High dose antidepressants may increase self-harm risk among children, young adults

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1.  In patients younger than 24 years of age, higher doses of antidepressants doubled the risk of deliberate self-harm. 

2.  In adults, there was no significant increase in the risk of deliberate self-harm with the use of higher dose anti-depressants. 

Evidence Rating Level: 2 (Good)

Study Rundown:  A meta-analysis published in 2006 found that the rates of suicidal ideation and behavior were two times higher in children who were randomized to receive antidepressants.  An aspect of antidepressant use that has not been well studied is the relationship between deliberate self-harm (DSH) and antidepressant dose, as well as the impact of age on this outcome.  The researchers restricted the analyses only to new initiators of therapy and to the most commonly prescribed selective serotonin reuptake inhibitors (SSRIs).  The patients were then divided into 3 categories: modal dose, lower than modal dose, higher than modal dose.

Propensity score-matched analyses revealed that in patients aged 10-24, the rates of DSH in the higher dose group were double that of patients in the modal dose group.  In patients aged 25-64, there was no significant increase in rates of DSH in the higher dose group.  Readers should be aware that this is an observational study based on claims data.  Therefore it would be difficult to verify that the patients were compliant with the dosages prescribed. Also, a randomized clinical trial would have been able to evaluate the impact of the initiation of antidepressants as compared to placebo in the same age group.

Click to read the study, published today in JAMA Internal Medicine

Click to read an accompanying editorial in JAMA Internal Medicine

Relevant Reading: Suicidality in Pediatric Patients Treated With Antidepressant Drugs

In-Depth [propensity score-matched cohort study]:  This cohort study collected information from the PharMetrics Claims database on 162,625 patients aged 10-64 years who were initiated on SSRI therapy between January 1, 1998 and December 31, 2010.  The patients were then divided into 3 categories: modal dose, lower than modal dose, higher than modal dose of SSRIs.  The first occurrence of DSH was the outcome of interest.  Rates of DSH were calculated over a 1-year exposure period.  In the matched cohorts, 142 patients in the younger age group and 81 in the older age group had an episode of DSH within 1 year of treatment initiation.  Among the younger age group, rates of DSH among high-dose participants was double that of modal-dose participants (HR, 2.2; 95% CI, 1.6-3.0).  For patients in the older age group, there was no significant increase in DSH among the high-dose participants (HR, 1.2; 95% CI, 0.8-1.9).

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