Magazine article Clinical Psychiatry News

Start Cholinesterase Therapy Early in Dementia. (Mild to Moderate Disease)

Magazine article Clinical Psychiatry News

Start Cholinesterase Therapy Early in Dementia. (Mild to Moderate Disease)

Article excerpt

STOCKHOLM -- Cholinesterase inhibitor treatment should be started as early as possible in the course of dementia, and it should be continued as long as the perception of benefit outweighs the cost and side-effect profile, Dr. Jean-Marc Orgogozo said at the Eighth International Conference on Alzheimer's Disease and Related Disorders.

Decisions about which cholinesterase inhibitors to use in which patients, when to start using them, and whether to stop using them are "empirical, based on negotiation between the patient, physician, and family," said Dr. Orgogozo, professor of neurology at the University of Bordeaux (France).

He offered his recommendations based on published data and common practice of dementia specialists in the United States and Europe.

As a general rule, cholinesterase inhibitors should be stopped when adverse events are severe or persistent or when the physician and patient caregiver see no benefit after 6 months of therapy.

The drugs should not be stopped merely on the basis of a decline in Mini-Mental State Examination score, since the decline may have been worse if the patient had not been taking the drug, Dr. Orgogozo noted.

Also, the drugs should never be stopped at the time of nursing home placement--a highly stressful event for the patient and family members. "There is a risk of worsening. It's certainly not the time to stop treatment," said Dr. Orgogozo, also head of neurology at CHU Pellegrin in Bordeaux.

When the drug is stopped, patients should be carefully monitored and the drug restarted if there is a significant decline in function after 2-3 weeks, Dr. Orgogozo recommended.

The currently available cholinesterase inhibitors--tacrine, donepezil, rivastigmine, and galantamine--have been shown to be about equally effective in slowing decline in cognitive and global functioning in trials lasting 6-12 months, and open-label extension trials suggest continuing benefit for up to 2 years.

Tacrine is rarely used any more because of its high rate of liver toxicity. Among the other three, dosing is a bit easier for donepezil than for the others. (See box.) Individual patients may differ in tolerance and clinical response to each of the agents, so it may be worthwhile to empirically switch from one to another if the patient's response or tolerance to one is inadequate, Dr. Orgogozo said at the meeting, also sponsored by the Alzheimer's Association.

In one 24-week trial, 290 patients who had moderate to severe Alzheimer's disease were randomized to receive either donepezil (5 mg/day for the first 28 days and 10 mg/day thereafter) or placebo. …

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