February, 2001 — The Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) accepts Keller et al article "Efficacy of Paroxetine in the Treatment of Adolescent Major Depression, A Randomized Controlled Trial" for publication (see Aug, 1999 and July, 2001)

Despite the fact that Dr Keller has been made aware of the concerns of the 3 JAMA reviewers, and the JAACAP reviewers (see July 27, 2000), the safety concerns are not addressed (see transcript page 371–383) in the version accepted for publication, including those by the JAACAP reviewers.

March, 2001 —In an email to PR company Cohn and Wolfe, SKB writes: "Originally we planned to do extensive media relations surrounding this study [329] until we viewed the results. Essentially the study did not really show Paxil was effective in treating adolescent depression, which is not something we want to publicize."

April 25, 2001 — An e-mail from Sally Laden to GSK makes the following request: (see page 355) "Marty Keller is a corresponding author and will need a supply of reprints. I anticipate that he will need a sizable quantity because of the importance of this paper. Probably in the vicinity of 500 reprints. Dr. Keller is wondering if GSK will fund the purchase of these reprints."

Subsequent testimony confirmed that GSK paid for the reprints, they were delivered to Dr. Keller, and presumably used to send to practitioners inquiring about the use of paroxetine in treating their patients.

June 6, 2001 — Tobin vs SmithKline Beecham Pharmaceuticals Verdict. A U.S. District Court jury in Wyoming awards $6.4 million to the relatives of Don Schell, a Gillette man. With a prior history of a poor response to an SSRI, Don was put on Paxil. Forty-eight hours later he put three bullets from two different guns through the heads of his wife, Rita, his daughter, Deborah, and his granddaughter, Alyssa. Then he shot and killed himself. The jury rules that the global pharmaceutical company is 80 percent responsible for the deaths for failure to provide doctors with pertinent information and warnings. (From Let Them Eat Prozac, by David Healy, 2004)

June 11, 2001 — Dr David Healy concludes, based on reading records of trials carried out by the manufacturers which showed healthy volunteers were suffering withdrawal symptoms after taking the drug for just a couple of weeks, that thousands of people in the UK could be hooked on the anti-depressant drug Seroxat (paroxetine/Paxil), without knowing it.

Dr Healy had been given access to GSK's archives because he was an expert witness in the Tobin case. He says more than half of people on Seroxat/Paxil (paroxetine) may have "significant" withdrawal problems: (see page 14) "It was clear from early on that the company had recognised that people who had been on this drug even for relatively brief periods of time could go through withdrawal when they halted, and they ran healthy volunteer trials to look at this further and found that in some instances up to 85% of the volunteers who had been on this drug for only two or three weeks had withdrawal problems when they halted."

June 14, 2001 — Ian Hudson, who had just changed jobs from worldwide safety director for GSK to Director of Licensing at the U.K. Medicines Control Agency, repeats his position from the Tobin trial that an individual case cannot tell you one way or the other if a drug is responsible for a violent or suicidal act – only randomised controlled trials can do that. This is reported in several news outlets as is Dr Healy's response that: "randomised control trials are the wrong tool to establish whether serious side effects are occurring. The way to investigate what is happening is to carry out a challenge-rechallenge trial, where people are given the drug, taken off it and then put back on."

Dr. Healy notes that GSK has never done such trials.

Ian Hudson is now head of MHRA, which watches over the safety of the British public. "If he takes the position with the MHRA that he took at the trial, then none of us is safe with any drug in the UK at the moment," says Dr Healy. "How would Mr. Hudson even be able to blame alcohol for making someone drunk?"

During his Tobin deposition, when Dr Hudson is asked if, as Director of Safety for SmithKline Beecham, he believes Paxil causes akathisia in some patients, he responds: I"I've seen no evidence to suggest a cause and effect relationship between Paroxetine and akathisia. I've seen some case reports, but I've seen nothing that suggests a cause and effect relationship."

June 25, 2001 —GSK complies with a request from the British Regulator to issue a warning to doctors and to patients about Seroxat (paroxetine). GSK insists the timing of the warning has nothing to do with the Tobin decision.

The warning reads: "The possibility of suicide is inherent in depression and may persist until significant therapeutic effect is achieved, and it is general clinical experience with all antidepressant therapies that the risk of suicide may increase in the early stages of recovery." Dr Healy objects to this wording, noting that: "The person taking the drug is left thinking he or she has a problem, rather than that the pill caused them the problem."

July 2001STUDY 329 IS PUBLISHED

Article "Efficacy of Paroxetine in the Treatment of Adolescent Major Depression, A Randomized Controlled Trial" by Keller MB, et al, is published in The Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP). The study concludes that: "Paroxetine is generally well tolerated and effective for major depression in adolescents." The article is published without having addressed the concerns of the reviewers (see July 27, 2000). That is:

August 16, 2001 — In a memo to all GSK sales representatives selling Paxil, copied to Dr. Martin Keller, Sales management for the product make this statement about Study 329: "This cutting edge, landmark study is the first to compare efficacy of an SSRI and a TCA with placebo in the treatment of major depression in adolescents. Paxil demonstrates REMARKABLE efficacy and safety in the treatment of adolescent depression."

December, 2001 — In the U.K, the Drug Safety Committee of the MHRA, the CSM: "reviewed the suicidal behaviour, aggression and akathisia issue, December 2001, concluding the possibility of this affecting "a small high-risk population could not be ruled out ", and advised the risk of akathisia occurring be added to all SSRI Summaries of Product Characteristics (SPC). The UK assessment report was discussed at the PhVWP which agreed, but considered further discussion was required to clarify definition of the term akathisia."