Anatomy of an Epidemic (26 page)

The best-attended events of the conference were the industry-sponsored symposiums. At every breakfast, lunch, and dinner hour, the doctors could enjoy a sumptuous free meal, which was then followed by talks on the chosen topic. There were symposiums on depression, ADHD, schizophrenia, and the prescribing of antipsychotics to children and adolescents, and nearly all of the speakers hailed from top academic schools. The fact that they all were being paid by the drug companies was openly acknowledged, as the APA, as part of a new disclosure policy, had published a chart listing all the ways that pharmaceutical money flowed to these “thought leaders.” In addition to receiving research monies, most of the “experts” served as consultants, on “advisory boards,” and as members of “speakers’ bureaus.” Thus, you could see that Joseph Biederman, a psychiatrist at Massachusetts General Hospital in Boston who, during the 1990s, led the way in popularizing juvenile bipolar disorder, received research grants from eight firms, acted as a “consultant” to nine, and served as a “speaker” for eight. His long list of pharmaceutical clients was not all that unusual, and at times, speakers had to update their information in the disclosure guide when they strode to the podium, as they had recently added yet another pharmaceutical company to their list of clients. After Harvard Medical School’s Jean Frazier dutifully relayed such information, at a symposium devoted to the merits of putting children on multiple psychiatric drugs, she said, without any apparent hint of irony, “I hope you find my presentation unbiased.”

The speakers put on very polished presentations, evidence of the training in public speaking they had received from the
pharmaceutical firms. They regularly opened with a joke before moving on to their PowerPoint slides, which were splashed on ballroom screens larger than those found in most theaters. Often the diners were given handheld remote devices to answer multiple-choice questions during the presentations, with dramatic music playing as they keyed in their responses, much as it might during “Final Jeopardy,” and when their collective wisdom was splashed on the screens, most usually got the answer right. “You guys are so smart,” one speaker said.

Patty Duke provided the 2008 APA meeting with its celebrity patient story. AstraZeneca sponsored her talk, and the company spokesman who introduced her, apparently worried that somehow the audience might miss the point of what she had to say, informed everyone that “the take-home message is that mental illness is diagnosable and recognizable, and that treatment works.” Then the Oscar-winning actress, clad in a pumpkin orange dress, told of how she had suffered from undiagnosed bipolar illness for twenty years, during which time she drank excessively and was sexually promiscuous. Diagnosis and medication “made me marriage material,” she said, and whenever she speaks to patient groups around the country, she hammers this point home. “I tell them, ‘Take your medicines!’” she said. The drugs fix the disease “with very little downside!” The audience clapped loudly at that, and then America’s favorite identical cousin offered the psychiatrists a final benediction: “We are beyond blessed to have people like you who have chosen to take care of us and to lead us to a balanced life…. I get my information from you and NAMI [National Alliance on Mental Illness], and if I resisted such information, I would deserve to have a net thrown over me. When I hear someone say, at one of my talks, ‘I don’t need the medication, I don’t take it,’ I tell them to ‘sit down, you are making a fool of yourself.’”

That led to a standing ovation, and so, as I put away my notebook, it seemed certain that this was a meeting where the bottomline message, no matter where you went, would be quite well controlled. Nearly everything was set up and organized in a way that told of a profession quite confident in its therapeutics, and while I knew that Martin Harrow would be giving a talk on his
long-term study of schizophrenia outcomes, he had been allotted only twenty minutes, and his session had been assigned to one of the convention center’s smallest rooms. His presentation would be the one exception to the rule, and so I didn’t expect to hear anything startling on the Tuesday afternoon that I squeezed my way into a crowded, slightly larger room for a forum titled “Antidepressants in Bipolar Disorder.” I figured that the speakers would simply present trial results that justified, in one way or another, the use of these drugs, but soon I was writing furiously away. The discussion, which was led by the top bipolar experts in the country, including the two grand old men of biological psychiatry in the United States, Frederick Goodwin and Robert Post, focused on this question: Do anti-depressants
worsen
the long-term course of bipolar disorder? And notably so?

“The illness has been altered,” said Goodwin, who in 1990 coauthored the first edition of his text
Manic-Depressive Illness
, which is considered the bible in the field. Today “we have a lot more rapid cycling than we described in the first edition, a lot more mixed states than we described in the first edition, a lot more lithium resistance, and a lot more lithium treatment failure than there was in the first edition. The illness is not what Kraepelin described anymore, and the biggest factor, I think, is that most patients who have the illness get an antidepressant before they ever get exposed to a mood stabilizer.”

This was the opening salvo in what turned into an hour-long confessional. Although not all the speakers agreed that antidepressants had been disastrous for bipolar patients, that was the general theme, and nobody questioned Goodwin’s bottom-line summary that bipolar outcomes had noticeably worsened in the past twenty years. Antidepressants, said Nassir Ghaemi, from Tufts Medical Center, can cause manic switches and turn patients into “rapid cyclers,” and may increase the amount of time they spend in depressive episodes. Rapid cycling, Post added, led to a very bad end.

“The number of episodes, and it’s a very rich literature [documenting this], is associated with more cognitive deficits,” he said. “We are building more episodes, more treatment resistance, more cognitive dysfunction, and there is data showing that if you have
four depressive episodes, unipolar or bipolar, it doubles your late-life risk of dementia. And guess what? That isn’t even the half of it…. In the United States, people with depression, bipolar, and schizophrenia are losing twelve to twenty years in life expectancy compared to people not in the mental health system.”

These were words that told of a paradigm of care that had completely failed, of treatment that made patients constantly symptomatic and cognitively impaired, and led to their early death as well. “Now you just heard that one of the things we do doesn’t work very well in the long term,” Post practically screamed. “So what the hell should we be doing?”

The confessions came fast and furious. Psychiatry, of course, had its “evidence base” for using antidepressants in bipolar disorder, but, Post said, the clinical trials conducted by pharmaceutical companies “are virtually useless for us as clinicians…. They don’t tell us what we really need to know, what our patients are going to respond to, and if they don’t respond to that first treatment, what should be the next iteration, and how long they should stay on things.” Only a small percentage of people, he added, actually “respond to these crummy treatments, like antidepressants.” As for recent pharma-funded trials that had shown that bipolar patients withdrawn from antipsychotic medications relapsed at high rates, which theoretically served as evidence that patients needed to take these drugs long-term, those studies “were designed to get relapse [in the placebo group],” Goodwin said. “It isn’t evidence that the drug is still needed; it’s evidence that if you suddenly change a brain that has adapted to the drug, you are going to get relapse.” Added Post: “Right now, fifty years after the advent of antidepressant drugs, we still don’t really know how to treat bipolar depression. We need new treatment algorithms that aren’t just made up.”

This was all much like the moment in
The Wizard of Oz
when the curtain is pulled back and the mighty wizard is revealed as a frail old man. For anyone in the audience who had spent his or her morning in Pfizer’s welcoming center, answering video-game questions about the wonders of Geodon for bipolar illness, it must have been crushing. Thirty years earlier, Guy Chouinard and Barry Jones had rattled the profession with their talks on drug-induced
“supersensitivity psychosis,” and now the profession was being asked to confront the fact that bipolar outcomes were worse today than they had been thirty years earlier, and that antidepressants were a likely culprit. Stimulants, it seemed, could make bipolar patients worse too, and at last Ghaemi told the audience that psychiatry needed to adopt a “Hippocratic” approach to the use of psychiatric medications, which would require them to stop prescribing them unless they had good evidence they were truly beneficial over the long term. “Diagnosis, not druggery,” he said, and at one point, several in the audience—which had grown increasingly agitated by this discussion—booed him.

“Can fifty thousand psychiatrists be wrong?” he asked, speaking about the profession’s use of antidepressants as a treatment for bipolar disorder. “I think that the answer is yes, probably.”

Readers of this book, having come this far in the text, cannot be surprised to learn that outcomes for bipolar disorder have dramatically worsened in the pharmacotherapy era. The only surprising thing is that this failure was so openly discussed at the APA meeting. Given what the scientific literature revealed about the long-term outcomes of medicated schizophrenia, anxiety, and depression, it stood to reason that the drug cocktails used to treat bipolar illness were not going to produce good long-term results. The increased chronicity, the functional decline, the cognitive impairment, and the physical illness—all of these can be expected to show up in people treated with a cocktail that often includes an antidepressant, an antipsychotic, a mood stabilizer, a benzodiazepine, and perhaps a stimulant, too. This was a medical train wreck that could have been anticipated, and unfortunately, as we trace the history of this story, the details will seem all too familiar.

Although “bipolar” illness is a diagnosis of recent origin, first showing up in the APA’s
Diagnostic and Statistical Manual
in 1980 (DSM-III), medical texts dating back to Hippocrates contain
descriptions of patients suffering from alternating episodes of mania and melancholia. “Melancholia,” wrote German physician Christian Vater in the seventeenth century, “often passes into mania and vice versa. The melancholics now laugh, now are saddened, now express numberless other absurd gestures and forms of behaviour.” The English mad doctor John Haslam told of how “the most furious maniacs suddenly sink into a profound melancholy, and the most depressed and miserable objects become violent and raving.” In 1854, a French asylum doctor, Jules Baillarger, dubbed this illness
la folie à double forme
. It was an uncommon, but recognizable form of insanity.
¹

When Emil Kraepelin published his diagnostic texts, he put these patients into his manic-depressive group. This diagnostic category also included patients who suffered from depression or mania only (as opposed to both), and Kraepelin reasoned that these varied emotional states all arose from the same underlying disease. The splitting of manic-depressive disorder into separate unipolar and bipolar factions got its start in 1957, when a German psychiatrist, Karl Leonhard, determined that the manic form of the illness seemed to run more in families than the depressive form did. He called the manic patients “bipolar,” and other researchers then identified additional differences between the unipolar and bipolar forms of manic-depressive illness. Onset occurred earlier in bipolar patients, often when they were in their twenties, and it also appeared that bipolar patients were at somewhat higher risk of becoming chronically ill.

In his 1969 book,
Manic Depressive Illness
, George Winokur at Washington University in St. Louis treated unipolar depression and bipolar illness as separate entities, and with this distinction having been made, he and others began reviewing the literature on manic-depressive illness to isolate the data on the “bipolar” patients. On average, in the older studies, about one-fourth of the manic-depressive group had suffered from manic episodes and thus were “bipolar.” By all accounts, this was a rare disorder. There were perhaps 12,750 people hospitalized with bipolar illness in 1955, a disability rate of one in every 13,000 people.
²
That year there were only about 2,400 “first admissions” for bipolar illness in the country’s mental hospitals.
³

As Winokur discovered, the long-term outcomes of the manic patients in the pre-drug era had been pretty good. In his 1931 study, Horatio Pollock reported that 50 percent of the patients admitted to New York State mental hospitals for a first attack of mania never suffered a second attack (during an eleven-year follow-up), and only 20 percent experienced three or more episodes.
⁴
F. I. Wertham, from Johns Hopkins Medical School, in a 1929 study of two thousand manic-depressive patients, determined that 80 percent of the manic group recovered within a year, and that fewer than 1 percent required long-term hospitalization.
⁵
In Gunnar Lundquist’s study, 75 percent of the 103 manic patients recovered within ten months, and during the following twenty years, half of the patients never had another attack, and only 8 percent developed a chronic course. Eighty-five percent of the group “socially recovered” and resumed their former positions.
⁶
Finally, Ming Tsuang, at the University of Iowa, studied how eighty-six manic patients admitted to a psychiatric hospital between 1935 and 1944 fared over the next thirty years, and he found that nearly 70 percent had good outcomes, which meant they married, lived in their own homes, and worked. Half were asymptomatic during this lengthy follow-up. All in all, the manic patients had fared as well as the unipolar patients in Tsuang’s study.
⁷