Prolactinomas are the most common hypersecretory pituitary adenoma. Traditional first line therapy is dopamine agonists, which are highly effective and tolerated in most patients. However, dopamine agonists have the potential for psychiatric complications such as psychosis, impulse control disorders and anxiety/depression. The 2023 Pituitary Society prolactinoma guidelines suggest that aripiprazole may be considered in individuals with a psychiatric disorder and prolactinoma, potentially enabling dopamine agonist dose reduction or even cessation.
We present a man with an invasive giant prolactinoma initially responding to cabergoline, who then developed severe mood disturbance, followed by initiation of aripiprazole for mood stabilisation. Marked prolactin elevation (approx. 350% increase) developed within 5 weeks of aripiprazole commencement despite stable cabergoline dosing (Figure 1), culminating in the requirement for surgical resection of the adenoma (Figure 2). This represents the first case of aripiprazole causing dopamine agonist failure, reflecting competitive binding secondary to the higher binding affinity of aripiprazole for D2 receptors (Ki = 0.34 nM) vs. cabergoline (Ki = 0.7 nM).
A systematic review was also performed investigating aripiprazole use in prolactinomas. Twelve case reports were identified, demonstrating that aripiprazole monotherapy can effectively reduce serum prolactin (Table 1 and 2) and that concurrently commenced dual aripiprazole/dopamine agonist therapy also permits prolactin lowering (Table 3 and 4). However, there have been no cases until now assessing the effect of aripiprazole addition to established dopamine agonist therapy.
This case of aripiprazole-induced dopamine agonist failure is a critical caveat to the previously suggested use of aripiprazole in prolactinoma management. Specifically, we caution against the addition of aripiprazole to dopamine agonists where timely prolactinoma treatment is essential – for example, individuals with aggressive prolactinomas or those presenting with visual defects. In addition, all patients on dual aripiprazole/dopamine agonist therapy for prolactinomas should be closely monitored.