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.

Adding Atomoxetine to an SSRI: A Negative Study

August 2007

What to do for a patient who responds only partially to an initial antidepressant is a question that has troubled clinicians for the past 50 years. As we have noted in recent summaries of the STAR*D trials, common approaches are to augment the first medication with a second or to switch to a different agent (BTP 2007;30:27-28, 2006;29:33-35). There is no one clear and obvious answer.

The usual first-line agents for depression today are the selective serotonin reuptake inhibitors (SSRIs). Venlafaxine (Effexor and others) and duloxetine (Cymbalta) inhibit the uptake of both norepinephrine and serotonin and are often used as second-line treatments. Tricyclic antidepressants as well inhibit the uptake of both norepinephrine and serotonin.

For a depressed patient who responds only partially to an SSRI, an alternative would be to add an agent that selectively inhibits the uptake of norepinephrine, such as reboxetine, which is available in many countries but not in the United States. Atomoxetine (Strattera), another selective norepinephrine reuptake inhibitor, is available in the United States but labeled only for attention deficit hyperactivity disorder (ADHD). Funded by atomoxetine's manufacturer, Michelson and others used it to augment sertraline (Zoloft and others) in patients who did not achieve remission on treatment with the SSRI alone.1

All patients were treated initially for 8 weeks with open-label sertraline, up to 200 mg daily. One hundred forty-six subjects remained symptomatic and were randomly assigned under double-blind conditions to receive 8 more weeks of treatment with either atomoxetine, 40 to 120 mg daily, or placebo, in addition to sertraline. The results were negative. Patients assigned to atomoxetine augmentation showed no greater improvement in depression than those who received placebo. Significantly more patients in the atomoxetine group reported dry mouth, insomnia, and constipation.

Theories about antidepressant mechanisms of action and how we might take advantage of them have been extant for decades. The STAR*D trial and most research over the years have failed to find empirical justification for preferring one type of antidepressant over another. This trial similarly came up empty-handed in an attempt to exploit a very reasonable theory that adding a norepinephrine reuptake inhibitor to an SSRI would help more depressed patients achieve remission.

1Michelson D, Adler LA, Amsterdam JD, Dunner DL, Nierenberg AA, Reimherr FW, Schatzberg AF, Kelsey DK, Williams DW: Addition of atomoxetine for depression incompletely responsive to sertraline: A randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007;68:582-587.