`Negative' Clinical Trial Is Complex Creature

On the surface this trial appeared to be just one more negative, or failed, drug trial funded by industry. However, it found itself published in a prestigious journal, illustrating the adage, “the devil is in the details.”

Those details, however, are anything but common, according to Steven Roose, M.D., a professor of clinical psychiatry at Columbia University College of Physicians and Surgeons and a psychopharmacology researcher at the New York State Psychiatric Institute.

The trial did not just show that the highly selective serotonin reuptake inhibitor citalopram (Celexa) did not beat placebo in treating depression in those over age 75; the trial raised several questions, partially answered others, and above all, clearly showed that the beast known as a clinical drug trial is a complex being—one that science is far from clearly defining or understanding.

Roose was first author on the multisite, randomized, controlled study, on behalf of the Old-Old Depression Study Group, which includes researchers at Duke University, the University of Pittsburgh, Cornell Institute of Geriatric Psychiatry at Weill Medical College, UCLA-Neuropsychiatric Institute, the University of Pennsylvania, and the Mental Illness Research Education and Clinical Center at the Forest Research Institute in Philadelphia. The research, funded by Forest Laboratories, maker of Celexa, appears in the November American Journal of Psychiatry.

“First of all, to set the stage,” Roose told Psychiatric News, “older people are the most rapidly growing segment of the population. Second, depression is a very prevalent illness and a very important illness in this population because it significantly impairs quality of life, it leads to suicide, and when depression is comorbid with other medical illnesses common to this population—like cardiovascular disease—the other illness is often made significantly worse by the depression. So, we really wanted and need to find safe and effective treatments for depression in the old-old.”

Citalopram seemed a logical choice. It is highly selective for the brain serotonin reuptake transporter and therefore was thought to be associated with fewer adverse effects than more general serotonin reuptake inhibitors. It was also thought to have a lower likelihood of drug-to-drug interactions. Thus the drug should be relatively safe in the geriatric population.

Forest agreed to the researchers' demand that all control over study design and methodology would rest with the researchers. In addition, all data had to be in the researchers' possession, and all analyses had to be completed by the group.

“That was something that was rather unprecedented,” Roose noted, “and it was an important precedent.”