Antipsychotic Rx often relates to non-approved indications

18 feb 2015—For individuals with dementia living in nursing homes, the provider's rationale for use of antipsychotic drug therapy frequently relates to indications for which these drugs are not approved, according to a study published online Jan. 30 in the Journal of the American Geriatrics Society.

Alice F. Bonner, Ph.D., R.N., from Northeastern University in Boston, and colleagues conducted a qualitative, descriptive study set in 26 medium-sized and large facilities housing individuals living with dementia. The authors collected data from medical record abstraction and interviews with prescribers, administrators, direct care providers, and family members. They developed a coding scheme and coded reasons for antipsychotic prescribing.

The researchers found that among the 204 nursing home residents in the study, the major categories of reasons for antipsychotic medication use were behavioral, psychiatric, emotional states, and cognitive diagnoses or symptoms. Verbal and physical aggression were the most commonly identified behavioral reasons. Psychosis was most frequently described in the psychiatric category. The most common emotional states cited were anger and sadness.

"The rationale for use of antipsychotic drug therapy frequently relates to a wide variety of indications for which these drugs are not approved and for which evidence of efficacy is lacking," the authors write. "These findings have implications for clinical practice and policy."

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Antipsychotics for Alzheimer's up death risk: study

LONDON, 09 jan 2009– Antipsychotic drugs prescribed to treat aggression in older Alzheimer's patients appear to significantly raise their risk of dying prematurely, British researchers said Friday.

The results from the first long-term study on the effect of the medicines on people with Alzheimer's highlights the need to seek less harmful treatments for many of these patients, Clive Ballard of King's College London and colleagues said.

During their three-year study, men and women given a placebo were 42 percent less likely to die than people who remained on their antipsychotic medication, the study published in the journal Lancet Neurology found.

"Our data add further serious safety concerns about the long-term use of antipsychotics in this population, and clinicians should certainly try to replace antipsychotics with safer management approaches," the researchers wrote.

Alzheimer's is an incurable brain disease that worsens over time and is the most common form of dementia, affecting 26 million people globally, according to the Alzheimer's association.

Antipsychotic drugs have increasingly been used to treat the personality changes and aggression often associated with the disease, but the new findings suggest for many they may not be worth the risk.

"Our opinion is that there is still an important but limited place for atypical antipsychotics in the treatment of severe (symptoms), particularly aggression," the researchers wrote.

"However, the accumulating safety concerns ... emphasize the urgent need to end unnecessary and prolonged prescribing."

In the study carried out between 2001 and 2004, 128 patients aged from 67 to 100 years were assigned to continue their antipyschotic treatment for 12 months or switched to a placebo.

The drugs included the generic treatments thioridazine, chlorpromazine, haloperidol, trifluorperazine and Johnson & Johnson's Risperdal, or risperidone.

No one at Johnson & Johnson was immediately available for comment.

After one year, slightly more people in the antipsychotic group had died but after 36 months, survival in the placebo group was 59 percent compared to 30 percent among the people on the drugs.

Other researchers noted that, because antipyschotic drugs are also linked to higher risk of stroke and a decline in brain function, the latest findings underscore the need to find other ways to help such patients.

"This work highlights the pressing need to develop and evaluate alternative pharmacological and non-pharmacological treatments for behavioral symptoms in dementia," Richard Perry, a neurologist at Imperial College Healthcare in London, said in a statement.

Atypical Antipsychotic Drugs Increase Mortality in Older Adults With Dementia

June 8, 2007 — Atypical antipsychotic drugs are associated with an increased risk for death in elderly patients with dementia, according to the results of a retrospective cohort study published in the June 5 issue of the Annals of Internal Medicine.
"Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety," write Sudeep S. Gill, MD, MSc, from the Queen's University in Kingston, Ontario, Canada, and colleagues. "In April 2005, the U.S. Food and Drug Administration (FDA) issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk for death compared with placebo.... The mortality rate was approximately 1.6 to 1.7 times higher than with placebo and was greater with antipsychotics than with placebo in 15 of the 17 trials reviewed by the U.S. FDA."
Using population-based data from Ontario, Canada, the current study aimed to determine the risk for all-cause mortality in older adults with dementia who received atypical antipsychotic drugs, conventional antipsychotic drugs, or no antipsychotic drug and who were followed up between April 1, 1997, and March 31, 2003.
Mortality risk was calculated at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. There were 2 pairwise comparisons: atypical vs no antipsychotic drug use and conventional vs atypical antipsychotic drug use. The investigators stratified groups by residence in the community or in long-term care, and they used propensity score matching to adjust for differences in baseline health status.
Using 27,259 matched pairs, new use of atypical antipsychotic drugs was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling population (adjusted hazard ratio [HR], 1.31; 95% confidence interval, 1.02 - 1.70; absolute risk difference, 0.2 percentage point) and the long-term care population (adjusted HR, 1.55; 95% confidence interval, 1.15 - 2.07; absolute risk difference, 1.2 percentage points).
Although excess risk seemed to persist to 180 days, unequal rates of censoring with time may have affected these results. Compared with use of atypical antipsychotic drugs, use of conventional antipsychotic drugs was associated with a higher risk for death at all time points. Unmeasured confounders increasing the risk for death could decrease or abolish the observed associations, according to the results of sensitivity analysis.
"Older adults with dementia who are exposed to atypical antipsychotics have a small but significant increase in overall mortality that is evident as early as 1 month after initiation of treatment, and this risk may persist for 6 months," the authors write. "The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics."
Study limitations include lack of data on causes of death, lack of continuation of initial treatments after 1 month of therapy in many patients, possible unmeasured confounders, use of administrative data and observational study techniques, risk estimates being relatively small, inability to examine the risk for death posed by individual antipsychotic drugs or dose–response relationships, inability to match all potentially eligible patients, and the sample being restricted to older adults with dementia.
"These findings highlight the need to carefully balance potential risks and benefits when considering antipsychotic treatment for older adults with dementia and emphasize the need to limit use of these drugs to situations in which nonpharmacologic measures have provided an inadequate response," the authors conclude.
A Canadian Institutes for Health Research operating grant; a Chronic Disease New Emerging Team program grant; the Canadian Diabetes Association; the Kidney Foundation of Canada; the Heart and Stroke Foundation of Canada; the Canadian Institutes for Health Research Institutes of Nutrition, Metabolism & Diabetes and Circulatory & Respiratory Health; an Ontario Ministry of Health and Long-Term Care Career Scientist Award; a New Investigator Award through the New Emerging Team program; a Chair in Health Management Strategies from the University of Toronto; a Canadian Institutes for Health Research Investigator Award; and a fellowship grant from Eli Lilly supported this study. Some of the authors have disclosed various financial relationships with Pfizer Canada, Janssen-Ortho, Janssen, Novartis, Pfizer Inc, Eli Lilly, and/or AstraZeneca.
Ann Intern Med. 2007;146:775-786.

Antipsychotics for Dementia Raises Mortality Rate

Using antipsychotic drugs to treat patients with dementia may be fatal, according to researchers here.
They found a sharply increased risk of death that was evident within a month of starting the drugs, reported Sudeep Gill, M.D., of Queen's University and St. Mary's of the Lake Hospital, and colleagues, in the June issue of Annals of Internal Medicine.
The mortality rate was higher with the older "conventional" medications than with the newer "atypical" antipsychotics, Dr. Gill said. "Our study adds to mounting concerns about the use of antipsychotic drugs in dementia."
The finding - from a large population-based cohort study here - reinforces warnings issued two years ago by both the FDA and Health Canada, Dr. Gill and colleagues reported.
On the basis of meta-analyses of randomized controlled trials, both agencies warned of an increased mortality risk when the atypical antipsychotic drugs were used to treatment patients with dementia. But the warnings were based on relatively small trials and did not address the issue of older medications.
The atypical drugs include such medications as olanzapine (Zyprexa) and risperidone (Risperdal), while the conventional drugs include such agents as haloperidol (Haldol) and chlorpromazine (Thorazine).
To fill in the gaps, Dr, Gill and colleagues conducted a retrospective study of 27,259 matched pairs of dementia patients - those treated with antipsychotics at least once and those who were never given the drugs from April 1, 1997 through March 31, 2002.
Patients in the cohort were matched according to whether they lived in the community or in long-term care facilities and whether they had atypical or older antipsychotic medications, Dr. Gill and colleagues said.
Data were derived from four administrative health care databases in Ontario, including pharmacy, hospitalization, physician billing and outpatient services records.
The researchers used the method of propensity score matching to ensure that the cohorts were well matched and to account for most possible confounding factors.
Analysis found:
New use of atypical antipsychotics in the community was associated with a 31% increase in the risk of all-cause mortality 30 days after starting the prescription, compared to dementia patients not using the drugs. The hazard ratio was 1.31, with a 95% confidence interval from 1.02 to 1.70.
New use of atypical antipsychotics in long-term care facilities was associated with a 55% increase in the risk of all-cause mortality, compared to dementia patients not using the drugs. The hazard ratio was 1.55, with a 95% confidence interval from 1.15 to 2.07.
When the older drugs were compared to the atypical medications, the 30-day mortality risk was even greater. In the community, the hazard ratio was 1.55 (with a 95% confidence interval from 1.19 to 2.02) while in the long-term care facilities it was 1.26 (with a 95% confidence interval from 1.04 to 1.53).
"The clinical message is that even short-term use of these drugs can be associated with an increased risk of death," Dr. Gill said. "Physicians need to carefully weigh potential risks and benefits of using these drugs to manage symptoms of dementia, and they need to reassess the use soon after they're initiated to see if they can be safely discontinued."
While the antipsychotics may benefit some patients, "they are not appropriate for everyday use for everyone with dementia," he said.
But, he added, "this study shouldn't lead to a panic about these drugs. The risk for an individual patient is relatively small. But our results are clinically important."
The researchers noted that the study was limited by its design and may be unable to account for all possible confounding factors.