Psychological effects of dopamine agonist treatment in patients with hyperprolactinemia and prolactin-secreting adenomas

Abstract

Background: Dopamine agonists (DAs) are the main treatment for patients with hyperprolactinemia and prolactinomas. Recently, an increasing number of reports emphasized DAs' psychological side effects, either de novo or as exacerbations of prior psychiatric disease. Methods: Review of prospective and retrospective studies (PubMed 1976, September 2018) evaluating the psychological profile of DA-treated patients with hyperprolactinemia and prolactinomas. Case series and case reports of psychiatric complications were also reviewed. Results: Most studies were cross-sectional and had a control group of healthy volunteers or patients with nonfunctioning pituitary adenomas. There were few prospective studies, with/without control group, that included small numbers of patients. Compared with controls, patients with hyperprolactinemia generally had worse quality of life, anxiety, depression and certain personality traits. Patients receiving DAs had higher impulsivity scores than normoprolactinemic controls. Impulse control disorders (ICDs) were reported in both genders, with hypersexuality mostly in men. Multiple ICDs were sometimes reported in the same patient, usually reversible after DA discontinuation. In case reports, DA therapy was temporally associated with severe depression, manic episodes or psychosis, which improved after discontinuation and administration of psychiatric medications. Gender type of DA, dose and duration of therapy did not correlate with occurrence of psychiatric pathology. Conclusion: Patients with hyperprolactinemia receiving DAs may develop changes in mood and behavior regardless of prior psychiatric history. Increased awareness for ICDs, depression, mania and other types of psychosis is needed by all physicians who prescribe DAs. Larger prospective controlled clinical studies are needed to delineate prevalence, risk stratification and management.

Pituitary society guidance: pituitary disease management and patient care recommendations during the COVID-19 pandemic—an international perspective

“…At the time of the visit, he was not taking any psychiatric medications and was not under the care of a mental health team. Given this patient's significant psychiatric history, lack of ongoing psychiatric care, and the well-recognized adverse effects of DA therapy, including increased impulsivity, depression and psychosis [17], a DA was not initiated. Counseling on potential DA side-effects is crucial, as they may also present in individuals with no prior psychiatric history [17].…”

“…Given this patient's significant psychiatric history, lack of ongoing psychiatric care, and the well-recognized adverse effects of DA therapy, including increased impulsivity, depression and psychosis [17], a DA was not initiated. Counseling on potential DA side-effects is crucial, as they may also present in individuals with no prior psychiatric history [17]. Furthermore, during the COVID-19 pandemic when there is reduced access to routine medical and mental health care, patients who develop symptoms of severe depression may not have ready access to mental health services, or may not seek care.…”

Depression and Impulsivity Self-Assessment Tools to Identify Dopamine Agonist Side Effects in Patients With Pituitary Adenomas

“…Dopamine agonists (DA) are the most effective treatment for prolactinomas and are a first-line therapy, causing both inhibition of prolactin secretion and pituitary tumor shrinkage (1,6). Cabergoline and bromocriptine are the most widely used agents and are approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), while quinagolide is approved in just some countries (7). These medications are also used to treat symptomatic nontumoral hyperprolactinemia, and more rarely as an adjuvant treatment for acromegaly and Cushing's disease (8,9).…”

“…Concerns about the psychiatric effects of DA surfaced after isolated cases of psychosis, depression, hypersexuality, impulse control disorders (ICD) and other psychiatric symptoms were reported (7). Psychiatric effects of DA are theorized to be caused by multiple complex mechanisms, which include cross-stimulation of D3 receptors expressed on the mesocorticolimbic dopaminergic pathway, central nervous system dopamine depletion in hyperprolactinemia followed by sudden replacement and recovery of normal levels of gonadal sex steroids, especially testosterone, after central hypogonadism (7,10). It is controversial whether hyperprolactinemia per se has a role (7).…”

Could hormonal remission in prolactinomas be achieved with surgery? Our experience

“…Bromocriptine, an ergot derivative that binds to and stimulates dopamine (D2) receptors on lactotrophic cells, represents the initial treatment. It has proved to be effective in suppressing PRL secretion, reducing prolactinoma size and restoring gonadal function in many patients [12][13][14]. In the collaborative European multicenter study on 459 women with prolactinomas, normoprolactinemia was achieved in 59 % when using bromocriptine [15].…”