ABSTRACT
OBJECTIVE: Concerns exist over hypertyrosinaemia that is observed following treatment with nitisinone. It has been suggested that tyrosine may compete with tryptophan for uptake into the central nervous system, and or inhibit tryptophan hydroxylase activity reducing serotonin production. At the National Alkaptonuria (AKU) Centre nitisinone is being used off-licence to treat AKU, and there is uncertainty over whether hypertyrosinaemia may alter mood. Herein results from clinical and biochemical assessments of depression in patients with AKU before and after treatment with nitisinone are presented. PATIENTS AND METHODS: 63 patients were included pre-nitisinone treatment, of these 39 and 32 patients were followed up 12 and 24â¯months after treatment. All patients had Becks Depression Inventory-II (BDI-II) assessments (scores can range from 0 to 63, the higher the score the more severe the category of depression), and where possible urinary monoamine neurotransmitter metabolites and serum aromatic amino acids were measured as biochemical markers of depression. RESULTS: Mean (±standard deviation) BDI-II scores pre-nitisinone, and after 12 and 24â¯months were 10.1(9.6); 9.8(10.0) and 10.5(9.9) (pâ¯≥â¯0.05, all visits). Paired scores (nâ¯=â¯32), showed a significant increase at 24â¯months compared to baseline 10.5(9.9) vs. 8.6 (7.8) (pâ¯=â¯0.03). Serum tyrosine increased at least 6-fold following nitisinone (pâ¯≤â¯0.0001, all visits), and urinary 3-methoxytyramine (3-MT) increased at 12 and 24â¯months (pâ¯≤â¯0.0001), and 5-hydroxyindole acetic acid (5-HIAA) decreased at 12â¯months (pâ¯=â¯0.03). CONCLUSIONS: BDI-II scores were significantly higher following 24â¯months of nitisinone therapy in patients that were followed up, however the majority of these patients remained in the minimal category of depression. Serum tyrosine and urinary 3-MT increased significantly following treatment with nitisinone. In contrast urinary 5-HIAA did not decrease consistently over the same period studied. Together these findings suggest nitisinone does not cause depression despite some observed effects on monoamine neurotransmitter metabolism.