How Everyone Became Depressed (27 page)

It was therefore not such a stretch for Donald Klein and Max Fink to think about panic in the patients at Hillside Hospital in eastern Queens whom they started on the new TCA imipramine, once it became available for trials in the United States in the late 1950s. In one of the earliest double-blind studies in American psychopharmacology, discussed above, in 1962 Klein and Fink reported that anxious patients with symptoms of panic responded to imipramine whereas anxious patients with phobic symptoms did not. Klein and Fink had basically used a psychopharmacological torch to carve out panic from the great block of anxious illness and make it a separate disease. After 1962, Klein went on to differentiate panic as a separate illness while Fink turned to other subjects.
⁹⁴
And panic disorder is indissolubly associated with Klein’s work. Many authorities thought that panic was related to depression, but in 1982 Klein showed that imipramine had a specific effect on panic unrelated to depression.
⁹⁵
In the 1970s panic with and without agoraphobia—the differentiation was somehow seen as important—boomed as a diagnosis and was incorporated into DSM-III in 1980
⁹⁶
(see p. xxx).

Klein had experienced great success with imipramine (Tofranil)—and there is considerable evidence of the effectiveness of the tricyclics in panic
⁹⁷
— but other drug classes seemed effective too. In 1967 Smith Kline & French Laboratories in Philadelphia began indicating their antipsychotic drug Stelazine (trifluoperazine) for “the panic-prone patient.”
⁹⁸
This was not illogical, as the antipsychotics had a long history of efficacy in anxiety disorders, to which panic indisputably belonged. The benzodiazepine lorazepam (Ativan) became advertised for panic in 1987 (“Documented efficacy in panic attacks”).
⁹⁹

These were relatively uncontroversial developments. But the panic pool was poisoned by a debacle that occurred after the Upjohn Company, in Kalamazoo, Michigan, sought systematically to expand the panic market with a lavish promotion of its benzodiazepine alprazolam (Xanax), which had been launched for anxiety in 1981. They asked Gerald Klerman, a senior figure, to lead an international trial to establish its efficacy, and the trials and its conclusions proved terribly controversial. English psychiatrist Peter Tyrer, later editor of the British Journal of Psychiatry, recalled the lavish marketing meeting at Key Biscayne, Florida, in 1982, “where for the first time I felt physically dirty after being tarnished by the broad sweep of the Upjohn brush into every part of ‘agoraphobia with panic,’ which I and others have named ADS (the alprazolam deficiency syndrome) ever since.”
¹⁰⁰
Upjohn launched Xanax for panic after FDA approval in 1990. These events led to an unpleasant exchange between Isaac Marks at the Maudsley and Klerman in the late 1980s, on the grounds that panic did not exist as a separate disease and the larger anxiety syndrome was readily responsive to psychotherapy rather than drugs (the Maudsley crowd had always been uneasy about psychopharmacology). At the time of Klerman’s death in April 1992, his draft reply to Marks lay as yet unsent on his writing table, and his widow Myrna Weissman objected to Marks’s actions.
¹⁰¹

Yet despite these British reservations, panic disorder does seem to be a disease of its own. Whereas garden-variety anxiety has always been part of the nervous syndrome, paroxystic expressions of anxiety, now called panic, do appear to be a thing apart. And Donald Klein is correctly considered among the pioneers of psychopharmacology rather than the foremost advocate of a passing diagnostic fad. (On the specificity of alprazolam for panic there is, however, some dubiety. There is substantial agreement that the benzodiazepines as a whole, not just alprazolam, are effective in panic. Upjohn’s marketing campaign deafened serious discussion of these issues for a long time.)

Panic disorder is of interest here because its symptoms often match those of the historic nervous breakdown. Just as the acute nervous breakdown was distinct from chronic expressions of the nervous syndrome, acute attacks of panic seem to be different from general chronic anxiety and mixed anxiety-depression.
¹⁰²

In sum, the years after 1960 saw the return of the true depression, melancholia, which had never really been a part of the nervous syndrome; those years saw the rise of the false depression, major depression, pieces of which had always been a part of the nervous syndrome. Finally, those years witnessed the rise of panic disorder, which had once been part of the nervous breakdown. Blinded by artifacts and stumbling about in a kind of nosological gloom, psychiatry lost track of the diseases that had once been its core diagnoses and substituted for them heterogeneous artifacts that were meaningful only to the pharmaceutical industry.

We might have thought that the concept of nerves ended in 1957 when the United States Post Office Department initiated a fraud proceeding against John Winters of New York City, who had been promoting a product called Orbacine containing bromide and niacin for “every-day nervousness and its symptoms.”
¹
Although Winters’ claims went a bit beyond nerves, the Post Office wanted an end to the whole business and Orbacine disappeared.

But the concept of nerves had enemies other than the Post Office. Three in particular had tried to do away with it: psychoanalysis, psychopharmacology, and the DSM series. All failed to kill it completely, and the concept lingers on because of its obvious face value: Our patients clearly have a nervous illness or something resembling it. They do not have a “mood disorder.”

In medicine the nervous syndrome, the condition that dare not speak its name, has taken on various allures. Once upon a time, hysteria was the equivalent of a nervous diagnosis in women. There were physicians who had little patience with calling their former hysteric patients “depressed”: They remained hysteric! Jacques Frei, a member of the department of psychiatry of the University of Lausanne in Switzerland, noted in 1984 “the importance that depressive symptomatology has taken today as a call for help among female hysterics. . . . It seems that the hysterical woman today has a better chance of a hearing if she presents with a depressive picture, even evoking suicidal ideas.”
²
Although hysteria today is discredited as a diagnosis, it is interesting that older clinicians such as Frei saw it as a diagnosis that trumped depression; he even argued that his patients at Cery Hospital were modeling their symptoms to conform to the new diagnoses.

The 1950s and 1960s saw alternative diagnoses to the nervous syndrome come and go, fragments of clinical experience that seemed to make sense to individual physicians but were not more widely taken up because their originators did not have prestigious academic appointments. Take “the housewife syndrome” that Palma Formica proposed in 1962. (Formica, a young unknown family doctor in Old Bridge, New Jersey, was later celebrated as a female medical pioneer in New Jersey.) Just as soon as the patients entered her office, they began crying. Their chief complaint was fatigue. “Her commonest complaint—chronic tiredness—is largely ignored in the medical

literature. . . . Her daily, mechanical repetition of monotonous, exhausting, routine duties that stretch endlessly into the future.” The strain of making the family budget meet ends, the numerous obligations to school and church, “and still have energy left for companionship with her husband, contribute to constant weariness and a conviction of defeat.” Are these patients depressed? No. They have insight. “Nor are they neurotic.” How do they cope? First, they try “will power.” “They do not seek medical help until they are completely miserable, and their irritability and inertia have nearly disrupted the family.” The women are then embarrassed “to take up a physician’s time” with what they presume to be trivia. The symptoms themselves of “the housewife syndrome” were various aches and pains, “an excessive desire for sleep but inability to sleep soundly,” and “constant lassitude, uninterest in home duties and in the marital relation. They invariably end their recital with, ‘Doctor, I am so tired: I never used to feel this way.’”
³
The housewife syndrome never caught on, but it clearly is a restatement of nerves, even though it is possible that Dr. Formica was unfamiliar with that ancient diagnosis.

That was suburban New Jersey in the early 1960s. Then came DSM-IIIin 1980, the ascent of psychopharmacology, the end of the dominance of psychoanalysis, and the triumph of major depression. What alternatives have more recently come along?

As one alternative to the major depression trap, the late twentieth century saw a revival in thinking about mixed anxiety-depression as a single disorder. There were voices from all about the vast psychiatric hall.

Edward Sachar, head of psychiatry at Columbia University, was a kind of Wunderkind of biological psychiatry, having begun with psychoanalysis and moved rapidly to heading teams of combined laboratory and clinical investigators on the biological side. It is therefore interesting that in 1979 he articulated the existence of a syndrome going beyond clinical depression (though he continued to call it depression):

“ . . . From the welter of conditions involving unhappiness, misery, grief, disappointment, despair etc have emerged certain depressive syndromes that seem clearly to be ‘somatic affections.’”
⁴
There would be no reason for naming these sprawling syndromes depression, since the patients did not necessarily seem depressed but expressed their distress on the somatic side. (see below on depressive equivalents)

Speculation continued to flow in the direction of nerves, without using that term. At the Food and Drug Administration—not exactly a bastion of innovative thinking about the classifying of illness—Paul Leber, head of the neuropharmacology section of the office that approves new drugs, mused casually in 1983 to an advisory committee: What came first in a given illness, the depression or the anxiety? The FDA had been in the past reluctant to grant labeling for both. “What do you think of the idea of outpatient dysphoria, the mixed state, as being real? One that responds in the first week to benzodiazepines and in the third week to classical antidepressants? You would have to rework the nosology of the field.”
⁵
Indeed. Restoring mixed anxiety-depression would entail dethroning major depression. It would be a first tapping step toward nerves. Discussions of mixed anxiety-depression then surged in the 1990s and after.

The terms nervousness and nerves have now vanished from psychiatry, but elsewhere in medicine they remain current although not widely discussed concepts.

In 1955 Paul Hoch at the New York State Psychiatric Institute, one of the leaders of biological thinking in postwar American psychiatry, said rather contemptuously that the family doctors were indiscriminately diagnosing the new antipsychotic drug chlorpromazine (Thorazine) for “nerves” and the like. Of course, by then forward-thinking psychiatrists would never use such a term, but it remained, he believed, current among slow-lane types in family medicine.
⁶

In 1968, at a conference at McGill University, Stephen Taylor, an important figure in English psychiatric epidemiology, was discussing a survey of neurotic disorders that he and Sidney Chave had undertaken earlier. What they essentially found was the nerve syndrome. “We found, among people who were not necessarily attending their doctors, a sub-clinical neurosis syndrome. The symptoms, which tend to cluster, are: mild depression; undue irritability; ‘nerves’ or excessive nervousness, and insomnia. This group constitutes about 30 percent of the population.”
⁷
So nerves had not been entirely forgotten! Except that in the United States this syndrome would have been called “depression.”

And was there a touch of nerves in the many anxiety diagnoses that DSM had created in 1980? Eugene Paykel and George Winokur, editors of a special issue on anxiety in 1986 of the Journal of Affective Disorders, said in their editors’ preface, “Whether these classifications [agoraphobia, obsessional illness] are appropriate remains for further research. The distinction between generalized anxiety disorder and simple nervousness also needs to be evaluated.” This is a circumspect way of saying that “We don’t believe in generalized anxiety disorder and think that it is plain old nervousness.”
⁸
But that these international leaders in 1986 would be discussing nervousness is an interesting testimonial to the staying power of the diagnosis, conceived in the eighteenth century and not struck entirely dead even by the potent DSM.

Wherever one looked, casual references to nerves leapt off the pages, as though it were something so natural it did not even have to be explained. At an FDA meeting in 1992 on side effects of Upjohn’s hypnotic drug Halcion, generically named triazolam, Lawrence Olanoff, a physician and vice-president of clinical development of Upjohn, said in passing that they had evaluated the drug for “nervousness” and did not find any particular safety issues in that indication.
⁹

These scattered references over the years and continents do not represent solid diagnoses but an almost subliminal current of thought that bubbled from below, fed by decades and centuries of experience, into the profession’s consciousness. The word “nerves” was all of a sudden just there, part of a kind of unspoken agenda of diagnosis and treatment that was felt to be right but did not fit in with the official schemes at all.

There was as well the diagnosis of “depressive equivalents”: illnesses in patients who do not look depressed, but in whom depression was assumed to exist as the real underlying problem. Since the patient does not actually appear depressed, we would agree to the notion of depressive-equivalents only if we thought that depression was some kind of master diagnosis, and that anyone with anxiety, somatic symptoms, obsessive thinking, and so forth must at bottom be depressed. Yet perhaps the whole concept of somatic symptoms supposedly caused by underlying mood and anxiety disorders is equivalent to the nervous syndrome rather than equivalating depression? Only because the attention of the profession was becoming increasingly riveted upon depression was depression sought out as the supposed puppeteer that caused everything else in the body to move.

The doctrine of depressive equivalents actually has quite a history. It had long been known that major psychiatric illnesses were often accompanied by changes in blood pressure and heart rate (vasomotor disturbances), indeed that psychiatric symptoms often seemed secondary to the headaches, irritable bowels, thyroid disturbances, and skin eruptions that psychiatrists observed in their in-patients. These were called “vasomotor neuroses,” a term coined around 1900.
¹⁰

The next step was asserting that such vasomotor changes could represent a “depressive equivalent,” that the patients were depressed even though they did not seem to have mood symptoms. In 1929 Walter Cimbal, a national figure in German psychiatry who practiced in the Hamburg suburb of Altona, proposed the concept of “vegetative equivalents of depressive disorders.” “Gentlemen,” he told a medical meeting, “I want to convince you that neurotic disorders of the autonomic system are not only accompanying symptoms of a manic-depressive or a thyrogenic mood disorders, but that they might present even as equivalents in place of such an episode. Next to such an equivalent, the actual depressive mood change may recede to the point of being scarcely perceptible or it might be reduced to a slightly increased lability and irritability.”
¹¹
This opened the door to calling almost any autonomic dysregulation a “depressive equivalent.”

In 1934 Berthold Wichmann, a young assistant at the university psychiatric clinic in Münster, decided that the autonomic changes were so impressive that their terminology should be unhitched entirely from psychiatric lingo, and he called them “vegetative dystonia,” an independent disease entity (vegetative means autonomic nervous system; the other great nervous system in the body, the voluntary, controls movement and the muscles). He played down mental changes as secondary to these vast autonomic tides.
¹²

Both “depressive equivalents” and “vegetative dystonia” went on to become major diagnoses in Europe after World War II. But vegetative dystonia remained unfamiliar in the Anglo-Saxon world. [George Beaumont of Geigy (later Novartis) said they were not able to conduct a clinical trial of opipramol (Insidon) in England for “psychovegetative dystonia” because nobody had ever heard of it.
¹³
] The doctrine of depressive equivalents, on the other hand—depression without depression—went on to enjoy epic success in Anglo-American psychiatry.
Under the influence of the doctrine that said “the overwhelming number of neurotic states are in reality mild or severe depressions,”
¹⁴
Adalbert Kral in Montreal—who had trained in Prague and needed no lessons in German psychiatry—proposed in 1958 the concept of “masked depression.” At the Allan Memorial Institute, which was the department of psychiatry of McGill University, there had been a number of middle-aged men having a positive family history of depression with the following symptoms: “At first, the clinical picture was in all cases dominated by anxiety, tension and hypochondriacal ruminations. Depressive mood and psychomotor retardation were minimal.” The patients had loads of somatic changes, such as insomnia, weight loss, and impotence. They were unresponsive to psychotherapy but did well on electroconvulsive therapy (ECT). Kral concluded that their underlying problem must be depression: “It would seem therefore that in the cases reported, anxiety and tension formed only part of the clinical picture and masked the underlying depression.” Possibly so, but 50 years earlier the diagnosis would have been nerves, or “neurosis,” and it is unclear why it must be concluded that the patients were depressed: Other illnesses as well respond to ECT.
¹⁵

And so the concept of affective equivalents—depression without depression—diffused in the English-speaking world. But it spread with a kind of psychoanalytic overlay that brings the whole concept into question. After the work of psychoanalyst Franz Alexander in 1950, arthritis, asthma, peptic ulcer, and dermatitis were all seen as depressive equivalents because all were, following psychoanalytic theory, considered psychogenic.
¹⁶
In 1965, for example, Anthony Hordern, a psychiatrist at King’s College Hospital in London, declared that “Depressive states are also encountered as affective equivalents—periodic, spontaneously remitting ‘physical’ illnesses, such as rheumatism, asthma, peptic ulcer and dermatitis.”
¹⁷
But today we definitely do not see asthma, peptic ulcer, and arthritis as psychogenic! And dermatological conditions usually have organic not psychological causes.
¹⁸
So the whole notion that these were somehow the psychic equivalents of depression collapses. “I ask myself if it is really justified to utilize the term ‘masked depression’ in cases where there is no sign of depression,” said Dutch psychiatrist Herman van Praag at a conference in 1973.
¹⁹
What can be said is that these “equivalence” patients may or may not have had a mood disorder, and that the concept of depression was being stretched to its outer limits.