Anti-psychotic Drugs Pose Fatal Risks in People With Alzheimer’s

January 27, 2009

January 27, 2009

Patients with Alzheimer’s disease who take anti-psychotic drugs may be at increased risk for death, a new long-term study reports. Such drugs are commonly used to ease symptoms of psychosis like agitation, aggressiveness and delusions. They are sold under brand names like Risperdal, Haldol, Seroquel and Zyprexa.

Anti-psychotic medications to ease agitation and delusions are commonly prescribed to people with Alzheimer’s disease. Such behavioral problems can make care giving difficult, be distressing to the patient, and pose dangers for the patient or others. Many people with Alzheimer’s who are given these drugs reside in nursing homes, where shouting, hitting and other aggressive behaviors can make day-to-day care difficult.

Earlier studies have shown that drugs in this class can ease aggression and other psychotic symptoms over the short term. However, improvements tend to be modest at best, and after six to 12 weeks, benefits tend to wane. In addition, anti-psychotic drugs are also often over-prescribed to people with only mild symptoms like wandering, sleeplessness or an unwillingness to cooperate with help staff.

Earlier short-term studies have also shown that giving psychosis-fighting medications can increase the risk of fatal strokes, even when such drugs are given for only a few months. The current trial, called the DART-AD trial, confirm that these drugs present fatal risks over the long term as well.

The study, published online in the British medical journal Lancet Neurology, followed 165 patients with moderate to severe Alzheimer’s disease. All were living in long-term care facilities in the United Kingdom. Half were randomly assigned to continue taking anti-psychotics, while the others were switched to a look-alike placebo pill for 12 months.

The researchers found that after two to three years, those patients who were taking anti-psychotic drugs were at double the risk of dying.

Shorter-term studies had already raised concerns about the potential dangers of anti-psychotic medications. As a result, in June 2008, the Food and Drug Administration required that all these drugs carry a boxed warning on medication packages warning doctors about the potentially fatal risks.

The authors of the current study urge doctors to limit their prescribing of these drugs to people with Alzheimer’s. In the paper, they concluded that “accumulating safety concerns, including the substantial increase in long-term mortality, emphasize the urgent need to put an end to unnecessary and prolonged prescribing.”

The researchers don’t mean that giving anti-psychotic drugs, in all instances, is unnecessary. Rather they emphasize that doctors need to evaluate the potential risk versus benefit for each patient.  Many doctors are currently making small reductions in the dose of anti-psychotic drug given with the aim of finding the minimum dose required to produce a beneficial effect (where such benefits appear to occur).

An editorial that accompanied the study urged that if doctors do prescribe anti-psychotics to Alzheimer’s patients, that they should be given in low doses for short durations, with regular attempts to stop the drugs. “High levels of prescription of anti-psychotic drugs for neuropsychiatric symptoms in dementia are putting many vulnerable patients at risk of death and other adverse events,” they wrote.

In addition to fatal strokes, some antipsychotic medications can have troubling side effects like trembling and  movement disorders resembling those that occur in Parkinson’s disease. Unsteadiness, chest infections, and further clouding of memory and thinking have also been linked to these drugs, particularly in those taking older anti-psychotics like haloperidol and thioridazine.

But even the newer generation of anti-psychotic drugs, the “atypical” anti-psychotics that were originally thought to be safer than the older drugs, pose serious risks, including a threefold risk of fatal strokes.

Despite the known risks, it is estimated that 30 percent to 60 percent of patients with Alzheimer’s who live in nursing homes or other institutional settings are prescribed anti-psychotics. While these drugs sometimes provide help, many experts feel that they remain overused.

And many note that non-drug approaches to treating aggressive behaviors remain underutilized. In nursing homes, for example, ensuring an adequate ratio of staff to patients, and training staff in behavioral and psychological approaches, can help, research shows. Approaching problems from the patient’s point of view, and not arguing or contradicting someone who cannot think clearly, also helps to ease agitation and may even remove what might be an important source of agitation in people with Alzheimer’s.

Even simple environmental changes like increasing the lighting to eliminate dark and scary shadows or using contrasting colors of foods and dinnerware can make life easier and help ease agitation for people with Alzheimer’s. In many cases the problem can be fixed or eased by making changes in the patient’s environment.

Because behavioral problems may arise from improperly treated medical issues, it’s important to rule out physical problems as well. Too high a dose of certain medications or medical problems like constipation or pain can all aggravate behavioral complaints.

Anti-psychotic drugs still have a place in the care of someone with Alzheimer’s disease. If your doctor does prescribe such a medication, it is important to follow directions carefully. But such drugs should, in general, be given for short periods of time, the authors of the current report advise, and behavioral therapies and environmental approaches should be part of regular care.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Clive Ballard, M.D., Maria Luisa Hanney, Ph.D., Megan Theodoulou, MRCPsych, et al: “The Dementia Anti-psychotic Withdrawal Trials (DART-AD): Long-Term Follow-Up of a Randomised Placebo-Controlled Trial.” Lancet Neurology, early online publication, January 9, 2009, doi:10.1016/S1474-4422(08)70295-3

Commentary: “Anti-psychotic Drugs for Dementia: A Balancing Act.” The Lancet Neurology.


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