Not Enough Research on SSRIs and Pregnancy
October 15, 2008. By Heidi Turner
“I delivered Caroline at full term. She had no seizures during the pregnancy. She was born via C-section and immediately after birth started having seizures. The doctor took her out and took her right to NICU (neonatal intensive care unit). I couldn’t even hold Caroline right away; they just took her away. She was put on 4 seizure medications and on the ventilator.
“At 3 days old, Caroline basically died. They had tried to take her off the ventilator and she died. The doctors did 2 minutes of chest compressions and intubated her. She was hypotonic from the medicine. Luckily, they brought her back. The following week they tried to take her off the ventilator again and she coded again.”
Caroline was born November 29, 2006 and was not able to breathe on her own until December 20, 2006. She did not leave the hospital until March 5, 2007.
“Caroline was so stiff at birth that she needed special casts on her legs and splints on her hands. The doctor said he thought it was the Effexor that caused this.
“On January 11, 2007, we put Caroline into surgery because she was being fed through her nose at the time. The surgery was to put in a g-tube and nissan wrap (to prevent reflux) around her esophagus. That day was the first time her father and I saw her without tape all over her face and wires everywhere.
“In March she was released from the hospital. Caroline got really sick right before April and she was hospitalized again for 14 days withrespiratory failure. She had 50 percent oxygen and almost died again. This past March, (2008), she had to go into the hospital again for respiratory problems.
“She had tubes in her ears because she has too many ear infections [related to her inability to properly swallow]. She is doing sign language and can say ‘Mom.’ She has a walker through Medicaid. She wears a patch over one eye 4 hours a day and cannot take anything by mouth. She still hasn’t learned to suck or swallow and has developmental delays.
“I’ve taken her to a metabolic doctor and the tests came back negative. All of her genetic testing also came back negative. The only thing that was different between this pregnancy [and an earlier pregnancy] was the 300 mgs of Effexor. Her EEG and MRIs of her brain have been fine, although she seems weaker on one side of the brain.
“It’s been quite a struggle. I have a 4 year old and during that pregnancy I took Wellbutrin and a low dose of Effexor. There didn’t seem to be anything wrong, except that she was really irritable after she was born. She cried a lot and was colicky. I didn’t think about it at the time, but now I wonder if she suffered withdrawal from Effexor.
“I would tell other women to try not to take antidepressants when they are pregnant. There is not enough research on it. If they really need to, they should take the lowest dose possible. I did not know about this—I was not told about everything that was going on with Effexor.”
OCTOBER 8, 2008
Suit Alleges Pfizer Spun Unfavorable Drug Studies
By KEITH J. WINSTEIN
Pfizer Inc. marketers urged the suppression of medical studies that reached unfavorable conclusions about the effectiveness of the company’s big-selling drug Neurontin, according to internal Pfizer documents submitted in a lawsuit against the company.
In 2004, Pfizer’s Warner-Lambert unit pleaded guilty to felony charges that it promoted Neurontin for uses not approved by the Food and Drug Administration, including bipolar disorder and chronic nerve pain. The FDA originally approved the drug as an antiseizure treatment for epilepsy and in 2002 for one kind of pain related to shingles.
Pfizer paid $430 million to resolve the charges and reimburse state Medicaid programs for unapproved, or off-label, uses of Neurontin. Pfizer said it made sure there was no improper marketing after it purchased Warner-Lambert in 2000. Pfizer has booked about $12 billion in Neurontin sales since then and, though the drug is now subject to generic competition, it remains a strong seller.
Documents and emails released this week in the case in U.S. District Court in Boston suggest Pfizer’s marketers influenced the drug’s scientific record to boost sales at least until 2003 by declining to release or altering the conclusions of studies that found no beneficial effect from Neurontin for various off-label conditions. The case consolidates lawsuits by health insurers and consumers seeking refunds for their Neurontin expenditures, based on alleged civil fraud. Plaintiffs are seeking $4.9 billion.
In a statement, Pfizer said it was “committed to the communication of medically or scientifically significant results of all studies, regardless of outcome.” The company pointed to examples where it published studies of Neurontin with negative outcomes.
According to documents in the Boston case, a European study done in the late 1990s by Warner-Lambert to measure Neurontin’s use for diabetic nerve painproduced consternation at Pfizer after it failed to find a significant effect. “I think we can limit the potential downsides of the … study by delaying the publication for as long as possible,” wrote Michael Rowbothan, then Neurontin’s marketing team leader, in a 2000 email sent after Pfizer bought Warner-Lambert. He added that “it will be more important to how WE write up the study.”
The study’s scientific manager, Beate Roder, wrote in an email to employees after Pfizer agreed to buy Warner-Lambert that she had been instructed “that we should take care not to publish anything that damages Neurontin’s marketing success.” Neurontin has been widely prescribed for diabetic nerve pain, according to market researchers.
In 2002, Angela Crespo, then Neurontin’s senior marketing manager, emailed an outside firm that was contracted to write up the study’s results: “We are not interested at all in having this paper published because it is negative!!” Pfizer declined to make the three employees in the emails available for interviews.
The company’s writeup of the study was subsequently rejected by two medical journals. Some of the reviewers for these journals said the company was putting too rosy a spin on the results, the court documents show. The paper was never published, although Pfizer later summarized some of the study’s results in a broad review published in 2003 in an obscure medical journal, Clinical Therapeutics.
That review excluded another study that Pfizer conducted in Scandinavia, which examined Neurontin’s effectiveness for post-operative nerve pain. The study found that Neurontin didn’t work measurably better than a sugar pill, according to a Pfizer internal report. The study’s finding has never been published, though the analysis was completed in 2003. Pfizer presented a summary of the study at a 2002 conference.
By declining to publish negative studies, “Pfizer created the illusion of Neurontin’s efficacy in the scientific record” that encouraged doctors to use the drug even where it doesn’t work, said Tom Greene, a Boston attorney heading the litigation. U.S. District Judge Patti Saris in Boston last year denied Mr. Greene’s motion for class-action status; the plaintiffs are seeking a second try in her court this week.
“Ethically, one is compelled to publish results,” said Kay Dickersin, a professor of epidemiology at Johns Hopkins University in Baltimore, who wrote a report for plaintiffs that was submitted in the case. Ms. Dickersin said her fee will be paid toJohns Hopkins to set up a fund to distribute Pfizer’s documents.
Ms Dickersin said that in exchange for being experimented upon in trials, patients are told they are contributing to human knowledge. To withhold negative results from the public breaks that ethical obligation to such patients, she argued. Pfizer says it has committed to publish all medically significant results.
In 2004, Pfizer completed a five-year study of Neurontin on patients suffering from bipolar disorder in Spain. A 2004 internal Pfizer report summarized the finding: The study “did not show statistically differences between Gabapentin and Placebo.” (Gabapentin is the generic name for Neurontin’s chemical formula.)
But in 2006, a Spanish psychiatrist, Eduard Vieta, who has been a paid consultant to Pfizer, published a report on the same study in the Journal of Clinical Psychiatryalong with a Pfizer employee, Katia Verger, and other scientists. Their report claimed a statistically significant benefit. One difference: Dr. Vieta modified the scale used to assess how severely patients exhibited the symptoms of bipolar disorder, also known as manic-depressive disorder. That change increased Neurontin’s score in the study. The change wasn’t disclosed in the journal. Making such a change after a study’s parameters were set, especially without disclosing the change, is generally considered improper by scientists.
Dr. Vieta’s article also said it included results from all patients the doctors in the study intended to treat, a principle known as “intention to treat.” But in reality, Dr. Vieta’s article excluded 16 patients who hadn’t complied with the study protocol, such as by not taking all the pills they were given.
The two modifications had the effect of turning a failure into a success.
In an interview, Dr. Vieta, of the University of Barcelona, said the modifications to the formula were requested by the journal and were a more-conservative technique. “Nobody in Pfizer wrote the manuscript,” he said. He said the company’s 2004 report of the study “takes a broader interpretation of the intention-to-treat concept” but that it was appropriate to exclude some patients from the analysis.
Pfizer said that “an implication that Pfizer improperly influenced any aspect of the published Vieta study for commercial reasons is without basis,” adding that the drug lost its patent protection and top-selling status in 2004.
Write to Keith J. Winstein at firstname.lastname@example.org
Epilepsy and Psychiatric Drugs like Neurontin Double Risk of Suicidal Behavior
Monday, October 06, 2008 by: David Gutierrez
Key concepts: Epilepsy, The FDA and Suicide
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(NaturalNews) The FDA issued a warning on earlier this year that anti-epileptic drugs double the risk of suicidal thoughts among people that take them, regardless of whether they are used as a treatment=2 0for epilepsy or other conditions.
Anti-epileptics, also known as anticonvulsants, are taken by millions of people as treatment for epileptic seizures, bipolar disorder, and severe pain like that from migraine headaches.
“All patients who are currently taking or starting on any anti-epileptic drug should be closely monitored for notable changes in behavior that could indicate the emergence or worsening ofsuicidal thoughts or behavior or depression,” the FDA said. The agency also advised that doctorsconsider whether the benefits of prescribing the drugs outweigh the risks for each individual patient.
The FDA warning currently applies only to the 11 anti-epileptic drugs included in the agency’s comprehensive review of 199 clinical trials: carbamazepine, marketed as Carbatrol; Equetro, Tegretol and Tegretol XR; felbamate, marketed as Felbatol; gabapentin, marketed as Neurontin; lamotrigine, marketed as Lamictal; levetiracetam, marketed as Keppra; oxcarbazepine, marketed as Trileptal; pregabalin, marketed as Lyrica; tiagabine, marketed as Gabitril; topiramate, marketed as Topamax; valproate, marketed as Depakote, Depakote ER, Depakene and Depacon; and zonisamide, marketed as Zonegran.
But the agency said that all anticonvulsants probably carry the same risks, and that the new warnings may be applied to the entire class of=2 0drugs.
The FDA has convened an advisory panel to decide on what next steps to take. For now, the labels of the 11 drugs studied must be updated to warn of the increased risk of suicidal thoughts and behaviors. In addition to prescribing the drugs more carefully, the FDA said, doctors should make sure that patients and their families know to be alert for the warning signs of suicide and to contact a doctor immediately if those signs occur.
Warning signs include increased depression, withdrawal from loved ones, giving away prized possessions, a preoccupation with death, talking or thinking about self-injury, and overt suicidal thoughts. These symptoms can emerge within one week of beginning an anticonvulsant and can last for months.
The FDA reviewed nearly 200 clinical studies on 11 anticonvulsant drugs, including a total of 43,892 participants – 27,863 of whom received drugs and 16,029 who received a placebo. While the absolute risk of suicide for those taking anticonvulsants was low, at 0.43 percent, this was nearly twice the risk experienced by those on a placebo (0.22 percent). This means that for every 1,000 people taking anticonvulsants, 2.1 would experience suicidal thoughts or behaviors who would not otherwise have done so.
Four suicides occurred among participants taking anticonvulsants during the studies, while none occurred among those taking placebos.
The FDA noted that while all patients taking anticonvulsants experienced a heightened risk of suicidal thoughts, the risk was greater among those being treated for epilepsy than those being treated for other conditions.
The review of the epilepsy drugs was launched in 2005, partially in response to criticism of the FDA’s handling of the painkiller Vioxx, which was withdrawn from the market in 2004 after studies found that it increased the risk of heart attacks and strokes. In addition, New York attorney Andrew Finkelstein petitioned the FDA in 2004 to warn doctors about the suicidal risks of Pfizer’s anticonvulsant Neurontin (also sold generically as gabapentin).
“All I asked them to do is tell everybody that they’re investigating this and in the meantime to take caution,” Finkelstein said in response to the recent warning. “How many lives could have been saved had they done what I asked them to do four years ago?”
Finkelstein said that he became aware of the risk in 2003 when a client reported that he began considering suicide within weeks of beginning treatment with Neurontin, and then tried to take his life a few months later. The lawyer took out a commercial on national cable television asking if anyone had experienced similar effects, and received more than 20,000 responses. Finkel stein and colleagues launched an investigation, uncovering more than 300 suicides and 500 other suicide attempts among those taking the drug.
A total of nearly 1,000 lawsuits have since been filed against Pfizer, almost 300 of them by Finkelstein’s firm, alleging that the company unnecessarily exposed patients to increased suicide risk from its marketing of Neurontin. Among the accusations are that Pfizer illegally marketed Neurontin for then-unapproved uses, such as treatment for bipolar disease or migraines.
In 2004, a division of the company pleaded guilty to two felonies relating to its off-label marketing of the drug.
The current FDA warning is expected to worsen Pfizer’s position in the lawsuits, which could end up costing it hundreds of millions of dollars in liability fees, Finkelstein said. In addition, sales of all the drugs may very well drop.
An estimated 2.7 million people suffer from epilepsy in the United States alone, and many of those take anticonvulsant drugs. In response to the FDA warning, Peter Bergin, president of the New Zealand League Against Epilepsy, warned these patients that stopping the drugs abruptly also carries risks.
“If a patient taking an anti-epileptic drug does feel suicidal or depressed, then they should speak with their doctor,” Bergin said. “We need to stress that patients should not stop their anti-epileptic drugs of their own accord, since there is a risk that a person will develop a series of seizures in rapid succession if they do so, and this can sometimes result in serious injury or even death.”