Use of fluoxetine, a selective serotonin-uptake inhibitor, in the treatment of obesity: a dose-response study (with a commentary by Michael Weintraub).

Pharmacologic measures which increase serotonergic activity in the brain decrease food consumption and lead to decreased weight in animals. Fluoxetine, an inhibitor of serotonin reuptake, decreases food intake in animals and is associated with weight loss in depressed and otherwise healthy obese patients. To determine the most effective daily fixed dose which causes weight loss in nondepressed obese patients, fluoxetine (10, 20, 40 or 60 mg) or placebo was administered once daily for 8 weeks to 655 patients consisting primarily of women (mean age 40 years, mean weight 95 kg). Diet and activity were not controlled. The placebo-treated patients lost 0.6 +/- 2.3 kg. With the 60-mg fluoxetine dose, patients lost an average of 4.0 +/- 3.9 kg (P less than 0.001), with intermediate responses at the lower doses. Weight loss was proportional to the initial body mass index (weight/height squared). There were no statistically significant differences between any fluoxetine treatment group and placebo for discontinuations from the study. There were statistically significant dose-dependent increases in reports of asthenia, somnolence and sweating. Thus, fluoxetine 60 mg daily appears to be potentially effective for use in weight reduction.

Terazosin: an effective once-daily monotherapy for the treatment of hypertension.

The safety and efficacy of once-daily terazosin as monotherapy were evaluated in five randomized, double-blind, placebo-controlled studies in which 351 patients with mild to moderate hypertension participated. The five studies included two dose-titration studies and three fixed-dose studies. In the dose-titration studies, terazosin doses were titrated at weekly intervals until supine diastolic blood pressure was below 90 mm Hg. In the fixed-dose studies, titration continued until a predetermined dosage level of terazosin or corresponding placebo was reached. The dose of terazosin ranged from 1 to 40 mg once daily, and responses were assessed after a four-week course of therapy at a constant dosage level. Terazosin administration resulted in significantly greater mean decreases in supine diastolic blood pressure in comparison with placebo in four of the five studies. Similar decreases were observed for supine systolic and standing blood pressures in selected studies. In all five studies, terazosin caused a significant decrease in supine and standing blood pressures from baseline to the final visit. Adverse experiences occurring with a significantly greater prevalence rate in terazosin-treated versus placebo-treated patients and 7 percent of placebo-treated patients), asthenia (17 percent of the terazosin group and 4 percent of the placebo group), and peripheral edema (10 percent of the terazosin group and 3 percent of the placebo group). On the basis of these studies, it appears that terazosin, when administered once daily as monotherapy, is both safe and effective for the treatment of mild to moderate hypertension.