BACKGROUND AND AIM: Premenstrual syndrome (PMS) is a common disorder in women that can affect normal aspects of their life. We conducted the present study to compare the effect of acupressure and fluoxetine on PMS. METHODS: This randomized clinical trial included 90 Iranian female students at Qazvin University of Medical Sciences with moderate to severe premenstrual syndrome. After convenient sampling, individuals were randomly assigned to three groups (30 acupressure, 30 fluoxetine, and 30 control) using block randomization. The tools used include the Beck Depression Inventory (BDI), and the Daily Record of Severity of Problems form (DRSP). The intervention was performed in three consecutive menstrual periods and was followed up three months later. The acupressure group applied acupressure to 4 points (LIV3, SP9, LI11, LI4) every other day, 14 days before menstruation, using the TENS device (6 sessions during the second half of the menstrual cycle). The fluoxetine group received oral fluoxetine 20 mg daily for 14 days prior to menstruation. The control group received no intervention. Data were analyzed using R software Version 4.1.1. RESULTS: There was a significant difference between the acupressure and fluoxetine groups with the control group in DRSP score (p < 0.001) after the intervention. However, no significant difference in DRSP score was observed between the two intervention groups during the intervention (p > 0.05), but the difference between the two groups became significant during the time of follow-up (p = 0.033). CONCLUSION: Acupressure can be recommended as a useful complementary method to selective serotonin reuptake inhibitors in women with PMS.

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