Antidepressant dose, age, and the risk of deliberate self-harm.
OBJECTIVE
A comprehensive meta-analysis of randomized trial data suggests that suicidal behavior is twice as likely when children and young adults are randomized to antidepressants compared with when they are randomized to placebo. Drug-related risk was not elevated for adults older than 24 years. To our knowledge, no study to date has examined whether the risk of suicidal behavior is related to antidepressant dose, and if so, whether risk depends on a patient's age.


OBJECTIVE
To assess the risk of deliberate self-harm by antidepressant dose, by age group.


METHODS
This was a propensity score-matched cohort study using population-based health care utilization data from 162,625 US residents with depression ages 10 to 64 years who initiated antidepressant therapy with selective serotonin reuptake inhibitors at modal or at higher than modal doses from January 1, 1998, through December 31, 2010.


METHODS
International Classification of Diseases, Ninth Revision (ICD-9) external cause of injury codes E950.x-E958.x (deliberate self-harm).


RESULTS
The rate of deliberate self-harm among children and adults 24 years of age or younger who initiated high-dose therapy was approximately twice as high as among matched patients initiating modal-dose therapy (hazard ratio [HR], 2.2 [95% CI, 1.6-3.0]), corresponding to approximately 1 additional event for every 150 such patients treated with high-dose (instead of modal-dose) therapy. For adults 25 to 64 years of age, the absolute risk of suicidal behavior was far lower and the effective risk difference null (HR, 1.2 [95% CI, 0.8-1.9]).


CONCLUSIONS
Children and young adults initiating therapy with antidepressants at high-therapeutic (rather than modal-therapeutic) doses seem to be at heightened risk of deliberate self-harm. Considered in light of recent meta-analyses concluding that the efficacy of antidepressant therapy for youth seems to be modest, and separate evidence that antidepressant dose is generally unrelated to therapeutic efficacy, our findings offer clinicians an additional incentive to avoid initiating pharmacotherapy at high-therapeutic doses and to closely monitor patients starting antidepressants, especially youth, for several months.
Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts.
Matthew
M
Miller
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
Sonja A
SA
Swanson
Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts.
Deborah
D
Azrael
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill.
Virginia
V
Pate
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill.
Til
T
Stürmer
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D016728:Self-Injurious Behavior / Q000139:chemically induced*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
D018687:Antidepressive Agents, Second-Generation; D017367:Selective Serotonin Reuptake Inhibitors