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November 2008

Metformin for Antipsychotic-Associated Weight Gain
Most studies with metformin (Avandamet and others) suggest that it attentuates weight gain or actually promotes weight loss in patients who are taking antipsychotics.

In Brief
Valproate Teratogenicity Increased by High Dose, Concomitant Drugs;Celecoxib, Naproxen Do Not Protect Against Alzheimer's Disease

Atomoxetine versus Methylphenidate for Pediatric ADHD
Methylphenidate (Ritalin and others) appears to be more efficacious than atomoxetine (Strattera) for treating attention-deficit/hyperactivity disorder in children but has more adverse effects.

Rivastigmine (Exelon) Patch
A transdermal system for delivering rivastigmine (Exelon) is now available in the United States for treating dementia associated with Alzheimer's or Parkinson's disease.

In Brief

November 2008

Last June, we discussed the teratogenic potential of anticonvulsants in pregnant women with bipolar disorder (BTP 2008;31:22-23). A recent study suggests that if valproate (Depakote and others) must be used during pregnancy, it should be prescribed at the lowest dose possible and preferably as monotherapy to lower the risk of fetal anomalies. Diav-Citrin and others collected data about pregnancy outcomes from 154 women who called the Israeli Teratology Information Service between 1994 and 2004 for information about gestational exposure to valproate and another 1315 callers exposed to nonteratogens (CNS Drugs 2008;22:325-334). Major anomalies (mental retardation, hypospadias, cardiovascular defects, and suspected fetal valproate syndrome) occurred in 6.7% of babies exposed in the first trimester to valproate, compared with 2.5% in controls. There were no cases of neural tube defect. The rate of major anomalies in a subgroup of infants who were exposed to polydrug therapy was fourfold greater than in controls. The highest teratogenic risk was associated with a daily dose ≥ 1000 mg.

Epidemiological studies suggest that the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of Alzheimer's disease. A recent placebo-controlled, double-blind trial, however, did not find a protective effect of celecoxib (Celebrex) or naproxen (Naprosyn and others) in elderly patients. In fact, these NSAIDs may worsen cognitive outcomes. The Alzheimer Disease Anti-inflammatory Prevention Trial (ADAPT) Research Group enrolled over 2500 subjects, aged 70 years and older, who were cognitively healthy but had a positive family history of Alzheimer's disease (Arch Neurol 2008;65:896-905). Subjects were randomly assigned to receive celecoxib, 200 mg bid; naproxen sodium, 220 mg bid; or placebo. Cognitive assessments were performed annually. The study was discontinued prematurely due to cardiovascular risks associated with the long-term use of celecoxib. The average follow-up was 2 years. Cognitive assessment scores over time were statistically significantly lower for both naproxen- and celecoxib-treated subjects compared with subjects taking placebo. The authors postulate that the epidemiological data may relate to other NSAIDs, specifically those that lower the production of the 42-residue form of amyloid ß, which does not include celecoxib and naproxen.

Heather S. Hopkins