March 23, 2006

When One Anti-Depressant Fails, Another May Work

By Karla Gale

NEW YORK -- A new study shows that when patients with major depression fail to respond to a course of Celexa (citalopram) or cannot tolerate its side effects, approximately one third of those whose treatment is augmented with either bupropion (Wellbutrin) or Buspar (buspirone) will experience a remission of their depression. If they are instead switched to Wellbutrin, Zoloft (sertraline), or Effexor (venlafaxine), about one out of four will remit.

These findings, based on two "level 2" studies from the Sequenced Treatment Alternatives to Relieve Depression or STAR*D trial, are reported in the New England Journal of Medicine this week.

In an editorial, Dr. David R. Rubinow, from the University of North Carolina in Chapel Hill, comments that "these 'practical trials' or 'effectiveness trials,' sponsored by the National Institute of Mental Health, provide real-world data on real-world outcomes (functional impairment) in real-world patients (including their coexisting illnesses)."

However, he also points out the discouraging finding that "at least half of patients with depression do not have a remission."

In level 1 of STAR*D, 28 percent to 30 percent of patients with non-psychotic major depression went into remission when treated with the Celexa for up to 14 weeks. The two current reports explore treatment strategies for patients who fail a first course of treatment.

Dr. A. John Rush, from the University of Texas Southwestern Medical Center in Dallas, and his team members switched 239 randomly selected patients to Wellbutrin, up to 400 milligrams daily; 238 were switched to Zoloft, up to 200 mg daily; and 250 to Effexor, maximal dose 375 mg.

Depression remission rates were 21.3 percent, 17.6 percent and 24.8 percent, respectively.

Rush's team reports that "these treatments did not differ significantly with respect to outcomes, tolerability, or adverse events." They note that intolerance or lack of response to one "selective serotonin reuptake inhibitor" (SSRI) does not predict failure with another SSRI.

In the second paper, by Dr. Madhukar H. Trivedi, also with the University of Texas Southwestern Medical Center, and associates, patients continued receiving Celexa for 12 more weeks. A total of 279 patients were randomly assigned to augmentation with Wellbutrin up to 400 mg/day, and 286 were assigned to Buspar up to 60 mg daily.

Remission rates were 29.7 percent for Wellbutrin and 30.1 percent for Buspar, a non-significant difference.

However, Wellbutrin plus Celexa was associated with a greater reduction in symptoms. Also, fewer patients taking Wellbutrin dropped out due to intolerance.

According to Trivedi's group, "these results do raise the question of whether to use augmentation agents (or other treatment combinations) as first-line treatment in an attempt to achieve greater remission rates sooner in more patients than with SSRIs alone."

In his commentary, Rubinow writes: "If we fail to make health care accessible, to make the treatments for depression available, and to destigmatize depression, we will guarantee the continued and unnecessary suffering of millions of our friends and neighbors."

SOURCE: The New England Journal of Medicine March 23, 2006.