(First Appeared in the Huffington Post in Four Parts, August 2014)

During my entire 30-plus-year career as a behavioral/developmental pediatrician in private practice, I have attended only one drug company-sponsored dinner where I was paid for just showing up. In 2003, I received a letter from Eli Lilly and Company, inviting me to hear a former Columbia Medical School classmate -- what an amazing coincidence -- talk about Strattera (atomoxetine), Lilly's new drug for the treatment of ADHD/ADD (attention deficit/hyperactivity disorder and non-hyperactive inattention). The dinner would be at the Ritz-Carlton in San Francisco, one of the city's fanciest venues. As an additional inducement, I was offered a $500 "consulting fee" and a continuing medical education (CME) credit in return for listening to this one-hour presentation

I had been to enough industry-sponsored CME lectures to know that the session would have a biological/medication slant that I don't share. Plus, the presentations were often insultingly simplistic and capped off by an obvious sales pitch. Still, I was intrigued; what would I have to do for my $500? After a bit of a struggle, I arranged to have the money donated to the Omega Boys Club of San Francisco. Then I went to the dinner.

In the lobby, I saw a colleague, a friendly chap with a very strong biological/medication orientation, and we decided to sit together. After a leisurely, wine-accompanied repast, the lecture began, presented by my former classmate, Phil Buber (my pseudonym for him).

I remembered Phil as a nice, unassuming, somewhat lumbering guy, but not one of my med school's brighter stars. He did a decent job covering the symptoms of childhood ADHD: six of nine behaviors required for diagnosis on the impulsive/hyperactive side and/or six of nine behaviors on the inattentive side as enumerated in American psychiatry's bible, the Diagnostic and Statistical Manual (DSM), Edition IV.

Phil proceeded to give a perfunctory description of non-drug behavioral approaches to treatment. Then, right on schedule and according to script, he disparaged the medications currently in use for ADHD. Coming from a drug company shill, this should have been a surprise, but to the cognoscenti in the audience, it was not. We all knew that Lilly had been touting Strattera as the first effective, non-stimulant medication for the treatment of ADHD/ADD. The best known of the stimulants -- Ritalin, Adderall, and the newer Concerta -- had grown into a $2 billion a year industry. They were all variations of amphetamine, a potentially abusable and addictive drug. Strattera was the first non-amphetamine brought to market for ADHD.

Even though there was contradictory evidence on the long-term risks of Ritalin-type drugs, Phil exploited the specter of later amphetamine addiction. (Later that year, Lilly's national campaign, which was directed at parents, would attempt to cash in on that same worry. Subsequent research concluded that childhood intake of amphetamines neither led to nor prevented future drug abuse or addiction.) He droned on about the benefits of Strattera and exaggerated the risks of Adderall and Concerta, but I had already made up my mind about the drug, whose structure and pharmacology reminded me of the tricyclics (more about them later). If I were going to prescribe medication, I would stick to the stimulants. However, I knew my dinner partner was a pioneer and a risk taker, inclined to try new drugs with his patients.

We were still sitting together when Phil went around the room, polling the doctors in attendance on our attitudes about Strattera. He asked me, "So, Larry, what do you think about using atomoxetine with your patients?"

"Well, Phil, I'm a bit conservative when it comes to new drugs," I said. "So, I'll tell you what. When my friend here tells me in five years that Strattera works and has fewer side effects than Concerta, I might be ready to prescribe it." The group laughed uneasily.

Strattera's backstory, which reflected marketing choices rather than an effective alternative, was the most intriguing -- and instructive -- thing about it. Atomoxetine, its generic version, had languished on the Eli Lilly shelves for more than a decade. In the 1980s, testing had shown it to be an adequate treatment for depression, but Lilly had just introduced its blockbuster product, Prozac, which seemed to be a bit more effective and also better tolerated. Consequently, Lilly didn't need another antidepressant to compete with its very, very successful product

But then, a fortuitous set of circumstances coalesced in the late 1990s: ADHD diagnosis rates and treatments soared, and parents, desperate to treat their "chemically imbalanced" offspring, worried about the potential long-term side effects of amphetamines on their children

Lilly also had another ace in its deck. It had recruited Harvard University's preeminent academic child psychiatrist, Dr. Joseph Biederman, and his team to take on atomoxetine research. Dr. Biederman, winner of many academic awards, was arguably at the time the single most powerful and influential psychiatrist in America. He later became embroiled in conflict-of-interest scandalsthat were covered by major American media outlets, and his reputation has since suffered. But at that particular moment, he was at the height of his powers. All Biederman had to do was whisper the name of a new drug at a medical conference, and tens of thousands of prescriptions for that drug would be written by MDs across the nation.

At one point, Biederman's team had promoted tricyclics -- older, non-stimulant antidepressant drugs -- as alternatives for ADHD when stimulant drugs failed to improve behavior, side effects were too great, or there was a risk of abuse. However, in the 1980s, after several reports of children suddenly dying while taking desipramine (one of the tricylics), use of these types of compounds for ADHD essentially ended.

I had not been surprised when an article by Biederman and his team appeared in the July 2002 Journal of the American Academy of Child & Adolescent Psychiatry on the use of atomoxetine as a treatment for ADHD. I was surprised, however, to learn that on the very same day the article was released to the press, Biederman hosted a Wall Street news conference under the auspices of Eli Lilly.

The timing and blatant nature of the pecuniary partnership between America's leading academic child psychiatrist and a Fortune 500 mega-corporation had left me feeling sad, angry, and alone. Where were other doctors, patients, the public, and the press? Why weren't they speaking out about this obvious conflict of interest?

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I never got a confirming report from my dinner-meeting colleague on Strattera. Indeed, in the ensuing years, despite a massive marketing campaign directed at both physicians and patients, Lilly failed to get Strattera approved as a first-line ADHD drug by any of the major pediatric or professional child psychiatric organizations. In a head-to-head competition with Concerta, Strattera was found to be only six-tenths as effective as Concerta in ameliorating the symptomatic behaviors of ADHD. It was especially poor in addressing the inattentive behaviors (daydreaming) of the non-hyperactive form of ADHD. (The study was funded by Janssen, maker of Concerta.)

Nonetheless, while the risk of abuse in a child under 13 is essentially zero, parents fear stimulant drugs' reputation, and Lilly's marketing of Strattera as a non-stimulant alternative had some impact. It ultimately occupies only around 5 to 7 percent of the ADHD medication market. While that may not sound like much, 5 percent represents $500 million annually in what is currently a $9 billion market for ADHD medicines overall.

There are many complex and related reasons why, in 2012, the U.S. comprised 4 percent of the world's population but produced and used 70 percent of its legal stimulants. On balance, however, drug companies were -- and continue to be -- the largest single influence. Not only do they fund ADHD research and professional education, they market to doctors, teachers, parents, and, ultimately, even the children of this country.

Of course, drug companies have always promoted their products to doctors, albeit with significant restraints. A century ago, organized medicine began to separate itself from the patent-medicine makers of the time, garnering in the process a newfound respect from the general public. This shift was influenced by the 1910 Flexner Report on the state of American medical schools. By the 1920s, drug company ads in doctors' journals were carefully scrutinized before being run. (This was well before the FDA demanded certain standards of effectiveness and safety in pharmaceutical products.)

There were also innocuous promo inducements. In the 1950s and early 1960s, my father -- a general practitioner in Queens, New York -- let me go through his professional mail looking for drug company boxes and trinkets. I'd find packets of writing pads, a ballpoint pen, sometimes a weird and cheap artifact with the name of the drug and the company on it. I'd play with them for a while, then toss them out.

But by the 1980s, the relationship between doctors and the drug industry was changing. During the Reagan administration, with the passage of the Bayh-Dole Act, academic medical researchers and for-profit corporations were encouraged to integrate their efforts. The act allowed businesses, nonprofits, and universities to claim ownership of discoveries that had been funded by federal money; previously, patents to scientific breakthroughs achieved with federal sponsorship had to be transferred to the government.

For me, the first signs of change came in the mid-1990s, with Shire Pharmaceuticals' introduction and marketing of Adderall. Shire, a company based in the United Kingdom (technically on the Isle of Jersey in the English Channel for tax purposes), was and continues to be the most aggressive and dominant marketer of legal amphetamines in the United States.

Typically, Shire's approach has been to buy smaller drug companies outright. Take, for example, Richwood Pharmaceuticals. In early 1994, Richwood -- a company started by Roger Griggs -- acquired a defunct New Jersey manufacturing plant. Twenty years earlier, the plant had produced Obetral, an amphetamine product used for the treatment of obesity. Under pressure from the FDA, women's groups, and trial lawyers, the market for diet pills was shut down, and Obetral went into obscurity.

Not surprisingly, a change in the national education laws in 1991, which for the first time included ADHD as a covered diagnosis for services and accommodations, led to an upsurge in its diagnosis. Mr. Griggs, whose purchase of the plant had likely been inspired by this development, brought back the former obesity drug and renamed it Adderall. Enter Shire, which bought Richwood Pharmaceuticals for $186 million in 1997.

That same year, I began noticing ads in the major professional journals promoting Adderall as a long-acting stimulant over Ritalin, a methylphenidate product that had been a mainstay ADHD treatment since the 1960s. Ritalin itself had replaced Benzedrine, one of the first legal amphetamine products like Adderall. Methylphenidate, the active ingredient in Ritalin, while not identical to amphetamine, is very similar in both structure and action.

Ritalin became the predominant stimulant prescribed by doctors for two reasons. First, Ciba-Geigy (now Novartis), the makers of Ritalin, organized some modern research that established its short-term effectiveness; Benzedrine was supported by only a few original studies carried out by Charles Bradley, a pediatrician who, in 1937, was the first to note stimulants' effects on children's behavior. Second, Ritalin wasn't an amphetamine. Simple as that.

Parents and doctors had known about amphetamines' risks of abuse and addiction since the 1930s. With Ritalin, doctors could tell their patients' parents that their children weren't taking an amphetamine, which technically, it wasn't, even though the positive effects, side effects, and risks were essentially the same for both drugs when tested in large groups of children and adults.

Thirty years later, Ritalin was the most widely known and frequently reviled of the stimulant-type drugs for children, and part of Shire's advertising campaign was strikingly analogous to the earlier Ciba-Geigy approach. This time, Adderall was marketed as the "not-Ritalin." On a much, much larger scale, doctors could tell parents that this was Adderall, not Ritalin, and everyone could heave a sigh of relief. At least it's not Ritalin!

As someone who knew how similar the two drugs were, I found the switcheroo ironic, almost amusing. But I considered another part of the Shire marketing campaign to be supremely disingenuous. Shire compared Adderall's length of action, which varied from about four to eight hours (depending on the individual), to Ritalin's, which was generally three to four hours. Length of action was quite important, because in the 1990s, there were no real long-acting (ten- to twelve-hour) stimulants as there are today (Concerta, Adderall XR, Vyvanse, Metadate CD, etc.).

Absent this feature, many children required multiple daily doses. In schools across the country, children lined up in potentially stigmatizing and embarrassing queues around lunchtime for their second dose of the day. A long-acting drug that covered at least the school day (six hours) would therefore have great appeal. So, in comparing Adderall's length of action to Ritalin's, Shire executed a masterpiece of marketing.

However, the company didn't mention the Dexedrine Spansule, a stimulant product made up of dextroamphetamine, the active isomer of amphetamine. (All molecules have right- and left-sided mirror images; in ADHD treatment, only the right-sided molecules are active in the brain.) This drug had been available for thirty years and consistently delivered about six to eight hours of more focused, steady behavior. It was also cheaper than Adderall.

Nevertheless, thanks to a relentless advertising campaign in professional journals, regular visits by Shire drug reps to doctors' offices, and a barrage of professional medical educational speakers on the benefits of this new preparation, Adderall quickly passed Ritalin as the most frequently prescribed brand-name stimulant drug in America. Generic methylphenidate (cheaper than Ritalin or Adderall) remained the overall most prescribed drug for ADHD.

Over the years, Shire has become associated with virtually every kind of stimulant and delivery system available. When long-acting Concerta came out, Shire quickly followed with Adderall XR. Another of Shire's drug-company acquisitions had developed Daytrana, a skin patch, which allowed methylphenidate to be absorbed transdermally instead of being swallowed, an obvious benefit for younger children who couldn't be depended upon to swallow pills intact. But Daytrana turned out to be problematic and never really sold well, in part because of persistent skin irritation at the site of the patch and the fact that children could remove the patch themselves if they wanted to.

Shire was much more successful with their 2007 purchase of New Rivers Pharmaceuticals, which developed a compound molecule called lisdexamfetamine, a drug initially created to make abuse more difficult. Shire named it Vyvanse. With Vyvanse, the amphetamine molecule is linked to the amino acid lysine, which renders the amphetamine inactive until digestive enzymes cleave the chemical bond and free it up. In other words, the pill has to be swallowed in order to be effective. The risk of abusing the drug is greatly diminished because, if crushed and snorted (the most common method), its amphetamine component doesn't work.

Yet Shire has never highlighted the anti-abuse aspect of Vyvanse; I suspect they are concerned they'd be criticized for having promoted and sold the most widely misused and abused of the stimulants, Adderall. Instead, they've heavily marketed Vyvanse as "the longest lasting" of the long-acting stimulants. In fact, Vyvanse may last all of an hour or two longer than Concerta or Metadate CD.

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In the late 1990s, under the guise of corporate "freedom of speech" initiatives, drug companies pressed for the right to advertise their products directly to consumers. For the previous 70 years, the FDA, whose mandate is to protect the public from impure, ineffective, or dangerous drugs or food, believed that pharmaceutical promotions were best filtered through doctors, who were thought to be better judges of the difference between fact and commercial hype.

Nonetheless, drug companies pressed the case of "patient education" and their rights of free speech. Within the U.S. climate of corporate rights, there were legal precedents for allowing direct advertisement to consumers. Shire and Janssen began to lobby for the right to direct-advertise their controlled drugs as well, despite the fact that the U.S. was a signatory to a 1972 UN treaty on narcotics production and international trade that specifically prohibited advertisement to the public of potentially abusable and addictive drugs. (New Zealand is the only other developed country that allows direct-to-consumer drug advertising.)

The Drug Enforcement Administration (DEA) was concerned about international repercussions but ultimately decided that the trend in legal decisions was so likely to affirm the rights of stimulant makers to advertise to the public that it didn't even try to block the companies. As a result, since 1999, the public has been inundated with a plethora of TV and magazine ads showing smiling "successful" children surrounded by parents and sibs.

A typical headline reads, "Thanks to new ways for effectively managing ADHD, homework may be a more relaxing time at the Wilkin house. Help turn everyday challenges into daily successes." A toll-free telephone number is offered for "the latest treatment information" about ADHD. At the bottom of the page, in very small print, is a statement that the advertisement is sponsored by a drug company. And with ADHD, that company is most likely Shire, makers of Adderall.

Once one company began advertising to the public, all their competitors did so as well. It wasn't long until advertising as part of the cost of drug development rose sharply and was reflected in the cost of the drug itself. In 2005, a full-page ad for Adderall overlaid the cover of People magazine. More recently, Shire paid for 50,000 comic books intended to "educate" children about ADHD and the benefits of treatment, including taking medication. It's hard to say how much this sort of direct-to-the-public advertising has affected consumer demand. I'm certain the companies themselves know, but they clasp this proprietary information tightly against their corporate chests.

Many studies have shown that patients now come to their doctors asking about a specific drug. In most cases, the doctor complies and writes the prescription, even when costs to the consumer and the insurance company are substantially higher. It remains unclear whether or not the public's health has actually improved with drug-company-sponsored "education," or whether the costs of health care have simply increased. These newer drugs not only come with higher price tags, they rarely have substantially greater benefits; sometimes, they have even more side effects than older versions.

"Free" samples given to doctors to distribute to their patients is another time-honored promotional strategy to introduce new products. One might believe a spirit of charity drives companies to give away their new drugs, and I suppose there are situations in which a truly indigent family benefits from these samples. But by far the majority are distributed to private doctors' offices, where the patients are middle class or higher.

Because stimulant drugs for ADHD can potentially be abused, their makers of are not allowed to offer actual samples, but they give doctors' offices vouchers; the patient can then take the voucher to the pharmacy along with the prescription and get the medication free or at a highly-reduced cost (initially, at least). Drug companies know full well that once a patient gets started on a newer, more costly product, he/she is likely to ask the doctor to continue the newer drug. And doctors generally comply.

Unlike most of the other stimulant makers, Shire is really a one-disease company, selling various versions of amphetamine or non-stimulant products. This merchant of legal speed in 2012 earned $1.5 billion for the current top selling stimulant, Vyvanse, $892 million for Adderall XR, and $464 million for Intuniv -- a highly-advertised sedating non-stimulant drug for ADHD (personal communication/Alan Schwarz). The annual market for stimulant prescription drugs in America in 2012 was $9 billion and another approximately $1.1 billion for non-stimulants (personal communication/Alan Schwarz). These numbers seem incredible.

Between 1996, when I wrote my first book, Running on Ritalin, and 2013, methylphenidate production has multiplied six times, to 80,000 kilograms annually. Amphetamine has increased almost 30 times to 65,000 kilograms annually. In 2013, the DEA approved the U.S. production of 175,000 kilograms of legal stimulants, equaling 193 tons, enough for 550 mg. (roughly 27 Adderall 20 mg. tablets) for every American man, woman, and child.

The enormous amount of legal amphetamines used in this country tracks the rate of ADHD diagnoses in children, which has also exploded in the past 15 years. A CDC telephone survey in 2013 reported that 11 percent of American children's parents had been told by a professional that their child had either ADHD or ADD. Dissecting the data further, 19 percent of high school boys had received the diagnosis, and two-thirds reported using medication.

Regional variations reveal even more extreme situations. North Carolina and a number of other southern states report diagnosis rates of 30 percent among high school boys, while rates in the western states tend to be a great deal lower -- roughly 10 percent. These numbers sober even the most committed ADHD/medication advocates. Can one in three boys really have a psychiatric disorder? What does it say about our country that our use of pills has replaced effective non-drug interventions for underperforming or misbehaving children?

This is the critical moral rub. Pills do work for ADHD, at least in the short term. However, after 80 years, there is no long-term evidence that children who take medication do better as adults. Indeed, there are suggestions that the medications make no difference whatsoever in long-term outcomes. Nevertheless, the pills work quickly and efficiently to improve performance and behavior. This is not a paradoxical effect applicable only to those diagnosed with the condition; everyone becomes more methodical and deliberate when taking this drug.

Non-drug interventions for ADHD also work. Behavioral modification techniques practiced by parents and teachers, and special education interventions (especially small-group instruction) are primary and proven therapies. They take longer and clearly cost more than pills, but they prioritize engagement with the child over efficiency.

When presented with the option of either drug or non-drug interventions, parents and teachers generally prefer that the latter be tried first. However, medical and school systems, insurance companies, and drug companies are interested in efficiencies and selling products. Many incentives and disincentives push doctors and patients to use pills as a first-line response instead.

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The annual American Psychiatric Association (APA) conference is huge, attracting thousands of doctors and other professionals from around the world. When it convened in San Francisco several years ago, I decided to attend a one-day session -- I'd heard that the previous year's exhibits had rivaled Disneyland's and was curious.

The conference was held in the city's biggest convention site, the Moscone Center; some of the center's rooms are as big as a football field when fully open. After signing in and getting my badge, I dutifully sat through a bland presentation of diagnostic terminologies in psychiatry before heading to the Exhibitors' Hall, where I suspected the most effort had been made to "educate" my fellow attendees and me. The room was enormous, perhaps three or four football fields long, with a 40-foot ceiling.

This massive space was packed wall to wall. Some exhibitors' displays were modest -- a desk in the front, a few posters attached to a curtained backdrop -- but many were gigantic: quarter-acre, 30-foot-high assemblies with neon signs and attractive women. Indeed, one had young women in bikinis handing out medical education literature and "gifts," all kinds of chotchkies: mugs, notepads, pens, binders, helium balloons, cloth shopping bags, backpacks. I saw doctors walking around laden with this stuff.

It felt more like a Middle Eastern bazaar than a doctors' convention. But instead of sheepskins and spices, the products being promoted were psychiatric drugs, and the vendors represented the largest pharmaceutical companies in the United States and the world. For all the buzz and activity, there was much more selling than educating going on. Sure, the drug reps suggested alternatives and mentioned side effects, but underneath and unacknowledged was their fundamental mission: to convince me to prescribe their product.

The Exhibitors' Hall was only the most overt example of the drug industry's influence on the convention, and on doctors. In fact, around that time, the large drug companies were underwriting 30 percent of all of the APA's $62.5 million annual budget. Much of the cost of the convention was covered in the form of "unrestricted" grants and payment for exhibition rights at the convention. These funds brought the price down for the individual doctor and also allowed the APA to offer presenters more money.

But these for-profit corporations were not charitable foundations committed to the promotion of knowledge for the benefit of humankind. They knew that assembling this many prescribing M.D.s in one place provided them with a powerful opportunity to influence these physicians to select their products. As an M.D., I could sign up from morning to night for meals paid for by drug companies as long as I was willing to listen to one of their medical experts tell me about the value of this particular drug for that particular condition. In fact, topics generally focused on conditions and their treatment.

For example, there was the industry-sponsored symposium, "Treating ADHD Across the Life Cycle," supported by Novartis (makers of Ritalin) and taught by that very same Joseph Biederman mentioned in this first part of this series and his highly-respected colleagues, Stephen Faraone and Thomas Spencer of Harvard Medical School. Only a complete naïf would fail to understand that a tilt to one of Novartis's products for treating attention and performance problems in children and adults should be expected.

Over the years, drug companies continually broke new barriers of propriety and aggression when it came to marketing their products, but the worst of the drug company/doctor practices began to recede after the FDA Prozac/suicide hearings in 2004-2005. Organized medicine, which realized it was losing its credibility by allowing the drug companies so much influence, set up better regulatory firewalls. The drug companies haven't stopped promoting to doctors and patients, but the frequency and intensity (especially to doctors) have decreased. Many of the previously patent-protected drugs for ADHD/ADD are now generic and not as profitable, which may also have something to do with the companies' reduced marketing enthusiasm.

Nonetheless, the societal pump has been primed. The market for stimulants is now self-sustaining and continues to grow. The ADHD/medication virus implanted by organized medicine in the 1980s and exploited by the drug industry in the 1990s and early 2000s no longer needs such levels of promotion to grow in the host society. Our culture and way of life make us susceptible to the allure and use of performance-enhancing stimulants.

Leading experts who once promoted the ADHD diagnosis and stimulant treatment have reacted with alarm to the latest trends. But the proverbial genie is out of the bottle. Created and promoted by the drug industry, it is now running amok amongst American children, parents, and teachers.

The adult ADHD market has also boomed, and this trend toward adult use of prescription stimulants is currently the most ominous sign of things to come. Just this year, Express Scripts, the nation's largest insurance prescription service, released data showing that, for the first time, adult use of stimulant drugs is topping pediatric use, 57.5 percent to 42.5 percent.

Other evidence points to a growing adult stimulant misuse/abuse/addiction epidemic. The number of emergency room visits by adults who've overdosed on stimulant drugs is rising in parallel with the growth of the adult ADHD diagnosis. Estimates are that nearly 30 percent of the legally produced stimulant drugs in the U.S. is being diverted to illegal (e.g., non-prescription) use. After alcohol and marijuana, prescription stimulants are the drug most abused by high school students. Admission rates to California rehabilitation hospitals for prescription-stimulant addiction now top those for opiates like Vicodin or Oxycontin, which have received much more publicity.

Addiction to prescription stimulants is akin to methamphetamine ("crank") addiction. As the addict lurches from highs to lows, his/her behavior becomes increasingly erratic. Crime, violence and paranoia are common. Addicts require multiple drugs (tranquilizers and opiates) to regulate moods. While only one in 10 to 20 misusers/abusers of prescription stimulants become addicted, as the number of general users reaches the millions, the casualties of this social phenomenon will become too great to ignore.

Our ADHD "epidemic" and concomitant use of stimulants are unlikely to end soon. Misuse and abuse in young adults will eventually lead to a backlash against the drug, as has historically occurred in regular 30-year cycles since amphetamine's American synthesis in 1929. In the meantime, we live in the United States of Adderall and must make appropriate choices for ourselves and for our children. It's a daunting task.

Post-Script

On July 18, 2014, Abb-Vie (formerly Abbott Laboratories, one of the largest drug companies in the world) agreed to pay Shire Pharmaceuticals of the U.K. and the maker of Adderall and Vyvanse $54 billion to merge. The combined company will be among the 50 largest corporations in the world. Shire stock has risen 50 percent since May on rumors of the merger. Come what may in the United States of Adderall, Shire will have more than greatly satisfied its stockholders.

(I wish to thank Susan Takasaki for editorial assistance)