Comparison of short term effects of risperidone and paliperidone on serum prolactin levels in female patients

Öz

Objective: Hyperprolactinemia is an adverse effect, which is related with the use of antipsychotics. All typical antipsychotics are considered to increase serum prolactin levels. Compared with typical antipsychotics, most of the atypical antipsychotics have a reduced tendency for increasing serum prolactin levels. However, effects of all atypical antipsychotics on serum prolactin levels are not always similar. In the present study, we aimed to compare short-term effects of risperidone and paliperidone, which are two similar atypical antipsychotics in terms of hyperprolactinemia and its associated symptoms. Methods: In this study, we screened data of female patients with diagnosis of schizophrenia and other psychotic disorders, bipolar disorder and who were treated with risperidone or paliperidone. The patients who had adequate sociodemographical and clinical data and who had screened in terms of prolactin levels before and fourth week of the treatment were included to study. Results: Forty-two patients have been treated with risperidone and 36 patients have been treated with paliperidone. Treatment groups were similar in terms of sociodemographic variables. The mean values of serum prolactin levels were significantly increased after four weeks of treatment in both groups (p<0.001). The discontinuation rates because of menstrual irregularities, galactorrhea, sexual dysfunction in risperidone and paliperidone groups were 11.9% and 30.6% respectively, and the rate was significantly higher in paliperidone group (?2=4.13, p=0.04). Conclusion: We suggest that beside its benefits and some superiorities compared to risperidone, paliperidone has no advantage over risperidone in terms of hyperprolactinemia and its associated symptoms. We also suggest that female patients should be monitorized regulary in terms of hyperprolactinemia and its associated symptoms while they are being treated with paliperidone. To our knowledge, the present study is the first to compare and demonstrate the effects of paliperidone and risperidone on serum prolactin levels in Turkey. Further studies with larger sample size are needed to highlight the short term and long term effects of paliperidone on serum prolactin levels in female patients.

Anahtar Kelimeler

• risperidone, paliperidone, prolactin

Kadın hastalarda risperidon ve paliperidonun serum prolaktin düzeyleri üzerine kısa dönem etkilerinin karşılaştırılması

Öz

Amaç: Hiperprolaktinemi antipsikotik kullanımı ile ilişkili bir yan etkidir. Tüm tipik antipsikotiklerin serum prolaktin düzeylerini yükselttiği kabul edilmektedir. Tipik antipsikotiklerle karşılaştırıldığında, atipik antipsikotiklerin serum prolaktin düzeylerini yükseltmeleri açısından daha düşük eğilimleri vardır. Ancak tüm atipik antipsikotiklerin serum prolaktin düzeyi üzerine etkileri her zaman benzer değildir. Bu çalışmada iki benzer atipik antipsikotik olan risperidon ve paliperidonun hiperprolaktinemi ve ilişkili belirtiler açısından kısa dönem etkilerini karşılaştırmayı amaçladık. Yöntem: Bu çalışmada, şizofreni ve diğer psikotik bozuklar ve iki uçlu bozukluk tanıları ile başvuran; risperidon veya paliperidon ile tedavi edilen kadın hastaların bilgileri taranmıştır. Sosyodemografik ve klinik bilgiler açısından yeterli veriye sahip ve tedavi başlangıcında ve 4. haftasında serum prolaktin düzeyleri açısından taranmış hastalar çalışmaya dahil edildi. Sonuçlar: Kırk iki hasta risperidon ile ve 36 hasta paliperidon ile tedavi edilmişti. Gruplar sosyodemografik değişkenler açısından benzerdi. Hem risperidon hem de paliperidon grubunda 4 hafta sonrasında ortalama serum prolaktin düzeyleri anlamlı olarak artmıştı (p<0.001). Risperidon ve paliperidon grubunda menstrual düzensizlikler, galaktore ve cinsel disfonksiyona bağlı olarak ilaç kesilme oranları sırasıyla %11.9 ve %30.6 idi ve bu oran paliperidon grubunda istatiksel olarak fazlaydı (?2=4.13, p=0.04). Tartışma: Paliperidonun faydaları ve risperidona bazı üstünlüklerinin olmasına rağmen, hiperprolaktinemi ve ilişkili belirtiler açısından paliperidonun risperidona göre avantajı olmadığını düşünüyoruz. Ayrıca kadın hastaların paliperidon ile tedavi edildikleri zaman, hiperprolaktinemi ve ilişkili belirtiler açısından düzenli bir şekilde takip edilmesi gerektiğini önermekteyiz. Bilgimize göre, bu çalışma Türkiye’de risperidon ve paliperidonun serum prolaktin düzeyleri üzerine etkilerini karşılaştıran ve gösteren ilk çalışmadır. Paliperidonun serum prolaktin düzeyi üzerine uzun ve kısa dönem etkilerini aydınlatacak daha ileri ve geniş örneklemli çalışmalara ihtiyaç bulunmaktadır.

Anahtar Kelimeler

• risperidon, paliperidon, prolaktin

Kaynakça

1. 1. Yen S, Jaffe R. Reproductive Endocrinology. Third ed. WB Saunders, 1991; Philedelphia.
2. 2. Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs. 2004;64:2291-314.
3. 3. Montejo AL. Prolactin awareness: an essential consideration for physical health in schizophrenia. Eur Neuropsychopharmacol. 2008;18:108-14.
4. 4. Szarfman A, Tonning JM, Levine JG, Doraiswamy PM. Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy. 2006;26:748-58.
5. 5. Knegtering H, van der Moolen AE, Castelein S, Kluiter H, van den Bosch RJ. What are the effects of antipsychotics on sexual dysfunctions and endocrine functioning? Psychoneuroendocrinology. 2003;28:109-23.
6. 6. La Torre D, Falorni A. Pharmacological causesof hyperprolactinemia. Ther Clin Risk Manag. 2007;3:929-51.
7. 7. Cookson J, Hodgson R, Wildgust HJ. Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis. J Psychopharmacol. 2012;26:42-51.
8. 8. Perkins DO. Antipsychotic-induced hyperprolactinemia: Pathophisology and clinical consequences. Adv Stud Med. 2004;4:982-6.

9. 9. Komossa K, Rummel-Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, Leucht S. Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD006626.
10. 10. Conley R, Gupta SK, Sathyan G. Clinical spectrum of the osmotic controlled release oral delivery system (OROS), an advanced oral delivery form. Curr Med Res Opin. 2006;22:1879-92.
11. 11. Berwaerts J, Cleton A, Rossenu S, Talluri K, Remmerie B, Janssens L, Boom S, Kramer M, Eerdekens M. A comparison of serum prolactin concentrations after administration of paliperidone extended-release and risperidone tablets in patients with schizophrenia. J Psychopharmacol. 2010;24:1011-8.
12. 12. Berwaerts J, Cleton A, Herben V, van de Vliet I, Chang I, van Hoek P, Eerdekens M: The effects of paroxetine on the pharmacokinetics of paliperidone extended-release tablets. Pharmacopsychiatry. 2009;42:158-63.
13. 13. Vermeir M, Boom S, Naessens I, Talluri K, Eerdekens M: Absorption, metabolism and excretion of a single oral dose of 1 mg paliperidone ina population of five healthy male subjects. Eur Neuropsychopharmacol. 2005; 15:S648.
14. 14. Chwieduk CM, Keating GM. Paliperidone extended release: a review of its use in the management of schizophrenia. Drugs. 2010;10:1295-317.
15. 15. American Psychiatric Assosiation Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revsion. Washington DC: American Psychiatric Assosiation. 2000.
16. 16. Hummer M, Huber J. Hyperprolactinaemia and antipsychotic therapy in schizophrenia. Curr Med Res Opin. 2004;20:189-97.
17. 17. Hamner M. The effects of atypical antipsychotics on serum prolactin levels. Ann Clin Psychiatry. 2002;14:163-73.
18. 18. Madhusoodanan S, Parida S, Jimenez C. Hyperprolactinemia associated with psychotropics-a review. Hum Psychopharmacol. 2010;25:281-97.
19. 19. Knegtering R, Baselmans P, Castelein S, Bosker F, Bruggeman R, van den Bosch RJ. Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels. Am J Psychiatry. 2005;162:1010-2.
20. 20. Tollefson GD, Beasley CM Jr, Tran PV, Street JS, Krueger JA, Tamura RN, Graffeo KA, Thieme ME. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry. 1997;154:457-65.
21. 21. Purdon SE, Jones BD, Stip E, Labelle A, Addington D, David SR, Breier A, Tollefson GD. Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia. Arch Gen Psychiatry. 2000;57:249-58.
22. 22. Kleinberg DL, Davis JM, de Coster R, Van Baelen B, Brecher M. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol. 1999;19:57-61.
23. 23. Kinon BJ, Stauffer VL, McGuire HC, Kaiser CJ, Dickson RA, Kennedy JS. The effects of antipsychotic drug treatment on prolactin concentrations in elderly patients. J Am Med Dir Assoc. 2003;4:189-94.
24. 24. Kearns AE, Goff DC, Hayden DL, Daniels GH. Risperidoneassociated hyperprolactinemia. Endocr Pract. 2000;6:425-9.
25. 25. David SR, Taylor CC, Kinon BJ, Breier A. The effects of olanzapine, risperidone and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther. 2000;22:1085-96.
26. 26. Kane J, Canas F, Kramer M, Ford L, Gassman-Mayer C, Lim P, Eerdekens M. Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial. Schizophrenia Research. 2007;90:147-61.
27. 27. Davidson M, Emsley R, Kramer M, Ford L, Pan G, Lim P, Eerdekens M. Efficacy, safety and early response of paliperidone extendedrelease tablets (paliperidone ER). Results of a 6-week, randomized, placebo-controlled study. Schizophrenia Research. 2007;93:117- 30.
28. 28. Marder SR, Kramer M, Ford L, Eerdekens E, Lim P, Eerdekens M, Lowy A. Efficacy and safety of paliperidone extended-release tablets. Results of a 6-week, randomized, placebo-controlled study. Biological Psychiatry. 2007;62:1363-70.
29. 29. Meltzer HY, Bobo WV, Nuamah IF, Lane R, Hough D, Kramer M, Eerdekens M. Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6-week, placebo-controlled studies. Journal of Clinical Psychiatry. 2008;69:817-29.
30. 30. Chwieduk CM, Keating GM. Paliperidone extended release: a review of its use in the management of schizophrenia. Drugs. 2010;70:1295-317.
31. 31. Emsley R, Berwaerts J, Eerdekens M, Kramer M, Lane R, Lim P, Hough D, palumbo J. Efficacy and safety of oral paliperidone extended-relaese tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies. International Clinical Psychopharmacology. 2008;23:343-56.
32. 32. Melkersson KI. Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite. Hum Psychopharmacol. 2006;21:529-32.
33. 33. Knegtering R, Baselmans P, Castelein S, Bosker F, Bruggeman R, van den Bosch RJ. Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels. Am J Psychiatry. 2005;162:1010-2.
34. 34. Suzuki H, Gen K, Otomo M, Inoue Y, Hibino H, Mikami A, Matsumoto H, Mikami K. Study of the efficacy and safety of switching from risperidone to paliperidone in elderly patients with schizophrenia. Psychiatry Clin Neurosci. 2013;67:76-82.
35. 35. Montalvo I, Ortega L, López X, Solé M, Monseny R, Franch J, Vilella E, Labad J. Changes in prolactin levels and sexual function in young psychotic patients after switching from longacting injectable risperidone to paliperidone palmitate. Int Clin Psychopharmacol. 2013;27:46-9.
36. 36. Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;6736:60733-43.