Manic and psychotic symptoms following subcutaneous leuprolide in a male patient with no prior psychiatric history.

To the Editor: Leuprolide is a synthetic luteinizing hormone– releasing hormone (LHRH) agonist used in the treatment of advanced prostate cancer. It is available as an immediate-release intramuscular injection, a depot suspension for intramuscular injection, and an extended-release suspension for subcutaneous injection. After a 45-mg dose of subcutaneous leuprolide, 99.1% of patients experience clinical castration by day 28, defined as serum testosterone levels < 50 ng/mL.1 In addition to this decrease in serum testosterone levels, decreases in sex hormone–binding globulin and estradiol are also seen.1,2 Although there have been reports3,4 of emotional lability, depression, and anxiety with LHRH agonists, the data are not consistent. Furthermore, all published reports on psychiatric side effects of LHRH agonists have been exclusively in female patients. The package insert1 of leuprolide depot subcutaneous injection does list anxiety, depression, and delusions as occurring in less than 5% of patients. Here, we describe a case of a 65-year-old man with no prior psychiatric history who developed manic and psychotic symptoms after receiving a 45-mg subcutaneous injection of leuprolide. This is the only case available in the literature that describes a male patient experiencing such severe psychiatric symptoms in association with leuprolide.