DM. The obstetricians and depression during pregnancy. Eur J Obstet Gynecol Reprod Biol 2004; 116:125-130.
2. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T. Perinatal depression. A systematic review of prevalence and incidence. Obstet Gynecol 2005;106:1071-1083.
3. Bennet HA, Einarson A, Taddio A, Koren G, Einarson TR. Prevalence of depression during pregnancy: Systematic Review. Obstet Gynecol 2004;103:698-709.
4. Gupta S, Masand PS, Rangwani S. Selective serotonin reuptake inhibitors in pregnancy and lactation. Obstet Gynecol Survey 1998;53:733-736.
5. Reefhuis J, Friedman JM. Selective serotonin-reuptake inhibitors and persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354:2188-2189.
6. Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 2006; 160:173-176.
7. Hale TW. Medications and mothers milk. 11th ed. Amarillo, Texas: Pharmasoft, 2004.
8. Pohland RC, Byrd TK, Hamilton M, Koons JR. Placental transfer and fetal distribution of fluoxetine in the rat. Toxicol Appl Pharmacol 1989;98:198-205.
9. Stowe ZN, Llewellyn AM, Strader JR, Kitts CD, Ritchie JC, Nemeroff CB. Placental passage of antidepressants. Amer Psychiatr Assoc, San Diego, May 1997.
10. Hendrick V, Stowe ZN, Altshuler LL, Hwang S, Lee E, Haynes D. Placental passage of antidepressant medications. Am J Psychiatry 2003;160:993-996.
11. Hendrick V, Smith LM, Suri R, Hwang S, Haynes D, Altshuler L. Birth outcomes after prenatal exposure to antidepressant medication. Am J Obstet Gynecol 2003; 188:812-815.
12. Oberlander TF, Misri S, Fitzgerald CE, Kostaras X, Rurak D, Riggs W. Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry 2004;65:230-237.
13. Kallen B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med 2004;158:312-316.
14. Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors. Literature review and implications for clinical applications. JAMA 2005;293:2372-2383.
15. Zeskind PS, Stephens LE. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 2004;113:368-375.
16. Isbister GK, Dawson A, Whyte IM, Prior FH, Clancy C, Smith AJ. Neonatal paroxetine withdrawal syndrome or actually serotonin syndrome? Arch Dis Child Fetal Neonatal Ed 2001;85:F147-148.
17. Laine K, Heikkinen T, Ekblad U, Kero P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry 2003;60:720-726. 18. American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics 1998;101: 1079-1088.
19. Sanz EJ, De-las-Cuevas C, Kiuru A, Bate A, Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: A database analysis. Lancet 2005;365:482-487.
20. Costei AM, Kozer E, Ho T, Ito S, Koren G. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med 2002;156:1129-1132.
21. Nordeng H, Lindemann R, Perminov KV, Reikvam A. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr 2001;90:288-291.
22. Nijhuis IJ, Kok-Van Rooij GW, Bosschaart AN. Withdrawal reactions of a premature neonate after maternal use of paroxetine. Arch Dis Child Fetal Neonatal Ed 2001;84:F77.
23. Knoppert D, Nimkar R, Principi T, Yuen D. Paroxetine toxicity in a newborn after in utero exposure. Clinical symptoms correlate with serum levels. Ther Drug Monitor 2006;28:5-7.
24. Jaiswal S, Coombs RC, Isbister GK. Paroxetine withdrawal in a neonate with historical and laboratory confirmation. Eur J Pediatr 2003;62:723-724.
25. Santos RP, Pergolizzi JJ. Transient neonatal jitteriness due to maternal use of sertraline (Zoloft). J Perinatol 2004;24:392- 394.
26. Stiskal JA, Kulin N, Koren G, Ho T, Ito S. Neonatal paroxetine withdrawal syndrome. Arch Dis Child Fetal Neonatal Ed 2001;84:F134-135.
27. Bot P, Semmekrot BA, van der Stappen J. Neonatal effects of exposure to selective serotonin reuptake inhibitors during pregnancy. Arch Dis Child Fetal Neonatal Ed 2006;91:F153.
28. Johnson K, Gerada C, Greenough A. Treatment of neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed 2003;88:F2-5.
29. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996;335:1010-1015.
30. Morag I, Batish D, Keidar R, Bulkenstein M, Heyman E. Paroxetine use throughout pregnancy: Does it pose any risk to the neonate? J Toxicol Clin Toxicol 2004;42: 97-100.
31. Nelva A, Guy C, Tardy-Poncet B, Bevens MN, Ratrema M, Benedetti C, Ollajnier M. Hemorrhagic syndromes related to selective serotonin reuptake inhibitor (SSRI) antidepressants. Seven case reports and review of the literature. Rev Med Interne 2000;21:152- 160.
32. Maayan-Metzger A, Kuint J, Lubetsky A, Shenkman B, Mazkereth R, Kenet G. Maternal selective serotonin reuptake inhibitor intake does not seem to affect neonatal platelet function tests. Acta Haematol 2006;115: 157-161.
33. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Louik C, Jones KL, Mitchell AA. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354: 579-587.
34. Franssen EJF, Meijs V, Ettahar F, Valeric PG, Keesen M, Lameijer W. Citalopram serum and milk levels in mother and infant during lactation. Ther Drug Monitor 2006;28:2-4.
35. Abdel-Latif ME, Pinner J, Clews S, Cooke F, Lui K, Oei J. Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers. Pediatrics 2006;117:e1163-e1169.
36. Finnegan LP. Neonatal abstinence syndrome. In: Nelson N, editor. Current Therapy in Neonatal Perinatal Medicine-2. Toronto: BC Decker, 1990; pp. 314-320.
37. Oberlander TF, Grunau RE, Fitzgerald C, Papsdorf M, Rurak D, Riggs W. Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 2005;115: 411-425.
38. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, Kulin N, Koren G. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258-262.
39. Casper RC, Fleisher BE, Lee-Ancajas JC, Gilles A, Gaylor E, DeBattista A, Hoyme HE. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003; 142:402-408.
Gil Klinger, MD, and Paul Merlob, MD
Neonatal Intensive Care Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel, and the Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
Address for Correspondence: Gil Klinger, MD, Neonatal Intensive Care Unit, Schneider Children's Medical Center of Israel, 14 Kaplan Street, Petah Tikva 49202, Israel. E-mail: gilkl@post.tau.ac.il
Copyright Gefen Publishing House Ltd. 2008
(c) 2008 Israel Journal of Psychiatry and Related Sciences, The. Provided by ProQuest LLC. All rights Reserved.
Source: Israel Journal of Psychiatry and Related Sciences, The
More News in this Category
Drug firms bankroll attacks on NHS
http://www.independent.co.uk/life-style/health-and-wellbeing/health-news/drug-firms-bankroll-attacks-on-nhs-947316.html
Independent.co.uk
Drug firms bankroll attacks on NHS
Special investigation: Charities' protests against Nice funded by pharmaceutical companies
By Jeremy Laurance, Health Editor
Wednesday, 1 October 2008
The rising tide of protest over the refusal by the NHS to provide expensive drugs for cancer and other conditions is being funded by the pharmaceutical industry, an investigation by The Independent has revealed.
Patient groups that have been among the most vocal in spearheading attacks on the National Institute for Clinical Excellence (Nice) over decisions to restrict access to drugs on the NHS depend for up to half of their income on drug companies, but details are often undisclosed.
The growing clamour over decisions by Nice to ban access to certain drugs has outraged patients and the public, and undermined confidence in the NHS.
Protests have been launched by charities including the National Kidney Federation, the Arthritis and Musculoskeletal Alliance, the National Rheumatoid Arthritis Society, Beating Bowel Cancer, the Royal National Institute for the Blind and the Alzheimer's Society. All of these charities received sums of up to six figures from drug companies in 2007.
The extent of the drug companies' support for the smaller charities has led to criticisms that supposedly grassroots patient organisations are puppets of the pharmaceutical industry, being used to bludgeon Nice into making the drugs available on the health service. A positive decision by Nice on a drug not only guarantees sales to the NHS but can influence global markets worth billions of pounds.
Yet none of the charities named has criticised the high prices charged by the pharmaceutical companies for their products in their recent campaigns.
The National Kidney Federation (NKF) accused Nice of taking a "barbaric, damaging and unacceptable" decision when it turned down four kidney cancer drugs for NHS use this year and pledged to campaign against the decision. It did not criticise the cost of the drugs, at more than £3,000 for a 30-tablet pack. Half the NKF's £300,000 budget comes from the pharmaceutical and renal industries.
The Arthritis and Musculoskeletal Alliance (Arma) organised a protest letter from 10 professors of rheumatology, published in The Sunday Times last month, over a recent Nice decision to restrict access to arthritis drugs. The letter made no mention of the cost of the drugs but Ros Meek, chief executive, admitted that "half, or more" of the charity's £147,000 income came from the drug industry.
The National Rheumatoid Arthritis Society described the same Nice decision as "another nail in the coffin" for arthritis treatment and launched an appeal against it this week, with Arma and three drug companies. The society received 49 per cent of its £300,000 budget from the pharmaceutical industry in 2005-06, reducing to 26 per cent of its £472,000 budget in 2006-07.
Beating Bowel Cancer, which condemned a Nice decision to turn down the bowel cancer drugs Avastin and Erbitux as "a scandal", and assisted a BBC Panorama programme on the postcode lottery in drugs for cancer, received 10 per cent of its £1m income from pharmaceutical companies last year. It also made no mention of the cost of the treatments. Two of the biggest campaigns against Nice decisions in recent years were organised by the Royal National Institute for the Blind (RNIB) and the Alzheimer's Society which, between them, represent millions of patients. Six figure sums were paid to both charities by drug companies last year but because they are large organisations, the donations accounted for less than 1 per cent of their total income.
The Association of the British Pharmaceutical Industry has tightened its code on drug company funding of patient groups, which requires companies to agree grants in writing and to be transparent. Both the RNIB and the Alzheimer's Society declare their drug company funding on their websites, in the spirit of the code, but many smaller charities do not. Tim Kendall, director of research at the Royal College of Psychiatrists said the pharmaceutical industry reached into "every corner of the health service" in order to gain influence.
"Drug companies will try to do anything to align their interests with those of patients. They do things at every level of the health service and we know they do it with patient groups. It is a multi-pronged approach to persuade patients that their drug is the one."
Cost effective? The medication selection process
1. The drug is licensed for use as safe and effective by the European Medicines Agency.
2. The Department of Health refers the drug to Nice for assessment.
3. Nice convenes a committee of 20, including doctors, nurses, specialists, patients, drug company representatives and health economists.
4. The committee compares the new drug with existing drugs on cost and effectiveness.
5. The committee decides if the drug is cost effective using the Quality Adjusted Life Year (Qaly), a measure of health gain for quality and length of life.
6. Drugs are mostly approved up to £30,000 per Qaly.
Independent.co.uk
Drug firms bankroll attacks on NHS
Special investigation: Charities' protests against Nice funded by pharmaceutical companies
By Jeremy Laurance, Health Editor
Wednesday, 1 October 2008
The rising tide of protest over the refusal by the NHS to provide expensive drugs for cancer and other conditions is being funded by the pharmaceutical industry, an investigation by The Independent has revealed.
Patient groups that have been among the most vocal in spearheading attacks on the National Institute for Clinical Excellence (Nice) over decisions to restrict access to drugs on the NHS depend for up to half of their income on drug companies, but details are often undisclosed.
The growing clamour over decisions by Nice to ban access to certain drugs has outraged patients and the public, and undermined confidence in the NHS.
Protests have been launched by charities including the National Kidney Federation, the Arthritis and Musculoskeletal Alliance, the National Rheumatoid Arthritis Society, Beating Bowel Cancer, the Royal National Institute for the Blind and the Alzheimer's Society. All of these charities received sums of up to six figures from drug companies in 2007.
The extent of the drug companies' support for the smaller charities has led to criticisms that supposedly grassroots patient organisations are puppets of the pharmaceutical industry, being used to bludgeon Nice into making the drugs available on the health service. A positive decision by Nice on a drug not only guarantees sales to the NHS but can influence global markets worth billions of pounds.
Yet none of the charities named has criticised the high prices charged by the pharmaceutical companies for their products in their recent campaigns.
The National Kidney Federation (NKF) accused Nice of taking a "barbaric, damaging and unacceptable" decision when it turned down four kidney cancer drugs for NHS use this year and pledged to campaign against the decision. It did not criticise the cost of the drugs, at more than £3,000 for a 30-tablet pack. Half the NKF's £300,000 budget comes from the pharmaceutical and renal industries.
The Arthritis and Musculoskeletal Alliance (Arma) organised a protest letter from 10 professors of rheumatology, published in The Sunday Times last month, over a recent Nice decision to restrict access to arthritis drugs. The letter made no mention of the cost of the drugs but Ros Meek, chief executive, admitted that "half, or more" of the charity's £147,000 income came from the drug industry.
The National Rheumatoid Arthritis Society described the same Nice decision as "another nail in the coffin" for arthritis treatment and launched an appeal against it this week, with Arma and three drug companies. The society received 49 per cent of its £300,000 budget from the pharmaceutical industry in 2005-06, reducing to 26 per cent of its £472,000 budget in 2006-07.
Beating Bowel Cancer, which condemned a Nice decision to turn down the bowel cancer drugs Avastin and Erbitux as "a scandal", and assisted a BBC Panorama programme on the postcode lottery in drugs for cancer, received 10 per cent of its £1m income from pharmaceutical companies last year. It also made no mention of the cost of the treatments. Two of the biggest campaigns against Nice decisions in recent years were organised by the Royal National Institute for the Blind (RNIB) and the Alzheimer's Society which, between them, represent millions of patients. Six figure sums were paid to both charities by drug companies last year but because they are large organisations, the donations accounted for less than 1 per cent of their total income.
The Association of the British Pharmaceutical Industry has tightened its code on drug company funding of patient groups, which requires companies to agree grants in writing and to be transparent. Both the RNIB and the Alzheimer's Society declare their drug company funding on their websites, in the spirit of the code, but many smaller charities do not. Tim Kendall, director of research at the Royal College of Psychiatrists said the pharmaceutical industry reached into "every corner of the health service" in order to gain influence.
"Drug companies will try to do anything to align their interests with those of patients. They do things at every level of the health service and we know they do it with patient groups. It is a multi-pronged approach to persuade patients that their drug is the one."
Cost effective? The medication selection process
1. The drug is licensed for use as safe and effective by the European Medicines Agency.
2. The Department of Health refers the drug to Nice for assessment.
3. Nice convenes a committee of 20, including doctors, nurses, specialists, patients, drug company representatives and health economists.
4. The committee compares the new drug with existing drugs on cost and effectiveness.
5. The committee decides if the drug is cost effective using the Quality Adjusted Life Year (Qaly), a measure of health gain for quality and length of life.
6. Drugs are mostly approved up to £30,000 per Qaly.
The ABPI's campaign orchestrates both lobbying and public relations in its overall strategy. - "The battle plan"
The Association of the British Pharmaceutical Industry (ABPI)
A Corporate Profile
By Corporate Watch UK
Completed September 2003
from - http://www.corporatewatch.org.uk/?lid=397
The ABPI's campaign orchestrates both lobbying and public relations in its overall strategy. At a briefing to the Pharmaceuticals Marketing Society in 2000, the ABPI described its “battle plan” thus: “to deploy ground troops in the form of patient support groups, symapthetic medical opinion and healthcare professionals... which will lead the debate on the informed patient issue. This will have the effect of weakening political, ideological and professional defences... Then the ABPI will follow through with high-level precision strikes on specific regulatory enclaves in both Whitehall and Brussels...”7
Aiming to create more informed patients, in January 2000, the ABPI launched its Electronic Medicines Compendium. The eMC, launched under the slogan “if you can eMC it you can believe it,” is a web site giving detailed information on thousands of prescription drugs. A spokesman added, “we intend to work closely with patient interest groups.”8
Proposals for relaxing DTC regulations at the European Union have twice been rejected by the Euopean Parliament and may be thrown out completely later this year. For more information see the Consumers Association web site.
Back to top
A Corporate Profile
By Corporate Watch UK
Completed September 2003
from - http://www.corporatewatch.org.uk/?lid=397
The ABPI's campaign orchestrates both lobbying and public relations in its overall strategy. At a briefing to the Pharmaceuticals Marketing Society in 2000, the ABPI described its “battle plan” thus: “to deploy ground troops in the form of patient support groups, symapthetic medical opinion and healthcare professionals... which will lead the debate on the informed patient issue. This will have the effect of weakening political, ideological and professional defences... Then the ABPI will follow through with high-level precision strikes on specific regulatory enclaves in both Whitehall and Brussels...”7
Aiming to create more informed patients, in January 2000, the ABPI launched its Electronic Medicines Compendium. The eMC, launched under the slogan “if you can eMC it you can believe it,” is a web site giving detailed information on thousands of prescription drugs. A spokesman added, “we intend to work closely with patient interest groups.”8
Proposals for relaxing DTC regulations at the European Union have twice been rejected by the Euopean Parliament and may be thrown out completely later this year. For more information see the Consumers Association web site.
Back to top
Are patient protests being manipulated?
http://www.independent.co.uk/life-style/health-and-wellbeing/health-news/analysis-are-patient-protests-being-manipulated-947317.html
Independent.co.uk
Analysis: Are patient protests being manipulated?
By Jeremy Laurance
Wednesday, 1 October 2008
It was the charge of barbarism that finally made Sir Michael Rawlins crack. The phlegmatic chairman of the National Institute for Clinical Excellence (Nice) is used to fielding brickbats over unpopular decisions to restrict access to cancer treatments and other drugs on the NHS.
But the jibe from the UK National Kidney Federation (NKF), which described Nice's decision to turn down four kidney cancer drugs as "barbaric, damaging and unacceptable," was too much. Sir Michael decided to strike back.
The resulting broadside, on the front page of The Observer, was headlined "Health chief attacks drug giants over huge profits: Watchdog slams high medicine prices". It was a stinging rebuke of the drug industry which Sir Michael accused of overpricing medicines to boost its profits. "We are told we are being mean but what nobody mentions is why the drugs are so expensive," he said.
It was an attempt to redress the balance of a debate too often cast as the people versus Nice. But Nice is merely a mechanism for sharing out a limited budget. The real argument should be between the people (who want the drugs), the pharmaceutical companies (who set the prices) and the Government (who fixes the NHS budget).
What escaped scrutiny was the role of the patient groups such as the NKF, who have lobbied vigorously against Nice decisions and the part played by the drug industry in their affairs.
The NKF, an umbrella organisation of kidney patients' associations, receives half of its £300,000 a year budget from the pharmaceutical and renal industries, according to its chief executive, Timothy Statham. In its press release issued on 19 August, it announced it was "incensed" by the draft Nice decision to turn down four drugs and would campaign to have it reversed. But it made no mention of the high cost of the drugs – £3,363 for a 30-capsule pack of sunitinib, one of the four – or criticism of the drug companies that make them. Professor Rawlins said the drugs could be made for a tenth of the cost.
Challenged about the omission, Mr Statham said it was an "important question" and he had requested meetings with the four companies. But he defended the NKF's reliance on industry funding.
"We receive sponsorship from as many of the renal industries as we can possibly sign up. We take the view that by having all the pharma and machine-maker companies on board, we cannot be subjected to overbearing influence by any one of them," he said.
That leaves unanswered the question of whether accepting funding from any company compromises a group's ability to question the behaviour of the industry as a whole. The way in which Nice is pilloried by patient groups, while the drug companies are ignored, suggests a reluctance to bite the hand that feeds them.
Nice is a rationing body, established in 1999 to ensure the cash-limited NHS gets best value for money from the profit-driven pharmaceutical industry. It aims to establish not only whether a drug is effective, but whether it is more effective than existing drugs and, if so, whether it is worth the extra price (£1,000 spent on a cancer drug means £1,000 less for nursing care for cancer patients).
The uneven nature of the debate is exposed each time Nice makes an unpopular decision. The smaller charities often make the biggest waves but the extent of their reliance on pharmaceutical company funding is bound to raise doubts about the independence of their judgement.
The Association of the British Pharmaceutical Industry, which speaks on behalf of drug companies, rejected the accusation that patient groups were being manipulated. Under its 2006 code, all funding of patient groups must be transparent and covered by a written agreement. A spokesman said: "If you ask the groups they will tell you they are only interested in representing the interest of their members."
Independent.co.uk
Analysis: Are patient protests being manipulated?
By Jeremy Laurance
Wednesday, 1 October 2008
It was the charge of barbarism that finally made Sir Michael Rawlins crack. The phlegmatic chairman of the National Institute for Clinical Excellence (Nice) is used to fielding brickbats over unpopular decisions to restrict access to cancer treatments and other drugs on the NHS.
But the jibe from the UK National Kidney Federation (NKF), which described Nice's decision to turn down four kidney cancer drugs as "barbaric, damaging and unacceptable," was too much. Sir Michael decided to strike back.
The resulting broadside, on the front page of The Observer, was headlined "Health chief attacks drug giants over huge profits: Watchdog slams high medicine prices". It was a stinging rebuke of the drug industry which Sir Michael accused of overpricing medicines to boost its profits. "We are told we are being mean but what nobody mentions is why the drugs are so expensive," he said.
It was an attempt to redress the balance of a debate too often cast as the people versus Nice. But Nice is merely a mechanism for sharing out a limited budget. The real argument should be between the people (who want the drugs), the pharmaceutical companies (who set the prices) and the Government (who fixes the NHS budget).
What escaped scrutiny was the role of the patient groups such as the NKF, who have lobbied vigorously against Nice decisions and the part played by the drug industry in their affairs.
The NKF, an umbrella organisation of kidney patients' associations, receives half of its £300,000 a year budget from the pharmaceutical and renal industries, according to its chief executive, Timothy Statham. In its press release issued on 19 August, it announced it was "incensed" by the draft Nice decision to turn down four drugs and would campaign to have it reversed. But it made no mention of the high cost of the drugs – £3,363 for a 30-capsule pack of sunitinib, one of the four – or criticism of the drug companies that make them. Professor Rawlins said the drugs could be made for a tenth of the cost.
Challenged about the omission, Mr Statham said it was an "important question" and he had requested meetings with the four companies. But he defended the NKF's reliance on industry funding.
"We receive sponsorship from as many of the renal industries as we can possibly sign up. We take the view that by having all the pharma and machine-maker companies on board, we cannot be subjected to overbearing influence by any one of them," he said.
That leaves unanswered the question of whether accepting funding from any company compromises a group's ability to question the behaviour of the industry as a whole. The way in which Nice is pilloried by patient groups, while the drug companies are ignored, suggests a reluctance to bite the hand that feeds them.
Nice is a rationing body, established in 1999 to ensure the cash-limited NHS gets best value for money from the profit-driven pharmaceutical industry. It aims to establish not only whether a drug is effective, but whether it is more effective than existing drugs and, if so, whether it is worth the extra price (£1,000 spent on a cancer drug means £1,000 less for nursing care for cancer patients).
The uneven nature of the debate is exposed each time Nice makes an unpopular decision. The smaller charities often make the biggest waves but the extent of their reliance on pharmaceutical company funding is bound to raise doubts about the independence of their judgement.
The Association of the British Pharmaceutical Industry, which speaks on behalf of drug companies, rejected the accusation that patient groups were being manipulated. Under its 2006 code, all funding of patient groups must be transparent and covered by a written agreement. A spokesman said: "If you ask the groups they will tell you they are only interested in representing the interest of their members."
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