by Ian Osborn
Nowhere can he find an escape from his imaginary terrors. Every little evil is magnified by the scaring specters of his anxiety.… Ever and anon he confesses about this and that sin. He has eaten or drunk something wrong; he has gone some way or other which the Divine Being did not approve of.… His reason always slumbers; his fears are always awake.
This OCDer would have been treated with the commonly prescribed drug for melancholia, the strong cathartic referred to as “black hellebore,” to induce bowel movements and restore the balance of black bile.
One of the most astonishing aspects of the entire history of medicine is the length of time that the Grecian humoral theory of disease held sway. Physicians continued to try to balance the body’s humors with laxatives, emetics, salivants, and blood letting until the 1700s. A case of clear-cut obsessive-compulsive disorder found in Hunter and Macalpine’s Three Hundred Years of Psychiatry demonstrates that in the best academic centers of the eighteenth century not much had changed in the medical treatment of OCD over the course of two thousand years.
TREATMENT OF HARM OBSESSIONS IN 1716
John Woodward (1665–1728) was a professor of medicine in London who kept detailed case histories on his patients, many of whom had psychiatric disorders. He was consulted on November 6, 1716, by Mrs. Holmes, a twenty-six-year-old woman, pregnant with child, for an illness that had started some five months before. Dr. Woodward explains that his patient had one day observed, pleasantly enough, a large porpoise playing in the Thames River. Strangely, however, thoughts of the porpoise had thereafter kept intruding on her mind, soon becoming quite unpleasant and bothersome. Subsequently other unpleasant thoughts had begun to torment Mrs. Holmes, including ideas of harm coming to her unborn baby: “The thoughts obtruded themselves upon her, much to her surprise, and without any reason that she could conceive. They molested and teased her … and persecuted her almost incessantly day and night. She never awakened but these thoughts first came into her mind, and they continued till she went to sleep again.”
As the months went by, Mrs. Holmes’s obsessions became worse and worse. Dr. Woodward tells us that “she had thoughts of the Devil tempting and vehemently urging her to fling her child into the fire, beat its brains out, and the like; to which she had the utmost horror and aversion; being naturally a mild, good natured, and very virtuous woman.” The doctor notes that she developed what we would now call mental compulsions: “She frequently endeavored to cast the thought out, and to introduce another that might be more pleasing to her; in which she sometimes succeeded; but the new thought, however pleasant at first, became, in a little time, as troublesome and disturbing as that of the other.” Eventually, he informs us, she became confined to her bed. “She was neither capable of business, nor any regular thought; she durst never be by her self, or alone, for fear of some ill accident.”
Dr. Woodward understood the basic nature of obsessions and was severely critical of a previous physician who had advised Mrs. Holmes to overcome her bad thought by trying to think more cheerful ones:
People in these cases are subject to the fury of a morbid principle, and wholly under the government of it. It is the nature and property of that principle to disturb the thoughts, pervert the reasoning power, and present melancholy and vexatious ideas and images of things. So that to advise them to think rightly, or to be cheerful, is just the same as to advise a man under a severe fit of the gout to be easy and to be in no pain.
Yet, despite a good deal of insight into the psychology of obsessions, Dr. Woodward, when finally consulted, merely prescribed strong purgatives and enemas, which, he tells us, “worked plentifully, giving at least a dozen stools.” He repeated this therapy a number of times, after which the intrusive thoughts disappeared and, Dr. Woodward assures us, Mrs. Holmes became “cheerful, easy, and well.” (What cured the patient? Not the laxatives and enemas, but perhaps Dr. Woodward’s optimism that a cure was available, as well as his reassurance that she was not to blame for her dreadful thoughts. Also important was the successful completion of what had been for Mrs. Holmes a medically difficult and therefore very stressful pregnancy.)
During the eighteenth and nineteenth centuries, great advances were made in the newly established fields of neurology and psychiatry, particularly in understanding the causes of disease. Mental problems were no longer attributed to imbalances in the body’s four humors but to imbalances in the brain and nervous system. Now, for the first time, it was possible to have a “nervous disorder.” Yet, while other branches of medicine were witnessing sweeping advances in medication treatments, in that regard psychiatry was progressing at a snail’s pace.
TREATMENT OF CONTAMINATION OBSESSIONS IN 1879
William Hammond (1828–1900), who was surgeon-general of the U.S. Army and president of the American Neurological Association, is famous for coining the term “athetosis” to describe a common form of involuntary movement. This man of many talents also authored a psychiatric text, A Treatise on Insanity in Its Medical Relations, and was something of a specialist in OCD. Citing fourteen cases that he had personally treated, he described the obsessive fear of contamination and named it “mysophobia.”
A typical case cited by Dr. Hammond is that of “a young lady, aged eighteen, tall and slender,” who presented to him on January 23, 1879. She had been entirely well until a year and a half before, when she had discovered lice in her hair. Thereafter, despite repeated washings with soap, carbolic acid, and many other detergents and disinfectants, she could not shake a fear of lice infestation. She spent over an hour a day minutely examining and cleansing her combs and brushes. When she went out into the street, on passing any person, she carefully gathered her skirts together, and she would not for any reason allow a child to approach her. Gradually the fear of lice infestation broadened to encompass other areas of her life:
Little by little the idea became rooted that she could not escape sources of contamination. She washed her hands, as her mother informed me she had ascertained by actual count, over two hundred times a day. Her fear of contamination extended to the soap with which she felt compelled to wash her hands, and she was then obliged to wash them again in pure water in order to remove all traces of the soap. Then as the towel with which she wiped them dry had been washed with soap, she rinsed her hands in water, and allowed them to dry without the aid of a towel.
In removing her clothes at night, she carefully avoided touching them with her hands, because then she would not have sufficient opportunity for washing. She therefore had someone else to loosen the fastenings, and then she allowed her garments to drop on the floor. A great source of anxiety with her was the fact that her clothes were washed in the laundry with the clothing of other people; but she saw no practicable way of escape from this circumstance.
When not washing her hands or examining her combs and brushes, she spent nearly all the rest of the day in carefully inspecting every article of furniture and dusting it many times. Thus, her whole life was one continued round of trouble, anxiety, and fear.
Dr. Hammond emphasizes that his mysophobia patients have full insight into the foolishness of their beliefs, a key diagnostic criterion for OCD. “I had no difficulty in getting her to admit the absurdity of her ideas. She stated that whenever she reflected upon the subject, she was convinced of their erroneous character, but that, nevertheless, she could not avoid acting as she did. For as soon as she was exposed to any possible source of contamination, the ideas returned in full force.”
Dr. Hammond treated all cases of mysophobia with bromides. These simple salts, including potassium bromide, calcium bromide, and sodium bromide, were widely used at the turn of the twentieth century for sedation, having been introduced into medicine 1853 as the very first drugs specific for that action. Dr. Hammond notes of bromides: “There are few cases of morbid impulses and morbid fears, in the early part of their course, which resist their systematic and intelligent employment … the patient once more sleeps well, and the mind gradually gets
rid of its aberrations and resumes its normal condition.” He also often prescribed ergot preparations, strong drugs obtained from a wheat fungus that have a long history in medicine and a multitude of actions. Both bromides and ergot drugs, however, cause at best only a moderate antianxiety action and often are severely toxic. In addition, they have no direct antiobsessional effects at all. Along with these medications, and probably more helpfully, Dr. Hammond recommended keeping mentally and physically active.
Like many other physicians of his time, Dr. Hammond attributed mental disorders to local abnormalities in various parts of the brain. Mysophobia was due to edema, an excess of fluid, in certain brain areas. The medications he prescribed worked, he thought, by diminishing the caliber of the blood vessels in the brain, thus lessening the flow of blood and correcting the excess of fluid.
Another common theory in the late 1800s was that of Henry Maudsley (1835–1918), the most widely known English psychiatrist of the nineteenth century. Maudsley attributed OCD, which he viewed as a type of depression, to lowered “mental energy.” In his 1895 Pathology of the Mind, the outstanding psychiatric textbook of that period, he hypothesizes that obsessions and compulsions are caused by “a drain of nerve force” due to either “innate nerve-weakness” or excessive life stresses:
The fundamental fault is probably loose-knit cerebral centers, the inhibitory ties being weak, and consequently, separate thought-tracts taking on separate actions. Once an irregular action is established, it is a torment to the individual no matter what the particular tract and its conscious idea or impulse be. Thus he is in despair because he has the urgent impulse to do some ridiculous thing; or cannot help repeating an act foolishly over and over again; or he is constrained to think of doing an indecent act and is in a fright lest he should some day do it; or he is urged by a morbid spirit of curiosity to continually ask himself the reason of this and the reason again of that reason and so backwards the reasons of reasons without end.
Maudsley recommended treatment with “nerve tonics” such as opium and morphine prescribed three times a day. Low doses of arsenic were sometimes judged helpful as well, especially in combination with a narcotic. Maudsley also stressed the importance of living an active, disciplined, and self-controlled life and of exercising regularly.
Of course, it has turned out that no sorts of “edema” or “lowered mental energy” can be demonstrated in the brains of those who suffer OCD or other mental disorders. The medication treatments of the nineteenth century proved disappointing. Thus Freud, who had himself trained as a neurologist and had experimented with the use of cocaine as a therapeutic agent, became disenchanted with the state of psychiatry and proposed his revolutionary theories.
The textbook I used in medical school, Freedman and Kaplan’s Comprehensive Textbook of Psychiatry, taught Freud’s theories and suggested treating OCD with psychoanalysis. Regarding the use of medications, the authoritative text stated: “There are no drugs that have a specific action on the obsessive-compulsive symptoms, although the use of sedative and tranquilizers as an adjunct to psychotherapy may be helpful in cases where anxiety is excessive.” I remember dutifully attempting to interpret my OCD patients’ dreams in order to get to the roots of their unconscious conflicts, while avoiding prescribing anything.
It is notable that even while advocating his psychological theories, Freud wrote in 1920: “Biology is truly a land of unlimited possibilities. We may expect it to give us the most surprising information, and we cannot guess what answers it will return in a few dozen years to the questions we have put to it. They may be of a kind which will blow away the whole of our artificial structure of hypothesis.” Regarding treatment, he predicted in 1938: “The future may teach us to exercise a direct influence, by means of particular chemical substances.”
These prophesies were borne out shortly after I started training. Freud’s prediction of “a few dozen years” wasn’t off by much. In 1967, a Spanish psychiatrist, Lopez-Ibor, reported a drug that was specifically effective for OCD, clomipramine (Anafranil). Many case reports of its successful use followed, and in the 1980s more than fifteen double-blind and placebo controlled studies demonstrated beyond a doubt that it was a uniquely effective treatment for OCD.
Clomipramine was developed by chemists who added a chlorine atom to the molecular structure of the standard antidepressant imipramine in the hopes of finding a better antidepressant. Instead, fortuitously, the new agent was observed by psychiatrists to be helpful for OCD. Imipramine itself had been developed through experimental changes to the molecule of a certain antihistamine, done in the hope of building a better antihistamine. The compound was accidentally observed to work in the treatment of depression. All of the early breakthroughs in medication treatments for mental disorders were due to such serendipity.
In the 1970s, however, a remarkable advance in pharmacological research technique ushered in a whole new era in the development of drugs for psychiatric disorders. Solomon Snyder and colleagues at Johns Hopkins University developed a practical method of screening drugs for their effects on specific chemicals in the brain. The key discovery was finding a way to keep brain tissue chemically alive after an animal had been sacrificed. Using this technique, a rat could then be given a drug, sacrificed, and its brain tissue examined to see what effects that drug was having on various brain chemicals. Serendipity was no longer necessary. “Designer drugs” with specific effects on certain neurochemicals could now be developed.
Prozac, Luvox, Zoloft, and Paxil were all designer drugs, identified by their specific effects on serotonin. All have been proven very effective anti-OCD agents. Prozac was the first to be introduced in the United States, and its effectiveness in the treatment of OCD has been shown in more than a dozen double-blind studies, the largest a thirteen-week investigation of 355 OCD patients at eight different treatment centers. In this study, patients received either placebo, Prozac at a dose of 20 milligrams per day, Prozac at 40 milligrams per day, or Prozac at 80 milligrams per day. Mean drops in Y-BOCS scores (see Appendix A) were, respectively, 0.9, 4.6, 5.5, and 6.5. Similar multi-center studies involving hundreds of patients have now also proven clearly the efficacy of Luvox, Zoloft, and Paxil in treatment of OCD. All of the effective anti-OCD medications have approximately the same efficacy. So far, no study has convincingly shown one medication to work better than another.
RECENT ADVANCES
Research in psychiatry and related fields is increasing exponentially. Every three to four years, the number of books written and studies published doubles. In the treatment of OCD, hot topics include how behavior therapy and medications can work best together and why a sizable minority of patients respond to neither treatment. One area of current clinical research that is especially interesting, and that may shed light on these very questions, suggests that there are essential similarities in the way behavior modification and medications work.
It has been clear since the early 1980s that approximately the same number of patients, 60–80 percent, are significantly helped by both behavior therapy and the serotonergic medications. (Although some studies do give a significant edge to behavior therapy, these usually do not include the relatively large number of patients, up to 30 percent, who drop out of behavior therapy. When dropouts are factored in, the two treatments again seem approximately equal.) Furthermore, the degree of improvement is similar with the two treatments. Even when they work, neither behavior therapy nor medication can cure OCD. They both produce similar drops in symptom scores, an average of 20–30 percent.
Another similarity is the length of time it takes the two treatments to work. Antiobsessional medications, it has been repeatedly observed, take more than two months to reach their full effect, a delay that has puzzled researchers, since the direct action of these medications on serotonin at the nerve synapses takes place within hours. Researchers have long concluded that secondary changes in the brain are responsible for the SRIs’ therapeutic effects. A similar delay in therapeuti
c action is observed with behavior therapy. Obsessions and compulsions are not markedly decreased until after a person has employed behavioral techniques for a minimum of twenty to thirty exposure sessions, which usually takes a month or more.
Another similarity between behavior therapy and medication that has recently been reported—and this finding has even received attention in the lay press—points to a fundamental likeness in the biochemical effects of the two treatments in the brain. Lewis Baxter, Jeff Schwartz and colleagues at UCLA studied this phenomenon using PET scanning, the imaging technique that provides a moving picture of the brain at work. The surprising observation was that behavior therapy and medication, when effective, produced identical changes in the brains of OCD patients: specifically, decreased activity in a small part of the brain known as the orbital frontal area.
Baxter’s research has forced a reanalysis of many basic assumptions about the differences between biological and psychological therapies. When I presented these findings to a group of general practitioners recently, a doctor put it this way: “But that can’t be true, can it? Behavior therapy is by definition a psychological therapy, and it shouldn’t produce physical changes in the brain.” So many of us thought until recently, but this new evidence points otherwise. Behavior therapy and medication, two treatments that for millennia have seemed to have no common ground, do, in fact, share some sort of a final, common, biochemical pathway.
The best theory advanced so far to explain this finding is that of Harvard psychiatrist Steve Hyman, who speculates on a common biochemical action for behavior therapy and serotonergic medications in a recent book, The Molecular Foundations of Psychiatry. Hyman suggests that both forms of therapy cause the same effect at the same place in the brain: changes in the concentrations of neurotransmitters, particularly serotonin, at the brain cell junctures. In the case of medications, a large amount of evidence, some of which was reviewed in Chapter 9, demonstrates that they directly affect serotonin levels at the brain synapses. As for behavior therapy, Hyman speculates that all psychotherapies, indeed, all life events, also affect us by causing synaptic changes: