How Everyone Became Depressed (22 page)

Then Spitzer came to the last candidate on the list. “Sit down for this one,” he advised Task Force members. It was melancholia.
Spitzer noted that Dartmouth (later UCLA) psychiatrist Peter Whybrow had suggested melancholia to the Task Force several years previously as preferable to major depression, but people rejected it “because it was outdated. Its resurrection now is a suggestion of Bernard Carroll and Michael Feinberg.” This is an interesting comment, given that Carroll in his letter had not proposed this, and the Carroll letter in Lancet did not envision such a resurrection either.
What positive could be said about melancholia? Spitzer noted that Freud had used the term, an argument that usually sufficed, in those days, to justify just about anything. And then: “Perhaps one of the strongest arguments in favor of the term Melancholia is historical continuity.” (It was, indeed, one of the jewels in the crown of psychiatry.)
And con? “The term is antiquated and will cause a lot of guffaws.”
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Spitzer proposed melancholia as a subtype of major depression (a “fifth-digit code”). The published version of DSM-III included the melancholia subtype of a “major depressive episode,” with at least three of six features (largely those he had enumerated above).
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But the melancholic subtype that emerged from Spitzer’s pen, weeks before the draft DSM-III was to go to the press, was a pale shadow of the historic melancholia, with its crushing burden of intolerable pain. As your three melancholic features, you could have loss of appetite, early morning wakening, and symptoms worse in the morning than in the afternoon. You did not need to have psychotic guilt about having killed all your children (when in fact you had not); or agitated pacing alternating with stupor and brooding about your sinfulness; or thoughts so slowed that you were unable to think, to concentrate, to read a book, and to remember by the bottom of the page what you had seen at the top. As Thomas Ban has pointed out, in research studies of the patients diagnosed with major depression, only 30% definitely fulfilled criteria for Kraepelin’s depressive states in manic-depressive illness, and only 14%for Kurt Schneider’s vital depression.
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Spitzer’s melancholic subtype was not real melancholia, and the uselessness of the subtype contributed further to erasing the real version from the collective memory of psychiatry.
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Carroll commented on Spitzer’s melancholia: “So what Spitzer did was to take this metaphysical concept that he had and to disembody it from the patients it happens in.”
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This was a world historic defeat for psychiatry.

The anxiety section of DSM-III ended up as a real dog’s breakfast, not to put too fine a point on it, because of the politics of the Task Force. The result was the further fragmentation of a concept that had begun as an organic part of the nervous syndrome, had transitioned to an ionic bond with depression in the diagnosis mixed anxiety-depression, and was now dismantled. Jean Endicott chaired the anxiety committee, though Don Klein seems to have been the driving force.

Readers of this book are familiar with panic as a paroxystic form of anxiety. This well-established concept was essentially extinguished by psychoanalysis, which had little interest in such fine differentiations; and aside from the brief awakening that panic experienced at Oskar Diethelm’s hand in 1932, panic went off the radar in psychiatry until Klein and Max Fink began trials in the early 1960s with the new antidepressant drug imipramine (Geigy’s Tofranil), the first member of the chemical class of tricyclic antidepressants, at Hillside Hospital in Glen Oaks, Long Island. The work Klein published with Fink was important and led to the understanding that drugs such as chlorpromazine were not just antipsychotics. But on his own, Klein observed on the ward a number of “extremely anxious patients” who had received no benefit from either sedatives or antipsychotics. “Such people, often feeling quite well, are doing something innocuous, such as walking down the street or having a meal, when suddenly they are struck by the worst experience of their life: they become suffused with terror, with a pounding heart and inability to catch their breath; the very ground underfoot seems unstable, and they are convinced that death from a stroke or heart attack is imminent.” Symptoms worsen, and eventually such patients are admitted to a place such as Hillside. “The happy thought struck us that perhaps these patients might benefit from imipramine. The logic behind this was not exactly coercive: it was more a case of our not knowing what else to do for them.” Slowly, these patients with “panic attacks,” soon to be called agoraphobia, began to get better. Imipramine did not work on any other type of anxious patients, but it had a slow but powerful effect on the panic patients.
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Klein did a double-blind study of 28 of these patients at Hillside, publishing the results in 1964. (Preliminary findings had appeared in a paper published with Max Fink in 1962.
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) Klein had, in effect, established panic as an independent illness separate from anxiety. The paper concluded that “The use of patterns of drug response as dissecting tools, allowing the discovery of specific . . . similarities within psychiatric subpopulations is emphasized.”
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The discovery of “pharmacological dissection,” that drugs could be used as a pharmacological torch to carve out illness entities in psychiatry, gave Klein an impressive reputation.

In 1967 Klein described the effectiveness of imipramine in panic with subsequent agoraphobia, meaning that “Their activities become progressively constricted until they are no longer able to travel alone for fear of being suddenly rendered helpless while isolated from help.”
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But there could also be agoraphobia without panic attacks. The diagnoses had started to multiply.

Bear in mind that DSM-II in 1968 had only one anxiety disorder, anxiety neurosis; obsessive-compulsive neurosis and phobic neurosis were separate diagnoses.
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Under “anxiety disorders,” the anxiety committee for DSM-III in its draft of August 1975 produced five separate conditions: panic disorder, generalized anxiety disorder, phobic disorder, obsessive-compulsive disorder, and somatic preoccupation disorder.

How did generalized anxiety disorder (GAD) get in there? Once panic was in, the question arose of differentiating it from anxiety, which was to be a separate diagnosis. James Sheehan at Harvard recalled hearing of a dinner involving the members of the anxiety committee. “ . . . They decided that, while they could identify this panic disorder, they should invent another disorder that would be a benzodiazepine-responsive disorder. So the pharmacological dissection was that panic disorder is the tricyclic responsive syndrome [imipramine] and generalized anxiety was going to be the benzodiazepine [Valium-style drugs] responsive syndrome. It sounded like it had a good ring to it—GAD—somebody said ‘gee that sounds wonderful, these people are generally anxious when they don’t have panic attacks.’ But nobody really went out to see where one ended and the other began.” Sheehan recalled that as he heard of this discussion, “I thought this doesn’t make sense to me because I don’t think there are two distinct syndromes and that really the anxiety neurosis concept is probably closer to the truth and maybe even hysteria is closer . . . It was chaos at the time.”
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GAD was said to be a residual category, a place to put the anxious patients who were not panicky, phobic, or preoccupied with their bodily symptoms. “Don insisted on panic disorder and generalized anxiety disorder,” said Paula Clayton later in an interview. “GAD got there because they weren’t going to give Don hysteroid dysphoria.”
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Hysteroid dysphoria was a coinage of Klein that ultimately became the diagnosis of atypical depression. Spitzer, however, had no patience with hysteroid dysphoria and refused to grant it to Klein, who was a sufficiently powerful figure that he had to be placated with something else, hence GAD. The horse-trading here is delicious.

Klein, it must be said, did not regard GAD as a residual category. He told Spitzer that it was the only disorder in the anxiety basin that was not autonomous. For panic disorder and so forth, “Although something may kick it off, we really expect the syndrome to continue even if the precipitant disappears. That’s not the case with Generalized Anxiety Disorder. Here implicitly we really do not expect autonomy.”
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[This issue has not really been resolved even to this day. In any event, DSM-IV did not take it on, and DSM-5 differs from DSM-IV only in the most trivial ways, hiving off packrat behavior into a separate category (“hoarding disorder”) for example.]

All this subdividing did not sit well with other committee members. Isaac Marks, a well-known specialist in anxiety at the Maudsley Hospital in London, found the distinction between generalized anxiety disorder and panic to be without foundation. In June 1977 he wrote Spitzer, “The evidence for the importance of panic attacks as a basis for classification is shaky at the present time and needs much better replication . . . ”
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And Michael Gelder, professor of psychiatry at Oxford who, unlike Marks, was not a committee member yet had been consulted, told Spitzer in May 1978, “As you know, I do not accept the existence of the diagnosis of panic disorder. Panics are symptoms of the agoraphobic syndrome and they may be present in some cases and absent in others.”
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(Klein hotly denied that this was true: “I have seen many patients with panic disorder who do not have agoraphobia.” It was such exchanges that led, in the draft of March 30, 1977, to the inclusion of the diagnoses “agoraphobia with panic attacks” and “agoraphobia without panic attacks,” a distinction that Klein subsequently found to be without a difference.)
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Simultaneously, the anxiety committee began to splinter the phobias into separate diagnoses: agoraphobia, social phobia, simple phobia, and mixed phobia had all cropped up by March 1976.
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There was more. An “atypical anxiety disorder” was added in December 1976,
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making the number of separate anxiety diagnoses now nine. Then, as we have seen, in March 1977 the “with and without panic attacks” qualification appeared. Then at the very end, on the final draft of November 15, 1979 just as DSM-III went to press, “post-traumatic stress disorder, acute versus chronic or delayed,” was shoved into the anxiety section.
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T o think that in 1968 we had started with one anxiety disorder, and now there was a veritable cascade. And people were asking themselves, is this science?
Did any of this concern depression? We saw above Spitzer’s resistance to mixed anxiety-depression. Then something strange happened. In a close to final draft, in January 1978, Spitzer allowed that “ . . . All of the manifestations of Anxiety Disorders can occur in individuals with Affective Disorders, although the converse is not true.”
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This would seem to demolish much of the firewall between anxiety and depression that he himself had constructed. And perhaps that is the reason this statement was not included in the published version.
After DSM-III was launched in 1980, there was a good deal of dissatisfaction with the splintering of anxiety. At Sheehan’s Psychosomatic Clinic at Massachusetts General Hospital, one of Harvard’s teaching hospitals, there were a succession of patients who “presented . . . for treatment of spontaneous panic attacks and phobic symptoms.” Of 100 consecutive such patients:

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Panic disorder, 100% of them
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Generalized anxiety disorder, 100%
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Agoraphobia, 100%
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Simple phobia,100%
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Conversion disorder [classic hysteria], 100%
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Atypical somatoform disorder, 100%
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Dysthymic disorder (atypical depression), 92% (depressed feelings, but no “vegetative” signs of depression)

Sheehan concluded that “Simultaneous assignment of the majority of the patients to all of these diagnostic categories suggests that these categories, as distinct entities, do not reflect the natural order. They do not ‘cut nature at the points.’”
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Juan Lopez Ibor, professor of psychiatry in Madrid, was more blunt. “Generalized anxiety, as currently defined, might be described as a waste basket of conditions.”
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DSM-III was big. It gave psychiatry a public profile much larger than ever before, and attuned people to psychiatric diagnosis as a kind of normal event, much like any other illness, rather than as some nightmarish visitation. But the line between the beneficial destigmatization of illness and the epidemic spread of an illness attribution is a thin one. At some point, medicine stops and culture takes over. Spitzer agreed subsequently with an interviewer that DSM-III and its successors had become “cultural events.” “It is amazing. I guess it defines things. . . . I guess it defines what is the reality.”
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M uch after the circumstances described in this chapter took place, Max Fink, one of the pioneers of biological psychiatry, commented on the shift from manic-depressive illness to major depression. “When it was manic-depressive illness, it was a small number of people. When it became major depression . . . 50 percent of the people are depressed. That’s absurd. That means there’s something wrong with the label.”
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“We are troubled on every side, yet not distressed; we are perplexed, but not in despair. Persecuted, but not forsaken; cast down, but not destroyed.”
II Corinthians, 4, 8–9

History has always known antidepressant remedies. In an era of faith, the faithful held to the Word as an augury of recovery: “cast down, but not destroyed.” But in a secular era and certainly by the middle of the twentieth century, pharmacological remedies were required.

Indeed they were urgently indicated, for the diagnosis of depression itself was starting to spread. Because of Kraepelin and Freud, by 1940 depression had become a common term for serious psychiatric disease. An editorial in the Lancet called depression “perhaps the most unpleasant illness that can fall to the lot of man.” Depression was thus, while not terribly common, a considerable public health issue.

What is puzzling in this story is that around 1940 depression began an inexorable, irreversible climb from awful but unusual to epidemic status. With the 1960s, depression started to become epidemic.

One reason for the upswing in depression in mid-twentieth century was the cheering of the pharmaceutical industry. The drugs of the first generation of psychoactive medications were indicated for nervous disease, but thereafter the firms switched to depression because here were clearly the markets of the future.

The early drugs represented an effective treatment for nervous disease. Their effect was sedation, and sedative drugs in medical practice go back to opium and to members of the belladonna family that have been known since Ancient times. Sedation means the process of calming, or allaying excitement. It does not necessarily involve the obtunding of consciousness, although large doses of sedatives may do that. Sedation means easing the pain of being, soothing the griefs and worries of existence, and calming the depressive and anxious agitation of the nervous syndrome. Although we all have worries and anxieties, we do not all have a pathological syndrome called nervousness. Historically, it was those with nerves who benefited from the early psychopharmacological treatments, beginning with the bromides at mid-nineteenth century. The first sedative made by chemical synthesis, chloral hydrate, was used clinically in 1869. A succession of sedatives from the organic chemical industry followed. None had huge currency because they either tasted foul or had an unpleasant odor.

The game changed at the turn of the century with the introduction of a new class of sedatives called the barbiturates. The first, Veronal (barbital), was ushered into the university psychiatric clinic at Jena, Germany, in 1903. Less addictive than opium and less dimming of consciousness than belladonna alkaloids such as scopolamine (commonly used as an anesthetic), the barbiturates calmed and soothed and sedated the cares of many. Of course they had side effects, including the risk of overdose; in particular, they could be accumulated and used to commit suicide. Yet there are many ways to commit suicide, and sinking an entire drug class for this reason was unnecessary pharmacoside (to coin a phrase).

The barbiturates achieved instant acceptance. “Veronal at present is very popular,” said Francis Boyd, lecturer on therapeutics in Edinburgh, in 1910.
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A torrent of barbiturates, often in combinations with other agents, poured onto the market. By 1932 Indonal, a combination of barbital and cannabis indica (a cousin of marijuana), was on sale in Britain, as were Veronidia (barbital and passion flower) and Alepsal (belladonna, phenobarbital, and caffeine).
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These were effective sedatives and hypnotics, and were found in medicine chests around the western world.

The medical press was filled with advertisements for the barbiturates as hypnotics and sedatives: Merck in Darmstadt flogged Veronal Sodium as suitable for rectal applications and as an essential companion in travel.
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In 1931, Dehaussy Laboratories in Lille, France, offered “Sedoneurol” (phenobarbital) to “calm without depressing” for the indication of “nervous instability.” Likewise, Buisson Laboratories in Paris proposed the abovementioned “Veronidia” as an “ideal sedative in nervous hyperexcitability, in all of its manifestations: various neuroses, palpitations, phobias, insomnia, anxiety neurosis, etc.”
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So the uptake of barbiturates for nervous diseases of various kinds was considerable, without, as far as one can tell, reaching the level of cocktail party chitchat, as was later to happen with the “antidepressants.” I realize this is a difficult judgment call for historians to make, since these people are all dead and we do not really know what drugs they mentioned as they convened socially. Yet there are hints: Virginia Woolf, for example, a prominent member of the London literary circle, took Veronal, but mentioned it only casually to her lover Vita Sackville-West (Woolf had just suffered one of her periodic nervous illnesses and believed Veronal had plunged her into it).
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Marcel Proust, the Parisian novelist, initially took the nonbarbiturate Trional, then around 1909 switched to Veronal, apparently swallowing the tablets in great numbers, discussing this only with a handful of intimate confidants.
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In 1936, 99,000 pounds of phenobarbital alone were sold in the United States; sales for all barbiturates equaled 2,200,000 doses a day.
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Some barbiturates, such as butabarbital (Soneryl), had a short half-life and were useful as sleeping agents; others, such as phenobarbital, with longer side chains had more lasting half-lives.
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Their calming and sedating effects were much demanded in psychological medicine, where agitation and “excitement” of an unpleasant sort are the order of the day. “Sedation” today is in bad odor, and the preferred concept is “anxiolysis.”

Thus, the effectiveness of the barbiturates lay in sedation. Arthur Foxe, a veteran Manhattan family doctor with an office on West 54th Street, said in 1943, “Sedatives hold their eminent position by virtue of their assistance in bringing about a more peaceful withdrawal from worldly affairs.”
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We would never encounter such a phrase in the pharmaceutical advertisements of today, yet Dr Foxe had touched on a truth: This sort of withdrawal is often called for, to calm the agitated spirit, rather than the use of antidepressants.

Despite the horror stories that have come down to us in the textbooks, the barbiturates in their day enjoyed a reputation as safe and effective agents, particularly as hypnotics. In 1957, Louis Lasagna, a pharmacologist then at Johns Hopkins—and later acknowledged as the dean of American pharmacology— reexamined “objections raised to barbiturates and other older hypnotics,” finding most of them overdrawn. This was 3 years before the introduction of Librium, the first of the benzodiazepines. Lasagna wrote that “Barbiturates and chloral hydrate remain the prime reliance of most physicians in managing the sleep disorders of their patients. When properly used, these older drugs are remarkably safe and effective, and produce untoward effects infrequently.”
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To be sure, there is a difference between sedation and the relief of anxiety: Sedation means controlling a high arousal state, whereas anxiolysis relieves an affective state characterized by excessive tension. A high arousal state may be present without the accompanying mood disorder of anxiety.
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Yet in the real world of medical practice, meliorating anxiety often does mean sedating the patient in some way. Notwithstanding the commercial hype surrounding the Valium-style drugs, the benzodiazepines, in the 1960s, their antianxiety and antidepressant action accomplished much the same thing as the sedation of the classical barbiturates.

But depression was part of the nervous package as well. The barbiturates were effective not just in the treatment of insomnia and anxiety, which were two of the pieces of the nervous syndrome, but also enjoyed success in the treatment of depression. English family doctors and patients alike looked back with fondness upon “the green medicine” for “mild or moderate emotional disorders”—a mixture of hyoscine (scopolamine) and phenobarbital in peppermint water. Said family practitioner Ian Tait in retrospect of his practice in a village in Sussex, “Long after the early antidepressants became available [late 1950s] the green medicine was often used as a first treatment. It very often worked. The pressure to prescribe antidepressants really came from the hospital.” Once discharged from the hospital, patients would invariably return with prescriptions for medications that none of the family doctors had ever used. “I certainly remember patients coming back and asking if they could go back on the old green medicine again, known and trusted and without significant side-effects.”
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The evidence for the effectiveness of the barbiturates for depression and anxiety is considerable. Several Midwestern universities had departments of psychiatry that, unlike most American psychiatry at the time, were fortresses of psychopharmacology. It was at the University of Wisconsin that Richard Bleckwenn in 1930, associate professor of neuropsychiatry, found the new barbiturate sodium amytal of the Eli Lilly Company useful in a number of conditions, including depression. “It can be said without reservation that no drug in common use . . . will produce the degree of mental rest and physical relaxation in so short a time or over so long a period apparently without danger to the patient as does ‘Sodium Amytal.’” He said of “manic-depressive psychosis”: “In the depressed stage of this disease, the favorable response takes the form of a greater willingness to eat and take fluids . . . They are more active, more talkative, have less constrained and less awkward attitudes, and certainly the course of their depressions [is] materially shortened.”
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At the University of Iowa, another powerhouse of biological thinking, in 1949 Jacques Gottlieb referred to sodium amytal specifically as an “effective anti-depressant,” and advocated it in combination with the amphetamine Benzedrine in the treatment of depression.
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As late as 1967 the World Health Organization accepted the barbiturates for the treatment of “depressive disorders.”
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By these years people had long stopped talking about nerves and sedation. But the barbiturates were effective in treating complaints that previously would have been deemed nervous.

The benzodiazepines (Valium-style drugs), introduced in 1960, did change the sedative picture, because they were not marketed as sedatives. In other respects, it is not at all clear that the benzodiazepines were superior to the barbiturates. Donald Klein and John Davis wrote in 1969 that “There is no very convincing evidence that these drugs [the “minor tranquilizers” including the benzodiazepines] are superior to short-acting sedatives, such as amytal, for the relief of manifest acute anxiety.” All, however, were superior to placebo, the authors said.
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The barbiturates were thus effective drugs and the “new antidepressants” argument for the rise of depression cannot be sustained: Depression and anxiety did not become a treatment focus in the 1960s and after because of the advent of miracle new drugs: The barbiturates too were quite efficacious. It was not the march of the antidepressants that prompted an epidemic of depression.

If the barbiturates and amphetamines were successful before the 1960s in the treatment of the components of nervousness, why did their success not occasion the epidemic spread of these diagnoses—just as the marketing of the “antidepressants” today has contributed to the spread of “depression”? The diagnoses of the pre-1960 era, such as mixed depression-anxiety, did not spread epidemically because the entire diagnostic and therapeutic concept of psychiatry, based on psychoanalysis, was opposed to them. Psychiatrists, whether analysts or not, were most often trained under the Freudian paradigm, which valued psychotherapy above all else and maintained that illness stemmed from anxiety over unconscious conflicts. Psychiatrists were often obliged to prescribe medications in order to reach patients otherwise unsuitable for psychotherapy, or unresponsive to it. But they did so reluctantly and with an absence of conviction. The setting in which a drug is given does influence treatment response. Heinz Lehmann found at the Douglas Hospital in Montreal that patients given phenobarbital in a group therapy session became very lively. If you gave it to them individually, they became sleepy.
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The New Y ork State Psychiatric Institute, the epicenter of postwar American psychiatry, was heavily oriented toward psychoanalysis. Phillip Politin—an analyst—and Paul Hoch, who was trained in Budapest and was not an analyst but was sympathetic, were in charge of the female service; they had been using sodium amytal to carry out narcotherapy, inducing patients into a semistupor and then hoping they would cough up revealing unconscious material. In 1948 they noted that the success of this approach had been uneven: “War neurosis responded well to this treatment but the civilian neuroses do not show the remarkable effects observed in the war neuroses . . . This method is not a substitute for intensive psychotherapy or prolonged analysis.”
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So there we had it: The true convictions of analytically schooled American psychiatry lay on the side of psychotherapy and against what many analysts contemptuously referred to as “pills.” Under such hostile conditions, drug treatments, and diagnoses responsive to pharmacotherapy, would not flourish. The physicians would not grant nervous diagnoses but rather would label their patients with anxiety neurosis. And the patients would not clamor for the drugs or the diagnoses because—and this is a cardinal rule of medicine that is as old as the hills—patients are always intent upon producing symptoms that their physicians will find convincing. If the doctor believes that I have neurotic anxiety, then I will give him neurotic anxiety (so that he will believe I do not have hysteria).
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Before World War II, other classes of drugs as well showed benefit in the treatment of nervous illness and its depressive component. Opium was used for melancholia by the Ancients, and its modern service in depressive illness goes back to the eighteenth century.
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In 1936 the amphetamines began to be indicated for depression, and methylene blue, an early ancestor of the antipsychotic phenothiazine drug class, showed promise as well. Here is not the place to explore these byways in the history of psychopharmacology, which have been detailed elsewhere.
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The point is that drugs effective in depressive illness have a long history and certainly do not begin with the introduction of the first official “antidepressants,” the tricyclic compound imipramine (Geigy’s Tofranil) in 1957.