Physicians and parents alike agree fervently that "one of the worst diseases afflicting humankind is schizophrenia." This malady numbers some 2 million cases in the U.S. - edging out Alzheimer's disease, diabetes and multiple sclerosis. In the worldwide population, its prevalence appears to be 1 percent.

Children are not born with schizophrenia, which stakes its claim during adolescence or early adulthood. That's when its victim begins to show signs and symptoms of the psychosis - "withdrawing from reality." The litany runs from hallucinations and delusions to flattened affect (restricted emotions), diminished motivation, disturbed work and social functioning.

When all 20 finger- and toenails of this thumbnail definition are enumerated, an alert psychiatrist, listening to the child's parents or guardians, can list schizophrenic features that impair the patient's ability to think clearly, relate to others and distinguish between reality and imagination, as well as manifest thought disorders and bizarre behavior. In its persecutory form, a schizophrenic believes he or she is being tormented, stalked, tricked, spied upon. Other versions insist that passages from books, newspapers, song lyrics or sundry environmental cues are aimed specifically at the patient.

Suicide, with a risk of 10 percent, is a major cause of death, which reflects on the mental stresses a schizophrenic may incur. Conventional, typical, antipsychotic drugs are marked by their relatedness to the brain's dopamine receptor. Their roster of more than two dozen negative side effects ranges from headache, insomnia, nausea and diarrhea to common sniffles and weight gain. One adverse event in particular is extrapyramidal disorder. Hospitalization may often be a recourse.

More and more new-generation or so-called nontypical remedies are becoming available, notably an injectable formulation of a chemical called risperidone. It carries the brand-name Risperdal-Consta and is manufactured by Alkermes Inc.

This long-winded rundown on Schizophrenia 101 leads up to a recently ended, large-scale clinical trial of Risperdal Consta, funded by Janssen Pharmaceutica, a subsidiary of Johnson & Johnson. It s reported in the June 2003 issue of the American Journal of Psychiatry and titled Long-acting injectable risperidone: Efficacy and safety of the first long-acting atypical antipsychotic. The article s senior author is neuroscientist John Kane, at the Albert Einstein College of Medicine in New York.

Clinical Trials In 41 U.S. Hospital Centers

"The journal article demonstrated," Kane told BioWorld Today, "that this new atypical antipsychotic medication is safe and effective in the treatment of schizophrenia." The study it reported was a 12-week, multicenter, double-blind, randomized, placebo-controlled clinical trial that enrolled 400 patients who had acute schizophrenia symptomology. It was conducted at 41 hospital centers in the U.S. "The need for a placebo was to demonstrate efficacy, comparing the drug to placebo, of which 98 patients received these controls.

"What's newsworthy," he continued, "is that this is the first of the new medications - the second generation - sometimes referred to as atypical' antipsychotics. They are the first that are available in a long-acting injectable formulation. And the technology we tested to make that possible is the first time this microsphere formulation has been used, to my knowledge, in a psychotrophic drug. It has not yet been approved by the U.S. Food and Drug Administration, but we expect that to happen in the not too distant future.

"It has been approved in about 20 countries around the world," Kane added. "So this will now make available a long-acting injectable drug, as an alternative to the current oral risperidone. And that's very important because there are many, many patients who have a great deal of difficulty taking their oral medication on a regular basis. As a consequence of that, there are inordinately high rates of relapse among patients with schizophrenia, who are living in the community.

"The currently employed conventional first-generation typical medications," Kane went on, "are associated with a variety of neurological side effects. However, the so-called atypical antipsychotics were found to be much less likely to cause these adverse events. That is why they were initially labeled atypical. That term has outlived its usefulness, because now there are several new atypical drugs that are no longer as atypical as they once were. They are becoming the standard medication - still only oral in the U.S. - used to treat schizophrenia. So it would make more sense to describe them as new or second-generation, as opposed to conventional.

"The new injectable drug enables the doctor or clinician to have complete assurance that the medication is in fact available to exert the desired therapeutic effect. If the schizophrenia patient misses an injection, then the clinical team knows immediately that the person is not getting the medication he needs, and can intervene. In contrast, when someone takes the oral form, the clinical team usually is not aware of noncompliance until well after the fact, and often only when the patient has begun to experience the relapse that results from discontinuing medication. So the new antipsychotic drug offers an enormous advantage from a public health standpoint in terms of preventing relapse and rehospitalization. When treatment is discontinued, the risk of relapse increases about fivefold," Kane observed.

Novel Drug Technology: Polymeric Microspheres

"Risperdal Consta is a synthetic chemical," Kane pointed out. "In this therapeutic formulation, it is embedded in a polymer that is gradually hydrolyzed after it's been injected intramuscularly into the buttocks. It's similar to that used in biodegradable surgical sutures. This new, long-acting injectable formulation makes use of microsphere technology developed by Alkermes Inc. It allows the risperidone to be released gradually into the body. The polymer from which the microspheres are made break down into carbon dioxide and water, which are then eliminated from the body.

"The FDA had approved the oral version in 1994," Kane recounted, "and it has been on the U.S. market since then. But the agency felt that the new injectable formulation of this compound, using the microsphere technology, should be treated as though it were a new medication. So it required a whole series of new studies, which have now been completed and submitted to the FDA." Discussions, he said, are ongoing with the agency, which issued a nonapprovable letter based on certain aspects of the preclinical data. J&J recently filed a response to the letter, supporting acceptance. "We're awaiting that approval," Kane concluded.