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Athanasoulia, Anastasia (2012): Predictors of neuropsychiatric side effects of dopamine-agonist therapy in patients with prolactinomas. Dissertation, LMU München: Medizinische Fakultät



Background: Prolactinomas are the most frequent pituitary adenomas. The treatment with cabergoline, the most common dopamine agonist used, is associated with side effects such as nausea, vomiting, dizziness, headaches, movement disorders and fatigue. There is some additional evidence from case reports and small studies that some patients report neuropsychiatric side effects such as depression, gambling, hypersexuality and impulsive control disorders. Objective: In this cross-sectional study we sought to investigate the baseline clinical, demographic and disease characteristics of our patient group as well as life-time comorbidities. Additionally, side effects under treatment with cabergoline (prevalence and enhancement) and whether genetic variants of the ABCB1 gene (coding MDR1 or P-gp) could account for difference in the central neuropsychiatric side effects were investigated. Methods: Questionnaires evaluating medical history, therapy side effects and further demographic characteristics were sent to all prolactinoma patients currently treated at the Max Planck Institute of Psychiatry in Munich. Additionally, DNA extracted either from blood or saliva samples was genotyped for each patient. Results: The clinical study included a total of 92 patients (23 male and 69 female, macro-to-microadenoma-ratio 1:1). The mean age of our group at the time of the study was 49,2 ± 13,8 years. Of the 79 patients treated with cabergoline, the following side effects associated with treatment were more prominent: fatigue (n=35), headaches (n=26), depressed mood (n=26), sleep disorders (n=26), dizziness (n=22), aggressiveness (n=17), anxiety (n=19) and weight loss (n=16). 18 patients reported of decreased and 16 of increased libido. Significant effects were observed for the C-carriers and heterozygous CT-individuals of rs1045642 that presented less frequent fatigue and sleep disorders under cabergoline. In the analysis of SNP rs2032582, G-carriers seemed to be protected from enhancement of dizziness under cabergoline. SNPs rs2235015 and rs2032583 were found to have no association with the examined symptoms. Conclusion: In our group we described an increased prevalence of symptoms such as fatigue and weight loss under cabergoline, as well as neuropsychiatric side effects such as depressed mood, aggressiveness and anxiety in comparison to the available data of the literature. We demonstrated that polymorphisms of SNPs rs1045642 and rs2032582 of the ABCB1 gene predispose for fatigue, sleep disorders and dizziness under cabergoline. This is the first study demonstrating that individual ABCB1 gene polymorphisms could account for a different occurrence or enhancement of central side effects of this systematically administered medication.