No treatment-emergent adverse events related to elevation of prolactin levels were reported in cariprazine-treated patients in clinical studies. Mean decreases in prolactin levels from baseline were seen in all treatment groups, with the exception of the risperidone group. No adverse events of hyperprolactinemia were reported. Decreased prolactin levels were more pronounced in women than men in clinical short-term and open-label studies.1
It’s highly probable that the prolactin decreases observed were due to the previously taken antipsychotic causing hyperprolactinaemia that normalized once it was discontinued and cariprazine treatment was initiated.1
Antipsychotic-induced hyperprolactinaemia may be associated with inhibition of D2 receptors in the tuberoinfundibular system.2 Cariprazine is a partial agonist of the D2 receptor, which suggests that cariprazine is not expected to increase prolactin levels,3 and decreases in prolactin levels have been observed in clinical trials with cariprazine.1
There are no data on the time course of changes in prolactin levels for cariprazine. In licensed dose ranges, cariprazine has been shown to decrease prolactin mean levels from baseline to study endpoint in short-term and long-term studies in the range of -13.4 to -17.1 ng/ml.4
In long-term safety studies in patients with schizophrenia receiving cariprazine (1.9-9 mg/day), mean prolactin levels fell by 18.3 ng/ml at 48 weeks versus baseline. While part of this reduction may be related to some of the patients coming off a prolactin-increasing antipsychotic, the reduction is consistent with the activation of D2 receptors at/near the natural tonic level of dopamine by the partial agonist effect of the drug.3
Reported time to recovery when the D2 partial agonist aripiprazole was given as an adjunct for risperidone-induced hyperprolactinaemia ranges from within the first 2 weeks to 24 weeks.5-7
When a switching strategy for antipsychotic-induced hyperprolactinaemia employing aripiprazole was used, normalization was seen about 4 weeks after complete discontinuation of the previously taken antipsychotic.8,9 These different time frames for recovery are possibly due to differences in study populations and the speed of titration of aripiprazole.5
References
- Reagila European public assessment report (EPAR).
- Molitch ME. Dopamine agonists and antipsychotics. European Journal of Endocrinology 2020, 183, C11-C13.
- Roberts RJ, et al. Update on schizophrenia and bipolar disorder: focus on cariprazine. Neuropsychiatr Dis Treat. 2016 Jul 25;12:1837-42.
- Ivkovic J, et al. Effect of Brexpiprazole on Prolactin: An Analysis of Short- and Long-Term Studies in Schizophrenia. J Clin Psychopharmacol. 2019; 39 (1):13-19.
- Ranjbar F, et al. Adjunctive treatment with aripiprazole for risperidone-induced hyperprolactinemia. Neuropsychiatr Dis Treat. 2015;11:549-555. https://www.ncbi.nlm.nih.gov/pubmed/25784810
- Shores LE. Normalization of risperidone-induced hyperprolactinemia with the addition of aripiprazole. Psychiatry (Edgmont). 2005;2(3):42-45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004714/
- Lee BJ, et al. Effect of aripiprazole on cognitive function and hyperprolactinemia in patients with schizophrenia treated with risperidone. Clin Psychopharmacol Neurosci. 2013;11:60-66.
- Chen CY, Lin TY, Wang CC, Shuai HA. Improvement of serum prolactin and sexual function after switching to aripiprazole from risperidone in schizophrenia: a case series. Psychiatry Clin Neurosci. 2011;65:99-97.
- Lu ML, Shen WW, Chen CH. Time course of the changes in antipsychotic-induced hyperprolactinemia following the switch to aripiprazole. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(8):1978-1981. https://www.sciencedirect.com/science/article/pii/S027858460800300X?via%3Dihub
