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SSRIs: It's not addiction, it's discontinuation syndrome

MagazineDecember 2010 (Vol. 21 Issue 9)SSRIs: It's not addiction, it's discontinuation syndrome

Hollywood celeb Lindsay Lohan's admission to a Los Angeles court last month that she's addicted to antidepressants reopens a contro-versy that the drugs industry has tried to keep under wraps for 30 years

Hollywood celeb Lindsay Lohan's admission to a Los Angeles court last month that she's addicted to antidepressants reopens a contro-versy that the drugs industry has tried to keep under wraps for 30 years.

After the hearing, Lohan's father Michael told journalists: "These drugs are killing my daughter and killing millions of kids in America, and someone has to stop it."

But, so far, no one has succeeded. Not even a US Senate hearing in 2007 could force an admission from SSRI makers that their drugs are addictive.
The drugs industry has played a damage-limitation game ever since Eli Lilly's first SSRI, Prozac (fluoxetine), was approved in 1977. It heralded a new family of drugs based on the idea that depressed people are low in sero-tonin, a brain chemical that acts on the nervous system-a theory that has never been proven (see box, page 8).

What's in a name?

The first indications that SSRIs were addictive appeared in 1992 for fluvox-amine (Br J Psychiatry, 1992; 160: 283-4), and opened the floodgates to similar reports for paroxetine a year later and, for sertraline, in 1994.

In a move to deflect concerns about the SRRIs' addictive qualities, Eli Lilly coined the term 'discontinuation syndrome' in 1996, a euphemism that started appearing on packaged inserts in 2001.

The World Health Organization (WHO) was not impressed. "SSRIs are an example of how a conceptual confusion over terminology can affect proper reporting, interpretation and communication of adverse drug reactions related to dependence" (www.who.int/medicinedocs/en/d/Js4896e/ 9.html). In other words, give the problem a different name, and it will throw everyone off the scent.

The depressing reality

Call it what you like, the reality remains the same: SSRIs are highly addictive. The independent Uppsala Monitoring Centre database lists three SSRIs-fluoxetine, paroxetine and sertraline-among the 30 highest-ranking drugs for dependency (www. who.int/medicinedocs/en/d/Js4896e/9.html). Of these, paroxetine is cited as the most addictive of them all (http://news.bbc.co.uk/2/hi/health/1382551.stm).

Claims of paroxetine's addictive qualities have dogged its manufacturer GlaxoSmithKline (GSK) from the time of its launch in 1992. GSK has always maintained that its SSRI is not habit-forming and that, at worst, around 2 per cent of patients might suffer from discontinuation syndrome. However, secret company papers from 1997 showed that 62 per cent of patients were addicted to the drug (Ann Neurol, 2008; 64: A7-9).

The US drugs monitoring agency, the Food and Drug Administration (FDA), issued a warning about the drug in 2002 and, that same year, the International Federation of Pharma-ceutical Manufacturers Association accused GSK of misleading the public and of breaching two codes of practice.

Since 1992, around 5000 Americans have sued GSK for downplaying the drug's serious side-effects, while law-suits citing similar issues have been issued in the UK. In 2004, GSK settled charges of consumer fraud by paying out $2.5 million. Legal discovery uncovered a deliberate and systematic suppression of unfavourable studies (Angell M. The Truth About the Drug Companies. Random House: London, 2005).

Although drug companies maintain that discontinuation syndrome is mild and short-lived, the packaged inserts admit that withdrawal reactions can be "intolerable", with symptoms such as dizziness, electric-shock effects, sweat-ing, nausea, insomnia, tremor, confu-sion, nightmares and vertigo (BMJ, 2005; 331: 824). Sexual dysfunction, such as loss of libido and impotence, is also common (J Sex Med, 2008; 5: 227-33).

But all this downplaying, aided and abetted by psychiatrists, keeps drug sales high, with global revenues in 2008 of $11 billion. Wyeth's Effexor (venlaxafine) leads the field with a 36-per-cent share of the total market and annual sales worth $3.93 billion (www. wikinvest.com/concept/Antidepressant_Drug_ Market).

A major driver of sales-at least in the US-is direct-to-consumer (DTC) advertising. There, drug companies can advertise prescription drugs directly to the public. Also, as depression is often subjective, many people can be con-vinced that they have it. As a result, $120 million of the $900 million spend on DTC in 2005 was dedicated to anti-depressants. In 2001 in the month after the 9/11 attack on the World Trade Center, GSK doubled its DTC advertising spend on paroxetine (CNS Drugs, 2009; 23: 103-20).

Depression was once a serious clinical condition suffered by a small minority, but it's now a lifestyle disease that many of us have from time to time, and SSRIs such as Prozac have become our chemical friends.

Behind this is the assumption that the drugs are safe and non-addictive. Not so, says Dr David Healy, a leading expert on antidepressants. He believes that more than half of paroxetine users are physically dependent on the drug (http://news.bbc.co.uk/2/hi/health/1382551. stm).

Safety is also an issue. GSK paid out $6.4 million after a man murdered three members of his family before killing himself after taking paroxetine for just two days. In Australia, a judge ruled that sertraline had caused a man to murder his wife and then attempt his own suicide. Healy believes that one in 1000 people taking paroxetine could suffer from such suicidal thoughts.

The drugs don't work

If the theory of chemical imbalance is false, it follows that SSRIs won't ease depression, at least not beyond the placebo effect.

In fact, an analysis of 74 SSRI studies bears this out. Researchers found that one-third of such studies were never published because the results were so poor. Around 94 per cent of the papers that were published had a positive result. Yet, when researchers from the US Food and Drug Administration (FDA) re-analyzed the findings, they found that the SSRI was effective in only half of the studies. These studies had been paid for by the manufacturer of the drug being tested (N Engl J Med, 2008; 358: 252-60).

Drug companies have an overly simplistic view of depression, which explains the overall ineffectiveness of SSRIs, say researchers from the Northwestern University Feinberg School of Medicine. Eva Redei, a professor of psychiatry at Northwestern, says that antidepressants are based on two false claims: that a stressful life causes depression; and that depression is caused by a chemical imbalance.

Redei believes that depression is in some way associated with the development and functioning of neurons, and only when this is properly understood can an effective antidepressant be developed (Presentation at the 39th Annual Society For Neuroscience Conference, October 17-21, 2009, Chicago, IL).

WDDTY VOL. 21 ISSUE 5


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