Nothing better reflects the difficulties of finding silver bullets for depression treatment than the results of the nearly completed Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the largest clinical trial of its kind. With results imminent from the last of 4 trials in the study, psychiatrists are hoping for considerably more clinical guidance than what the first 3 levels of the trials produced.
The STAR*'D study has been trying to glean insights on the best way to treat chronically depressed patients who do not respond to a first, then a second, and then a third treatment. The study has focused on the outcome of remission, not—as is typical in drug company trials—a simple improvement in condition. The results of the first 3 levels have been published, with the fourth level's results expected to hit the press before the end of 2006.
Matthew Menza, MD, professor and vice chair, department of psychiatry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, noted in an interview with Psychiatric Times that about 65% to 70% of the participants who stayed in the trial (4000 started at level 1) found significant relief, meaning that they experienced remission. "This is consistent with what we see in clinical practice," he explained. "If people stay in treatment, most people in the end get very significant relief, but it takes a lot of time and effort. This message should not get lost."
Looked at another way, though, the results are less impressive. For those participants who did not experience re mission with the first drug and agreed to continue to the next level, the chance of achieving remission was about 20%. "The results of STAR*D continue to be sobering," stated Robert Freedman, MD, editor-in-chief of The American Journal of Psychiatry. "By the third wave of the study, the rate of remission continues to be quite low, which underscores the persistence of depression and its resistance to current treatments."
Freedman, professor and chairman of the department of psychiatry at the University of Colorado at Denver and Health Sciences Center, explained in an interview that the hope going into STAR*D was that some secondary treatments "would clearly emerge as winners." That did not happen. "We learned [that] secondary treatments certainly help substantial numbers of people," Freedman continued, "but all of them have limited effects. That is what is sobering."
Moreover, citalopram (Celexa), a front-line treatment that was given to all 4000 participants who started out in level 1, "was not as effective as we had hoped," according to Freedman.
Menza acknowledged that even the 65% to 70% remission rate was open to question. STAR*D investigators have not gone back and studied those who experienced remission in level 1 to see if they had subsequent episodes of depression. Compiling that data might reduce the initial cited success rate, he pointed out.