Magazine article Clinical Psychiatry News

Drug Update: Alzheimer's Disease. (Clinical Rounds)

Magazine article Clinical Psychiatry News

Drug Update: Alzheimer's Disease. (Clinical Rounds)

Article excerpt

With the recent approval of galantamine, clinicians can now choose among four cholinesterase inhibitors for the treatment of Alzheimer's disease.

These agents appear to be most useful when started early in the disease. Their effects are modest: Compared with placebo or the natural history of the disease, treatment may delay symptom progression by 6-9 months. But after 6-9 months, when patients taking cholinesterase inhibitors resume their cognitive decline, abrupt withdrawal of these medications may result in a more precipitous decline.

Once a regimen is successfully begun, it should be continued indefinitely as long as the patient continues to tolerate treatment. Even tapered withdrawal risks triggering a setback. And even patients whose memory appears to have totally deteriorated may still derive ongoing benefit in terms of their behavior.

Experts recommend against combining cholinesterase inhibitors, but they differ on whether and how to switch from one cholinesterase inhibitor to another. Some say that switching may be beneficial-and is not difficult-if a patient does not respond to one drug or experiences unacceptable side effects, Others avoid switching, noting that tapering one medication and then titrating the new medication may leave the patient undertreated for a long time.

Because of concern about occult gastrointestinal bleeding, some clinicians prefer not to use cholinesterase inhibitors in patients taking warfarin or high-dose NSAIDs.

Vitamin E ([alpha]-tocopherol), an antioxidant, has shown promising effects in patients with Alzheimer's disease, delaying progression by 8 months in one study Although it may exacerbate some coagulopathies, vitamin E otherwise appears to be very safe, and it is available over the counter at relatively low cost. Therefore, many clinicians recommend prescribing 1,000 IU of vitamin B twice a day Treatment with other antioxidants or estrogen initially seemed promising, but both modalities have recently been the subject of negative studies. Ginkgo biloba has also failed to show benefit.

Drug          Dosage    Cost/Day *  Comment **

donepezil     5-10 mg/  $4.73       Efficacy of all four
(Aricept)     day                   drugs in class is
                                    fairly similar, so selection
                                    is based mainly on adverse
                                    effects and convenience.
                                    Start all drugs in
                                    class at low dosage;
                                    slowly titrate upward as
                                    needed. Because donepezil is
                                    among the safer agents in
                                    the class and the only one with
                                    a once-daily regimen, it's
                                    often preferred, although
                                    formulary considerations
                                    are also a factor.
                                    Mild side effects. Some
                                    patients experience a
                                    transient increase in
                                    agitation. Nausea, vomiting,
                                    and diarrhea can be reduced
                                    by taking donepezil
                                    with food. There have been
                                    case reports of interactions
                                    with paroxetine, and there
                                    has been conflicting evidence
                                    of interactions with
                                    cimetidine, digoxin,
                                    theophylline, and warfarin. … 
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