Data are limited concerning weight changes that occur beyond the acute phase of treatment with selective serotonin reuptake inhibitors. Michelson and associates analyzed changes in weight among patients who received long-term fluoxetine therapy.

Data were obtained from a study that initially included 839 patients who entered the 12-week acute-therapy phase of the study. After remission of depression had been achieved, 395 patients were randomly assigned to continuation of fluoxetine therapy, in a dosage of 20 mg daily, or placebo. Therapy was given for as long as 50 weeks.

Weight was assessed at each visit during the initial 12 weeks of acute treatment and at the 14th, 26th and 38th weeks during the continuation phase of therapy. Weight changes in the fluoxetine and placebo groups during the continuation period were compared.

A small (less than 0.5 kg) but significant weight gain occurred during the week following entry into the study but preceding the initiation of fluoxetine therapy. For all patients thereafter, a small but significant decrease in weight occurred during the 12 weeks of the acute-treatment phase. Data on patients who completed 38 weeks of continuation therapy revealed that weight loss occurred primarily during the initial four weeks of therapy. It was followed by stabilization of weight.

Significant weight gain occurred in the treatment and placebo groups from the beginning (week 12) of continuation therapy to 38 weeks of continuation therapy (a total of 50 weeks). Patients who received fluoxetine gained less weight than patients who received 12 weeks of fluoxetine therapy followed by 14 weeks of placebo, but it was not a significant value. Patients in each of the groups gained a mean of approximately 3 kg during the 50 weeks of follow-up.

The authors conclude that after recovery from acute depression, patients are likely to experience modest weight gain that increases over time. Fluoxetine may initially be associated with weight loss but does not appear to be associated with specific effects on weight during long-term therapy, even up to one year. The authors suggest that the weight gain during the continuation phase in the fluoxetine and placebo groups is consistent with previous studies. Recovery from acute depression is also associated with increased appetite, which could lead to increased food intake and weight gain.