Predictors of neuropsychiatric side effects of dopamine-agonist therapy in patients with prolactinomas
Beschreibung
vor 13 Jahren
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.
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.
Weitere Episoden
In Podcasts werben
Kommentare (0)