Antipsychotic Use Varies by Patient Age

| July 3, 2007 | 0 Comments

by Elisa F. Cascade and Amir H. Kalali, MD; Leslie Citrome, MD, MPH

Ms. Cascade is Vice President, Strategic Research and Safety, Quintiles Inc., Falls Church, Virginia; Dr. Kalali is Vice President, Global Therapeutic Group Leader CNS, Quintiles Inc., San Diego, California, and Professor of Psychiatry, University of California, San Diego; and Dr. Citrome is Professor of Psychiatry, New York University School of Medicine; and Director, Clinical Research and Evaluation Facility, Nathan S. Kline Institute for Psychiatric Research.

Financial Disclosures: Dr. Citrome is a consultant for, has received honoraria from, or has conducted clinical research supported by the following: Abbott Laboratories, AstraZeneca Pharmaceuticals, Barr Laboratories, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceuticals, Jazz Pharmaceuticals, and Pfizer Inc.
Abstract: Since their introduction in mid 1990s, atypical antipsychotics have been studied in a ever-expanding number of conditions. To gain a better understanding of current practice patterns, we investigated antipsychotic uses across different patient age groups. In both the 18 to 39 and 40 to 64 age groups, schizophrenia (ICD-9 295) and affective psychoses (ICD-9 296) account for approximately 70 percent of atypical antipsychotic use. In contrast, these diagnoses only represent 41 percent of use in patients age 0 to 17 and 36 percent in patients age 65 and older.

Key words: antipsychotics, patient age, prescriptions, off label, dementia, children


Since their introduction in mid 1990s, atypical antipsychotics have been studied in a ever-expanding number of conditions. To gain a better understanding of current practice patterns, we investigated antipsychotic uses across different patient age groups.


We obtained data from the following two sources: 1) total retail prescriptions of antipsychotics by age from Vector One National (VONA), which captures nearly half of all prescription activity in the US and 2) annual data from Verispan’s Prescription Drug and Diagnosis Audit (PDDA) database regarding most common uses of antipsychotics by age. PDDA is a syndicated data product that captures information from a rotating panel of 3,100 office-based physicians representing 29 specialties across the United States. Each panel member completes a one-page log on demographics, diagnoses, and medications for every patient seen during the reporting period.


Forty-five percent of atypical antipsychotics are prescribed to patients age 40 to 64. As seen in Figure 1, an additional 24 percent of antipsychotics are used by patients aged 18 to 39. The two remaining patient age groups, under 18 and ?65, accounted for 14 percent and 17 percent of antipsychotic use respectively.

Figure 2 displays the most common uses of atypical antipsychotics by age; diagnoses accounting for at least five percent of total use are pictured. In both the 18 to 39 and 40 to 64 age groups, schizophrenia (ICD-9 295) and affective psychoses (ICD-9 296) account for approximately 70 percent of atypical antipsychotic use. In contrast, these diagnoses only represent 41 percent of use in patients age 0 to 17 and 36 percent in patients age ?65.

For patients age 0 to 17, in addition to schizophrenia and affective psychoses, hyperkinetic syndrome (ICD-9 314) was also a common reason for antipsychotic use, accounting for 16 percent of diagnoses. Dementia was the other most common reason for atypical antipsychotic use in patients age ?65, with 17 percent of diagnoses.

Expert Commentary

Off-label use of antipsychotic medications for patients is controversial because of the limited evidence base supporting the efficacy of this as well as the potential for adverse events.[1]

Children and the elderly are two at-risk populations for which antipsychotic medications can be both helpful and potentially problematic. Cascade and Kalali observed that 14 percent and 17 percent of prescriptions of atypical antipsychotic medications were accounted for by patients in the age groups of less than 18 years and 65 years and older, respectively. Moreover, nonpsychotic disorders represented 59 percent of use in patients less than 18 years of age and 64 percent in patients age 65 years and older.

Pharmaceutical companies are restricted from marketing off-label uses of their products, including the pediatric use of agents only approved for adult use, as well as off-label diagnoses. Nevertheless, the agents are used extensively and the potential market is substantial. Table 1 provides the age distribution for the general US population as determined from census data2 together with Cascade and Kalali’s data on distribution of prescriptions of atypical antipsychotic medications.

A concern has been expressed about the exposure of persons under the age of 18 years to antipsychotic medications in the face of the lack of controlled clinical trials supporting this practice.[3,4] Of particular alarm are endocrine and metabolic adverse effects of atypical antipsychotics.[5] As per the data presented by Cascade and Kalali and the demographic distribution of the US population, the age group less than 18 years is not overrepresented in terms of numbers of prescriptions of atypical antipsychotics.

Nonetheless, Aparasu and Bhatara[3] found that among patients younger than 20 years examined using the 2003 to 2004 National Ambulatory Medical Care Survey and the outpatient department portion of the 2003 to 2004 National Hospital Ambulatory Medical Care Survey, that antipsychotic medications were prescribed in two million outpatient visits annually, representing one percent of overall visits by children and adolescents in 2003 to 2004. Most (99%) of these visits involved prescribing of atypical agents, more frequently risperidone, quetiapine, and aripiprazole, and more often in patients over nine years, males, and whites. Diagnoses associated with antipsychotic prescribing were bipolar disorder, psychoses, depression, disruptive behavior, and anxiety. Similar findings were reported by Olfsen and colleagues,[6] where national trends and patterns in antipsychotic treatment of youth seen by physicians in office-based medical practice were examined for the period 1993 to 2002. As with Aparasu and Bhatara,[3] patient visits by persons 20 years and younger from the National Ambulatory Medical Care Surveys were studied. The estimated number of office-based visits by youth that included antipsychotic treatment increased from approximately 201,000 in 1993 to 1,224,000 in 2002. Overall, 9.2 percent of mental health visits and 18.3 percent of visits to psychiatrists included antipsychotic treatment. From 2000 to 2002, 92.3 percent of visits with prescription of an antipsychotic included an atypical agent. Diagnoses recorded included disruptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%).

There are additional concerns about the prescription of antipsychotics to persons 65 years or older, particularly among those with dementia. Cascade and Kalali found that among the patients 65 years and older receiving atypical antipsychotics, dementia was a commonly stated indication. Atypical antipsychotics, such as olanzapine and risperidone, can successfully reduce aggression and/or psychosis in patients with dementia,[6] however the US Food and Drug Administration issued a Public Health Advisory in 2005 regarding deaths with antipsychotics in elderly patients with behavioral disturbances,[7] and consequently, the manufacturers of all of the atypical antipsychotics were required to include a boxed warning regarding this risk. Gill and colleagues[8] recently reported a population-based retrospective cohort study of antipsychotic use and all-cause mortality in older adults with dementia residing in Ontario, Canada, and found that the new use of atypical antipsychotics (approximately 75% were using risperidone, 20% olanzapine, and 5% quetiapine) was associated with a statistically significant increase in the risk for death at 30 days compared with non-use. Typical antipsychotic use (approximately 60% were using haloperidol, 18% loxapine, 10% thioridazine, 6% chlorpromazine, and 4% perphenazine) was associated with higher risk of mortality than for atypical antipsychotics. The data presented by Gill and associates8 is consistent with a meta-analysis9 of prospective double-blind placebo-controlled trials where risk of death was 54-percent higher among the atypical antipsychotic group versus the placebo group. However, mortality risk appears higher with the older antipsychotic agents, and this disadvantage for the older agents was also observed in two other population-based studies,[10,11] where short-term mortality in elderly people who were prescribed typical antipsychotics was approximately 50-percent higher than those prescribed atypical agents. Thus, risk of intervening with an antipsychotic requires a careful risk benefit evaluation. Certain populations will benefit from this intervention as noted in a small number of very frail patients with dementia, mean age 86 years, in a prospective Finnish study.[12] They found that about half of the patients used antipsychotic medication and that mortality within two years was 32 percent for those who received an atypical antipsychotic, 45 percent for those who received a typical antipsychotic, and 50 percent for those who did not use antipsychotics.

In summary, Cascade and Kalali provide some sobering statistics of potentially problematic off-label use of atypical antipsychotics in two vulnerable populations. The current use of these agents in children, adolescents, and the elderly should be carefully thought through in terms of potential risks versus benefits. Additional research in the form of controlled clinical trials involving children, adolescents, and the elderly should be undertaken for indications that show substantial promise.


1. Tremeau F, Citrome L. Antipsychotics for patients without psychosis? What clinical trials support. Current Psychiatry 2006;5(12):33–44.
2. US Department of Commerce. 2000 Census of Population and Housing: United States Profiles of General Demographic Characteristics. Issued May 2001. Available at: Access date: June 11, 2007.
3. Aparasu RR, Bhatara V. Patterns and determinants of antipsychotic prescribing in children and adolescents, 2003–2004. Curr Med Res Opin 2007;23:49–56
4. Olfson M, Blanco C, Liu L, et al. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. Arch Gen Psychiatry 2006;63:679–85
5. Correll CU, Carlson HE. Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry 2006;45(7):771–91.
6. Ballard C, Waite J. Atypical antipsychotics for aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev 2006; Issue 1. Art. No.: CD003476.pub2. DOI: 10.1002/14651858.CD003476.pub2.
7. US Food and Drug Administration. FDA Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances. April 11, 2005. Available at: Access date: June 3, 2007.
8. Gill SS, Bronskill SE, Normand ST, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007;146:775–86.
9. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934–43.
10. Schneeweiss S, Setoguchi S, Brookhart A, et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007;176:627–32.
11. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005;353:2335–41.
12. Raivio MM, Laurila JV, Strandberg TE, et al. Neither atypical nor conventional antipsychotics increase mortality or hospital admissions among elderly patients with dementia: A two-year prospective study. Am J Geriatr Psychiatry 2007;15:416–24.

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Category: Alzheimer's Disease, Dementia, Mental Disorders, Neurologic Systems and Symptoms, Neurology, Past Articles, Schizophrenia, Trend Watch

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