AACAP: Antidepressant Continuation Reduces Relapse in Kids

SAN DIEGO, Oct. 30 -- Antidepressant medication should be continued for at least six months past the acute stage of major depressive disorder in children and teens, as is done for adults, researchers reported here.

A total of nine months of Prozac (fluoxetine) treatment significantly reduced the pediatric depression relapse rate compared with placebo, particularly in younger children, according to Graham J. Emslie, M.D., of the University of Texas Southwestern Medical Center in Dallas.

However, relapse rates were high regardless of whether the participants received active medication, and getting the participants to stay on therapy over time was difficult, Dr. Emslie said at the American Academy of Child and Adolescent Psychiatry meeting.

Though many clinicians have extrapolated the adult benefit for antidepressant continuation to children and teens, no clinical trials had validated it.

"It's not a surprise," said commented Gregory N. Clarke, Ph.D., of Kaiser-Permanente in Portland, Ore. "It's what we all suspected, but things with children and adolescents haven't always turned out that way."

The double-blind continuation study followed on the heels of a 12- week acute treatment phase in which patients were treated with Prozac. The continuation study included the patients who went into remission after acute treatment.

The relapse rates were 42.0% for those on Prozac and 69.2% for patients on placebo at the end of the six months of continuation therapy (P=0.005). Using a stricter definition of relapse, the rate was 22% in the Prozac group compared with 48.1% in the placebo group (P=0.005).

Children ages 11 and younger had a better response to continuation therapy than older pediatric patients. Using the stricter relapse definition, the researchers reported:

• Children 11-years old or younger relapsed at a rate of 17.2% on Prozac versus 50% on placebo (P=0.009).
• Adolescents ages 12 and up relapsed at a rate of 28.6% on Prozac versus 45.8% on placebo (P=0.23).

These 50 patients randomized to Prozac and 52 randomized to placebo initially had low depression severity scores on the Clinical Global Impression scale (1.8 versus 1.7) and Children's Depression Rating Scale (23.3 versus 22.4). The mean age was 11 years and about 36% were girls in both groups.

Relapse was defined as a one time Child Depression Rating Scale-Revised score of 40 or more with a history of two weeks of clinical deterioration or clinical deterioration as judged by the clinician. The stricter definition of full relapse excluded the clinician-judged deterioration criteria. Participants had biweekly office visits until week 16 then monthly.

The investigators found, not surprisingly, that residual symptoms after acute treatment were associated with relapse. They reported:

• None of the patients on Prozac continuation therapy relapsed who had no residual symptoms compared to 36.7% who did have residual symptoms (P=0.002), and
• Even in the placebo group fewer patients relapsed who had no residual symptoms compared to those with residual symptoms (39.3% versus 58.3%, P=0.27).

Discontinuation was a problem, though, with only a third of patients who started on Prozac staying on for the full nine months. Seventy percent of the active treatment arm discontinued for any reason as did 78.8% of those on placebo. Only a small percentage was due to adverse events (2% in the Prozac arm and 0% in the placebo arm).

The study was funded by the National Institute of Mental Health.