Antidepressant Gets FDA OK for Hot Flashes

- Menopause is not a disease. Is a normal step in a woman life.
- Paroxetin is an antidepressive drug, with many adverse effects.
- Another bussines in the FDA.

The FDA has approved paroxetine (Brisdelle), a selective serotonin reuptake inhibitor (SSRI), to treat moderate to severe hot flashes associated with menopause.
"Today's approval provides women with the first FDA-approved, nonhormonal therapeutic option to help ease the hot flashes that are so common in menopause," said Hylton Joffe, MD, director of the division of bone, reproductive, and urologic products at the FDA's Center for Drug Evaluation and Research.
The safety and efficacy of the drug in this condition was established in two randomized, double-blind, controlled studies in 1,175 postmenopausal women with moderate to severe hot flashes.
Women in the study had a minimum of seven to eight hot flashes per day or 50 to 60 per week.
Treatment lasted 12 weeks in one study and 24 weeks in another, and both trials showed that paroxetine reduced hot flashes better than placebo.
The most common side effects with the drug included headache, fatigue, and nausea or vomiting,
The dosage approved for use in hot flashes (7.5 mg) is far lower than that used in conditions such as major depressive disorder, obsessive-compulsive disorder, panic disorder, and generalized anxiety disorder.
Still, the medication will contain a boxed warning about suicidality given that this side effect is included in the label for the drug when it is used in higher doses in the other conditions.
Additional warnings that will be included in the label will note a possible reduction in the efficacy of tamoxifen if both medications are used together, an increased risk of bleeding, and a risk of developing serotonin syndrome – symptoms of which include confusion, rapid heart rate, and high blood pressure.
The drug will be marketed by Noven Therapeutics of Miami.

Pharmalot: A Paroxetine study and retractation

 Pharma Blog » 2012 » February » 06

Brown University, A Paxil Study And Retractions

By Ed Silverman // February 6th, 2012 

For the past few years, an effort has been under way by a pair of academics to retract a study about the Paxil antidepressant in the Journal of the American Academy of Child and Adolescent Psychiatry that concluded the GlaxoSmithKline pill was “generally well tolerated and effective for major depression in adolescents.” Why? Since then, the 2001 paper has been discredited amid charges that primary and secondary outcomes were conflated, selective results were reported and ghostwriting was involved (see this).

The details became known more three years ago as documents emerged from investigations (look here) and lawsuits charging Glaxo hid various risks. By then, the FDA required Glaxo to place a Black Box warning about suicidality in youngsters and UK regulators recommended the drug not be given to those under 18 years of age. But by 2010, the paper had been cited in more than 200 other articles, many of which continued to point to the study as evidence that Paxil is effective in treating adolescent depression, according to BMJ.

The listed lead author of the paper, which was also known as study 329, was Martin Keller, a psychiatrist at Brown University (pictured to the right; background here). He was also among more than two dozen academics who were investigated by the Senate Finance Committee over alleged failures to properly disclose of federal grants to research drugs at the same time these professors had accepted payments from drugmakers (look here). Consequently, a pair of academics asked the JACAAP to issue a retraction, but were rebuffed. The editor told BMJ the paper does not contain any inaccuracies and negative findings are included in a results table and, as a result, there are no grounds for withdrawal (read here).

And so last October, the same two academics - Jon Jureidini, associate professor of psychiatry at the University of Adelaide, and Leemon McHenry, a lecturer in philosophy at California State University - were joined by two dozen others and wrote to Brown University officials to request that they seek a retraction (read the letter), but they were again rebuffed.

Last month, they received a letter from Ed Wing, who is the dean of the medical school, to say the university would not write the JACAAP to seek a retraction (here is the Wing letter). No explanation was given and he did not respond to a request for comment or The Brown Daily Herald, which first reported the official rejection (see here).

The controversy raised questions about if and when a journal article should be retracted. As BMJ noted in its coverage last year, the Committee on Publication Ethics expanded its own view and recommended retraction if journals “have clear evidence that the findings are unreliable.” The point is to “correct the literature and ensure its integrity” rather than to punish authors (here are the guidlines). And the International Committee of Medical Journal Editors urge retraction in the event of scientific fraud or if an error is “so serious as to vitiate the entire body of work (read here).

The Paxil study also underscored the ongoing dispute over ghostwriting, which has embroiled several drugmakers in scandal. The issue has become so contentious that, several months ago, a pair of University of Toronto academics suggested two legal remedies - pursuing class action lawsuits based on the Racketeer Influenced and Corrupt Organizations Act, or RICO, and filing claims of ‘fraud on the court’ against a drugmaker that uses ghostwritten articles in litigation (read here). And two other academics recently published a paper in which they suggested that all authors should be required to sign a statement guaranteeing that no ghostwriters participated in writing a submitted paper and that all medical writers should be listed as authors on the byline (see this).

However, the failure of universities to investigate instances where their professors may have engaged in ghostwriting has also generated criticism. Last year, Dalhouse University declined to examine allegations of ghostwriting and the involvement of psychiatry professor Stan Kutcher, who was listed as a co-author on Paxil study 329 (read here). “I find it very disturbing that a university that is suppose to be standing up for the highest academic values is unwilling to take any action when its faculty members violate those values,” Joel Lexchin, a professor of health policy at York University in Toronto and one of the academics who signed the letter to Brown University concerning a retraction, writes us.

The Department of Health & Human Services, by the way, was also reluctant to pursue the matter. In a letter last November to Jureidini, John Dahlberg, the director of the Division of Investigation Oversight in the Office of Research Integrity at the HHS, noted that Paxil effectiveness was “apparently exaggerated.” But he went on to say that his office was unable to pursue an investigation due to the statute of limitations.

Due to the statute, “…allegations of falsification, fabrication or plagiarism must be made within six years of the alleged misconduct… Further, given the significant lapse of time between the time the study was conducted and concerns raised, the likelihood of being able to conduct a fair and objective review, given the inevitable difficulties in locating records and relying on memories of events well over 10 years ago, seems remote” (here is the letter). Say Jureidini: “We are a bit stuck about where to take it from here.”

Related articles

• New BMJ Study Reveals Paxil During Pregnancy Increases Risk of Birth Defects: AttorneyOne.com Warns the Threat from Paxil Side Effects Remains (prweb.com)
• Brown University student uncovers lost Malcolm X speech (nj.com)
• Retract PAXIL 329 study and look at the author list, don't forget it (bipolarsoupkitchen-stephany.blogspot.com)