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.
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.
Rivastigmine (Exelon) Patch
As brain levels of acetylcholine synthesis decrease, severity of dementia may increase (BTP 2006;29:30-31).1 Cholinesterase inhibitor drugs diminish the breakdown of acetylcholine and thereby increase its availability in the brain. They are commonly prescribed to slow the progression of Alzheimer's disease. The most widely used cholinesterase inhibitors are donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon) (BTP 2004;27:47).
A few years ago, Kaduszkiewicz and coauthors reviewed 22 double-blind, randomized, controlled trials that compared one of these three cholinesterase inhibitors to placebo in patients with Alzheimer's disease (BTP 2006;29:30-31).2 Although 19 of the trials found the drugs to be statistically superior to placebo, the benefits were very small. Cholinomimetic agents appear to have relatively modest benefits against the symptoms of Alzheimer's disease, slowing cognitive decline by only about 3 months. More recently, a large, double-blind, placebo-controlled trial of rivastigmine found it was not statistically superior to placebo for slowing progression to Alzheimer's disease in patients with mild cognitive impairment (BTP 2007;30:37).3 Nonetheless, a transdermal system to deliver rivastigmine has been approved by the US Food and Drug Administration (FDA) for treating mild to moderate dementia associated with Alzheimer's or Parkinson's disease.4
In a random-assignment, double-blind, 24-week trial of almost 1200 patients with probable Alzheimer's disease, a 9.5-mg rivastigmine patch applied daily, a 17.4-mg rivastigmine patch applied daily, or rivastigmine, 6 mg po bid, were all superior to placebo. Oral rivastigmine has shown efficacy in the treatment of dementia associated with Parkinson's disease, but there are no published studies of rivastigmine patches in this condition.
Use of oral rivastigmine has been limited by adverse gastrointestinal effects, possibly caused by rapidly rising serum concentrations. With the patch, serum concentrations peak at a lower level and take a longer time to reach this level than with the oral preparation. The maximum serum concentrations with the patch are achieved within 8 to 16 hours of its administration. Most excretion is renal. After the patch is removed, the plasma half-life is approximately 3 hours.
The patch is to be applied to the upper or lower back, chest, or upper arm once daily, starting with the 4.6-mg (5 cm2) size. After 4 weeks the patch size can be increased to 9.5 mg, which is the recommended maintenance and maximum dose. The average total rivastigmine exposure over 24 hours with a 9.5-mg (10 cm2) patch is comparable to a 6-mg bid oral regimen.
If a patient taking 6 to 12 mg of oral rivastigmine daily is to be switched to the transdermal approach, the 9.5-mg patch may be used from the start and applied on the day following the last oral dose. Patients should remove one patch before applying the next, or cholinergic toxicity could occur. The same site should not be reused for 14 days. Bathing is not expected to affect the medication delivery system. Common side effects with the patch are nausea, vomiting, diarrhea, and skin irritation.
The rivastigmine patch adds a new option for administering a cholinesterase inhibitor. For now, these agents remain a mainstay, albeit of limited efficacy, for treating dementias.
1Francis PT: The interplay of neurotransmitters in Alzheimer's disease. CNS Spectr 2005;10(Suppl 18):6-9.
2Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, van den Bussche H: Cholinesterase inhibitors for patients with Alzheimer's disease: Systematic review of randomised clinical trials. BMJ 2005;331:321-327.
3Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, Tekin S, Burns A, Cummings J, del Ser T, Inzitari D, Orgogozo JM, Sauer H, Scheltens P, Scarpini E, Herrmann N, Farlow M, Potkin S, Charles HC, Fox NC, Lane R: Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: The InDDEx study. Lancet Neurology 2007;6:501-512.
4A rivastigmine patch for dementia. Med Lett Drugs Ther 2008;50:21-22.