But although discontinuation because of intolerability was most prevalent among patients taking risperidone or olanzapine, both SGAs were more effective than placebo for treating problem behaviors in some participants, Dr. Schneider notes. He adds that the patient population and most SGA dosages in CATIE-AD reflected typical geriatric psychiatric practice in the community.
An editorial in the October 12 New England Journal of Medicine2 praised CATIE-AD for allowing physicians to titrate and stop SGA regimens as needed while maintaining the double-blind design. Results of fixed-dose trials with prespecified time points are more difficult to apply to clinical practice because the course of Alzheimer’s disease and patients’ ability to tolerate specific drugs change over time.2
“This study can inform clinicians that they should not be prescribing medication and then not following up or maintaining it indefinitely,” says Dr. Schneider, who is professor of psychiatry, neurology and gerontology, University of Southern California, Los Angeles.
‘Black box’ fears?
Dr. Verma, however, reports that many clinicians have been hesitant to prescribe SGAs to older patients since last year—when the FDA ordered that SGAs carry “black box” warnings of a possible increased mortality risk in that population.
“CATIE-AD will intensify clinicians’ fears of litigation by implying that the risks of using SGAs outweigh their benefits, especially when SGAs are reported to be no better than placebo,” Dr. Verma predicts. “A lawyer could say to a clinician, ‘You used an SGA on Mr. Smith despite the risks, and he developed XYZ complication?’ Try to work yourself out of that one.
“A paper like this will be snapped up by pharmacy and therapeutics committees around the country, as well as Medicare, Medicaid, and other insurers,” Dr. Verma adds. “They’ll say, ‘These expensive drugs are no better than placebo. Why bother covering them?’”
Echoing Dr. Verma’s fears, the American Association for Geriatric Psychiatry (AAGP) responded to CATIE-AD by urging regulatory agencies not to overreact to the findings or “prevent physicians from exercising clinical judgment.”3 AAGP also is calling for more research “based on clinical and evidence-based protocols designed to help physicians know when and how to start, continue, and discontinue psychotropics” for older patients.3
Another problem with generalizing the CATIE-AD findings, Dr. Verma says, is that many Alzheimer’s patients are more severely impaired than those who participated in CATIE-AD.
“These are people who cannot be managed,” adds Barbara Kamholz, MD, clinical associate professor, University of Michigan, and staff psychiatrist, VA Medical Center, Ann Arbor. “They can’t get through the day. They can’t eat or use the bathroom properly. You can’t treat their medical problems if you can’t manage grossly abusive or violent behaviors.”
Dr. Schneider, however, notes that the outpatients in CATIE-AD were nearly as symptomatic as patients in nursing homes—as suggested by CATIE-AD patients’ mean Brief Psychiatric Rating Scale and Neuropsychiatric Inventory scores (28 and 37, respectively).
Also, Dr. Schneider says, most trials of SGAs conducted among nursing home patients have not yielded statistically significant results.4
‘Informing’ practice
Dr. Schneider warns against drastic interpretation of CATIE-AD, saying the trial should guide clinical practice, not radically alter it. He says he will keep prescribing SGAs for short-term acute treatment of older patients whose behavioral problems do not respond to psychosocial interventions, distraction, redirection, environmental manipulation, or other treatments.
“I’m not sure this study has changed my use of [SGAs],” Dr. Schneider says. “What it has done is better inform my considerations in prescribing. But I use [SGAs] in patients with significant behavioral problems—and especially with delusions, paranoia and aggression—who can’t be otherwise treated.”
Studies show that despite their risks, SGAs:
- are associated with one-tenth the risk of tardive dyskinesia compared with first-generation antipsychotics (FGAs) such as haloperidol5
- are less likely to cause extrapyramidal symptoms than FGAs.6
Dr. Verma notes that the cardiac, cerebrovascular, and cardiopulmonary side effects described in the “black box” warnings on SGAs are prevalent conditions in the elderly, independent of medication.
“Despite the side effects, 20% to 30% of patients [in CATIE-AD] continued to take [SGAs] for the entire study,”
Dr. Verma adds. “[SGAs] are not perfect drugs, but they’re the best we’ve got right now and better than what we had.”
Dr. Schneider acknowledges that no evidence supports use of other drug classes to treat problem behaviors in the elderly. “Antidepressants have their own adverse effects, and you wouldn’t expect them to work for delusions or aggression. And benzodiazepines are strongly associated with falling and oversedation.”
Dr. Kamholz fears that some psychiatrists might eschew SGAs in older patients and prescribe another type of medication that carries a greater side-effect risk.