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Adjunctive aripiprazole in risperidone-induced hyperprolactinaemia: double-blind, randomised, placebo-controlled trial

Published online by Cambridge University Press:  02 January 2018

G. Raghuthaman,
R. Venkateswaran and
R. Krishnadas
G. Raghuthaman
Affiliation:
Department of Psychiatry, PSG Institute of Medical Sciences and Research, Coimbatore, India
R. Venkateswaran
Affiliation:
Department of Child Psychiatry, CMC, Vellore, India
R. Krishnadas*
Affiliation:
ESTEEM, NHS Greater Glasgow and Clyde, Glasgow, UK
*
Rajeev Krishnadas, Department of Psychiatry, ESTEEM, Glasgow G21 4SF, UK. Email: rajeev.krishnadas@glasgow.ac.uk
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Abstract

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Background

Hyperprolactinaemia is a troublesome side-effect of treatment with antipsychotics.

Aims

This double-blind, placebo-controlled study aimed at examining the effect of adjunctive treatment with 10 mg aripiprazole on prolactin levels and sexual side-effects in patients with schizophrenia symptomatically maintained on risperidone.

Method

Thirty patients taking risperidone were enrolled into the trial (CTRI/2012/11/003114). Aripiprazole was administered at a fixed daily dose of 10 mg/day for 8 weeks. Serum prolactin was measured at baseline and at 8 weeks. Hyperprolactinaemia-related problems, psychopathology and side-effects were evaluated every 2 weeks.

Results

Prolactin levels decreased by 58% in the aripiprazole group compared with an increase by 22% in the placebo group. Prolactin levels normalised in 46% of patients in the aripiprazole group (number needed to treat, NNT=2). Aripiprazole improved erectile dysfunction in five out of six patients. There were no significant differences in change in psychopathology or side-effects between groups.

Conclusions

Adjunctive aripiprazole reduced prolactin levels in those treated with risperidone, with no effect on psychopathology and extrapyramidal symptoms. This is a potential treatment for hyperprolactinaemia observed during treatment with second-generation antipsychotics.

Information

Type
Research Article
Information
BJPsych Open , Volume 1 , Issue 2 , October 2015, pp. 172 - 177
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Copyright
Copyright © The Royal College of Psychiatrists 2015

Footnotes

Declaration of interest

None.

References

1 Kucka, M, Tomić, M, Bjelobaba, I, Stojilkovic, SS, Budimirovic, DB. Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs. Sci Rep 2015; 5: 8902.CrossRefGoogle ScholarPubMed
2 Melkersson, K. Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry 2005; 66: 761–7.CrossRefGoogle ScholarPubMed
3 Melkersson, KI. Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite. Hum Psychopharmacol 2006; 21: 529–32.CrossRefGoogle ScholarPubMed
4 O'Keane, V, Meaney, AM. Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia? J Clin Psychopharmacol 2005; 25: 26–31.CrossRefGoogle ScholarPubMed
5 Volavka, J, Czobor, P, Cooper, TB, Sheitman, B, Lindenmayer, JP, Citrome, L, et al. Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry 2004; 65: 57–61.CrossRefGoogle ScholarPubMed
6 Beumont, PJ, Corker, CS, Friesen, HG, Kolakowska, T, Mandelbrote, M, Marshall, J, et al. The effects of phenothiazines on endocrine function: II. Effects in men and post-menopausal women. Br J Psychiatry 1974; 124: 420–30.CrossRefGoogle ScholarPubMed
7 Beumont, PJ, Gelder, MG, Friesen, GH, Harris, GW, MacKinnon, PC, Mandelbrote, BM, et al. The effects of phenothiazines on endocrine function: I. Patients with inappropriate lactation and amenorrhoea. Br J Psychiatry 1974; 124: 413–9.CrossRefGoogle Scholar
8 Rosenberg, KP, Bleiberg, KL, Koscis, J, Gross, C. A survey of sexual side-effects among severely mentally ill patients taking psychotropic medications: impact on compliance. J Sex Marital Ther 2003; 29: 289–96.CrossRefGoogle ScholarPubMed
9 Leucht, S, Cipriani, A, Spineli, L, Mavridis, D, Örey, D, Richter, F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382: 951–62.CrossRefGoogle ScholarPubMed
10 Jauhar, S, Guloksuz, S, Andlauer, O, Lydall, G, Marques, JG, Mendonca, L, et al. Choice of antipsychotic treatment by European psychiatry trainees: are decisions based on evidence? BMC Psychiatry 2012; 12: 27.CrossRefGoogle Scholar
11 Peuskens, J, Pani, L, Detraux, J, De Hert, M. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs 2014; 28: 421–53.Google ScholarPubMed
12 Cavallaro, R, Cocchi, F, Angelone, SM, Lattuada, E, Smeraldi, E. Cabergoline treatment of risperidone-induced hyperprolactinemia: a pilot study. J Clin Psychiatry 2004; 65: 187–90.CrossRefGoogle ScholarPubMed
13 Stroup, TS, McEvoy, JP, Ring, KD, Hamer, RH, LaVange, LM, Swartz, MS, et al. A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: comparison of antipsychotics for metabolic problems (CAMP). Am J Psychiatry 2011; 168: 947–56.CrossRefGoogle ScholarPubMed
14 Lee, MS, Song, HC, An, H, Yang, J, Ko, YH, Jung, IK, et al. Effect of bromocriptine on antipsychotic drug-induced hyperprolactinemia: eight-week randomized, singleblind, placebo-controlled, multicenter study. Psychiatry Clin Neurosci 2010; 64: 19–27.CrossRefGoogle ScholarPubMed
15 Urban, JD, Vargas, GA, von Zastrow, M, Mailman, RB. Aripiprazole has functionally selective actions at dopamine D2 receptor-mediated signaling pathways. Neuropsychopharmacology 2007; 32: 67–77.CrossRefGoogle ScholarPubMed
16 Natesan, S, Reckless, GE, Nobrega, JN, Fletcher, PJ, Kapur, S. Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: comparing aripiprazole to other antipsychotics in animal models. Neuropsychopharmacology 2006; 31: 1854–63.CrossRefGoogle ScholarPubMed
17 Mailman, R, Murthy, V. Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? Curr Pharm Des 2010; 16: 488–501.CrossRefGoogle ScholarPubMed
18 Shapiro, DA, Renock, S, Arrington, E, Chiodo, LA, Liu, L-X, Sibley, DR, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 2003; 28: 1400–11.CrossRefGoogle ScholarPubMed
19 Li, X, Tang, Y, Wang, C. Adjunctive aripiprazole versus placebo for antipsychoticinduced hyperprolactinemia: meta-analysis of randomized controlled trials. PLoS One 2013; 8: e70179.CrossRefGoogle ScholarPubMed
20 Chen, HZ, Niu, FR, Qian, MC, Yu, BR, Shen, XH, Yang, SG, et al. The effect of aripiprazole plus risperidone on the level of hyperprolactinemia of male patients with schizophrenia. Zhong Hua Jing Shen Ke Za Zhi 2009; 42: 224–7.Google Scholar
21 Kane, JM, Correll, CU, Goff, DC, Kirkpatrick, B, Marder, SR, Vester-Blokland, E, et al. A multicenter, randomized, double-blind, placebo-controlled, 16-week study of adjunctive aripiprazole for schizophrenia or schizoaffective disorder inadequately treated with quetiapine or risperidone monotherapy. J Clin Psychiatry 2009; 70: 1348–57.CrossRefGoogle ScholarPubMed
22 Shim, J-C, Shin, JG, Kelly, DL, Jung, D-U, Seo, Y-S, Liu, K-H, et al. Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry 2007; 164: 1404–10.CrossRefGoogle ScholarPubMed
23 Moher, D, Hopewell, S, Schulz, KF, Montori, V, Gotzsche, PC, Devereaux, PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010; 340: c869.CrossRefGoogle ScholarPubMed
24 First, MB, Spitzer, RL, Gibbon, M, Williams, JBW. Structured Clinical Interview for Axis I DSM-IV Disorders. Biometrics Research, 1994.Google Scholar
25 Overall, JE, Gorham, DR. The brief psychiatric rating scale. Psychol Rep 1962; 10: 799–812.CrossRefGoogle Scholar
26 Simpson, GM, Angus, JW. A rating scale for extrapyramidal side-effects. Acta Psychiatr Scand Suppl 1970; 212: 11–9.Google ScholarPubMed
27 Barnes, TR. A rating scale for drug-induced akathisia. Br J Psychiatry 1989; 154: 672–6.CrossRefGoogle ScholarPubMed
28 McGahuey, CA, Gelenberg, AJ, Laukes, CA, Moreno, FA, Delgado, PL, McKnight, KM, et al. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther 2000; 26: 25–40.Google ScholarPubMed
29 Kelly, DL, Conley, RR. A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology 2006; 31: 340–6.CrossRefGoogle ScholarPubMed
30 Schulster, D, Gaines Das, RE, Jeffcoate, SL. International Standards for human prolactin: calibration by international collaborative study. J Endocrinol 1989; 121: 157–66.CrossRefGoogle ScholarPubMed
31 Cooper, HM, Hedges, LV, Valentine, JC. The Handbook of Research Synthesis and Meta-analysis. Russell Sage Foundation, 2009.Google Scholar
32 Carboni, L, Negri, M, Michielin, F, Bertani, S, Fratte, SD, Oliosi, B, et al. Slow dissociation of partial agonists from the D2 receptor is linked to reduced prolactin release. Int J Neuropsychopharmacol 2012; 15: 645–56.CrossRefGoogle ScholarPubMed
33 Davies, MA, Sheffler, DJ, Roth, BL. Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacology. CNS Drug Rev. 2004; 10: 317–36.CrossRefGoogle ScholarPubMed
34 Yasui-Furukori, N, Furukori, H, Sugawara, N, Fujii, A, Kaneko, S. Dose-dependent effects of adjunctive treatment with aripiprazole on hyperprolactinemia induced by risperidone in female patients with schizophrenia. J Clin Psychopharmacol 2010; 30: 596–9.CrossRefGoogle ScholarPubMed
35 Schlechte, JA. Clinical practice. Prolactinoma. N Engl J Med 2003; 349: 2035–41.CrossRefGoogle ScholarPubMed
36 Hanssens, L, L'Italien, G, Loze, J-Y, Marcus, RN, Pans, M, Kerselaers, W. The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913). BMC Psychiatry 2008; 8: 95.CrossRefGoogle ScholarPubMed
37 Takeuchi, H, Remington, G. A systematic review of reported cases involving psychotic symptoms worsened by aripiprazole in schizophrenia or schizoaffective disorder. Psychopharmacology (Berl) 2013; 228: 175–85CrossRefGoogle ScholarPubMed
38 Takeuchi, H, Uchida, H, Suzuki, T, Watanabe, K, Kashima, H. Predictors of clinical worsening after a switch to aripiprazole in patients with schizophrenia: a 1-year naturalistic follow-up study. J Clin Psychopharmacol 2009; 29: 394–5.CrossRefGoogle ScholarPubMed
39 Gugger, JJ, Tam, CL, Ashby, CR. Is there a link between aripiprazole and treatment-emergent psychosis? Curr Psychiatry 2011; 10: 53–8.Google Scholar
40 Manschreck, TC, Boshes, RA. The CATIE schizophrenia trial: results, impact, controversy. Harv Rev Psychiatry 2007; 15: 245–58.CrossRefGoogle ScholarPubMed
41 Chen, CK, Huang, YS, Ree, SC, Hsiao, CC. Differential add-on effects of aripiprazole in resolving hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1495–9.CrossRefGoogle ScholarPubMed
42 Levy, A. Interpreting raised serum prolactin results. BMJ 2014; 348: g3207.CrossRefGoogle ScholarPubMed
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