OBJECTIVE: To assess utilization patterns, frequency of side effects, and the cost of side effects associated with SSRI treatment. METHODS: Electronic medical records and medication profiles from HMO patients were retrospectively reviewed. Inclusion criteria were patients over 18 years old with a new prescription for an SSRI who were continuously enrolled in the HMO plan for at least one year (6 months before and 6 months after their index date). The perspective was that of the HMO. RESULTS: Of the 464 patients who met the inclusion criteria, 130 patients (28%) had 144 medication changes made after initial therapy - including 43 additions of medication, 43 switches to another antidepressant, 41 discontinuations of therapy due to side effects, and 17 dose changes due to side effects. A total of 160 patients (34%) had at least one side effect of the SSRI noted in their medical record. Costs to treat side effects were estimated for changes/additions of medication that appeared in the medication profiles (38 patients). The cost of added medications that were noted in the medical record but did not appear in the medication profile (e.g. non-prescription items such as Immodium) were not included in the estimate due to the perspective of the study. Other costs associated with side effects included physician visits (43 patients), lab tests for dosage adjustments (4 patients), and emergency room visits (3 patients). Sensitivity analyses indicated that the direct medical costs associated with the treatment of side effects ranged from approximately $4,600 US to $6,000 US for the 464 patients ($10 US -$13 US per patient) for the six-month period of analysis. CONCLUSION: Although one-third of patients noted at least one side effect of SSRI treatment, the direct medical costs associated with the side effects were relatively small. Future studies might investigate the indirect and intangible costs of these side effects.