Prozac Nation? Is the Party Over? euphoria, then medical doubts, then lawsuits.

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> SSRI-Research

> Fri, 20 Aug 2004 23:08:21 -0400

 

> [sSRI-Research] Prozac Nation? Is the Party

> Over? euphoria, then medical doubts, then lawsuits.

>

> Companies, People, Ideas

>

> Prozac Nation? Is the Party Over?

>

> Richard C. Morais, 09.06.04

>

> http://forbes.com/forbes/2004/0906/119_print.html

 

> There are three stages in the life of a new mental

> health drug: euphoria, then medical doubts, then

> lawsuits.

> Nancy Hugo, a 57-year-old housewife in Corvallis,

> Ore., had recently been prescribed the

> antidepressant Zoloft by her internist when she

> found herself in the bathroom, looking at a Bic

> shaver and wondering if she could get the blade out

> of its plastic. In the living room she zeroed in on

> a pair of long scissors she had inherited from her

> grandmother. " I kept on wanting to pick them up and

> gouge my eye out, " she recalls. Trying to occupy her

> mind at the computer, she fought the " urge to slam

> the phone into the side of my head. "

>

>

> About to Crash?

> America's top-selling antidepressants could

> soon experience a downturn. Now off-patent, Prozac

> is no longer a bestseller.

> Top five antidepressants

> Drug Manufacturer 2003 sales*($bil)

>

> Zoloft Pfizer $2.9

>

> XR Effexor Wyeth 2.1

>

> Wellbutrin SR GlaxoSmithkline 1.8

>

> Paxil GlaxoSmithkline 1.5

>

> Celexa Forest Laboratories 1.4

> *Wholesale prices of drugs, not including mail

> service. Source: IMS Health.

>

> Hugo survived the weekend; her drug doses were

> reduced and she was switched to antidepressant

> Paxil. This time, however, she experienced

> akathisia'a medicine-induced agitation and

> restlessness that some patients on antidepressants

> describe as the feeling of bugs crawling through the

> skin'and an extreme bout of mania. " What spooks me

> now is that I thought I'd recognize when I was

> having trouble with the medications, " she says. " But

> it was a week later before I realized, 'Oh, my God,

> what have I done?' "

>

> Both Zoloft and Paxil are Prozac-type drugs known as

> SSRIs, or selective serotonin reuptake inhibitors.

> Do such drugs cause mania and violent obsessions?

> That question is now being debated in many a

> doctor's office, court of law and legislature.

> Whatever the correct scientific answer, the mere

> fact that the question is being asked represents a

> new phase in the evolution of SSRI medications and a

> threat to the well-being of the companies that make

> the drugs.

>

> Since SSRIs arrived 16 years ago with the

> introduction of Eli Lilly & Co.'s Prozac, the

> category has expanded into a collection of

> blockbusters for Lilly, Pfizer, GlaxoSmithkline and

> other manufacturers. All told, the antidepressants

> category accounts for $14 billion a year of

> wholesale revenues just in the U.S., according to

> IMS Health. In the first five months of this year

> American doctors wrote 46 million prescriptions for

> antidepressants, up 5% over the same period last

> year, according to NDCHealth. Yes, this is a Prozac

> nation. Dr. Mark Vanden Bosch, an anesthesiologist

> at the Berkshire Medical Center in Pittsfield,

> Mass., who must be alert to drugs that might

> interact with anesthesia, estimates that a third of

> the patients checking into his hospital, for a wide

> range of operations, are on antidepressants.

>

> When Prozac was new, it was heralded (in, for

> example, the 1993 hit Listening to Prozac) as a

> wonder drug with little in the way of side effects.

> The few naysayers were for the most part fringe

> sorts like Scientologists. Now a giant pall of

> misgiving is descending on SSRIs: Tearful family

> members are telling their congressmen how the drugs

> caused their children to commit suicide; Britain has

> limited their use in children; a suit by New York

> Attorney General Eliot Spitzer claims

> GlaxoSmithkline suppressed evidence that the drugs

> don't work in children and can endanger them; and

> the Food & Drug Administration is studying whether

> it should mandate ominous warning labels.

>

> It's a pattern we have seen before in psychiatric

> drugs, says Harvard Medical School psychiatrist

> Joseph Glenmullen. A new class of chemicals creates

> a wave of euphoria in the medical community, while a

> handful of celebrities (such as, in the case of

> SSRIs, Mike Wallace of 60 Minutes) swear by the new

> pills. A decade later reports of side effects

> accumulate and doctors begin to have second

> thoughts. Another decade later the world discovers a

> new miracle drug and the old one is relegated to

> niche uses. It happened to the major tranquilizers

> (like Thorazine) introduced in the 1950s, and it

> happened to supposedly less addictive and relatively

> side-effect-free substitutes for morphine. Dr.

> Glenmullen made this point about the SSRIs five

> years ago in his book Prozac Backlash. He looks

> prescient now.

>

> The second-guessing about SSRIs comes just as the

> earliest patents have expired, or are about to. The

> combination of potentially dampened prescription

> volume and new price competition could bring a lot

> of disappointment to investors in Pfizer and its

> competitors.

>

> The touchiest issue is whether SSRIs provoke

> suicides in children. Eric Harris was on Solvay

> Pharmaceuticals' SSRI, Luvox, when he and Dylan

> Klebold went on their murder-suicide rampage through

> Columbine High School in Littleton, Colo. in 1999.

> Did the powerful drug push him into a dangerous

> mental zone, like the one Hugo experienced, or was

> it unable to stop what was already there? It's hard

> to know. (A Columbine survivor's lawsuit against

> Solvay was settled out of court, without any

> admission of liability, and resulted in a token

> contribution from Solvay to a charity.) The British

> health authorities have ruled that the side effects

> of SSRI antidepressants other than Prozac put

> children at an unacceptable risk of suicide. The

> National Institute of Mental Health in the U.S., in

> contrast, says that " some research " points to a drop

> in suicides among children since the drugs were

> introduced, " but it is not known if SSRIs are

> directly responsible. "

>

> " The suicides under SSRIs are violent, " says Vera

> Sharav, president of the Alliance for Human Research

> Protection, a group headquartered in New York City

> that is crusading for full disclosure of the drugs'

> side effects. " It's not like someone going into the

> bathroom and taking pills. It's jumping, knives,

> hanging. They're in pain. They're jumping out of

> their skins. "

>

> Glenmullen says he himself prescribes SSRIs when

> appropriate but is dismayed to see patients who have

> been prescribed antidepressants for every

> triviality, from nail-biting to boyfriend breakups.

> It is easy to see where overprescribing could become

> a habit. General practitioners, internists and

> family doctors are, at times, penalized by health

> insurers for making referrals to psychiatrists.

> These first-line doctors write 73% of all

> antidepressant scrips in America. Fact: We now spend

> more on mood-altering drugs for our children,

> including antidepressants, than we spend on

> antibiotics.

>

> Harried GPs do not always discuss with their

> patients such possible problems as withdrawal

> symptoms on discontinuance or the need for

> ever-increasing doses as the drug's efficacy wears

> off. In 1997 C.W. Tillman, a county official in

> Missouri, had an anxiety attack and was prescribed

> Paxil by his doctor; a few days later his adverse

> reactions included severe agitation, extreme

> sensitivity to light and noise, claustrophobia,

> diarrhea and vomiting. His doctor told him to stop

> taking the drug, let the symptoms clear up and start

> again. A month later Tillman had descended into a

> deep depression and took an overdose.

> Tillman'subsequently diagnosed as bipolar and now

> the Web site editor of NAMI, the National Alliance

> for the Mentally Ill, in Arlington, Va.'is grateful

> for SSRIs for eventually helping him manage his

> illness, but says doctors are undertrained in

> recognizing side effects.

>

> The brain runs on a cocktail of feel-good chemical

> transmitters, among them adrenaline, serotonin and

> dopamine. Basically, serotonin flows across a

> synapse briefly, from one nerve cell to another,

> after which the cell that sent it out mops up the

> excess. SSRIs work by blocking the sending cell's

> ability to reabsorb the excess serotonin. Result:

> The receptors in the second cell get a prolonged

> bath of the feel-good juice. The miracle in this

> class of drug is that SSRIs are better tolerated

> than earlier antidepressants and less likely to be

> fatal in an overdose.

>

> Now the downside: The brain adjusts to the

> artificial increase in serotonin with a compensatory

> drop in dopamine. No one knows the long-term effect

> of this drop in dopamine in the brain. " The gaping

> loophole in our drug safety system, " says

> Glenmullen, " is long-term safety. It takes decades

> for enough consumers to have had ill effects for

> problems to come to the authorities' attention. "

> Pfizer, the manufacturer of Zoloft, says it

> carefully monitors safety after drugs are approved

> and shares that information with the FDA.

>

> Doctors and patients have for some time been

> reporting mild tics and jerks in SSRI users. The

> tics are usually overlooked, but can develop into

> tardive dyskinesia (manifested by a freakish

> " involuntary tongue " that darts out of the mouth,

> twitching or " running " legs, jerking or wildly

> swinging arms and gagging). Do patients know they

> may be in for this? Knowing, they might, of course,

> still opt for medication. " A little discomfort is a

> small [price] to pay for a normal level of

> happiness! " writes Archibald Hart in Unmasking Male

> Depression.

>

> Thorazine, it turns out, creates similar side

> effects, but it was a while before doctors were

> aware of how frequently. Prescribed for everything

> from insomnia to anxiety, this type of tranquilizer

> was taken by an estimated 250 million worldwide. In

> 1973, at the 20-year mark, 2,000 cases of tics had

> been reported. Critics surfaced and were dismissed

> as alarmists. But by 1980 systematic studies using

> neurological screening tests discovered that 40% of

> all patients treated with the Thorazine class of

> tranquilizers had tics. Reclassified as

> antipsychotics, the Thorazine-style drugs were given

> a long list of FDA warnings and are used today only

> for severe mental illness.

>

> SSRI patients are also reporting memory loss. It's

> mostly anecdotal evidence at this point. But

> Harvard's Glenmullen says the reports of memory

> loss, tics and jerking side effects found in SSRI

> patients suggests to him the possibility of

> long-term brain damage. Is there a risk that, a

> decade hence, we will see an epidemic of

> Alzheimer's- or Parkinson's-like diseases? The

> regulators haven't given enough thought to the

> possibility, he says.

>

> Whatever the true hazards in SSRIs, there is no

> doubt that tort lawyers can make hay out of the

> situation. No overall litigation and settlement data

> are available on antidepressants (opponents claim

> pharma is settling cases quietly and sealing the

> records), and there are just the early signs of

> clustering activity'trial lawyers advertising for

> SSRI " victims, " seminars and other legal

> teamwork'familiar to mass torts, but watch events

> gather pace.

>

> " We went through a whole period of overprescribing

> SSRIs, " says Jeffrey Kodroff, a Philadelphia lawyer

> suing Pfizer over Neurontin, an epilepsy drug. " When

> the market started getting to the point of

> saturation, the market started emphasizing juvenile

> use, also for the purpose of getting patent

> extensions. If the studies show they are not only

> not efficacious, but cause problems, you're going to

> see a big backlash in usage of SSRIs. "

>

> The New York Attorney General's suit against

> GlaxoSmithkline, filed in June, alleges that Glaxo

> committed fraud by suppressing or selectively

> quoting from clinical studies that showed Paxil to

> be no better, or even worse, than a dummy pill in

> treating children with depression. Spitzer has also

> requested documents from Forest Laboratories, maker

> of SSRIs Celexa and Lexapro. Glaxo says Spitzer's

> allegations are bunk; it never targeted kids.

>

> To see what a successful Spitzer prosecution could

> provoke, look at what recently happened to Pfizer.

> Warner-Lambert's Neurontin was FDA approved for

> epilepsy, but the company, it was alleged, was

> encouraging doctors to prescribe it for " off-label "

> uses like bipolar disorders. A whistle-blower

> triggered federal and state criminal investigations

> into the marketing, and this May Pfizer (which had

> subsequently acquired Warner-Lambert) settled with

> the government, taking a $427 million pretax hit in

> criminal and civil fines.

>

> Four days after the settlement the Teamsters Health

> & Welfare Fund of Philadelphia & Vicinity, joined by

> Aetna and the Alaska State Employees Association

> health benefits trust, filed class actions against

> Pfizer alleging, among other things, that

> Warner-Lambert suppressed a Harvard Bipolar Research

> Program study finding that " patients did worse on

> Neurontin than those who were on a sugar pill. " Two

> years after the study was suppressed, the Teamsters

> suit alleges, " Neurontin accounted for $1.3 billion

> in sales, with over 80% of its use coming from

> nonapproved uses, such as treatment of bipolar

> disorder. " Pfizer says it will " vigorously defend "

> itself against any suits following its Neurontin

> settlement, and says " it is worth noting that those

> investigations did not result in a charge of fraud

> by Warner-Lambert. "

>

> A user of SSRIs for almost a decade, who says she

> can't wean herself off the drugs and spoke to us on

> the condition of anonymity, recently wrote her

> former Park Avenue psychiatrist: " I simply pray

> Glaxo follows the path of [Dow] Corning, who

> endangered women's lives with silicone implants they

> knew were dangerous. Bankruptcy. "

>

> Even if Pfizer, Glaxo and Lilly are right about the

> science, they could be on the wrong end of a tort

> suit. Look at the breast implant cases. Scientific

> studies showed that there was no connection between

> silicone and the autoimmune diseases supposedly

> caused by it. But still the implant manufacturers

> had to spend billions of dollars to settle lawsuits.

>

>

>

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