The Comparative Peripheral Anticholinergic-Like Adverse Event Profiles of Olanzapine and Risperidone

The central cholinergic system profile of olanzapine compared with placebo in Alzheimer's disease

“…These results are supported by recent in vivo binding and in vivo functional studies in normal animals and clinical populations who had relatively low levels of nonspeci®c anticholinergic-like activity for olanzapine (Schotte et al, 1996;Zhang and Bymaster, 1999;Raedler et al, 2000). Further, these data are consistent with the recently published data concerning olanzapine's relatively low occurrence of peripherally manifested anticholinergic-like events (Kennedy et al, 2000a). Cognitive effects as measured by the ADAS-Cog was not signi®cantly different at olanzapine doses of 5, 10, or 15 mg/day versus placebo.…”

“…Such events are of special concern in AD patients who are particularly vulnerable to anticholinergic adverse events even at low doses of antimuscarinic drugs. Treatment-emergent or worsening adverse clinical events that can indicate centrally mediated anticholinergic activity include confusion, delirium, or impairment of cognition (Richardson et al, 1985;Thienhaus et al, 1990;Tollefson et al, 1991;Flacker et al, 1998), and peripherally mediated events such as dry mouth, severe constipation, blurred vision, and dif®culties with urination (Lipowski, 1990;Kennedy et al, 2000a).…”

“…However, placebo-controlled trials of patients with schizophrenia (Beasley et al, 1996) showed that rates of peripheral anticholinergic-like adverse events were relatively low. Similarly, relatively low rates of peripheral anticholinergic-like events reported in a placebo-controlled trial of AD patients taking olanzapine (Street et al, 2000), as well as in double-blind olanzapine vs clozapine (Chengappa et al, 2000) and olanzapine vs risperidone (Kennedy et al, 2000a) comparator studies. These studies found that dry mouth, blurred vision, constipation, and micturition dif®culties occurred with risperidone in vivo (Arnt and Skarsfeldt, 1998) at a rate that was not signi®cantly different from that seen in patients treated with olanzapine (Kennedy et al, 2000a) despite risperidone's low antimuscarinic af®nity in vitro.…”

Atypical Antipsychotics and Serotoninergic Antidepressants in Patients with Epilepsy: Pharmacodynamic Considerations

“…This difference is likely to be related to the fact that olanzapine strongly blocks 5‐HT 6 serotoninergic receptors (Ki, 2.5 ± 0.9) (36), and these receptors inhibit ACh release. The cholinergic activity of olanzapine therefore depends on the relative preponderance of its 5‐HT 6 procholinergic action versus its anticholinergic muscarinic blockade (37). The epileptogenic safety of olanzapine also might be related to its action on neurosteroids, particularly on allopregnenolone, which exhibits anxiolytic and anticonvulsant properties.…”

A current review of olanzapine's safety in the geriatric patient: from pre-clinical pharmacology to clinical data

“…Clinical data include two studies comparing anticholinergic-like adverse events during treatment with OLZ versus RIS and CLZ, respectively, in patients age 18±65 with schizophrenia (Chengappa et al, 1999;Kennedy et al, 2000). These studies evaluated peripheral activity, in a posthoc analysis of spontaneously reported adverse events (Kennedy et al, 2000) and by directed enquiry into anticholinergic-like events (Chengappa et al, 1999). For OLZ-treated patients, four key anticholinergiclike events (blurred vision, dry mouth, constipation, and urinary dif®culties) occurred at relatively low rates compared to anticipated rates based upon characterized in vitro pharmacology.…”