Recent studies showed that some second-generation antipsychotics may lead to elevated levels of serum prolactin due to their antagonistic effects on the dopamine D2-receptor.1 In particular, despite its proven effectiveness in treating schizophrenia and preventing relapse, 2, 3 the long-acting injectable paliperidone palmitate once-monthly (PP1M) seems to be associated with a risk of hyperprolactinaemia, which is often asymptomatic but also occasionally causes sexual side effects, such as amenorrhoea, oligomenorrhoea, galactorrhoea and gynaecomastia. 4 In a recent interview, Prof. David Castle shared his insights on handling hyperprolactinaemia in patients on PP1M.
Q1: Once a patient on PP1M suffers from hyperprolactinaemia, how do you suggest handling the case?
Prof. Castle: A safe and effective regimen is to add oral aripiprazole, which can indeed reduce prolactin levels as shown by some studies.4 A low starting dose is recommended, i.e. 5 mg or even less. The practice can be continued in the long run, given that prolactin levels are under control and no abnormalities are observed during the routine monitoring. Another method is to lower the PP1M dosage, but the impact on the psychotic symptoms should be cautiously monitored. In addition, it is possible to discuss with an endocrinologist and the patient to come up with a management plan. Finally, switching to another antipsychotic may be considered, depending on patient conditions. In general, there is no significant difference in the treatment of hyperprolactinaemia between males and females. (Table 1 summarises the treatment strategies.)
Q2: What is the incidence of hyperprolactinaemia among patients on PP1M, based on your clinical experience?
Prof. Castle: It is difficult to answer this question because patients seldom talk about their sexual problems voluntarily. The question often needs to be asked directly by treating physicians. On the other hand, patients’ prolactin levels should be monitored from the baseline 2 to 6 months after medication initiation and then annually. Regarding the incidence of hyperprolactinaemia, we may refer to some research (Table 2). 5,6,7
Nevertheless, the sexual problems in patients with schizophrenia are complicated and may be related to other physical conditions, not just hyperprolactinaemia. For instance, cardiovascular diseases, alcohol abuse, or other medications being taken, such as certain antidepressants, may also cause sexual side effects among some patients. Therefore, when it comes to sexual problems, it is crucial to discuss with the patient and his/her partner to understand the whole context, including social, relationship and medical factors, in order to formulate respective interventions.
N/A = not available
PP3M = 3-month paliperidone palmitate
N.B.: From a pooled analysis of four double-blind placebo-controlled trials, the incidence of hyperprolactinaemia in patients on PP1M was < 2%.7
- Adding oral aripiprazole (≤ 5 mg) is a safe and effective approach to handling hyperprolactinaemia in patients on PP1M. Other methods can also be considered, e.g. reducing the PP1M dose.
- Sexual side effects are not always caused by hyperprolactinaemia. Other conditions potentially seen in patients with schizophrenic, such as cardiovascular problems, alcohol abuse and the influence of some antidepressants, may also affect sexual function.
- Based on current literature, the incidence of hyperprolactinaemia in patients on PP1M is not significant.
- Alpak G, et al. Bulletin of Clinical Psychopharmacology. 2014;24:253-6.
- Gopal S, et al. Int Clin Psychopharmacol. 2010;25:247-56.
- Chue P & Chue J. Expert Rev Neurother. 2012;12:1383-97.
- Holt RI & Peveler RC. Clin Endocrinol (Oxf) 2011;74:141-7.
- Hargarter L, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2015;58:1-7.
- Berwaerts J, et al. JAMA Psychiatry. 2015;72:830-9.
- Mauri MC, et al. Expert Opin Drug Saf. 2017;16:365-79.