Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.

Depression in the geriatric population is a frequent, serious, and potentially reversible disorder, yet relatively few blinded, controlled, antidepressant trials have been reported. A number of age-related issues complicate safe and effective pharmacotherapy. In a 6-week, double-blind trial in moderately tc severely depressed (nonpsychotic) outpatients over age 60, fluoxetine ( N = 335) was statistidy significantly more efficacious than placebo (N = 336) inoverallresponse(43.9%~~.31.6%,p= .002)andre~nission(31.6% vs. 18.6%, p < .001) rates. Analyses of early discontinuations because of an adverse drug event revealed no statistically significantly greater rate with fluoxetine (n = 39; I 1.6%) than was seen with placebo (n = 29; 8.6%). These results corroborate that major depression in an older population is responsive to antidepressant pharmacotherapy. Specifically, fluoxetine, at a conventional 20-mg dose, was both safe and effective relative to placebo in this special population.Mood disturbances are common among the elderly. The 6-month prevalence of major depression is 1% and 3.6%, respectively, for men and women over the age of 65 (Regier et al.

To determine the effect of fluoxetine on diazepam's pharmacokinetic and psychomotor responses, single oral doses of 10 mg diazepam were administered to six normal subjects on three occasions, either alone or in combination with 60 mg fluoxetine. Diazepam was given alone, after a single dose of fluoxetine, and after eight daily doses of fluoxetine. Psychometric data showed that fluoxetine had no significant effect on the psychomotor responses to diazepam. However, the pharmacokinetic data indicated a change in diazepam disposition after fluoxetine administration. Diazepam AUC was larger, the half-life was longer, and the plasma clearance was lower after fluoxetine administration, suggesting that fluoxetine inhibited the metabolism of diazepam. The reduced formation of an active metabolite, N-desmethyldiazepam, also suggested that fluoxetine inhibited diazepam's metabolism. The clinical implications of this pharmacokinetic drug-drug interaction are minor because psychomotor responses were unaffected and offsetting changes in the kinetics of diazepam and its metabolite occurred. Dosage modification of either fluoxetine or diazepam is unlikely to be necessary.

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