About 25% remit with second-try antidepressant

OB/GYN News, May 15, 2006 by Mary Ann Moon

After unsuccessful initial treatment with a selective serotonin reuptake inhibitor, about one-fourth of patients with depression will achieve remission by switching to another antidepressant, reported Dr. A. John Rush and his associates in the STAR*D study.

Any of several "second try" antidepressants appear to work equally well, including a different SSRI, the researchers noted.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial was designed to assess the relative efficacy and tolerability of several antidepressant treatments in outpatients diagnosed with nonpsychotic major depressive disorder.

In the initial stage of the ongoing study, more than 4,000 subjects were enrolled at both primary care and psychiatric settings, in both public and private practices, between 2001 and 2004. In this second stage of the study, a subgroup of 727 subjects who either did not achieve remission after treatment with citalopram (Celexa) or who were unable to tolerate that drug tried a second step of therapy.

The second-line drugs were sertraline (Zoloft), another SSRI, taken by 238 subjects; sustained-release bupropion, one of a different class of antidepressants that are not SSRIs, taken by 239 subjects; and extended-release venlafaxine (Effexor XR), a dual-action agent that inhibits reuptake of both serotonin and norepinephrine, taken by 250 subjects.

The primary outcome of the study was remission--the virtual absence of depressive symptoms--rather than treatment response, which is a reduction of at least 50% of symptoms. Remission carries a better prognosis and correlates with better daily functioning, said Dr. Rush, of the University of Texas, Dallas, and his associates.

Remission rates did not differ significantly for the three treatment groups: 17.6% for sertraline, 21.3% for bupropion, and 24.8% for venlafaxine. Mean time to remission also was not significantly different, at 6.2 weeks for sertraline, 5.4 weeks for bupropion, and 5.5 weeks for venlafaxine, the researchers said (N. Engl. J. Med. 2006;354:1231-42).

Side effects and serious adverse events also were similar among the three groups.

The study was specifically intended to mimic clinical practice, so participants and their treating clinicians were apprised of treatment assignments and doses. Subjects also had a variety of concomitant general medical conditions and were allowed to continue their regular medications, as well as take medicines to manage the side effects of the antidepressants or to reduce anxiety or aid sleep.

Given this careful study design, "these findings are generalizable to most adult outpatients with a nonpsychotic major depressive disorder who are treated in primary or specialty care settings," Dr. Rush and his associates noted.

Their results demonstrated that "contrary to the belief that intolerance of one SSRI predicts intolerance to another SSRI," sertraline was as well tolerated and effective as the other second-line agents, "even though 56% of patients in this trial could not tolerate citalopram."

In an editorial comment accompanying this report, Dr. David R. Rubinow of the University of North Carolina, Chapel Hill, praised the study for providing "real-world data on real-world outcomes (functional impairment) in real-world patients (including their coexisting illnesses)." He concurred with the investigators that "the results are generalizable and can be directly translated into practice." However, he also noted that the findings "are simultaneously illuminating and disconcerting" (N. Engl. J. Med. 2006;354:1305-7).

The study findings showed that attempts to achieve remission after an initial trial with an antidepressant has failed are justified, and that multiple agents can induce such a remission. In particular, intolerance of or failure to respond to an SSRI did not predict the same outcome with a second SSRI.

But the study results also suggested that at least half of depressed patients will not achieve remission after two attempts at antidepressant therapy.

Moreover, "if medications with various mechanisms of action are all roughly equivalent ... what can we possibly infer about the pathophysiology of depression, particularly since there was neither a placebo group nor a group that continued to receive citalopram?" Dr. Rubinow asked.

BY MARY ANN MOON

Contributing Writer