Neuropsychiatric and metabolic aspects of dopaminergic therapy: perspectives from an endocrinologist and a psychiatrist

Abstract

The dopaminergic treatment represents the primary treatment in prolactinomas, which are the most common pituitary adenomas and account for about 40% of all pituitary tumours with an annual incidence of six to ten cases per million population. The dopaminergic treatment includes ergot and non-ergot derivatives with high affinity for the dopamine receptors D1 or/and D2. Through the activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine agonists inhibit the prolactin synthesis and secretion, therefore normalizing the prolactin levels and restoring eugonadism, but they also lead to tumour shrinkage. Treatment with dopamine agonists has been associated – apart from the common side effects such as gastrointestinal symptoms, dizziness and hypotension – with neuropsychiatric side effects such as impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality and binge eating) and also with behavioral changes from low mood, irritability and verbal aggressiveness up to psychotic and manic symptoms and paranoid delusions not only in patients with prolactinomas but also in patients with Parkinson’s disease and restless leg syndrome. They usually have de novo onset after initiation of the dopaminergic treatment and have been mainly reported in patients with Parkinson’s disease, who are being treated with higher doses of dopamine agonists. Moreover, dopamine and prolactin seem to play an essential role in the metabolic pathway. Patients with hyperprolactinemia tend to have increased body weight and an altered metabolic profile with hyperinsulinemia and increased prevalence of diabetes mellitus in comparison to healthy individuals and patients with non-functioning pituitary adenomas. Treatment with dopamine agonists in these patients in short-term studies seems to lead to weight loss and amelioration of the metabolic changes. Together these observations provide evidence that dopamine and prolactin have a crucial role both in the regard and metabolic system, findings that merit further investigation in long-term studies.

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

“…The FDA reporting increased progressively after 2006 and almost reached a plateau after 2009 (23). A recent review of DA-associated ICDs reported to the FDA indicated that 62% of the patients experiencing ICDs were treated for PD, 24% for RLS and 3.5% for hyperprolactinemia (24). The significantly higher number of reports in patients receiving DA therapy for PD and RLS support the involvement of mesolimbic D3 receptors; pramipexole and ropironole have higher D3 affinity than cabergoline and bromocriptine.…”

“…Of note, the patient did not have these problems 25 years previously when she took bromocriptine. Table 1 summarizes the individual case reports of ICD during DA therapy administered for prolactinomas (24,27,28,29,30,31).…”

“…Comparing the risk between different DAs is not possible because of different types of DAs that were available at the time of the report in different countries. Challenging patients who experienced ICDs while taking one DA with another DA has been attempted in a few cases and led to reoccurrence of ICD in some patients (24,28). It is important to note that approximately 33% of reported patients developed multiple types of ICDs during DA therapy (32,33).…”

“…It is important to note that approximately 33% of reported patients developed multiple types of ICDs during DA therapy (32,33). Finally, discontinuation of DAs or even reducing the dose along with adding psychotherapy or psychiatric medications were associated with improved or resolved ICDs (24,27,29,31,32,33,34,35).…”

“…Based on the data accumulated, we suggest that physicians discuss the risk of ICDs at the time of DA therapy initiation and revisit this issue at follow-up visits. The ICD manifestations reported in the literature were mostly reversible after DA stopped or dose decreased; in some instances, ICDs only developed with one type of DA (24,27). Therefore, in case of mild manifestations, a smaller dose of DA or another DA approved for use in hyperprolactinemia can be attempted, while the patient is carefully monitored by both endocrinology and psychiatry.…”