Rifaximin for IBS Inhaled Corticosteroids and Intervention Effectiveness–Alzheimer’s Disease (CATIE-AD) Study Group, Although the cause of irritable bowel Fracture however, data about such treatment are syndrome (IBS) remains unclear, stud- Research has strongly suggested a link relatively sparse and inconsistent. Their ies suggest that bacterial overgrowth between inhaled corticosteroid use and own findings challenge the conven- in the small intestine may play a role. fracture risk, due to effects on bone tional wisdom. Accordingly, several antibiotics have mineral density. But the studies have They randomly assigned 421 outpa- been tested as IBS treatments—but been limited by short follow-up (less tients with AD and psychosis, aggres- each has fallen short. Neomycin than four years) and lack of informa- sion, or agitation to receive olanzapine, improves symptoms but eliminates tion on potential confounders (such quetiapine, risperidone, or placebo. bacterial overgrowth in only about 25% as physical activity), say researchers Study physicians adjusted dosages of patients, and treatment is stymied by from the University of Nottingham as clinically indicated, and treatment adverse effects. Other agents, such as and the London School of Hygiene continued for up to 36 weeks. At 12 doxycycline, have shown low efficacy. and Tropical Medicine, both in the weeks, the researchers found similar Researchers from Cedars-Sinai United Kingdom. To better quantify the response rates between the groups: Medical Center, Los Angeles, CA and relationship between inhaled cortico- 32%, 29%, 26%, and 21% in the olan- the University of Chicago, Chicago, IL steroids and facture, they conducted a zapine, risperidone, quetiapine, and have higher hopes for rifaximin. This study with over nine years of prescrib- placebo groups, respectively. antibiotic, recently FDA approved for ing and diagnostic data. Overall, 82% of patients discontin- treating travelers’ diarrhea, is “gut selec- Of 1,671 patients aged 75 or older, ued their study medication, with no tive,” with negligible systemic absorp- 982 had been prescribed an inhaled significant differences between groups tion, which should minimize adverse corticosteroid, and 187 had an incident in the time to discontinuation for any effects. Furthermore, a previous study fracture. After adjusting for age and reason. In terms of time to discontinu- demonstrated bacterial overgrowth gender, the researchers found a dose- ation due to lack of efficacy, however, eradication rates as high as 70%. response relationship between inhaled the researchers found an advantage for The researchers randomly assigned corticosteroid use and fracture risk. both olanzapine and risperidone over 87 patients with IBS to receive 10 days This proved independent of incident placebo and for olanzapine over que- of rifaximin 400 mg three times daily and historical exposure to oral cortico- tiapine. Discontinuation due to intoler- or placebo. Over the 10 weeks follow- steroids, type of airflow obstruction, ance of the study drug, adverse effects, ing therapy, rifaxamin treatment signifi- use of bronchodilators, self-reported or death was significantly less likely cantly improved global IBS symptoms activities of daily living, physical activ- with placebo compared to all three and bloating scores, compared with ity, and socioeconomic status. atypical antipsychotics. placebo. Adverse effects in both groups Source: Chest. 2006;130:1082–1088. Sedation occurred more commonly were similar and occurred rarely. with all the antipsychotics compared The researchers acknowledge that with placebo, and increased confusion their study’s small sample size limited Risks and Benefits of or mental status changes were more assessment of adverse effects and its Atypical Antipsychotics in AD likely with olanzapine and risperidone. duration was not long enough to “rec- These two drugs also were associated ognize any meaningful recurrence” of Considered to be safer and at least as with more extrapyramidal signs. All bacterial overgrowth. They also note effective as conventional antipsychotic three antipsychotics caused weight that recent data support using a higher drugs, atypical antipsychotics have gain, compared to an overall weight rifaximin dosage. They call for larger, become common choices for treat- loss in the placebo group. Accordingly, longer-term, multicenter studies to ing delusions, hallucinations, aggres- the researchers advise further investi- clarify these issues—and to compare sion, and agitation in patients with gation into the possible link between antibiotic therapy with other IBS treat- Alzheimer disease (AD). According antipsychotic drugs and metabolic syn- ment strategies. to the members of the multicenter drome in elders. ● Source: Ann Intern Med. 2006;145:557–563. Clinical Antipsychotic Trials of Source: N Engl J Med. 2006;355:1525–1538.

20 • FEDERAL PRACTITIONER • JANUARY 2007