Science / Medicine : THE ORDERLY DISORDER : New drug trials and therapy offer hope for those suffering from obsessive-compulsive behavior.

In a strange routine reminiscent of Lady Macbeth, a woman spends six hours a day repeatedly washing herself, pursued by the fear that she might pass on a deadly disease to anyone she touches. Another woman stops cooking for fear she will poison her husband and continually checks electrical appliances to make sure a fire has not started. And in a third case, a man cannot prevent himself from driving back to examine every place on the road where he has hit a bump, because the thought keeps forcing itself on him that he has run someone over.

All these people have symptoms of a mental disturbance known as obsessive-compulsive disorder. It is estimated that nearly 5 million people in the United States suffer from this disorder at some time in their lives. Although instances of obsessive-compulsive disorder have been described by psychiatrists since the turn of the century, there is no standard treatment for its victims.

However, a combination of interpersonal “behavior therapy” and a new drug approach suggests a more optimistic picture for persons suffering from obsessive-compulsive disorder. Preliminary results of a multicenter study of clomipramine, an antidepressant drug not approved for use in this country, indicate that it offers substantial help for their condition.

The Food and Drug Administration recently approved clomipramine for use in “serious or life-threatening situations” documented by physicians, said psychiatrist Joseph DeVeaugh-Geiss of Ciba-Geigy Pharmaceutical in Summit, N.J. DeVeaugh-Geiss, director of the 21-center clinical trial, presented the initial findings in May at the American Psychiatric Assn.’s annual meeting. The next step in the FDA chain of approval would be clomipramine’s use as a prescription drug. This would come after more extensive human trials.

Ciba-Geigy manufactures clomipramine under the brand name Anafranil and has sold it for 20 years in Europe, Canada and elsewhere. If the drug’s promise holds up in the multicenter study, the company will ask for full FDA approval. Some clinicians and researchers have used clomipramine under a “compassionate use” exception to federal regulations, but there has been little pressure to gain federal approval for one of a class of antidepressant drugs with--until now--no apparent superiority to others already available.

Obsessive-compulsive disorder, however, is not like the severe depression for which this group of drugs is commonly prescribed. According to the official manual of psychiatric diagnoses, the primary feature of obsessive-compulsive disorder is anxiety, although it may be accompanied by mild depression.

Obsessions are recurrent thoughts and impulses experienced as senseless or repugnant, while compulsions are ritual behaviors aimed at preventing harm to oneself or others. The combination of obsessive thoughts and compulsive rituals often begins during childhood or adolescence. Many victims are ashamed of their behavior and attempt to keep it secret, rarely seeking medical or psychological treatment.

In the Ciba-Giegy trials, 578 adult obsessive-compulsives--many of whom had gone seven years or more before seeking help--received either clomipramine or an inactive placebo for 10 weeks. The patients were divided into two groups: those with and without moderate levels of depression.

According to physicians’ ratings, obsessive-compulsive symptoms were reduced by about 40% in both clomipramine groups, compared to virtually no change in the placebo groups. Clomipramine patients rated themselves as significantly more improved than placebo patients.

Clomipramine, like other antidepressant drugs, is not without side effects in some cases, and DeVeaugh-Geiss noted that 10% of the patients dropped out of the clinical trial. Side effects include nausea, dry mouth, dizziness, tremor and impotence. But most patients, he said, felt that clomipramine’s benefits outweighed any of its side effects.

Effective clomipramine treatment often extends over a year or more, said psychiatrist Michele A. T. Pato of the National Institute of Mental Health in Bethesda, Md. “But I’m reticent to say that obsessive-compulsive patients are wedded to this drug for life,” she adds.

Pato reported at the psychiatric convention that 16 of 18 obsessive-compulsive patients who responded well to clomipramine over an average of 11 months of treatment became significantly worse after receiving a placebo for seven weeks. A gradual decrease in the clomipramine dose over several months might result in fewer symptoms returning, she noted.

Clomipramine’s power, Pato said, appears to lie in its ability to increase the availability of serotonin, a chemical that helps carry messages across brain cells and has been implicated in some types of depression. There is also evidence that a patient’s obsessive thoughts rapidly worsen after taking a drug that stimulates a certain class of brain cell receptor sites for serotonin.

For some reason, says National Institute psychiatrist Thomas Insel, these receptors are “supersensitive” in many obsessive-compulsives and may create a vulnerability to the disorder. The reasons for the supersensitivity might include a genetic defect that alters the receptors’ function or a lack of serotonin in the brain.

The range of environmental and physiological origins of obsessive-compulsive disorder remain poorly understood, Insel said, but one of the first attempts at a full explanation of the disturbance came from Sigmund Freud, the father of psychoanalysis.

Freud conceived of obsessions and compulsions in his patients as complex psychological defenses used to deal with unconscious conflicts. The patients are often preoccupied with aggression or filth, according to psychoanalytic theory, as a result of a childhood disturbance during a stage when the child is intensely concerned about control.

Obsessive-compulsives also retain the childhood belief that thinking about things can make them happen, thus rendering obsessive thoughts extremely disturbing and the bizarre rituals used to ward off the thoughts strangely effective in relieving tension.

In the Freudian scheme, the man obsessed with the thought that he may have run over someone feels an unconscious desire to kill, which makes him feel as guilty as if he had actually committed homicide. He knows his behavior is absurd, but he can only quiet his anxiety by checking each bump in the road to make sure there is no body.

A successful treatment appears to be behavior therapy. In fact, says psychologist Edna Foa of the Medical College of Pennsylvania in Philadelphia, behavior therapy should be the first treatment offered to obsessive-compulsives; only if it fails should clomipramine be considered.

Behavior therapy consists of supervised exposure to anxiety-provoking situations and prevention of compulsive rituals, often with the help of a patient’s friends and family. For example, a therapist will observe while a patient touches a doorknob that he fears is infected with germs and then discusses those fears with the patient. Then the therapist will recruit friends and family to follow up on these sessions and make sure, for instance, that the germ-fearing patient doesn’t take more than one shower a day.

There is a good deal of evidence that this approach often works. The latest study, reported by Foa at the psychiatric meeting, finds that after three weeks of behavior therapy--a total of 15 sessions, each about two hours long--16 of 21 obsessive-compulsive patients improved markedly for at least three months.

Clomipramine may help the 30% of obsessive-compulsive patients who do not respond to behavior therapy, Foa said.

National Institute psychiatrist Joseph Zohar said, “We think a combination of clomipramine with behavior therapy would probably be the most effective treatment for obsessive-compulsive disorder.”