OBJECTIVES: Graves' disease (GD), a common cause of hyperthyroidism, poses management challenges due to relapse risks and treatment variability. Methimazole (MMI) continues to be the preferred treatment, and acts by inhibiting thyroid hormone production through the blockade of key enzyme activity. This review assesses how MMI's treatment durations, dosages, and combination therapies contribute to effectively managing GD.

METHODS: Embase^® and MEDLINE databases were systematically searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The population, intervention, comparator, outcome and study design (PICOS) criteria were used to identify relevant studies investigating MMI in patients with GD.

RESULTS: Of the 709 records identified, eight publications encompassing seven trials were included. Improvement in thyroid function, as indicated by decreased levels of free triiodothyronine (FT3) and free thyroxine (FT4), was comparable between MMI and propylthiouracil (PTU) in two studies. Addition of selenium (Se) to MMI resulted in significant (p < 0.05) reductions in FT3 and FT4 levels, and increased thyroid-stimulating hormone (TSH) levels. Long-term MMI therapy can maintain euthyroidism, normal TSH serum level and reduced recurrence risk, with 83% of patients remaining relapse-free at 84 months. A Danish study on fixed low-dose antithyroid drug treatment (FLATD), i.e. MMI 5 mg/day with L-T4 of 1 µg/bodyweight in kg/day, demonstrated significantly lower relapse rates (p < 0.003) and prolonged time to relapse (p = 0.003) compared with the observation group. Two studies comparing low-dose MMI continuation versus discontinuation strategies showed that continuing treatment led to significantly lower recurrence and relapse rates, higher recurrence-free survival, and higher remission rate (p < 0.05).

CONCLUSIONS: The findings from this SLR show that variations of MMI, like long-term therapy, FLATD, and addition of Se, provide effective outcomes in sustaining euthyroidism, decreasing recurrence and relapse rates, and prolonging time to relapse.