High Dose Antidepressants May Make Youth More Depressed

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High initial antidepressant dose associated with higher rates of self harm among children and young adults

April 29, 2014 / Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

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(dailyRx News) Antidepressants have been linked to suicidal thoughts and self-harming behaviors among children and young adults. However, it may not be medication itself that leads to these behaviors.

A recent study found that children and young adults who started antidepressant therapy at a high dose had an increased risk of engaging in deliberate self-harming behaviors compared to those who started therapy at an average dose.

The researchers believe that these findings should encourage doctors to avoid prescribing high doses of antidepressants at the start of therapy, and to closely monitor their younger patients for several months after treatment starts.

"Tell a doctor if you have thoughts about harming yourself."

The lead author of this study was Matthew Miller, MD, ScD, from the Department of Health Policy and Management at the Harvard School of Public Health in Boston, Massachusetts.

The study included 162,625 U.S. residents aged 10 to 64 years old who were diagnosed with depression and started antidepressant therapy with selective serotonin reuptake inhibitors (SSRIs) between January 1, 1998 and December 3, 2010.

All participants had been actively enrolled in the same health plan for at least 15 months prior to starting treatment. None of the participants had been prescribed any sort of antidepressant in the 12 months prior to starting of treatment.

The researchers split up the participants into two groups based on age: participants aged 10 to 24 years old and participants aged 25 to 64 years old.

Then, the participants were categorized into three groups according to their initial medication dosage:

  • Those who took the modal dose (the most commonly prescribed dose for any given medication)
  • Those who took above the modal dose
  • Those who took below the modal dose

Of the participants aged 10 to 24 years old, 32,504 took the modal dose, 7,117 took higher than the modal dose and 14,542 took lower than the modal dose.

Among the participants aged 25 to 64 years old, 99,136 were in them modal dose group, 23,668 were in the higher than modal dose group and 20,065 were in the lower than modal dose group.

Participants provided data on psychiatric hospitalizations for substance abuse, any co-occurring psychiatric conditions and any prior deliberate self-harm.

The researchers conducted follow-up 30 days after patients started therapy, 90 days after starting therapy and a year after starting therapy.

The findings showed that 142 participants in the 10- to 24-year-old age group (68 in the modal dose group and 74 in the high dose group) had deliberately self-harmed within a year of starting therapy. The rate of deliberate self-harm in the 10- to 24-year-old modal group was 15 events per 1,000 person-years (number of participants multiplied by number of years in treatment) versus 32 events per 1,000 person-years in the high-dose group.

Among the 25- to 64-year-old age group, 81 participants engaged in deliberate self-harming within one year of starting therapy — 41 of them were in the modal group and 32 were in the high dose group. There were three deliberate self-harming events per 1,000 person-years in both the modal and high-dose group of participants aged 25 to 64 years old.

The findings revealed that most events occurred during the three months after starting therapy.

The researchers determined that the rate of deliberate self-harm among the 10- to 24-year-old age group was 2.2 times higher in the high-dose group compared to the modal dose group.

This doubled rate corresponds to one additional self-harming event for ever 150 participants who were treated with a high dose versus those who were treated with the modal dose.

Among the participants aged 25 to 64 years old, the overall risk for deliberate self-harm was extremely lower than that of the participants aged 10 to 24 years old.

Dr. Miller and team discovered that the difference in self-harm rates between the high-dose group and the modal group was not statistically significant.

This study was limited because all participant data came from insurance claims databases, so the researchers did not know the severity of each participant's psychiatric illness. Also, the researchers were not able to measure medication adherence.

Furthermore, the study did not address whether starting antidepressant therapy at the modal dose increased or decreased the risk of deliberate self-harm compared to not engaging in antidepressant treatment at all.

This study was published on April 28 in JAMA Internal Medicine.

The National Institute of Mental Health, the National Institute on Aging at the National Institutes of Health and the Agency for Healthcare Research and Quality provided funding.

Review Date: 
April 28, 2014
Last Updated:
April 29, 2014