May 7, 2014
Higher Dose Antidepressant Initiation Can Up Suicidal Behavior in Youths

Boston—Starting children and young adults at higher doses of antidepressant therapy appears to increase risk for suicidal behavior during the first 3 months of treatment, according to a new study.

The study, led by researchers from the Harvard School of Public Health in Boston, was published recently in JAMA Internal Medicine.

Background in the report notes that an FDA meta-analysis of antidepressant trials suggested that children who received antidepressants, compared to placebo, had twice the rate of suicidal ideation and behavior than children who were given a placebo. What was unclear, according to the authors, is whether the risk was related to dosage or the patient’s age.

For the study, researchers used data from 162,625 patients between the ages of 10 to 64 years who started antidepressant treatment with a selective serotonin reuptake inhibitor at modal or at higher than modal doses from 1998 through 2010.

Results indicate that the rate of suicidal behavior was almost doubled among children and adults 24 or younger who started antidepressant therapy at high doses, compared with a matched group of patients who received generally prescribed doses.

The authors suggest this corresponds to about one additional event of deliberate self-harm (DSH) for every 150 patients treated with high-dose therapy. No difference in risk was found for adults 25 to 64 years old.

“Considered in light of recent meta-analyses concluding that the efficacy of antidepressant therapy for youth seems to be modest, and separate evidence that dose is generally unrelated to the therapeutic efficacy of antidepressants, our findings offer clinicians an additional incentive to avoid initiating pharmacotherapy at high-therapeutic doses and to monitor all patients starting antidepressants, especially youth, for several months and regardless of history of DSH,” the authors write.

In a related commentary, David A. Brent, MD, of the University of Pittsburgh, and Robert Gibbons, PhD, of the University of Chicago, say that one of the strengths of the study was its focus on actual suicidal behavior instead of just “suicide events,” which could include thoughts of death.

“Their findings suggest that higher than modal initial dosing leads to an increased risk for DSH and adds further support to current clinical recommendations to begin treatment with lower antidepressant doses. While initiation at higher than modal doses of antidepressants may be deleterious, this study does not address the effect of dose escalation,” the commentators note.

“Moreover, while definitive studies on the impact of dose escalation in the face of nonresponse remain to be done, there are promising studies that suggest in certain subgroups, dose escalation can be of benefit,” they suggest, adding that “it should be noted that in this study, there was no pre-exposure to post-exposure increase in suicidal behavior after the initiation of antidepressants in youth treated at the modal dosage.”

U.S. Pharmacist Social Connect