Anatomy of an Epidemic (35 page)

That speculation made perfect sense. How could a severe mental illness have gone unrecognized for so long, with doctors only now noticing that thousands of kids were going wildly manic? But if there were something new
in the environment
stirring this behavior, as
Time
suggested to its readers, there would be a logical explanation for the epidemic. Infectious agents stir epidemics, and thus, as we trace the rise of juvenile bipolar disorder, this is what we’ll want to discover: Can we identify “outside agents” that are causing this modern-day plague?

As we learned earlier, manic-depressive illness was a rare condition prior to the psychopharmacology era, affecting perhaps one in ten thousand people. Although initial onset sometimes occurred in those fifteen to nineteen years old, it usually didn’t appear until people were in their twenties. But more to the point, it virtually
never
appeared in children under thirteen years of age, and both pediatricians and medical researchers regularly emphasized this point.

In 1945, Charles Bradley said that pediatric mania was so rare that “it is best to avoid the diagnosis of manic-depressive psychosis in children.”
⁶¹
An Ohio physician, Louis Lurie, reviewed the
literature in 1950 and found that “observers have concluded that mania does not occur in children.”
⁶²
Two years later, Barton Hall reviewed the case histories of 2,200 psychiatric patients five to sixteen years old, and found only two instances of manic-depressive illness. In both instances, the patients were over thirteen years of age. “These facts endorse the general belief that manic-depressive states are illnesses of the maturing or matured personality,” Hall said.
⁶³
In 1960, Washington University psychiatrist James Anthony scoured the medical literature for case reports of manic-depressive illness in children and could find only three. “Occurrence of manic depression in early childhood
as a clinical phenomenon
has yet to be demonstrated,” he wrote.
⁶⁴

But then, slowly but surely, such case reports began to appear. In the late 1960s and early 1970s, psychiatrists began prescribing Ritalin to hyperactive children, and suddenly, in 1976, Washington University’s Warren Weinberg, a pediatric neurologist, was writing in the
American Journal of Diseases of Childhood
that it was time for the field to realize that children could go manic. “Acceptance of the concept that mania occurs in children is important in order that affected children can be identified, the natural history defined, and appropriate treatment established and offered to these children,” he wrote.
⁶⁵

This was the moment in the medical literature that pediatric bipolar disorder was, in essence, “discovered.” In his article, Weinberg reviewed the case histories of five children suffering from this previously unrecognized illness, but he rushed past the fact that at least three of the five children had been treated with a tricyclic or Ritalin
prior
to becoming manic. Two years later, doctors at Massachusetts General Hospital announced that they had identified nine children with manic-depressive illness, and they, too, skipped over the fact that seven of the nine had been previously treated with amphetamines, methylphenidate, or “other medications to affect behavior.”
⁶⁶
Then, in 1982, Michael Strober and Gabrielle Carlson at the UCLA Neuropsychiatric Institute put a new twist into the juvenile bipolar story. Twelve of the sixty adolescents they had treated with antidepressants had turned “bipolar” over the course of three
years, which—one might think—suggested that the drugs had caused the mania. Instead, Strober and Carlson reasoned that their study had shown that antidepressants could be used as a
diagnostic
tool. It wasn’t that antidepressants were causing some children to go manic, but rather the drugs were
unmasking
bipolar illness, as only children with the disease would suffer this reaction to an anti-depressant. “Our data imply that biologic differences between latent depressive subtypes are already present and detectable during the period of early adolescence, and that pharmacologic challenge can serve as one reliable aid in delimiting specific affective syndromes in juveniles,” they said.
⁶⁷

The “unmasking” of bipolar illness in children soon speeded up. The prescribing of Ritalin and antidepressants took off in the late 1980s and early 1990s, and as this occurred, the bipolar epidemic erupted. The number of hostile, aggressive, and out-of-control children admitted to psychiatric wards soared, and in 1995 Peter Lewinsohn from the Oregon Research Institute concluded that 1 percent of all American adolescents were now bipolar.
⁶⁸
Three years later, Carlson reported that 63 percent of the pediatric patients treated at her university hospital suffered from mania, the very symptom that doctors in the pre-psychopharmacologic era almost never saw in children. “Manic symptoms are the rule, rather than the exception,” she noted.
⁶⁹
Indeed, Lewinsohn’s epidemiological data was now already out of date. The number of children discharged from hospitals with a bipolar diagnosis rose fivefold between 1996 and 2004, such that this “ferocious mental illness” was now said to strike one in every fifty prepubertal children in America. “We don’t have the exact numbers yet,” University of Texas psychiatrist Robert Hirschfeld told
Time
in 2002, “except we know it’s there, and it’s underdiagnosed.”
⁷⁰

An epidemic had come of age, and history reveals that it rose in lockstep with the prescribing of stimulants and antidepressants to children.

Given that chronology, we should be able to find data that explains why stimulants and antidepressants would have that iatrogenic effect. There should be data showing that if you treat 5 million children and adolescents with these drugs, then 20 percent or so will deteriorate in ways that will lead to a bipolar diagnosis. There should be evidence of iatrogenic harm that adds up mathematically to an epidemic.

We’ll start with Ritalin.

Even before the prescribing of Ritalin took hold, it was well known that amphetamines could stir psychotic and manic episodes. Indeed, amphetamines did this with such regularity that psychiatric researchers pointed to this effect as evidence supporting the dopamine hypothesis of schizophrenia. Amphetamines upped dopamine levels in the brain, suggesting that psychosis was caused by too much of this neurotransmitter. In 1974, David Janowsky, a physician at the University of California at San Diego School of Medicine, tested this hypothesis by giving three dopamine-elevating agents—d-amphetamine, l-amphetamine, and methylphenidate—to his schizophrenia patients. While all three drugs made them more psychotic, methylphenidate turned out to be tops in this regard, doubling the severity of their symptoms.
⁷¹

Given this understanding of methylphenidate, psychiatry could expect that giving Ritalin to young children would cause many to suffer a manic or psychotic episode. Although this risk isn’t well quantified, Canadian psychiatrists reported in 1999 that nine of ninety-six ADHD children they treated with stimulants for an average of twenty-one months developed “psychotic symptoms.”
⁷²
In 2006, the FDA issued a report on this risk. From 2000 to 2005, the agency had received nearly one thousand reports of stimulant-induced psychosis and mania in children and adolescents, and given that these MedWatch reports are thought to represent only 1 percent of the actual number of adverse events, this suggests that 100,000 youths diagnosed with ADHD suffered psychotic and or manic episodes during that five-year period. The FDA determined that
these episodes regularly occurred in “patients with no identifiable risk factors” for psychosis, meaning that they were clearly drug-induced, and that a “substantial portion” of the cases occurred in children ten years or less. “The predominance in young children of hallucinations, both visual and tactile, involving insects, snakes and worms is striking,” the FDA wrote.
⁷³

Once this drug-induced psychosis occurs, the children are usually diagnosed with bipolar disorder. Moreover, this diagnostic progression, from medicated ADHD to bipolar illness, is well recognized by experts in the field. In a study of 195 bipolar children and adolescents, Demitri Papolos found that 65 percent “had hypomanic, manic and aggressive reactions to stimulant medications.”
⁷⁴
In 2001, Melissa DelBello, at the University of Cincinnati Medical Center, reported that twenty-one of thirty-four adolescent patients hospitalized for mania had been on stimulants “prior to the onset of an affective episode.” These drugs, she confessed, may “precipitate depression and/or mania in children who would not have otherwise developed bipolar disorder.”
⁷⁵

Yet there is an even bigger problem with stimulants. They cause children to cycle through arousal and dysphoric states on a
daily
basis. When a child takes the drug, dopamine levels in the synapse increase, and this produces an aroused state. The child may show increased energy, an intensified focus, and hyperalertness. The child may become anxious, irritable, aggressive, hostile, and unable to sleep. More extreme arousal symptoms include obsessive-compulsive and hypomanic behaviors. But when the drug exits the brain, dopamine levels in the synapse sharply drop, and this may lead to such dysphoric symptoms as fatigue, lethargy, apathy, social withdrawal, and depression. Parents regularly talk of this daily “crash.” But—and this is the key—such arousal and dysphoric symptoms are the very symptoms that the National Institute of Mental Health identifies as characteristic of a bipolar child. Symptoms of mania in children, the NIMH says, include increased energy, intensified goal-directed activity, insomnia, irritability, agitation, and destructive out bursts. Symptoms of depression in children include loss of energy, social isolation, a loss of interest in activities (apathy), and a sad mood.

The ADHD to Bipolar Pathway

Stimulants used to treat ADHD induce both arousal and dysphoric symptoms. These drug-induced symptoms overlap to a remarkable degree the symptoms said to be characteristic of juvenile bipolar disorder.

In short, every child on a stimulant turns a bit bipolar, and the risk that a child diagnosed with ADHD will move on to a bipolar diagnosis after being treated with a stimulant has even been quantified. Joseph Biederman and his colleagues at Massachusetts General Hospital reported in 1996 that 15 of 140 children (11 percent) diagnosed with ADHD developed bipolar symptoms—which were not present at initial diagnosis—within four years.
⁷⁶
This gives us our first mathematical equation for solving the juvenile bipolar epidemic: If a society prescribes stimulants to 3.5 million children and adolescents, as is the case in the United States today, it should expect that this practice will create 400,000 bipolar youth. As
Time
noted, most children with bipolar illness are diagnosed with a different psychiatric disorder first, with “ADHD the likeliest first call.”

Now let’s look at the SSRIs.

It is well established that antidepressants can induce manic episodes in adults, and naturally they have this effect on children, too. As early as 1992, when the prescribing of SSRIs to children was just getting started, University of Pittsburgh researchers reported
that 23 percent of boys eight to nineteen years old treated with Prozac developed mania or maniclike symptoms, and another 19 percent developed “drug-induced” hostility.
⁷⁷
In Eli Lilly’s first study of Prozac for pediatric depression, 6 percent of the children treated with the drug suffered a manic episode; none in the placebo group did.
⁷⁸
Luvox, meanwhile, was reported to cause a 4 percent rate of mania in children under 18.
⁷⁹
In 2004, Yale University researchers assessed this risk of antidepressant-induced mania in young and old, and they found that it is
highest
in those under thirteen years of age.
⁸⁰

The incidence rates cited above are from short-term trials; the risk rises when children and teenagers stay on antidepressants for extended periods. In 1995, Harvard psychiatrists determined that 25 percent of children and adolescents diagnosed with depression convert to bipolar illness within two to four years. “Antidepressant treatment may well induce switching into mania, rapid cycling or affective instability in the young, as it almost certainly does in adults,” they explained.
⁸¹
Washington University’s Barbara Geller extended the follow-up period to ten years, and in her study, nearly half of prepubertal children treated for depression ended up bipolar.
⁸²
These findings give us our second mathematical equation for solving the bipolar epidemic: If 2 million children and adolescents are treated with SSRIs for depression, this practice will create 500,000 to 1 million bipolar youth.