Increased Incidence of Pneumonia in Elderly Patients on Antipsychotics
Abstract & Commentary
By Allan J. Wilke, MD, Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of MedicineHuntsville Regional Medical Campus, Huntsville. Dr. Wilke reports no financial relationship to this field of study.
Synopsis: Current use of antipsychotic medications by the elderly places them at increased risk for hospitalization for pneumonia.
Source: Knol W, et al. Antipsychotic Drug Use and Risk of Pneumonia in Elderly People. J Am Geriatr Soc. 2008;56:661-666.
Three years ago the US Food and Drug Administration (FDA) issued a "black box" warning about the use of atypical antipsychotics to treat behavioral disorders in elderly patients with dementia.1 Various theories have been proposed to explain the morbidity and mortality associated with antipsychotics, including their anticholinergic and alpha-adrenergic properties. Their use is also associated with an increase in infections, though the mechanism is unclear. These investigators from the Netherlands conducted a nested case-control study using the PHARMO database to determine whether an association exists between use of antipsychotic medications and pneumonia. PHARMO has the pharmacy dispensing records of 950,000+ Dutch patients. The pharmacy records can be linked to hospital discharge records. The researchers selected a cohort of patients, at least 65 years old, with at least one prescription for an antipsychotic medication during the study period (April 1985 to December 2003). Within this group, they looked at patients with a hospitalization for pneumonia. The index date was defined as the first hospital day. Each patient was paired with four controls (elderly patients without a pneumonia diagnosis). Patients were deemed to be current users of antipsychotic medication if a prescription for one had ended within seven days of the index date, recent past users if the use ended 8 to 30 days earlier than the index date, and past users if the use ended 31 to 365 days earlier. If the prescription was older than a year, the patient was determined to have no exposure.
Almost 23,000 patients received an antipsychotic drug prescription during the study period. Five hundred forty-three (543) patients were hospitalized with pneumonia, 65 of which were determined to be aspiration pneumonia. 2,163 controls were assigned to the cases. The median age of the cases and controls was approximately 81 years. More cases were male (60% vs 30%). Chronic obstructive pulmonary disease, heart failure, diabetes mellitus, Parkinson's disease, cerebrovascular disease, lung cancer, stomach cancer, and use of antibiotics, benzodiazepines, immunosuppressants, acid-suppressants, and drugs with potential extrapyramidal symptoms (all risk factors for pneumonia) were present more commonly in cases than controls. Unexposed cases and controls were the reference groups. Among the 543 cases with pneumonia, fully 243 (45%) were current users of antipsychotic drugs. Only 30% of controls were current users. No difference was seen in recent past or past users. When the researchers looked at duration of drug use in current users, they found a 4.5-fold increase in risk of pneumonia during the first week of use. After 90 days of use, risk returned to baseline. Among the 243 cases of current use of antipsychotic medication, 37 patients were using atypical antipsychotics. They were more likely to develop pneumonia than the cases who were using conventional antipsychotics (adjusted odds ratio 3.1 versus 1.5). Because the number of patients using the atypical antipsychotics was small, the 95% Confidence Interval was broad (1.9-5.1).
Commentary
The authors speculate as to the mechanism whereby antipsychotic drugs increase the risk of pneumonia in the elderly. They list decreased cough reflex, dysphagia, dyskinesia, xerostomia, sedation, and immune system dysfunction as possibilities. A previously published study found no increased risk of mortality from pneumonia in patients taking atypical antipsychotics, however, there was an increased risk with conventional antipsychotics.2
The indications for use of antipsychotic drugs in the elderly are no different than in other patients: schizophrenia, bipolar disorder, acute mania, and acute agitation. However, we are seeing increased use, especially of atypical antipsychotics, in patients with dementia and "behaviors."This is disturbing, because these medications are associated with greater morbidity and mortality.3,4,5 As the medical director of a long-term care facility, I am frequently on the receiving end of pleas such as, "Dr. Wilke, Mr. Smith in Room 8 is yelling out again. Isn't there anything you can give him?" I've heard Mr. Smith, and there is a real temptation to comply with the nursing staff's request. The unspoken request is that I sedate Mr. Smith. Is sedation in his best interest or that of the staff? When I remind the staff of this, I am rejoined, "Well, how about for just a short while?" While this is appealing, even short-term use can result in serious events, including hospitalization and death.6
Are the atypical antipsychotics inherently more dangerous than conventional ones? It depends on through whose lens you're viewing. If you are a gastroenterologist, you could point to a recent study that suggests that conventional antipsychotics are associated with a greater risk of hospitalization for acute pancreatitis than atypical ones.7 From an orthopedist's point of view, atypical antipsychotics with a high degree of somnolence (olanzapine [Zyprexa®] and quetiapine [Seroquel®]) may lead to unintended injury.8 All antipsychotic medications appear to increase the risk of hospitalization for femur fracture. My advice is to use antipsychotic medications sparingly in the demented elderly and only when they are indicated (dementia with psychosis). And when Mr. Smith yells out, search for other reasons for his behavior (undertreated pain, for instance).
References
1. http://www.fda.gov/cder/drug/advisory/antipsychotics.htm, accessed June 1, 2008.
2 Barnett MJ, et al. Risk of mortality associated with antipsychotic and other neuropsychiatric drugs in pneumonia patients. J Clin Psychopharmacol. 2006;26:182-187.
3. Schneider LS, et al. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294:1934-1943.
4. Wang PS, Set al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med. 2005;353:2335-2341.
5. Gill SS, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007;146:775-786.
6. Rochon PA, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008;168:1090-1096.
7. Gasse C, et al. Risk of hospitalization for acute pancreatitis associated with conventional and atypical antipsychotics: a population-based case-control study. Pharmacotherapy. 2008;28:27-34.
8. Said Q, et al. Somnolence effects of antipsychotic medications and the risk of unintentional injury. Pharmacoepidemiol Drug Saf. 2008;17:354-364.
9. Liperoti R, et al. Conventional or atypical antipsychotics and the risk of femur fracture among elderly patients: results of a case-control study. J Clin Psychiatry. 2007;68:929-934.
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