Phentermine stimulates the release of norepinephrine, and to a lesser extent serotonin (5-HT, 5-hydroxytryptamine) and dopamine, from nerve terminals. Only one RCT, published in 1968, evaluated the effect of at least 8 months of phentermine therapy on body weight.334 In that study, 108 obese women were randomized to receive an LCD and treatment with either daily phentermine (30 mg/day), daily phentermine every other month alternating with daily placebo every other month, or daily placebo for 36 weeks. Of the 64 subjects who completed the study, those randomized to either continuous or every-other-month phentermine therapy achieved the same 13% weight loss, which was greater than the 5% weight loss observed in the placebo group. In a more recent trial, subjects who completed 28 weeks of therapy with one half (15 mg/day) or one fourth (7.5 mg/day) the usual dose of phentermine had a 7.4% and 6.7% weight loss, respectively, compared with 2.3% weight loss in the placebo group.335 The most common side effects of phentermine are dry mouth, insomnia, and constipation. Although all sympathomimetic agents can increase blood pressure and heart rate, these abnormalities usually do not occur with phentermine therapy in the presence of weight loss.