Study 329

Study 329
Paroxetine, sold as Paxil and Seroxat
Study type	Eight-week, double-blind, randomized clinical trial
Dates	1994 to 1997
Location	10 centres in the United States and two in Canada
Lead researcher	Martin Keller, now professor emeritus of psychiatry and human behavior, Brown University
Funding	SmithKline Beecham, now GlaxoSmithKline
Publication date	July 2001
Article	"Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial"
Journal	Journal of the American Academy of Child and Adolescent Psychiatry

Study 329 was a clinical trial conducted in North America from 1994 to 1997 to study the effect on teenagers of paroxetine, an SSRI anti-depressant. It was funded by the British pharmaceutical company SmithKline Beecham (SKB), known since its merger with GlaxoWellcome in 2000 as GlaxoSmithKline (GSK). SKB released paroxetine in 1992; marketed as Paxil and Seroxat, it attracted sales of $11.6 billion from 1997 to 2006. Study 329 became controversial because the article that reported the trial results, apparently authored by the researchers but actually ghostwritten for the drug company, significantly downplayed the negative findings. The study is cited as a failure of pharmacovigilance, one in which "the sponsor company remained in control of the message."

Led by Martin Keller, then professor of psychiatry at Brown University, the trial was the largest at the time to examine the pediatric efficacy of SSRIs. SKB acknowledged internally in 1998 that study 329 had shown no statistically significant difference on the primary outcomes between paroxetine and placebo. In addition, more subjects in the paroxetine group had experienced suicidal ideation. GSK said that the significance of the latter was not noticed until later, when a meta-analysis, a study of several trials, was performed.

Study 329 was published in July 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), in the name of Keller and 21 other researchers. The article included the negative results, but did not highlight them or account for them in its conclusion, which stated: "Paroxetine is generally well tolerated and effective for major depression in adolescents." The company relied on the article to promote paroxetine for off-label use in teenagers. A month after publication, a GSK manager told its sales force that study 329 had shown paroxetine "demonstrates REMARKABLE Efficacy and Safety in the treatment of adolescent depression."

In May 2003 GSK passed study 329 and eight other trials on paroxetine and teenagers to Britain's Medicines and Healthcare Products Regulatory Agency (MHRA). The MHRA concluded that the data showed no good evidence of efficacy and a clear increase in suicidal behaviour. The following month the MHRA and US Food and Drug Administration (FDA) advised physicians not to prescribe paroxetine to the under-18s. The MRHA launched a criminal inquiry into GSK's conduct, but announced in 2008 that there would be no charges. In 2004 New York State Attorney Eliot Spitzer sued GSK for having withheld the data, and in 2012, in a separate case in the United States, the company was fined $3 billion, including a sum for withholding data on paroxetine, preparing a misleading article about study 329, and unlawfully promoting the drug for the under-18s. The JAACAP article about study 239 was never retracted. The journal's editors say the negative findings are included in a table, and that therefore there are no grounds to withdraw it.

Clinical trial

photograph

Study 329 compared Paxil/Seroxat (paroxetine, above) a selective serotonin reuptake inhibitor, with Tofranil (imipramine), a tricyclic antidepressant.

Funded by SmithKline Beecham, study 329 was an eight-week, double-blind, randomized clinical trial conducted in 12 centres in the United States and Canada between 1994 and 1997. The study compared paroxetine, a selective serotonin reuptake inhibitor marketed as Paxil and Seroxat, with imipramine, a tricyclic antidepressant marketed as Tofranil, in teenagers with a diagnosis of major depressive disorder at least eight weeks in duration. Martin Keller, then professor of psychiatry at Brown University, had proposed the trial to the company in 1992 as the largest study until then to examine the pediatric efficacy of SSRIs. The trial's protocol named two primary and six secondary outcomes by which it would measure efficacy.

After a screening phase from April 1994 until March 1997, 275 male and female patients aged 12–18 were randomly assigned paroxetine, imipramine or placebo (an inert pill). Of the 275, 93 were given paroxetine, 95 imipramine and 89 placebo; the paroxetine group were given 20 mg of paroxetine daily for four weeks, rising to 30 mg at week five and 40 mg at week six if the clinician thought it appropriate. One hundred and ninety completed the trial. The trial ended in May 1997 and the blind was broken in October.

The results showed that, according to the eight outcomes Keller had first specified, paroxetine was no more effective than placebo. According to Melanie Newman, writing for the BMJ, "[t]he drug only produced a positive result when four new secondary outcome measures, which were introduced following the initial data analysis, were used instead. Fifteen other new secondary outcome measures failed to throw up positive results."

In addition, 11 subjects on paroxetine, compared to five on imipramine and two on placebo, experienced serious adverse events (SAE), including behavioral problems and emotional lability. The researchers defined an event as an SAE if it resulted in hospitalization, involved suicidal gestures, or was regarded as serious by the subject's doctor. In the 93 taking paroxetine, the SAEs consisted of one subject experiencing headache while tapering off, and 10 experiencing psychiatric problems. Seven of the ten were hospitalized. Two of the ten experienced worsening depression, two conduct problems such as aggression, one euphoria, and five emotional lability, including suicidal ideation and behaviour. Of the 95 patients on imipramine and the 89 on placebo, one in each group experienced emotional lability. The article in JAACAP later concluded that, of the 11 patients who experienced SAEs, "only headache (1 patient) was considered by the treating investigator to be related to paroxetine treatment."

1998 SmithKline Beecham position paper

In October 1998 the neurosciences division of SmithKline Beecham's Central Medical Affairs (CMAT) department distributed a position paper, "Seroxat/Paxil Adolescent Depression: Position piece on the phase III clinical studies." The paper discussed study 329 and study 377, a 12-week trial on paroxetine and teenagers conducted in the 1990s in Europe, South America, South Africa and the Middle East. The document was leaked during a lawsuit in California, and first published by the Canadian Medical Association Journal in March 2004.

According to the paper, the company had decided not to submit 329 and 377 trial data to regulators. It discussed how to "effectively manage the dissemination of these data in order to minimise any potential negative commercial impact." An attached memo said the results were disappointing and would not support a label claim that paroxetine could be used to treat adolescents: "The best that could have been achieved was a statement that, although safety data was reassuring, efficacy had not been demonstrated. Consultation of the Marketing Teams via Regulatory confirmed that this would be unacceptable commercially ..."

The paper said that study 329 had shown "trends in efficacy in favour of Seroxat/Paxil across all indices of depression ... [but had] failed to demonstrate a statistically significant difference from placebo on the primary efficacy measures." Study 377 had shown a high placebo response rate and had "failed [to] demonstrate any separation of Seroxat/Paxil from placebo." The company decided to publish study 329 but not 377, and not to submit either trial to the regulators, because they were "insufficiently robust to support a label change" for adolescent use:

(i) regulatory agencies would not approve a statement indicating that there are no safety issues in adolescents, as this could be seen as promoting off-label use

(ii) it would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine.

In response to the leaked document, a GSK spokesperson said that "the memo draws an inappropriate conclusion and is not consistent with the facts ... GSK abided by all regulatory requirements for submitting safety data. We also communicated safety and efficacy data to physicians through posters, abstracts, and other publications."

JAACAP article

Authorship

Although the article in JAACAP named 22 physicians or other researchers, led by Martin Keller, it had been written by Scientific Therapeutics Information (STI), a PR company in Springfield, New Jersey, specializing in communications for the pharmaceutical industry. STI had worked with SmithKline Beecham on its promotion of paroxetine for years. In 1993, for example, it sent a proposal to GSK for a meeting in the Ritz Carlton Hotel in Palm Beach, Florida, between its psychiatrist advisory board and Paxil advisory board.

In April 1998 Sally K. Laden and John A. Romankiewicz of STI sent SmithKline Beecham an estimate of $17,250 to work on six drafts of the paper, including the final draft for submission, to cover the period up to March 1999. The sum was payable in three installments: $8,500 upon initiation, $5,125 after draft three, and $3,625 upon submission to the journal. The first draft was ready by December 1998.

STI planned to submit the article to the Journal of the American Medical Association (JAMA). The estimate covered all writing, editing, library research, copy editing, art work and coordination with the phsyicians who would be named as authors. Martin Keller would be listed as the main author. Internal SmithKline Beecham documents show that Laden and STI coordinated the entire publication process, including writing the cover letter to the journal that published the article, JAACAP, which she sent to Keller with the instruction that he transfer it to his own letterhead.

Publication

GlaxoSmithKline global headquarters, Brentford, west London

The article was submitted first to JAMA, which rejected it in November 1999. Concerns cited by JAMA reviewers included that "the main finding of the study is the high placebo response rate," and that the named authors should state that they had been "granted full access to the data set to verify the accuracy of the report." Early drafts of the paper for JAMA did not mention the serious adverse events (SAEs). A SmithKline Beecham scientist, James McCafferty, added a paragraph about these in July 1999, which said that 11 patients on paroxetine had experienced SAEs, against two on placebo: "worsening depression, emotional lability, headache, and hostility were considered related or possibly related to treatment."

In December 1999 Laden rewrote and submitted the paper to JAACAP, led at the time by editor-in-chief Mina K. Dulcan. According to Newman in the BMJ, JAACAP's reviewers wrote that the results did not "clearly demonstrate efficacy for paroxetine," and asked whether, because of the high placebo response rate, SSRIs should be regarded as first-line therapy. JAACAP accepted the article in January 2001, and published it in July. Twenty-two researchers were listed, led by Martin Keller, including James P. McCafferty of GSK, though his company connection was not included. Of STI and Sally Laden, the published article said only: "Editorial assistance was provided by Sally K. Laden, M.S."

The article concluded: "Paroxetine is generally well tolerated and effective for major depression in adolescents." McCafferty's paragraph about worsening depression and emotional lability possibly being related to the treatment had been removed. The only SAE attributed to paroxetine in the JAACAP article was headache: "Of the 11 patients, only headache (1 patient) was considered by the treating investigator to be related to paroxetine treatment." The article continued: "Because these serious adverse events were judged by the investigator to be related to treatment in only 4 patients (paroxetine, 1; imipramine, 2; placebo, 1), causality cannot be determined conclusively." It concluded: "The findings of this study provide evidence of the efficacy and safety of the SSRI, paroxetine, in the treatment of adolescent depression."

2001 GlaxoSmithKline sales memo

GSK used the JAACAP article to promote paroxetine to doctors for use in their teenage patients. The drug had not been approved for adolescents, but doctors are allowed to prescribe drugs for what is known as off-label use. In the UK paroxetine was prescribed for the under-18s 32,000 times in 1999, and in the US 2.1 million times in 2002, the latter earning the company $55 million that year. On 16 August Hawkins sent a memo about study 329 to "all sales representatives selling Paxil":

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.

The memo said that paroxetine was "significantly more effective than placebo" on certain outcomes. Hawkins added: "Paxil was generally well tolerated in this adolescent population and most adverse events were not serious. The most common adverse events occurred at rates that were similar to rates in the placebo group."

Investigations, legal action

Overview

Paroxetine attracted sales of $11.6 billion from 1997 to 2006, including $2.12 billion in 2002, the year before it lost its patent. By 2009 GSK had paid almost $1 billion to settle paroxetine-related lawsuits related to 450 suicides, addiction, and antitrust and other claims. An additional 600 unsettled claims related to birth defects. The lawsuits produced thousands of internal company documents, some of which entered the public domain. These formed the basis of a series of investigative pieces about paroxetine by Alison Bass for The Boston Globe, developed into a book, Side Effects (2008), and by Shelley Jofre for BBC Panorama, including one in 2007 about study 329. In 2012 GSK paid a $3 billion settlement, including a criminal fine of $1 billion, after pleading guilty to several charges brought by the US Department of Justice, including withholding safety data about paroxetine and preparing the misleading article about study 329.

MHRA criminal inquiry

The first investigation was triggered in May 2003, when GSK sent a briefing paper to Britain's Medicines and Healthcare Products Regulatory Agency (MHRA) about an application to have paroxetine approved for children. GSK disclosed the data from nine clinical trials, including study 329 and study 377. The latter was an unpublished 12-week trial on paroxetine and teenagers conducted in the 1990s in Europe, South America, South Africa and the Middle East.

The MHRA's Committee on the Safety of Medicines analysed the data, which involved 1,697 child and adolescent subjects, and concluded in an assessment dated 4 June 2003 that "there is no good evidence of efficacy in major depressive disorder in the population studied" and "a clear increase in suicidal behaviour versus placebo." Their analysis suggested an increased rate of suicidal thinking and behaviour of 3.4 percent on paroxetine versus 1.2 percent on placebo. The MHRA issued an advisory to physicians on 10 June not to prescribe paroxetine to the under-18s. The US Food and Drug Administration (FDA) followed suit nine days later.

The MRHA launched a criminal inquiry into GSK's conduct, but announced in 2008 that there would be no charges. Medical ethicists Linsey Goey and Emily Jackson write that the 1998 SmithKline Beecham position paper, in which the company said it had decided not to show studies 329 and 377 to regulators, represented a prima facie breach of the Medicines Act 1968 and Regulations, which required pharmaceutical companies to pass to the regulator trial data with safety and efficacy implications. After a four-year investigation, government lawyers advised that the law was not clear enough to prosecute the company, in part because studies 329 and 377 had not been conducted in the UK. In March 2008 the Medicines for Human Use (Marketing Authorisations Etc.) Regulations 1994 were amended to prevent a repetition of the GSK case.

FDA-mandated review

In March 2004 the FDA mandated that drug companies review the use of their SSRIs in children. In 2006 GSK researchers published a review of five of their trials involving paroxetine and adolescents or children, including study 329 and the unpublished 377. They wrote that suicidal thinking or behaviour had occurred in 22 of 642 patients on paroxetine (3.4 percent) against 5 of 549 on placebo (0.9 percent). The article concluded that: "Adolescents treated with paroxetine showed an increased risk of suicide-related events. ... The presence of uncontrolled suicide risk factors, the relatively low incidence of these events, and their predominance in adolescents with MDD make it difficult to identify a single cause for suicidality in these pediatric patients.

People v. GlaxoSmithKline

Eliot Spitzer filed a lawsuit against GSK in 2004.

On 2 June 2004 New York State Attorney Eliot Spitzer filed a lawsuit against GSK in the New York State Supreme Court for having withheld clinical trial data about paroxetine, including from study 329. Spitzer alleged that GSK had "deprived physicians of the information needed to evaluate the risks and benefits of prescribing paroxetine for children and adolescents with MDD [major depressive disorder]." GSK denied any wrongdoing, and said it had disclosed the data to regulators, at medical conventions and in other ways to physicians.

GSK settled the case in August 2004, agreeing to pay $2.5 million, make its trial data about paroxetine and children available on its website, and establish a clinical trial register that would host summaries of all company-sponsored trials going back to 27 December 2000. By October 2004 several other drug companies, including Pfizer, Eli Lilly and Merck, had agreed to create their own registers. In 2013 GSK joined AllTrials, a British campaign to have all clinical trials registered and the results reported.

United States v. GlaxoSmithKline

Further information: GlaxoSmithKline § 2012 criminal and civil settlement

In October 2011 the US Department of Justice filed a lawsuit under the False Claims Act accusing GSK of promoting drugs for unapproved uses, failing to report safety data, reporting false prices to Medicaid, and paying kickbacks to physicians in the form of gifts, trips and sham consultancy fees. The complaint included preparing the JAACAP article about study 329, exaggerating paroxetine's efficacy while downplaying the risks, and using the article to promote the drug for adolescent use, which was not approved by the FDA.

GSK pleaded guilty in 2012 and paid a $3 billion settlement, including a criminal fine of $1 billion. The fine included an amount for "preparing, publishing and distributing a misleading medical journal article that misreported that a clinical trial of Paxil [paroxetine] demonstrated efficacy in the treatment of depression in patients under age 18, when the study failed to demonstrate efficacy."

Call for retraction

Child psychiatrist Jon Jureidini called for the JAACAP article about study 329 to be retracted.

Child psychiatrist Jon Jureidini of the Women's and Children's Hospital in Adelaide, and Ann Tonkin of the University of Adelaide, asked JAACAP in 2003 to retract the study 329 paper. In 2005 philosopher Leemon McHenry complained to the journal that Keller and some of the other 20 researchers named as authors had worked for GSK, but had not declare their conflict of interest. Keller had acted as a consultant for several drug companies; The Boston Globe reported in 1999 that he had earned $500,000 the previous year from consultancy work, which, the newspaper said, he did not disclose to the journals that published his work or to the American Psychiatric Association.

Jureidini and McHenry called again for the paper's retraction in 2009, arguing that its conflation of primary and secondary outcomes and failure to highlight negative data suggested an intention to deceive on the part of GSK. Editor-in-chief Andrés Martin responded that there was no justification for retraction, and that publication of the paper had "conformed to the best publication practices prevailing at the time."

In 2010 GSK told Melanie Newman for the BMJ that "GSK remains firm in the belief that we acted properly and responsibly in the conduct of our clinical trials programmes, documentation and submission of resuts from studies of paroxetine to regulators, and in communicating important safety information."

Anti-depressants and suicidality

Further information: Antidepressants and suicide risk

In 2007 the FDA proposed that all anti-depressants include a boxed warning of an increased risk of suicidal thoughts and behaviour in young adults (18–24) during the first one to two months of treatment. A 2012 Cochrane Collaboration report on the use of SSRIs in children and adolescents suggested that fluoxetine (Prozac) might be the medication of first choice, although caution is advised because of an "increased risk of suicide-related outcomes in those treated with antidepressant medications."

See also

• AllTrials
• ClinicalTrials.gov
• Drug Industry Document Archive
• IFPMA Clinical Trials Portal

References

Primary sources

• Hawkins, Zachary. "To all sales representatives selling Paxil", Paxil Product Management, GlaxoSmithKline, 18 August 2001, courtesy of the Drug Industry Document Archive, University of California, San Francisco.
• Keller, Martin, et al. "Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial", Journal of the American Academy of Child and Adolescent Psychiatry, 40(7), July 2001, pp. 762–772. doi:10.1097/00004583-200107000-00010 PMID 11437014
• Laden, Sally. Sally Laden to Jim McCafferty, 7 December 1998.
• Laden, Sally. Sally Laden to Jim McCafferty, 18 December 1998.
• Laden, Sally. Sally Laden to the Paxil Marketing Team, 25 April 2001.
• Laden, Sally. Sally Laden to Jim McCafferty, 7 August 2001.
• McCafferty, James. James McCafferty to Sally Laden, 21 July 1999.
• Romankiewicz, John A. "Paxil Advisory Board Meeting, Scientific Therapeutics Information, 1 October 1993.
• SmithKline Beecham, "Seroxat/Paxil Adolescent Depression: Position piece on the phase III clinical studies", October 1998.
• The People of the State of New York against GlaxoSmithKline, Supreme Court of the State of New York, 2 June 2004.
• Deposition of Sally K. Laden, in Cheryl J. Cunningham v. SmithKline Beecham and William P. Williams v. SmithKline Beecham, United States District Court, Northern District of California, 15 March 2007.
• United States v. GlaxoSmithKline, United States District Court for the District of Massachusetts, 26 October 2011.

Secondary sources

• Bass, Alison. Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial, Algonquin Books, 2008.
• Apter, Alan, et al. "Evaluation of Suicidal Thoughts and Behaviors in Children and Adolescents Taking Paroxetine," 16(1–2), 22 March 2006, pp. 77–90. doi:10.1089/cap.2006.16.77 PMID 16553530
• Federal Drug Administration. "FDA statement regarding the anti-depressant Paxil for pediatric population", 19 June 2003.
• Goldacre, Ben. Bad Pharma, Fourth Estate, 2013 [2012].
• Heck, Isabel. "Controversial Paxil paper still under fire 13 years later", The Brown Daily Herald, 2 April 2014.
• Jackson, Emily. Law and the Regulation of Medicines, Bloomsbury Publishing, 2012.
• Jureidini, Jon N.; Tonkin, Ann. "Paroxetine in major depression" (letter), Journal of the American Academy of Child and Adolescent Psychiatry, 42(5), May 2003, p. 514.
• Jureidini, Jon N.; McHenry, Leemon B.; Mansfield, Peter R. "Clinical trials and drug promotion: Selective reporting of study 329", International Journal of Risk & Safety in Medicine, 20, 2008, pp. 73–81. doi:10.3233/JRS-2008-0426
• Kagle, Abigail. "Driven to Settle: Eliot Spitzer v. GlaxoSmithKline and Undisclosed Clinical Trials Data Regarding Paxil", University of Columbia Law School, undated.
• Kondro, Wayne; Sibbald, Barbara. "Drug company experts advised staff to withhold data about SSRI use in children", Canadian Medical Association Journal, 170(5), 2 March 2004, p. 783. doi:10.1503/cmaj.1040213 PMID 14993169
• McGoey, Linsey; Jackson, Emily. "Seroxat and the suppression of clinical trial data: regulatory failure and the uses of legal ambiguity", Journal of Medical Ethics, 35(2), February 2009, pp. 107–112. doi:10.1136/jme.2008.025361 PMID 19181884
• McHenry, Leemon B., Jureidini, Jon N. "Industry-sponsored ghostwriting in clinical trial reporting: a case study," Accountability in Research: Policies and Quality Assurance, 15(3), July–September 2008, pp. 152–167. doi:10.1080/08989620802194384 PMID 18792536
• Newman, Melanie. "The Rules of Retraction", BMJ, 341(7785), 11 December 2010, pp. 1246–1248. doi:10.1136/bmj.c6985 PMID 21138994
• Sifferlin, Alexandra. "Breaking Down GlaxoSmithKline’s Billion-Dollar Wrongdoing", Time magazine, 5 July 2012.
• Neville, Simon. "GlaxoSmithKline fined $3bn after bribing doctors to increase drugs sales", The Guardian, 3 July 2012.
• Thomas, Katie; Schmidt, Michael S. "Glaxo Agrees to Pay $3 Billion in Fraud Settlement", The New York Times, 2 July 2012.
• United States Department of Justice, "GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data", 2 July 2012.

Further reading

Documents

• Drug Industry Document Archive, University of California, San Francisco.
• "Paxil Study 329: Paroxetine vs Imipramine vs Placebo in Adolescents", Healthy Skepticism.
• "Seroxat", Centre of Risk for Healthcare Research and Practice, Barts and The London School of Medicine and Dentistry.
• Wheadon, David E. (GlaxoSmithKline). Statement: Anti-Depressant Use Among Children, United States House Committee on Energy and Commerce, 9 September 2004.

Articles, media

• Amsterdam, Jay D.; McHenry, Leemon. "The Paroxetine 352 Bipolar Trial: A Study in Medical Ghostwriting," International Journal of Risk and Safety in Medicine, 24(4), 2012, pp. 221–231. doi:10.3233/JRS-2012-0571 PMID 23135337
• Charland, Louis C. "Why Psychiatry Should Fear Medicalization," in K. W. M. Fulford, et al (eds.), The Oxford Handbook of Philosophy and Psychiatry, University of Oxford, 2013, pp. 159–175.
• Healy, David. Pharmageddon, University of California Press, 2012, p. 109ff.
• Jofre, Shelley. "Secrets of the Drug Trials", BBC Panorama, 29 January 2007 (transcript); "Company hid suicide link", BBC News, 29 January 2007.
• Jureidini, Jon N.; Leemon B. McHenry, "Conflicted medical journals and the failure of trust", Accountability in Research: Policies and Quality Assurance, 18(1), January 2011, pp. 45–54. doi:10.1080/08989621.2011.542683 PMID 21287414
• Jureidini, Jon N. "Restoring invisible and abandoned trials: a call for people to publish the findings" (letter), BMJ, 13(346), 13 June 2013. doi:10.1136/bmj.f2865
• McHenry, Leemon. "Of Sophists and Spin-Doctors: Industry-Sponsored Ghostwriting and the Crisis of Academic Medicine", Mens Sana Monographs, 8(1), 2010, pp. 129–145. doi:10.4103/0973-1229.58824 PMID 21327175
• Stern, Simon; Lemmens, Trudo. "Legal Remedies for Medical Ghostwriting: Imposing Fraud Liability on Guest Authors of Ghostwritten Articles", PLOS Medicine, doi:10.1371/journal.pmed.1001070

Correspondence in JAACAP (chronological)

• Weintrob, Alex. "Paroxetine in adolescent major depression", Journal of the American Academy of Child and Adolescent Psychiatry, 41(4), April 2002, pp. 363–364.
• Parsons, Mitch. "Paroxetine in adolescent major depression", 41(4), April 2002, p. 364.
• Keller, Martin; Ryan, Neal D.; Wagner, Karen Dineen. "Paroxetine in adolescent major depression", 41(4), April 2002, p. 364.
• Jureidini, Jon; Tonkin, Ann. "Paroxetine in major depression", 42(5), May 2003 p. 514.
• Keller, Martin, et al. "Paroxetine in major depression", 42(5), May 2003, pp. 514–515.
• Connor, Daniel F. "Paroxetine in major depression", 43(2), February 2004, p. 127.