. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol. 2009 Feb;8(2):151-7. PubMed.

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  1. Alzheimer patients can be extremely difficult to treat. They can be very dangerous to the caregivers, not to mention the well-documented depression they cause in caregivers.

    I know that some clinicians do not think that antipsychotic medications are very effective, but I certainly think they are. I further think that the violent and psychotic patients have more brain damage. Also, violent and psychotic behaviors are very maladaptive and may suggest greater degrees of neuropathology. The pathology, or the maladaptation, likely leads to a higher risk of mortality. Thus, association of medicine use with mortality does not prove causation.

    Until I see a study that carefully looks at the neuropathology associated with this increase in mortality of patients receiving antipsychotic medication, I will presume that the patients who are given these drugs actually have a higher risk of mortality and the drugs may actually decrease this risk. In any case, given the severe difficulty with managing patients that leads to the use of such medications, isn't there the issue of allowing patients to die with dignity? These drugs, just like morphine for cancer patients, will provide some measure of better end-of-life care.

    Actually, I don't believe that real-life placebo-controlled trials of antipsychotic medications can be conducted, having been involved in many such trials. The most agitated patients need to be managed acutely and cannot participate in such trials. Those who get into such trials probably aren't affected severely enough to warrant the treatment. Looking at placebo discontinuation probably doesn't solve this problem, because dementia patients need to be closely followed over time and have their antipsychotic medications decreased whenever possible, anyway. This issue is noted as a future need, but it has always been just part of appropriate patient care. Antipsychotics are not maintenance medications in this condition; they are for acute management. The need for monitoring and constant medication adjustment could be the best argument for why these drugs really should only be prescribed by those familiar with treating such patients.

    There has been some evidence that the use of antipsychotic medications has increased in spite of the black box warning. When a patient is severely agitated, I still think that antipsychotics are the best medication to use.

    It should be noted that there is now more experience with trazodone, SSRIs, melatonin, and low doses of the atypical antipsychotic medications, so these patients are a little easier to manage. Further, long-term use of cholinesterase inhibitors and memantine probably decreases the overall behavior problems, though much better research is needed on all of these issues.

    View all comments by John (Wes) Ashford

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  1. Antipsychotics on Trial Again—DART-AD Confirms Increased Mortality