Cabergoline not linked to higher impulse control disorder risk
Findings show therapy still promising as 'safe agent' in Cushing's disease
Cabergoline, which is often used as an off-label therapy for recurrent or persistent Cushing’s disease, is not associated with a high risk for impulse control disorders(ICDs), a concern raised about this kind of medication.
These are the findings of a small study in Turkey that suggests cabergoline “still holds promise as a safe agent in” Cushing’s disease, the researchers wrote in “Risk of impulse control disorders in patients with Cushing’s disease: do not blame cabergoline but do not give up caution,” which was published in Pituitary.
Larger studies are needed to better “characterize the effects of [cabergoline] treatment on [impulse control disorders] development in patients with [Cushing’s disease],” the researchers added.
Transsphenoidal surgery, a minimally invasive procedure to remove pituitary tumors, is the first-line treatment for Cushing’s. It leads to long-term remission in about 50% of the cases, however.
Some patients receive pharmacological treatment to reduce cortisol levels.
Pasireotide (sold as Signifor and Signifor LAR) is the only pituitary-targeted therapy approved for Cushing’s patients for whom surgery is ineffective or not an option. It works to reduce the secretion of adrenocorticotropic hormone (ACTH), which drives excess cortisol production.
Cabergoline and impulse control disorders
Cabergoline, sold under the brand name Dostinex, among others, is a dopamine agonist that mimics the action of dopamine, a major brain chemical messenger that in the pituitary suppresses ACTH production.
Cabergoline binds to dopamine receptor proteins in ACTH-producing pituitary cells, activating them and reducing both ACTH and cortisol.
Dopamine agonists have been linked with ICDs, which are common psychiatric conditions wherein a person is unable to resist an impulse, drive, or temptation to perform a risky behavior. Gambling, compulsive shopping, overeating, and compulsive sexual behaviors are examples of ICDs.
A team led by researchers in Turkey analyzed data from adults, ages 18-65, with Cushing’s disease to assess the temporal association between Cabergoline and ICDs, as well as their general frequency, in Cushing’s. The adults were recruited at five centers in Istanbul from September 2021 to September 2022.
A total of 14 patients (mean age at disease onset, 48.1; 78.6%, women) were scheduled to receive cabergoline and were included in the prospective analysis, where patients are followed to evaluate the occurrence of a certain outcome.
The patients underwent measures to assess ICDs and other psychiatric conditions, such as anxiety and depression, before starting cabergoline (baseline), and after three, six, and 12 months of treatment. Only six patients completed the one-year evaluation.
All but one patient had active Cushing’s at baseline. Most (85.7%) had transsphenoidal surgery, while the remaining two (14.3%) were waiting for it. All had received previous pharmacological treatments, most commonly ketoconazole, an antifungal, and pasireotide.
Cabergoline was prescribed for recurrent or persistent Cushing’s in 11 patients, as a bridge treatment before surgery in two patients, and due to intolerance to pasireotide in one patient.
After a median follow-up of 7.3 months and a median weekly cabergoline dose of 2.75 mg, five patients (38.4%) showed normal cortisol levels.
Treatment-related side effects were reported in three patients: nausea and major depressive episode, each in one woman, and an ICD in the form of gambling in a man. No significant changes were seen in psychological and impulsivity test results before and after treatment.
Low risk of ICDs with cabergoline
The team also conducted a cross-sectional analysis, which looks at data at a single point in time. It included 34 patients (mean age, 45.5; 88.2%, women) who’d already been treated with cabergoline for at least three months and 34 age- and sex-matched patients who’d never been treated with a dopamine agonist (treatment-naïve).
Patients in the cabergoline group had received the therapy for a median of 12 months at a median weekly dose of 2 mg. Excess cortisol levels were controlled in 12 of them (35.3%).
The same battery of tests was done to both groups, with results showing no significant differences in psychological distress and impulsivity.
Depression was the most common psychiatric disorder in both groups, affecting 35.3% of cabergoline-treated patients and 29.2% of treatment-naïve patients. Impulse control disorders were detected in 8.8% of patients in the cabergoline group and 5.9% of those in the treatment-naïve group, a difference that didn’t reach statistical significance.
Despite the low risk of ICDs observed in the cross-sectional study, “the development of compulsive gambling in one patient and major depressive episode in another patient after a brief period of [cabergoline] use was noteworthy,” the researchers wrote. “Overall, our results suggest a relatively low risk of impulse control disorders in cabergoline-treated patients with Cushing’s disease, favoring cabergoline use in selected cases.”
Still, caution was recommended about the psychiatric side effects when cabergoline is started, “given the catastrophic consequences of these conditions, the researchers said.