Psychiatry - November 2008 - (Page 30)

TABLE 2. AEs reported in donepezil clinical trials (%)* (Coninuted from previous page) MILD TO MODERATE AD SEVERE AD Placebo ADVERSE EVENT n/a Donepezil Odds Ratio [95% CI] Placebo Donepezil Odds Ratio [95% CI] up to 10mg/day P-value n/a 10mg/day P-value (n=355) (n=747) (n=392) (n=501) 1.52 [0.63–3.63] 1.52 [0.63–3.63] 2.02 [0.62–6.54] 2.02 [0.62–6.54] 2.02 [0.62–6.54] 2.02 [0.62–6.54] 2.09 [1.15–3.80] - Nervousness Pain, various locations Personality disorder Somnolence - - 1.14 [0.72–1.80] 2.02 [0.63–6.47] 2.02 [0.63–6.47] 1.7 [0.85–3.40] 3.06 [0.99–9.45] - 2 3 0.351 8 9 0.582 2 3 0.351 - - - 1 2 0.241 5% of patients in the active group are highlighted in gray. Hyphens indicate that data were not reported in the PI documents (presumably below threshold cutoff). TABLE 3. AEs leading to discontinuation in one galantamine trial (%)* PLACEBO ADVERSE EVENT n/a (n=286) Any AE Anorexia Dizziness Nausea Syncope Vomiting 7 <1 <1 <1 0 0 GALANTAMINE 16mg/day (n=279) 7 1 2 2 0 1 GALANTAMINE 24mg/day (n=273) 10 <1 1 4 1 3 *The most frequent AEs (adverse events) leading to discontinuation in at least 1% of galantamine-treated patients in a single trial with a 4-week-per-dose dose escalation schedule ratios and P values in Tables 2, 4, 6, and 7, which were calculated specifically for this manuscript. Cholinesterase inhibitors. Donepezil. Donepezil is a reversible antagonist of acetylcholinesterase (AChE), with a plasma half-life of about 70 hours and a time to peak plasma concentration of 3 to 4 hours. Doses of 5 and 10mg, administered once daily, have been shown to be effective in patients with mild to 30 Psychiatry 2008 [ N O V E M B E R ] moderate AD; for patients with severe AD, the recommended daily dose—also administered QD or once daily—is 10mg.1 The most frequent AEs leading to discontinuation in donepezil trials, occurring in at least two percent of patients receiving up to 10mg/day of the drug and at twice the incidence seen in placebo patients, are shown in Table 1. Individual AEs experienced during clinical trials, reported in at least two percent of patients receiving up to 10mg/day donepezil and at a higher frequency than in placebo-treated patients are shown in Table 2. There is evidence of a lower incidence of the most frequent gastrointestinal symptoms in patients who were titrated to the target dose of 10mg/day over six weeks, compared to the group titrated to the same dose within one week.1 In Table 2, the data from studies in mild-tomoderate AD are presented separately from studies in severe AD, following the approach used in the PI document. The statistically significant odds ratios of drug versus placebo in each set of data are highlighted gray. In most cases, gastrointestinal effects have been mild and transient, usually lasting less than three weeks. Diarrhea, nausea, and vomiting were shown to occur more frequently with the 10-mg daily dose than with the 5mg dose. Galantamine. Galantamine is a ChEI with the plasma half-life of approximately seven hours and a time to peak plasma concentration of about one hour. Recommended doses of 16 and 24mg are administered twice daily as an immediate-release

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Psychiatry - November 2008 Editor's Message Editorial Advisory Board Contents PsychRx Letters to the Editor Measuring Adverse Events in Psychiatry Nonsuicidal Self Injury in Adolescents Relative Tolerability of Alzheimer's Disease Treatments Biracial Identity Development and Recommendations in Therapy Depression and Cardiovascular Disease: Just an Urban Legend? Three Risk Management Basics Journal Watch Classified Advertising Information for Authors

Psychiatry - November 2008

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