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.

A Tale of Two Interactions

August 2007

Two recent reports highlight drug interactions that could be clinically relevant. High levels of methadone can cause QTc prolongation (BTP 2007;30:29-30). Uehlinger and others measured methadone levels in 14 patients on methadone maintenance treatment for opiate addiction who were given quetiapine (Seroquel and others).1

Subjects were studied during methadone treatment alone and again after the addition of quetiapine, 50 to 300 mg/day, for a mean of 30 days. R-methadone, the active metabolite of methadone, increased by an average of 21% after quetiapine was introduced. The authors opine that the interaction could involve the cytochrome P450 2D6 enzyme system or the P-glycoprotein transporter system.

Citrome and colleagues examined the effects of carbamazepine (Tegretol and others) on the pharmacokinetics of aripiprazole (Abilify).2 Nine men with schizophrenia or schizoaffective disorder were treated with aripiprazole, 30 mg/day, for 14 days. Then carbamazepine, titrated to a trough serum concentration of 8 to 12 mg/L, was added. With carbamazepine, the mean peak aripiprazole concentration fell by 66% (P = .001) and the area under the plasma concentration-time curve was reduced by 71% (P = .002). Aripiprazole's active metabolite similarly decreased.

Adding quetiapine to a methadone regimen could conceivably slow cardiac conduction and raise the risk of a life-threatening arrhythmia. And carbamazepine can lower aripiprazole levels, which leads Dr Citrome's group to call for a doubling of aripiprazole doses if carbamazepine is added and a reduced dose if it is deleted.

1Uehlinger C, Crettol S, Chassot P, Brocard M, Koeb L, Brawand-Amey M, Eap CB: Increased (R)-methadone plasma concentrations by quetiapine in cytochrome P450s and ABCB1 genotyped patients. J Clin Psychopharmacol 2007;27:273-278.

2Citrome L, Macher JP, Salazar DE, Mallikaarjun S, Boulton DW: Pharmacokinetics of aripiprazole and concomitant carbamazepine. J Clin Psychopharmacol 2007;27:279-283.