Reanalysis Confirms Long Held Suspicions — Paxil Is Unsafe and Ineffective for Teens

By Dr. Mercola

Antidepressants are among the most prescribed types of drugs in the US,¹ despite the fact that many of them have also been linked to violence against self and others.

In 2004, the US Food and Drug Administration (FDA) revised² the labeling requirements for antidepressant medications (SSRIs and others), warning that:

“Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders.

Anyone considering the use of [Insert established name] or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.”

These labeling revisions were in large part driven by lawsuits in which pharmaceutical companies were forced to reveal previously undisclosed drug data.

The following year, the FDA issued yet another advisory; this time warning women that taking Paxil during pregnancy could result in a number of debilitating birth defects,³ including congenital heart defects.

GlaxoSmithKline Has Paid $4 Billion in Settlements Related to Paxil

A civil lawsuit filed in 2004⁴ charged GlaxoSmithKline (GSK) with fraud, claiming the drugmaker hid results from studies on Paxil showing the drug did not work in adolescents and in some cases led to suicidal ideation.

Rather than warning doctors of such potential side effects, GSK encouraged them to prescribe the drug to teens and children, which led to a significant increase in prescriptions — and violence, including suicides and homicides.

A study⁵ by the Institute of Safe Medication Practices published in 2010 identified 31 commonly-prescribed drugs disproportionately associated with violent acts. Paxil ranks third on this list.

A study by the Drug Safety Research Unit in Southampton showed that one in every 250 subjects taking Paxil or Prozac were involved in a violent episode.

In 2011, a whopping 14 million prescriptions for Paxil were written in the US,⁶ potentially equating to some 56,000 drug-induced incidents of violence annually from this drug alone.

GSK has paid out more than $1 billion to settle more than 800 different lawsuits related to Paxil,⁷ in addition to a $3 billion settlement with the US Department of Justice for the illegal marketing of Paxil and other drugs.

Yet Paxil has remained a “staple” in the psychiatrist’s arsenal. Perhaps this will finally change once the most recent research into Paxil becomes more widely known...

GlaxoSmithKline’s Paxil Research Refuted By New Study

In 2001, GSK published a study^8,9 known as “Study 329,” showing Paxil was both safe and effective for teenagers but now, a reanalysis^10,11,12 of the original data has concluded neither is true.

As reported by The New York Times:¹³

“Antidepressant trials are an extremely tricky enterprise, in part because anywhere from a third to more than half of subjects typically improve on placebo.

Choices about how to measure improvement — and how to label side effects — can make all the difference in how good a drug looks. And so it was in the Paxil study.

The original research... tracked depression scores over eight weeks in three groups of about 90 adolescents each, one taking Paxil, one on placebo pills, and one taking imipramine, an older generic drug for depression.

The Paxil group did no better than the other two groups on the study’s main measure — a standard depression questionnaire — but did rate higher on other, ‘secondary’ measures, like another scale of mood problems, the authors reported.

Researchers consider secondary measures like these as akin to circumstantial evidence, potentially meaningful but not as strong as the primary ones...”

The reanalysis of all of the original raw data provided by GSK found no evidence that Paxil was effective for the treatment of major depression in teens. In fact, its effectiveness, both clinically and statistically, was right on par with placebo.

It also found that serious side effects such as suicidal tendencies were mislabeled and misrepresented. As it turns out, the elevated risk for suicidal ideation was only gleaned by digging into the actual patient files, where the exact nature of the behavior was recorded.

In terms of harms, the difference between Paxil and placebo was “striking,” according to the researchers.

Severe adverse events were 260 percent more frequent on Paxil compared to placebo, psychiatric adverse events were 400 percent more frequent, and suicide was 10,300 percent more frequent — during the eight-week long study, 11 individuals in the Paxil group engaged in suicidal behavior, compared to just one in the placebo group.

Reanalysis Reignites Call for Retraction of GSK’s Study 329

When Study 329 was originally published it received a lot of criticism, and calls for retraction have been made a number of times, citing both research flaws and ghostwriting, as well as undisclosed financial conflicts of interest.

In an accompanying article¹⁴ to this new research, Peter Doshi, associate editor for The BMJ notes that the original manuscript for Study 329 was written by a writer on GSK’s payroll — not any of the 22 named authors.

“It is often said that science self corrects. But for those who have been calling for a retraction of the Keller paper for many years, the system has failed,” Doshi writes.

“None of the paper’s 22 mostly academic university authors, nor the journal’s editors, nor the academic and professional institutions they belong to, have intervened to correct the record.

The paper remains without so much as an erratum, and none of its authors — many of whom are educators and prominent members of their respective professional societies — have been disciplined.”

Still, while the reanalysis has reignited calls for a retraction of Study 329, the authors have downplayed any wrongdoings of the original researchers, focusing instead on marshalling for greater transparency and data sharing to raise the scientific integrity of drug research.

Co-author Jon Jureidini told Time Magazine:¹⁵ It’s not the point of this paper to humiliate GSK or to accuse anyone of fraud. It’s an attempt to honestly present the data. This is what the original paper should have looked like. If the original paper had reported things this way, there never would have been a problem.”

Barriers to Accurate Reporting of Harms in Drug Studies

The reanalysis has done more than simply reverse the original findings however. It also highlights the importance of making raw study data openly available for review and assessment by the scientific community.

Had this “double-check” analysis been done a decade ago, a lot of lives could have been spared. It might also have prevented the “contamination” of other studies. Study 329 has been cited in 334 other studies¹⁶ — all noting of course that Paxil is effective and well tolerated.

It can be mindboggling to consider the snowball effect any given flawed study can have... Had Study 329 reported Paxil ineffective and unsafe, how might it have affected the conclusions of those other 334 studies?

The analysis was also able to identify a number of barriers that make it difficult to accurately report adverse side effects associated with drugs, and hopefully this will be able to help researchers improve the way these kinds of studies are done and analyzed in the future. The 10 potential barriers to accurate reporting of side effects include:

Using an idiosyncratic coding system	Failing to transcribe all adverse events (AE) from clinical record to AE database
Filtering data on AE’s through statistical techniques	Restricting reporting to events that occurred above a given frequency in one group
Coding events under different headings for different patients	Grouping events together
Insufficient consideration of severity	Coding of relatedness to study medication
Masking effects of concomitant drugs	Ignoring effects of drug withdrawal

When Crime Pays — the Case of Risperdal

Writing for The New York Times,¹⁷ Nicholas Kristof recently addressed a similar situation in which a drug company made big bucks from a drug approved and marketed based on false information. The drug in this case is Risperdal, a billion-dollar antipsychotic that has been promoted to both young boys with autism and elderly dementia patients with devastating effects.

In the elderly, the drug is associated with stroke and subsequent death, and in boys it can promote the development of breasts. One young man was recently awarded $2.5 million in damages after the drug caused him to develop a 46DD bust.¹⁸

“Yet Johnson & Johnson marketed Risperdal aggressively to the elderly and to boys while allegedly manipulating and hiding the data about breast development. J&J got caught, pleaded guilty to a crime and has paid more than $2 billion in penalties and settlements. But that pales next to some $30 billion in sales of Risperdal around the world. In short, crime pays, if you’re a major corporation,” Kristof writes.

“J&J may in the end have to pay a total of $6 billion in settlements for its misconduct. But... the company made $18 billion in profits on Risperdal, just within the United States... That’s why we need tougher enforcement of safety regulations, and why white-collar criminals need to be prosecuted (as Attorney General Loretta Lynch has promised will happen). Risperdal is a cautionary tale: When we allow businesses to profit from crimes, we all lose.”

Key Factors to Overcoming Depression Without Drugs

While there are instances where drugs may be warranted, antidepressants are rarely the most appropriate answer for depression. It’s important to realize that your diet and general lifestyle are foundational factors that must be optimized if you want to resolve your mental health issues, because your body and mind are so closely interrelated. Depression is indeed a very serious condition; however it is not a “disease.” Rather, it’s a sign that your body and your life are out of balance.

Mounting and compelling research demonstrates just how interconnected your mental health is with your gastrointestinal health for example. While many think of their brain as the organ in charge of their mental health, your gut may actually play a far more significant role. Research tells us that the composition of your gut flora not only affects your physical health, but also has a significant impact on your brain function and mental state. Previous research has also shown that certain probiotics can even help alleviate anxiety.^{19, 20}

So the place to start is to return balance — to your body and your life. Fortunately, research confirms that there are safe and effective ways to address depression that do not involve unsafe (and ineffective) drugs. This includes but is not limited to the following. For additional suggestions, please review the links listed under Related Articles:

Eat real food	Dramatically decrease your consumption of processed foods, sugar (particularly fructose), and grains. There's a great book on this subject, The Sugar Blues, written by William Dufty more than 30 years ago, that delves into the topic of sugar and mental health in great detail. In addition to being high in sugar and grains, processed foods also contain a variety of additives that can affect your brain function and mental state, especially MSG, and artificial sweeteners such as aspartame.
Optimize your gut flora	Increase consumption of probiotic foods, such as fermented vegetables and kefir, to promote healthy gut flora. Mounting evidence tells us that having a healthy gut is profoundly important for both physical and mental health, and the latter can be severely impacted by an imbalance of intestinal bacteria. Remember your gut is your second brain and produces more neurotransmitters than your brain.
Get adequate vitamin B12	Vitamin B12 deficiency can contribute to depression and affects one in four people.
Optimize your vitamin D levels	Vitamin D is very important for your mood. In one study, people with the lowest levels of vitamin D were found to be 11 times more prone to be depressed than those who had normal levels.21 The best way to get vitamin D is through sensible sun exposure. SAD (Seasonal Affective Disorder) is a type of depression that we know is related to sunshine deficiency, so it would make sense that the perfect way to optimize your vitamin D is through sun exposure.
Optimize your omega-3 to omega-6 ratio	To normalize your omega-3 to omega-6 ratio, take high quality omega 3 oils such as krill oil and radically reduce if not completely eliminate industrial processed omega 6 oils. DHA, an animal based omega-3 fat, is crucial for good brain function and mental health.22 Dr. Stoll, a Harvard psychiatrist, was one of the early leaders in compiling the evidence supporting the use of animal based omega-3 fats for the treatment of depression. He wrote an excellent book that details his experience in this area called The Omega-3 Connection.
Evaluate your salt intake	Sodium deficiency creates symptoms closely resembling those of depression. Make sure you do NOT use processed salt (regular table salt), however. You'll want to use an all natural, unprocessed salt like Himalayan salt, which contains more than 80 different micronutrients.
Exercise daily	Exercise is one of the most effective strategies for preventing and overcoming depression. Studies have shown there is a strong correlation between improved mood and aerobic capacity. There’s a growing acceptance that the mind-body connection is very real, and that maintaining good physical health can significantly lower your risk of developing depression in the first place.
Get adequate amounts of sleep	You can have the best diet and exercise program possible but if you aren't sleeping well you can easily become depressed. Sleep and depression are so intimately linked that a sleep disorder is actually part of the definition of the symptom complex that gives the label depression.