Between weeks 104 and 156 we attempted to optimize response by adjusting the doses of fenfluramine and phentermine. Dosing changes were based on an algorithm that aimed to achieve 120% of ideal body weight (IBW) while minimizing adverse effects. The dose groups were as follows: stage I, 30 mg fenfluramine plus 15 mg phentermine in the morning; stage II--continuous or targeted intermittent, 60 mg fenfluramine plus 15 mg phentermine in the morning; stage III, 60 mg fenfluramine plus 30 mg phentermine in the morning; stage IV, 60 mg fenfluramine plus 30 mg phentermine in the morning and 30 mg fenfluramine in the evening; and stage V, 60 mg fenfluramine plus 30 mg phentermine in the morning and 60 mg fenfluramine in the evening. Seventy-seven participants began this segment of the study and 59 completed to week 156. Completers of this segment of the study gained an average of 2.7 +/- 0.5 kg between weeks 104 and 156 but remained 9.4 +/- 0.8 kg (10.5%) below baseline. On average, weight loss from baseline by group was as follows: for stage I (n = 2), 14.1 +/- 6.8 kg; for stage II continuous (n = 14), 10.9 +/- 0.7 kg; for stage II targeted intermittent (n = 7), 8.8 +/- 2.4 kg; for stage III (n = 9), 7.7 +/- 2.6 kg; for stage IV (n = 8), 10.5 +/- 2.6 kg; and for stage V (n = 19), 8.4 +/- 2.4 kg. Upward dose adjustment (n = 36) resulted in further weight loss in 11 and no gain in six participants.(ABSTRACT TRUNCATED AT 250 WORDS)