Anatomy of an Epidemic (27 page)

These results, Winokur wrote, revealed that there “was no basis to consider that manic depressive psychosis permanently affected those who suffered from it. In this way it is, of course, different from schizophrenia.” While some people suffered multiple episodes of mania and depression, each episode was usually only “a few months in duration,” and “in a significant number of patients, only one episode of illness occurs.” Most important of all, once patients recovered from their bipolar episodes, they usually had “no difficulty resuming their usual occupations.”
⁸

Today, according to the NIMH, bipolar illness affects one in every forty adults in the United States, and so, before we review the
outcomes literature for this disorder, we need to try to understand this astonishing increase in its prevalence.
⁹
Although the quick-and-easy explanation is that psychiatry has greatly expanded the diagnostic boundaries, that is only part of the story. Psychotropic drugs—both legal and illegal—have helped fuel the bipolar boom.

In studies of first-episode bipolar patients, investigators at McLean Hospital, the University of Pittsburgh, and the University of Cincinnati Hospital found that at least one-third had used marijuana or some other illegal drug prior to their first manic or psychotic episode.
¹⁰
This substance abuse, the University of Cincinnati investigators concluded, may “initiate progressively more severe affective responses, culminating in manic or depressive episodes, that then become self-perpetuating.”
¹¹
Even the one-third figure may be low; in 2008, researchers at Mt. Sinai Medical School reported that nearly two-thirds of the bipolar patients hospitalized at Silver Hill Hospital in Connecticut in 2005 and 2006 experienced their first bout of “mood instability” after they had abused illicit drugs.
¹²
Stimulants, cocaine, marijuana, and hallucinogens were common culprits. In 2007, Dutch investigators reported that marijuana use “is associated with a fivefold increase in the risk of a first diagnosis of bipolar disorder” and that one-third of new bipolar cases in the Netherlands resulted from it.
¹³

Antidepressants have also led many people into the bipolar camp, and to understand why, all we have to do is return to the discovery of this class of drugs. We see tuberculosis patients treated with iproniazid dancing in the wards, and while that magazine report was probably a bit exaggerated, it told of lethargic patients suddenly behaving in a manic way. In 1956, George Crane published the first report of antidepressant-induced mania, and this problem has remained present in the scientific literature ever since.
¹⁴
In 1985, Swiss investigators tracking changes in the patient mix at Burghölzli psychiatric hospital in Zurich reported that the percentage with manic symptoms jumped dramatically following the introduction of antidepressants. “Bipolar disorders increased; more patients were admitted with frequent episodes,” they wrote.
¹⁵
In a 1993 practice guide to depression, the APA confessed that “all anti-depressant treatments, including ECT [electroconvulsive therapy],
may provoke manic or hypomanic episodes.”
¹⁶
A few years later, researchers at Yale University School of Medicine quantified this risk. They reviewed the records of 87,290 patients diagnosed with depression or anxiety between 1997 and 2001 and determined those treated with antidepressants converted to bipolar at the rate of 7.7 percent per year, which was three times greater than for those not exposed to the drugs.
¹⁷
As a result, over longer periods, 20 to 40 percent of all patients initially diagnosed with unipolar depression today eventually convert to bipolar illness.
¹⁸
Indeed, in a recent survey of members of the Depressive and Manic-Depressive Association, 60 percent of those with a bipolar diagnosis said they had initially fallen ill with major depression and had turned bipolar after exposure to an antidepressant.
¹⁹

This is data that tells of a process that routinely
manufactures
bipolar patients. “If you create iatrogenically a bipolar patient,” explained Fred Goodwin, in a 2005 interview in
Primary Psychiatry
, “that patient is likely to have recurrences of bipolar illness even if the offending antidepressant is discontinued. The evidence shows that once a patient has had a manic episode, he or she is more likely to have another one, even without the antidepressant stimulation.”
²⁰
Italy’s Giovanni Fava put it this way: “Antidepressant-induced mania is not simply a temporary and fully reversible phenomenon, but may trigger complex biochemical mechanisms of illness deterioration.”
²¹

With illegal and legal drugs greasing the road to bipolar illness, it is little wonder that a rare disorder in 1955 has become commonplace today. SSRIs took the country by storm in the 1990s, and from 1996 to 2004, the number of adults diagnosed with bipolar illness rose 56 percent. At the same time, psychiatry’s steady expansion of diagnostic boundaries over the past thirty-five years has helped fuel the bipolar boom too.

When bipolar disorder was first separated from manic-depressive illness, the diagnosis required a person to have suffered bouts of mania and depression so severe that each type had resulted in hospitalization. Then, in 1976, Goodwin and others at the NIMH suggested that if a person had been hospitalized for depression but not for mania, and yet had experienced a mild episode of mania
(hypomania), he or she could be diagnosed with bipolar II, a less severe form of the disease. Then the bipolar II diagnosis was expanded so that it included people who had never been hospitalized for either depression or mania, but simply had experienced episodes of both. Next, in the 1990s, the psychiatric community decided that a diagnosis of hypomania no longer required four days of “elevated, expansive, or irritable mood,” but rather simply two days of such moodiness. Bipolar illness was on the march, and with the diagnostic boundaries expanded in this way, researchers were suddenly announcing that it affected up to 5 percent of the population. But even that didn’t end the bipolar boom: In 2003, former NIMH director Lewis Judd and others argued that many people suffer “subthreshold” symptoms of depression and mania, and thus could be diagnosed with “bipolar spectrum disorder.”
²²
There was now bipolar I, bipolar II, and a “bipolarity intermediate between bipolar disorder and normality,” one bipolar expert explained.
²³
Judd calculated that 6.4 percent of American adults suffer from bipolar symptoms; others have argued that one in every four adults now falls into the catchall bipolar bin, this once-rare illness apparently striking almost as frequently as the common cold.
²⁴

With the psychopharmacology revolution in full bloom during the 1960s, it seemed that every major psychiatric disorder should have its own magic bullet, and once bipolar disorder was separated from manic-depressive illness, psychiatry found a suitable candidate in lithium. Salts made from this alkali metal had been hanging around the fringes of medicine for more than 150 years, and then suddenly, during the early 1970s, lithium was touted as a cure of sorts for this newly identified disease. “I have not found another treatment in psychiatry that works so quickly, so specifically, and so permanently as lithium for recurrent manic and depressive mood states,” said Columbia University psychiatrist Ronald Fieve, in his 1975 book,
Moodswing
.
²⁵

Nature’s lightest metal, lithium was discovered in 1818, found in rocks off the Swedish coast. It was reported to dissolve uric acid and thus was marketed as a therapy that could break up kidney stones and the uric crystals that gathered in the joints of people who suffered from gout. In the late 1800s and early 1900s, lithium became a popular ingredient in elixirs and tonics, and it would even be added to beers and other beverages. However, lithium was eventually found to have no uric-acid–dissolving properties, and in 1949, the FDA banned it after it was found to cause cardiovascular problems.
²⁶

Its revival as a psychiatric drug began in Australia, where the physician John Cade fed it to guinea pigs and observed that it made them docile. In 1949, he reported that he had successfully treated ten manic patients with lithium; however, he neglected to mention in his published article that the treatment killed one person and made two others severely ill. As makers of lithium tonics had long known, lithium can be toxic even in fairly small doses. Both intellectual function and motor movement may become impaired, and if too high of a dose is given, a person may lapse into a coma and die.

As a group, psychiatrists in the United States showed little interest in lithium until bipolar made its appearance as a distinct illness. Prior to that time, Thorazine and other neuroleptics were used to curb manic episodes and thus there was no need for another drug that seemed to have similar brain-dampening effects. But once George Winokur published his book in 1969 dividing manic-depressive illness into unipolar and bipolar forms, psychiatry had a new disease in need of its own antidote.

Since no pharmaceutical company could patent lithium, the APA took the lead in getting the FDA to approve it. Only a few placebo-controlled trials of the drug were ever conducted. In 1985, UK researchers who scoured the scientific literature could only find four of any merit. However, in those studies, lithium produced a good response in 75 percent of the patients, which was much higher than the response rate in the placebo group.
²⁷
The second part of the evidence base for lithium came, as usual, from withdrawal studies. Investigators who analyzed nineteen such trials in 1994 found that 53.5 percent of the patients withdrawn from lithium relapsed,
versus 37.5 percent of the lithium-maintained patients. That was taken as evidence that lithium prevented relapse, although the researchers noted that in the few studies where patients had been
gradually
withdrawn from the drug, only 29 percent relapsed (which was lower than the rate among the drug-maintained patients).
²⁸

All in all, this was not particularly robust evidence that lithium benefited patients, and during the 1980s, several investigators began raising concerns about its long-term effects. They noted that readmission rates for mania in both the United States and the United Kingdom had risen since lithium was introduced, and eventually it became clear why bipolar patients were turning up at hospital emergency rooms with such great frequency.

Various studies found that more than 50 percent of lithium-treated patients would quit taking the drug in fairly short order, usually because they objected to how the drug dulled their minds and slowed their physical movements, and when they did, they relapsed at astonishingly high rates. In 1999, Ross Baldessarini reported that half of all patients relapsed within five months of quitting lithium, even though in the absence of exposure to the drug, it took nearly three years for 50 percent of bipolar patients to relapse. The time between episodes following lithium withdrawal was
seven times shorter
than it was naturally.
²⁹
“The risk of recurrence after discontinuation of lithium therapy … especially of mania, is much higher than predicted by a patient’s course before treatment or by general knowledge of the natural history of the illness,” Baldessarini wrote.
³⁰
Other investigators noted the same phenomenon: “Manic relapse is readily triggered [by lithium withdrawal], probably by the release of supersensitized receptors or membrane pathways,” explained Jonathan Himmelhoch from the University of Pittsburgh.
³¹

This meant that bipolar patients who were treated with lithium and then stopped taking it ended up “worse than if they had never had any drug treatment,” wrote UK psychiatrist Joanna Moncrieff.
³²
A Scottish psychiatrist, Guy Goodwin, concluded in 1993 that if patients were exposed to lithium and then quit taking it within the first two years, the risk of relapse was so great that the
drug may be “harmful to bipolar patients.” The higher hospitalization readmission rates for bipolar patients since the introduction of lithium “could be explained entirely” by this drug-induced worsening, he said.
³³

Yet the patients who stayed on lithium weren’t faring particularly well either. Roughly 40 percent relapsed within two years of their initial hospitalization, and by the end of five years, more than 60 percent fell sick again.
³⁴
There was a core group of good, long-term lithium responders—perhaps 20 percent of those initially treated with the drug—but for the majority of patients, it provided little long-term relief. In 1996, Martin Harrow and Joseph Goldberg, from the University of Illinois, reported that at the end of 4.5 years, 41 percent of the patients on lithium had “poor outcomes,” nearly one-half had been rehospitalized, and as a group they weren’t “functioning” any better than those not taking the drug.
³⁵
This was a dismal finding, and then Michael Gitlin at UCLA reported similar five-year results for his lithium-treated bipolar patients. “Even aggressive pharmacological maintenance treatment does not prevent relatively poor outcome in a significant number of bipolar patients,” he wrote.
³⁶

Although lithium is still in use today, it lost its place as a first-line therapy once “mood stabilizers” were brought to the market in the late 1990s. As Moncrieff wrote in 1997, summing up lithium’s record of efficacy: “There are indications that it is ineffective in the long-term outlook of bipolar disorders, and it is known to be associated with various forms of harm.”
³⁷

There are really two narratives to be dug out of the scientific literature regarding the treatment of bipolar illness with psychiatric drugs. The first tells of lithium’s rise and fall as a magic bullet for the disorder. The second tells of how bipolar outcomes have dramatically worsened during the psychopharmacology era, with experts in the field documenting this at every turn.