Paxil is Forever

doctor please, some more of these

In a year of tumbling stock prices, accounting scandals, and shaky consumer spending,the British pharmaceutical giant GlaxoSmithKline has had remarkably good news to report so far. More than eight million prescriptions have been written for Advair, its asthma medication, in the year and a half it has been on the market; Trizivir has become the most frequently prescribed drug for new HIV patients; and despite competition from a new generic version, the antibiotic Augmentin is still selling well.

But it is the antidepressant drug Paxil that seems to be GlaxoSmithKline's unstoppable star. During the first half of this year, the drug's sales were up 18 percent in the United States. Every day an estimated 3,000 to 5,000 Americans begin taking Paxil. In 2001 alone, 25 million new scripts were written for the drug. Paxil's strong sales--$2.1 billion last year--are often cited by Wall Street analysts as one reason GlaxoSmithKline's stock remains an attractive prospect in an otherwise gloomy market.

Indeed, during the past 15 years the antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, have revolutionized mental health care. And for tens of millions of Americans, Paxil and its pharmaceutical cousins--Prozac, Zoloft, Celexa, and Luvox--have proven a godsend. They boast far fewer side effects than their predecessors and it's virtually impossible to take a lethal quantity of the new pills. Most people know someone who has been on one of the drugs for years.

The SSRIs have been a boon to the pharmaceutical industry, too, becoming the third most commonly prescribed type of drug, with sales of more than $13 billion a year worldwide. A bonus: Many patients use SSRIs for years, which takes some of the sting out of the cost of bringing a new prescription drug to market.

For years Eli Lilly's Prozac was the most widely prescribed SSRI. Pfizer's Zoloft has likewise taken a turn as the top seller. But it's Paxil that has shone as a marketer's dream. When the drug was introduced in 1992, the market seemed so saturated with antidepressants that it was hard to imagine Paxil would ever catch up. A decade later, it's poised to become the world's best-selling SSRI. GlaxoSmithKline has steadily and energetically added to the list of disorders Paxil can be used to treat, and spent billions of dollars to make sure the buying public knows where to turn in case anxiety or melancholy sets in.

Unfortunately GlaxoSmithKline leaves out one little detail: For thousands of people, it seems that Paxil could well be addictive.

 

The chemical serotonin is presentthroughout the human body. Among other places, it exists in blood, in the mucous membranes of the gastrointestinal system, and in certain kinds of tumors. Serotonin plays a vital role in regulating sleep, appetite, sensory perception, body temperature, pain, and mood.

In the brain, serotonin acts as a neurotransmitter, a chemical messenger that facilitates communication between two nerve cells. Serotonin molecules are released from a "sender" cell into the space between nerve cells known as the synapse. From there, they are scooped back up by a "receiver" cell.

When physicians describe depression as an illness resulting from a chemical imbalance in the brain, one of the possibilities they speak of is an interruption in the supply of serotonin in the synapses. Perhaps too little of the chemical is being manufactured, for instance, or too little of its chemical precursors--the molecules used to make the neurotransmitter. Sometimes there aren't enough receptor sites, and sometimes serotonin is taken back up before it can get to those sites.

Research into serotonin's role in mood disorders has been going on for decades. Physicians have long known that in many instances, depression is caused by a lack of another chemical important to brain function, norepinephrine. Perhaps, they posited, a lack of serotonin somehow caused or allowed a dip in norepinephrine. If that were the case, the manipulation of serotonin levels would indirectly raise norepinephrine.

Before Prozac came on the U.S. market in 1988, depression was often treated with a class of drugs known as tricyclic antidepressants. These drugs were quite effective at manipulating both serotonin and norepinephrine but caused a wide range of bothersome side effects.

"In the old days, the pre-Prozac days of tricyclic antidepressants, you were told to treat endogenous depressions for six to 12 months and then to taper off," explains Kevin Turnquist, a psychiatrist with the Hennepin County Mental Health Initiative. "In most cases, it worked well for those people; in fact, the tricyclics worked slightly better. The problem was the side effects. A week's dose was lethal."

As a consequence, tricyclics were not widely prescribed. The advent of Prozac, Paxil, and the other selective serotonin reuptake inhibitors changed that. Although each is a slightly different chemical cocktail, the SSRIs all work in roughly the same way: They slow the action of brain cells that take serotonin out of the synapses, raising the amount of the chemical circulating in the brain. And they do it with relatively few side effects. "Plus," notes Turnquist, "you could just give one dose, start a patient on 20 milligrams and let them stay on it. It's much easier and safer for the doctor to prescribe."

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