Case Report of Refractory Hyperhomocysteinemia Related to the Antipsychotic Drug Olanzapine

ABSTRACT

Background: Hyperhomocysteinemia is a metabolic disorder linked to cardiovascular diseases, neurological disorders, and pregnancy complications. Olanzapine, a widely used antipsychotic, is recognized for its association with metabolic abnormalities; however, its connection to refractory hyperhomocysteinemia remains unclear. Case presentation: The patient experienced a significant increase in blood homocysteine levels (> 150 μmol/L) due to infertility and was unable to reduce them to normal (<10 μmol/L) despite treatment with up to 6g/day of betaine, high-dose B vitamins, and methocobalamin. Long-term administration of olanzapine (5 mg/day) was found to be associated with the condition, and levels decreased briefly after switching to aripiprazole (94 μmol/L). However, due to serious adverse reactions, the use of alanzapine was resumed, resulting in an increase in blood homocysteine levels once again (113~125 μmol/L). Genetic testing revealed a homozygous mutation at MTHFR 1298, and intensive complementary therapy along with a strict low-protein diet resulted in fluctuating levels of 100~150μmol/L.. The patient was ultimately managed successfully through in - vitro fertilization (IVF), but continuous treatment with olanzapine led to long-term non-remission of hyperhomocysteinemia. Conclusion: This case suggests that olanzapine may exacerbate metabolic disorders by interfering with methylation cycling, and that genetic factors (e.g., MTHFR mutations) may become more refractory. Multidisciplinary collaboration is needed to balance the treatment and metabolic management of neurological disorders, and to further explore mechanisms and optimize intervention strategies in the future. medications are extensively utilized in the