August 2007

Lithium and the Risk of Alzheimer's
Lithium treatment may decrease the risk of Alzheimer's disease in patients with bipolar disorder.

T3 Augments SSRI Treatment
Adding triiodothyronine (T3) to sertraline (Zoloft and others) treatment increased response and remission rates in depressed patients.

Adding Atomoxetine to an SSRI: A Negative Study
Adding atomoxetine (Strattera) to sertraline (Zoloft and others) did not increase remission rates for depressed patients who responded incompletely to the antidepressant alone.

A Tale of Two Interactions
Quetiapine (Seroquel and others) can raise levels of r-methadone, and carbamazepine (Tegretol and others) can lower levels of aripiprazole (Abilify).

Risperidone and Prolactin in Young Patients
Prolactin levels increased in children and adolescents treated with risperidone (Risperdal) for pervasive development disorder.

In Brief
Topiramate and Cognitive Impairment in Children; Brain Structure Abnormalities in Pedophiles

More on Antidepressants and Suicide
A meta-analysis of studies of children and adolescents with depression, obsessive compulsive disorder, or anxiety disorders found a small increased risk of suicidal ideation/suicide attempt, but no completed suicides.

More on Antidepressants and Suicide

August 2007

The US Food and Drug Administration (FDA) has ordered that all antidepressants carry an expanded black-box warning about the risk of suicidal ideation in young adults in addition to children and adolescents.1 Information about the benefits of antidepressant treatment and the risks of not treating depression has also been added.

A recent meta-analysis from Bridge and colleagues combined data from 27 studies of children and adolescents: 15 studies of major depressive disorder and 6 studies each of obsessive compulsive disorder (OCD) and non-OCD anxiety disorders.2

As in the FDA analysis, there was an overall small but increased risk of suicidal ideation/suicide attempt associated with antidepressant treatment, but the pooled risk differences within each indication were not statistically significant. There were no completed suicides in any of these studies. The efficacy of antidepressants versus placebo was strongest in non-OCD anxiety disorder, intermediate in OCD, and more modest in depression. Of particular note, benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempt across all of these indications. As a limitation, none of the studies in this analysis was designed to measure suicidal ideation or attempts. Data on suicidality were collected as part of adverse event reporting and may not have been systematically assessed.

In both depression and anxiety, adolescents in this analysis had a better response to treatment than did children. In depressed children under age 12, only fluoxetine (Prozac and others) was superior to placebo, whereas in adolescents, several antidepressants were efficacious. Data from the depression trials revealed that the efficacy of treatment was inversely proportional to the length of the illness, which suggests that diagnosing and treating depression early in children may improve outcomes.

Bridge et al call for future studies to assess baseline characteristics that might predict treatment response and to document emergent suicidal ideas and attempts. The authors recommend the cautious use of antidepressants as a first-line treatment in young patients and a more efficient system to monitor their clinical response and adverse events.

Heather S. Hopkins

1Friedman RA, Leon AC: Expanding the black box—Depression, antidepressants, and the risk of suicide. N Engl J Med 2007;356:2343-2346.

2Bridge JA, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus HA, Ren L, Brent DA: Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment. A meta-analysis of randomized controlled trials. JAMA 2007;297:1683-1696.