An expert system is proposed to predict the risk of adverse side effects in patients taking antidepressants. The system predicts the risk of seven adverse drug reactions (serotonin syndrome, nausea, suicidal ideation, somnolence, gastrointestinal symptoms, sexual dysfunctions and hepatobiliary disorders) based on physiological information, including sex, age and pharmacological factors such as type of antidepressant and concurrent medication. The risk of side effects is categorized into four degrees: none, low, medium, and high. The effectiveness of the proposed expert system was validated using 54 patient profiles compiled from databases with high classification rates, especially for hepatobiliary disorders and gastrointestinal symptoms. The system utilizes fuzzy logic to handle the inherent imprecision to identify a patient’s age group. Furthermore, fuzzy logic does not require extensive databases and provides clinicians with an understanding of the rationale for the recommendation.