Suicide Risk and Antidepressants

Background

1990

• Case reports

2003

• Advisory: pediatric patients

2004

• Warning: children and adolescents

2005

• Advisory: suicidality in adults

2007

• Current black box warning

The Warning

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. (Continues)

The Warning

Anyone considering the use of [brand name here] or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.

(Continues)

The Warning

Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.

Defining Suicidality

Suicidal ideation Preparatory act

Nonfatal selfharm or

attempt Death

More about the black box warning

9 antidepressants 24 short term placebo controlled trials

N=4587

Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006; 63:332.

More about the warning

N=4587 Antidepressant

• 4% suicidality

Placebo

• 2% suicidality

No completed suicides

Hammad TA, Laughren TP, Racoosin JA. Suicide rates in short-term randomized controlled trials of newer antidepressants. J Clin Psychopharmacol 2006; 26:203.

What Should We Do?

MonitorInform

Age Specific Effect

Children and Adolescents

Young Adults: 18-25 25-64 YO 65 or older

Small increase in suicidality

Small increase in suicidality

No detectable effect

Probably protective

Leon AC. The revised warning for antidepressants and suicidality: unveiling the black box of statistical analyses. Am J Psychiatry 2007; 164:1786.

Is there any difference between antidepressants?

No difference in risk between classes: SSRIs, SNRIs, TCAs, MAOIs and other antidepressants.

Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry 2003; 160:790.

Effects of the Black Box Warning

• Decline in:• rates of diagnosis of pediatric depression.• treatment with SSRIs.

Libby AM, Orton HD, Valuck RJ. Persisting decline in depression treatment after FDA warnings. Arch Gen Psychiatry 2009; 66:633.

Key points

• The FDA warning alerts about increased risk of suicidality• Age specific effect: increased risk in children, adolescents and adults

18 – 25 years.• No actual suicides were completed in the studies reviewed• The FDA recommends monitoring during the first few weeks of

treatment• No difference between antidepressant classes