Psychiatric side-effects of interleukin-2.

Psychiatric Side-Effects of Interleukin-2

Interleukin-2, the sometimes-promising, sometimes-disheartening experimental anticancer drug, last week took another stumble in the medical literature. In the September ANNALS OF INTERNAL MEDICINE, the genetically engineered immune-system booster is blamed for a variety of "clinically significant neuropsychiatric' effects, including severe paranoid delusions and hallucinations. No new data were reported on the drug's anticancer properties.

Perhaps no other drug undergoing clinical trials has so encouraged, then disheartened and again inspired its would-be beneficiaries--be they pharmaceutical investors or cancer patients. Reports of near-miraculous tumor shrinkage have been dampened by problems with toxicity (SN: 12/13/86, p.373), and all along there have been questions about behavioral changes that appeared to be related to interleukin-2.

Kirk D. Denicoff, David R. Rubinow and their colleagues at the National Institute of Mental Health and Steven A. Rosenberg and his colleagues at the National Cancer Institute are the first to use a battery of psychological tests to measure the degree of psychiatric distrubance that can be directly attributed to interleukin-2 therapy. They find that a number of serious psychiatric disturbances are associated with the drug and are doserelated.

The study is accurate, says Edward Bradley, director of clinical biology for Emeryville, Calif.-based Centus Corp.--the company holding U.S. patent rights to interleukin-2. But the research can easily be misinterpreted, he told SCIENCE NEWS. "What it boils down to is that the patients are often irritable, they can be tired, they can be not quite as sharp as they normally are. . . . That's what Rosenberg means when he says "neuropsychiatric effects.''

The study reported more serious behavioral abnormalities than these, however. Of 44 cancer patients studied, 15 were deemed by standardized tests to have "severe behavioral changes,' including 12 cases of "severe agitation and combative behavior' that necessitated the use of psychiatric drugs or physical restraints. Seven patients developed delusions, including five with paranoia who were "convinced that at least someone on the staff was trying to hurt or kill them.' Severe cognitive changes were identified in 22 patients, with all of them meeting standard psychiatric critera for delirium. Symptoms included disorientation to time by as much as three days and an "inability to identify correctly the obvious occupations of those in attendance,' the researchers report.

Bradley, of Cetus, says that while such findings may sound alarming, "A lot of the words are standard words in psychometric evaluation. I think it would be wrong to say that this is any different from what goes on in lots and lots of common medical situations where a degree of emotional alteration or intellectual impairment is expected.' He compares the effects of interleukin-2 to the fogginess or irritability that may accompany the use of antihistamines.

Bradley points out that the researchers, who declined to be interviewed about their work, do note in their article that "every patient studied recovered from the neuropsychiatric side effects.' Adds Bradley, "In the context of a patient in the hospital who is being treated for a life-threatening and otherwise universally fatal malignancy, and when [the psychiatric effect] is self-limited, then as far as the physician goes this is no big deal.'

The scientists also found that patient education before treatment, family contact during treatment and sources of stimulation such as television or music were helpful in mitigating negative reactions. Nevertheless, they conclude, "clinically significant neuropsychiatric changes . . . were common and may be treatment-limiting.'

They report that the causes of the changes are under investigation and that subsequent research may shed light on the mutual regulatory interactions of the immune and central nervous systems.