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Psychology and Psychiatry

Therapeutics: From Behavioral Control To Biological Disease

The nature of psychiatric care has changed immensely since the early-twentieth century, shaped not only by prevailing psychiatric theory but also—and often more importantly—by practical realities such as setting, needs, and resources. State hospitalization and outpatient psychotherapy both largely have been replaced by a proliferation of psychotropic drugs, with considerable implications for how society views mental illness, as well as how people make sense of more everyday aspects of human feelings and behaviors.

Somatic therapies and behavioral control.

In the early twentieth century, American psychiatry was almost exclusively institutionally based. Nineteenth-century asylum founders had created these institutions as a means of providing a psychologically therapeutic environment in combination with physical treatment regimens, but by the turn of the century their optimism had worn off, replaced by a biological fatalism regarding the patients' chances of improving. By the early twentieth century, state mental hospitals—a designation that had replaced that of asylum—were vastly overcrowded institutions for the care of severely ill patients, many of whom became permanent residents.

In such a setting, where a handful of psychiatrists often cared for thousands of patients, patients were categorized not by diagnosis but by behavior and prognosis, and were housed in wards with labels such as "acutely excited," "chronic quiet," "chronically disturbed," and "convalescing." Disordered behavior was the primary target of psychiatric interventions, which consisted almost exclusively of somatic therapies: hydrotherapy (e.g., continuous baths or wet-sheet body wraps), insulin-induced comas, electroconvulsive therapy, and lobotomy. These treatments were believed to be therapeutic by virtue of their success in subduing out-of-control (diseased) behavior; and behavior, not diagnosis, determined the need for a particular somatic cure.

Psychotherapy.

As the overcrowding of state hospitals suggests, there was little place for psychotherapy in institutional psychiatry. It was not until the rise of psychoanalysis and out-patient psychiatry that psychotherapy became an important intervention within the field. Though psychoanalysis was largely a treatment sought by well-to-do and well-educated individuals suffering from everyday anxiety, unhappiness, or boredom, in the 1950s analysts began treating not only those suffering from neurotic ills but also traditional psychiatric patients with severe psychotic disorders such as schizophrenia. These efforts led to significant controversy in the ensuing decades, contributing to psychiatry's abandonment of psychotherapy in favor of more biological approaches. For the most part, however, the demise of psychotherapy within psychiatry can be attributed to two causes: the advent of psychotropic drugs in the 1950s and competition from the growing fields of psychology and social work in the 1960s and 1970s. By the 1990s psychiatry had largely ceded matters of the mind to psychology, content to concern itself with matters of the brain.

Psychopharmacology and biological disease.

Though psychiatrists have long had at their disposal a number of drugs capable of sedating patients (for example bromides, barbiturates, hyoscine, and chloral hydrate), these drugs were never seen as therapeutic but rather as "chemical straitjackets." The age of psychopharmacology did not begin until the 1950s with the discovery of chlorpromazine, the first of what have come to be referred to as the antipsychotic drugs. Other classes of drugs followed, inducing a veritable therapeutic revolution in psychiatry. Since the last third of the twentieth century, the major classes of psychotropic drugs include antipsychotics, antidepressants, anxiolytics, mood stabilizers, and a miscellaneous assortment of other medications, and their use has largely displaced psychotherapeutic interventions as the mainstay of psychiatry practice.

Unlike the somatic therapies and psychotherapy, psychotropic drugs carry with them an implied diagnostic specificity: separate classes of drugs for psychosis, depression, anxiety, and bipolar disorder. Much as psychoanalytic theory and treatment went hand-in-hand (a psychodynamic cure for a psychodynamic ailment), the implied specificity of these drugs fits well with biopsychiatric thinking: a specific neurochemical cure for each neurochemical trouble. As with psychoanalysis, the language of biopsychiatry has heavily pervaded American culture, carrying with it both a scientific logic that links psychiatry to the rest of medicine and a compelling description of human experience that allows people to see themselves readily in biological terms, much as people in the twentieth century readily saw their present troubles as the product of their troubled personal pasts.

From "major tranquilizers" to antipsychotic drugs.

The early stages of the psychopharmacologic revolution began in the 1930s and 1940s, when researchers began modifying phenothiazine compounds in an effort to develop synthetic anti-histamines. Henri Laborit, a French military surgeon, was interested in these drugs for their analgesic, sedative, and hypothermic properties, believing that they might be of benefit in preventing shock associated with anesthesia. In 1949 he noted that promethazine—a phenothiazine derivative—produced a "euphoric quietude" in patients, prompting chemist Paul Charpentier, of the pharmaceutical company Rhône-Poulenc, to search for phenothiazine derivatives with even greater effects on the central nervous system. The result was chlorpromazine, a compound that would eventually become known as the first antipsychotic drug.

Initially Rhône-Poulenc believed that chlorpromazine might have a variety of applications, for conditions ranging from nausea to itching, and they named it Largactil to emphasize its many uses. By 1951, however, physicians began recognizing its ability to calm agitated patients without overly sedating them. Smith, Kline & French bought the North American rights in 1952 and received U.S. Food and Drug Administration (FDA) approval to market it under the trade name Thorazine in May 1954. By 1956, 4 million patients in the United States had taken chlorpromazine—primarily for psychiatric applications—yielding $75 million in profits in 1955 alone.

Psychiatrists began referring to these drugs as antipsychotics in the mid 1960s, but until that time they were generically referred to as the "major tranquilizers," and psychiatrists considered them useful for most types of mental disorder. Smith, Kline & French recognized that state hospitals, housing more than half a million captive potential consumers, represented an enormous market. The introduction of chlorpromazine did away with the use of lobotomy almost overnight: The drug was easy to administer; rapidly and therapeutically eliminated recalcitrant, hostile, and violent behavior; and ostensibly produced relatively minor side effects. Perhaps more importantly for the course that psychiatry has taken since, physicians also prescribed it for the nonpsychotic patients who had so recently made their way into state hospitals and outpatient care, thus cementing the medical status of these new diagnoses. It was not until the mid-1960s—by which time the success of Thorazine had led to a proliferation of similar drugs—that psychiatrists winnowed down the application of these drugs primarily to the treatment of psychotic disorders, a fact reflected in the increasing use of the term antipsychotic. This transformation from tranquilizer to antipsychotic, implying the discovery of a biological cure for a specific psychiatric disease, reinforced the conviction that schizophrenia (and, by extension, most psychiatric illness) was at its root a biological disorder of the brain.

The discovery of a drug that seemed effective in treating a specific disorder—or at least in controlling its particular set of symptoms—provided researchers with a major opportunity to explore the workings of the disordered brain. Basic science research into the biological action of antipsychotic drugs laid the foundation for the remarkable progress that has taken place in the neurosciences since the mid-twentieth century. In the late 1950s, Arvid Carlsson discovered the neurotransmitter status of dopamine and demonstrated that antipsychotic drugs block dopamine receptors in the brain, research for which he was awarded the Nobel Prize in 2000. His discoveries also led researchers and psychiatrists to formulate the "dopamine hypothesis" of schizophrenia: since antipsychotic drugs work by blocking dopamine, the cause of schizophrenia must be an excess of dopamine. This bit of logic, compellingly simple and yet disturbingly circular, has been repeated with other classes of psychiatric drugs and the disorders that they seem to ameliorate. Research into the action of apparently effective drugs has been the source of many accepted models of psychiatric illness, largely because scientists lacked better ways of making sense of what goes on inside the living brain—an unfortunate reality that many hope to remedy thanks to the advent of high-quality brain imaging.

The basic nature of antipsychotic drugs changed little in the decades that followed, and the initial optimism that the drugs possessed antischizophrenic properties was increasingly tempered as the drugs' limitations became more apparent. By the late 1960s and 1970s, psychiatrists also began to notice that the drugs produced a number of untoward side effects, foremost among them being tardive dyskinesia, a late-appearing, difficult-to-reverse disorder characterized by involuntary movements of the tongue, jaw, limbs and/or trunk. Psychiatrists continued to prescribe the drugs widely, however, largely because they were simply the best available treatment for a terrible and incurable disease.

In the 1980s, a new era in antipsychotic drugs began, coupled with new hopes for better outcomes. Clozapine, a drug that was actually synthesized in the late 1950s and used briefly until clinicians discovered that it could cause a fatal blood disease called agranulocytosis, was "rediscovered" in the mid-1980s. A number of large, multicenter studies found clozapine to be highly effective in treating refractory patients—that is, patients whose condition responded poorly to other antipsychotic drugs. Clozapine was approved for use in 1989 under the trade name Clozaril and reintroduced alongside a system for carefully monitoring patients for any signs of agranulocytosis. Clozaril became the first of a number of "atypical" antipsychotic drugs, which cause markedly fewer motor side effects compared to the older drugs but, as is increasingly evident, produce a wide range of other problems, most notably severe weight gain and insulin-resistant diabetes. Because these new drugs—six of which are on the market in the United States as of 2004—do much more than simply block dopamine receptors, their success has led scientists to rethink the dopamine hypothesis of antipsychotic drug action and of schizophrenia, but also has reinforced broader claims for the biological basis of psychiatric illness and hopes for more successful cures to follow.

Psychopharmacology and the psychopathology of everyday life.

Antipsychotic drugs are in many ways the most important class of psychotropic drugs, given their relative success in managing the most striking and debilitating psychiatric symptoms as well as their role in the early history of psychopharmacology. However they make up a relatively small share of the prescriptions written for psychiatric indications (though they are among the most profitable of all drugs, psychotropic or otherwise). The bulk of the psychotropic drug market, oddly enough, is devoted to the kinds of diagnoses that might never have made it onto the psychiatric landscape if not for the expansive territory staked out by psychodynamic psychiatrists in the mid-twentieth century.

Thanks to the widespread diagnosis and medical treatment of disorders like depression, anxiety, and attention deficit disorder, biopsychiatry has become as vital a part of American culture in the early twentieth century as psychoanalysis was a half-century earlier. As with antipsychotic drugs, the drugs used to treat these disorders were discovered to work only by accident, and the biological explanations for the disorders were gleaned from the actions of the drugs that seemed to treat them. When Prozac, the first of the selective serotonin reup-take inhibitors (SSRIs), was introduced in 1988, it was not long until the SSRIs (a class of drugs that also includes Paxil, Zoloft, and Celexa) became the leading treatment for depression. Less than two decades later—thanks in no small part to direct-to-consumer drug advertising—the belief that depression is caused by a serotonin deficiency had become an established bit of cultural knowledge.

Polypharmacy and off-label use.

Intriguingly, in spite of the apparent biological specificity of the drugs on the market, psychiatric practice does not adhere neatly to the categories for which drugs are named (and approved by the FDA). Psychiatrists often prescribe multiple drugs for a single patient with a single diagnosis, and this polypharmacy often combines drugs from different classes of drugs. It is not uncommon for a patient with a diagnosis of schizophrenia or bipolar disorder to be prescribed one or more antipsychotic drugs, a mood stabilizer, an antidepressant, and an anxiolytic, the combination of which is intended—in some unarticulated and scientifically unproven way—to improve the management of their disorder. Off-label prescribing—that is, the prescription of a drug for a condition other than that for which it is approved—is increasingly common. For example, psychiatrists routinely prescribe atypical antipsychotic drugs for patients with non-psychotic diagnoses, including children diagnosed with conduct disorders—a practice that is reminiscent of the widespread use of antipsychotic drugs in the state hospitals of the 1950s. It remains to be seen whether these practices will be validated by clinical research and, if so, what sort of biological explanations will be used to explain their effectiveness.

Importance.

Since the mid-twentieth century, there has been a massive transformation in the understanding of how to treat psychiatric disease and, therefore, the understandings of its causes. For psychiatrists who cared for severely ill patients, antipsychotic drugs initially represented a different, albeit better and more efficient, means of treating behavioral symptoms, while for other psychiatrists the new drugs were merely adjuncts to the more important therapeutic task of psychological understanding and interpretation. As biological theory became more compelling, pharmaceutical marketing more effective, and cost-effectiveness a more essential determinant of therapeutic practice, drug therapy increasingly became the primary, and often only, means of psychiatric intervention. In a dramatic reversal of fortune, psychotherapy in the early-twenty-first century is at best an adjunct to pharmacotherapy and at worst a wasteful use of scarce health care resources.

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