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The Food and Drug Administration (FDA) issued a public health advisory on April 11, 2005 to warn that the drugs known as the atypical antipsychotics are associated with an increased risk of death when used to treat dementia in elderly patients. We have warned consumers since the first edition of Worst Pills, Best Pills, published in 1988, that antipsychotic drugs are used inappropriately for dementia in the elderly.
The atypical antipsychotics affected by the FDA advisory are aripiprazole...
The Food and Drug Administration (FDA) issued a public health advisory on April 11, 2005 to warn that the drugs known as the atypical antipsychotics are associated with an increased risk of death when used to treat dementia in elderly patients. We have warned consumers since the first edition of Worst Pills, Best Pills, published in 1988, that antipsychotic drugs are used inappropriately for dementia in the elderly.
The atypical antipsychotics affected by the FDA advisory are aripiprazole (ABILIFY), olanzapine (ZYPREXA), quetiapine (SEROQUEL), risperidone (RISPERDAL), clozapine (CLOZARIL), and ziprasidone (GEODON). These drugs are approved by the FDA to treat schizophrenia. The combination of olanzapine with fluoxetine (SYMBYAX), also included in the FDA’s advisory, is approved for the treatment of depressive episodes associated with bipolar disorder. None of these drugs, however, are approved for the treatment of behavioral disorders in patients with dementia.
The atypical antipsychotics are categorized into three drug classes based on their chemical structure. Because the increase in the number of deaths was seen with atypical antipsychotic medications in all three chemical classes, the FDA concluded that the effect is probably related to common pharmacologic effects of all atypical antipsychotic drugs, including those that have not been systematically studied in the dementia population.
The FDA’s warning was based on the results of 17 clinical trials comparing olanzapine, aripiprazole, risperidone, or quetiapine to a placebo. Of these 17 clinical trials, 15 showed an increase in the number of deaths in the groups treated with atypical antipsychotics compared to the patients receiving a placebo. These studies involved a total of 5,106 patients. Several analyses showed an approximately 1.6 to1.7-fold increase in deaths in these studies compared to patients receiving a placebo. Examination of the specific causes of these deaths revealed that most were either due to heart related events — for example, heart failure and sudden death — or infections, mostly pneumonia.
Over the duration of these clinical trials, which averaged about 10 weeks in length, the rate of death in the patients treated with atypical antipsychotics was about 4.5 percent, compared to a rate of about 2.6 percent in the placebo group. This is a difference in the absolute risk of death of 1.9 percent. Knowing the difference in the risk of death, the number of patients that need to be treated before seeing one death can be calculated. This number is called the Number Needed to Harm. In this case, it is 53. This means that out of every 53 elderly patients treated for dementia with an atypical antipsychotic drug for 10 weeks, one will die.
We first altered readers about problems with the atypical antipsychotic drug risperidone in the June 2003 issue of Worst Pills, Best Pills News. Its manufacturer, Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson, warned that cerebrovascular adverse events such as stroke and transient ischemic attacks were reported in clinical trials involving elderly patients being treated for dementia-related psychosis, including fatalities.
This new warning about the atypical antipsychotic drugs is another tragic example of the substantial harm that patients face when they are prescribed drugs for uses that are not approved by the FDA. The use of a drug for an indication that is not approved by the FDA is referred to as an “off-label” use. Only uses that have been shown to be safe and effective after FDA review can be listed on a drug’s approved product labeling. Sadly, some of the worst drug disasters in history have resulted from off-label prescribing.
To make matter worse, a study published in the
Neither quetiapine [SEROQUEL] nor rivastigmine [EXELON, a drug for Alzheimer’s disease] are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.
Pharmacists from the Drug Information Branch of the FDA’s Center for Drug Evaluation and Research have prepared consumer-friendly patient information leaflets for each of the atypical antipsychotic drugs. These leaflets are based on the drug’s approved professional product labeling. They can be accessed on the FDA’s Web site.
What You Can Do
If a family member is currently receiving an atypical antipsychotic to manage dementia, you should discuss the drug’s new warning with the prescribing physician. If the decision is made to try another drug, you should learn about the drug’s risks before the drug is given to your family member.
