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Original Investigation |

Antidepressant Dose, Age, and the Risk of Deliberate Self-harm

Matthew Miller, MD, ScD1; Sonja A. Swanson, ScM2; Deborah Azrael, PhD1; Virginia Pate, PhD, PhD3; Til Stürmer, MD, ScD3
[+] Author Affiliations
1Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts
2Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
3Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill
JAMA Intern Med. 2014;174(6):899-909. doi:10.1001/jamainternmed.2014.1053.
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Importance  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.

Design, Setting, and Participants  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.

Main Outcomes and Measures  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 and Relevance  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.

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Figure 1.
Probability of Remaining Free of Deliberate Self-harm and Time Since Initiating High- vs Modal-Dose Antidepressant Therapy, by Age Group
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Figure 2.
Bias Analysis for 10- to 24-Year-Old Cohort

DSH indicates deliberate self-harm; RD, risk difference. The dotted line indicates the strength of confounding implied if true RD is 2 attempts per 1000. The shaded area indicates the strength of confounding implied if the true risk difference is null or protective.

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