Increased risk of self-harm among children, young adults on high-dose therapy

Antidepressants initiated at high doses increased the risk of suicidal behavior during the first 90 days of treatment among children and young adults, according to recent findings.

Matthew Miller, MD, ScD, of the department of health policy and management at the Harvard School of Public Health, and colleagues evaluated 16,625 people aged 10 to 64 years who began antidepressant therapy at either high-dose or modal-dose to determine the risk of deliberate self-harm by antidepressant dose and age group.

High-dose selective serotonin reuptake inhibitor therapy was initiated in 45% of patients. Patients aged 10 to 24 years on high-dose therapy were more likely to deliberately self-harm (31.5 events per 1,000 person years) compared with those on modal-therapy (14.7 events per 1,000 person years). Patients aged 25 to 64 years on high-dose therapy were also more likely to deliberately self-harm (3.2 events per 1,000 years) compared with those on modal-therapy (2.8 events per 1,000 person years).

Patients aged 10 to 24 years on high-dose therapy were two times more likely to participate in deliberate self-harm compared with those on modal-dose therapy (HR=2.2; 95% CI, 1.6-3.0); this was lower among patients aged 25 to 64 years (HR=1.2; 95% CI, 0.8-1.9).

During the first 90 days of therapy, there were seven more deliberate self-harm events among every 1,000 patients aged 10 to 24 years on high-dose therapy compared with those on modal-dose therapy.

“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, out 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 deliberate self-harm,” the researchers wrote.

In an accompanying editorial, David A. Brent, MD, of the Western Psychiatric Institute and Clinic, University of Pittsburgh, and Robert Gibbons, PhD, of the University of Chicago, wrote that the effect of dose escalation was not addressed by the study.

“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 wrote. “Finally, 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.”

For more information:

Brent DA. JAMA Intern Med. 2014;doi:10.1001/jamainternmed.2013.14016.

Miller M. JAMA Intern Med. 2014;doi:10.1001/jamainternmed.2014.1053.

Disclosure: See the study for a full list of disclosures.