Effect of Adjunctive Aripiprazole on Sexual Dysfunction in Schizophrenia: A Preliminary Open-Label Study

Abstract

Introduction: Although adjunctive aripiprazole improves hyperprolactinemia, sufficient evidence for its effects on sexual dysfunction has not been obtained. We assessed the usefulness of adjunctive aripiprazole for schizophrenia with sexual dysfunction.

Methods: 22 Japanese schizophrenia patients with antipsychotic-induced hyperprolactinemia and sexual dysfunction were enrolled, and 19 of them completed the study. Aripiprazole was administrated in a flexible titration schedule to participants according to the judgment of each doctor, and patients were followed for 24 weeks. Serum prolactin, Clinical Global Impression Scales-Severity (CGI-S), and Nagoya Sexual Function Questionnaire (NSFQ) were measured at baseline and at 4, 8, 12, and 24 weeks.

Results: Prolactin at week 4 and later was significantly lower than that at baseline. Compared to baseline, we observed a significant improvement in total sexual dysfunction as measured by NSFQ at week 8 and later. In males, erectile dysfunction was significantly reduced at week 24. In females, menstrual irregularity and galactorrhea were significantly reduced at week 24. CGI-S did not significantly change.

Discussion: Although the small sample size is a limitation in this study, adjunctive aripiprazole may be useful treatment for sexual dysfunction including hyperprolactinemia in schizophrenia.

Key words

adjunctive treatment - aripiprazole - hyperprolactinemia - schizophrenia - sexual dysfunction

• References

• 1 Smith SM, O’Keane V, Murray R. Sexual dysfunction in patients taking conventional antipsychotic medication. Br J Psychiatry 2002; 181: 49-55
• 2 Malik P, Kemmler G, Hummer M et al. Sexual dysfunction in first-episode schizophrenia patients: results from European First Episode Schizophrenia Trial. J Clin Psychopharmacol 2011; 31: 274-280
• 3 Ghadirian AM, Chouinard G, Annable L. Sexual dysfunction and plasma prolactin levels in neuroleptic-treated schizophrenic outpatients. J Nerv Ment Dis 1982; 170: 463-467
• 4 Montejo AL, Majadas S, Rico-Villademoros F et al. Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics. J Sex Med 2010; 7: 3404-3413
• 5 Olfson M, Uttaro T Carson et al. Male sexual dysfunction and quality of life in schizophrenia. J Clin Psychiatry 2005; 66: 331-338
• 6 de Boer MK, Castelein S, Wiersma D et al. The facts about sexual (dys)function in schizophrenia: an overview of clinically relevant findings. Schizophr Bull 2015; 41: 674-686
• 7 Fujii A, Yasui-Furukori N, Sugawara N et al. Sexual dysfunction in Japanese patients with schizophrenia treated with antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 288-293
• 8 Kikuchi T, Iwamoto K, Sasada K et al. Reliability and validity of a new sexual function questionnaire (Nagoya Sexual Function Questionnaire) for schizophrenic patients taking antipsychotics. Hum Psychopharmacol 2011; 26: 300-306
• 9 Kikuchi T, Iwamoto K, Sasada K et al. Sexual dysfunction and hyperprolactinemia in Japanese schizophrenic patients taking antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 2012; 37: 26-32
• 10 Rettenbacher MA, Hofer A, Ebenbichler C et al. Prolactin levels and sexual adverse effects in patients with schizophrenia during antipsychotic treatment. J Clin Psychopharmacol 2010; 30: 711-715
• 11 Montejo AL. Prolactin awareness: an essential consideration for physical health in schizophrenia. Eur Neuropsychopharmacol 2008; 18 (Suppl. 02) S108-S114
• 12 Kelly DL, Wehring HJ, Earl AK et al. Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (dopamine partial agonist, aripiprazole, for the management of symptomatic elevated prolactin). BMC Psychiatry 2013; 13: 214
• 13 Nunes LV, Moreira HC, Razzouk D et al. Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review. J Sex Marital Ther 2012; 38: 281-301
• 14 Peuskens J, Pani L, Detraux J et al. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs 2014; 28: 421-453
• 15 Shim JC, Shin JG, Kelly DL et al. Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry 2007; 164: 1404-1410
• 16 Mir A, Shivakumar K, Williamson RJ et al. Change in sexual dysfunction with aripiprazole: a switching or add-on study. J Psychopharmacol 2008; 22: 244-253
• 17 Yasui-Furukori N, Furukori H, Sugawara N et al. Dose-dependent effects of adjunctive treatment with aripiprazole on hyperprolactinemia induced by risperidone in female patients with schizophrenia. J Clin Psychopharmacol 2010; 30: 596-599
• 18 American Psychiatric A . Diagnostic criteria from DSM-IV-TR[TM]: American Psychiatric Association. 2000
• 19 Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 2004; 64: 2291-2314
• 20 Guy W. National Institute of Mental H, Psychopharmacology Research B et al. ECDEU assessment manual for psychopharmacology. Rockville, Md.: U.S. Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976
• 21 Overall JE, Gornham DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: 799-812
• 22 Hanssens L, L’Italien G, Loze JY et al. 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
• 23 Zhao J, Song X, Ai X et al. Adjunctive aripiprazole treatment for risperidone-induced hyperprolactinemia: an 8-week randomized, open-label, comparative clinical Trial. PloS One 2015; 10: e0139717
• 24 Aizenberg D, Zemishlany Z, Dorfman-Etrog P et al. Sexual dysfunction in male schizophrenic patients. J Clin Psychiatry 1995; 56: 137-141
• 25 Marques TR, Smith S, Bonaccorso S et al. Sexual dysfunction in people with prodromal or first-episode psychosis. Br J Psychiatry 2012; 201: 131-136
• 26 Meston CM, Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry 2000; 57: 1012-1030
• 27 Montejo AL, Montejo L, Navarro-Cremades F. Sexual side-effects of antidepressant and antipsychotic drugs. Curr Opin Psychiatry 2015; 28: 418-423
• 28 Baskerville TA, Douglas AJ. Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders. CNS Neurosci Ther 2010; 16: e92-e123
• 29 Giuliano F, Allard J. Dopamine and sexual function. Int J Impot Res 2001; 13 (Suppl. 03) S18-S28
• 30 Melis MR, Argiolas A. Dopamine and sexual behavior. Neurosci Biobehav Rev 1995; 19: 19-38
• 31 Lal S, Ackman D, Thavundayil JX et al. Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects. Prog Neuropsychopharmacol Biol Psychiatry 1984; 8: 695-699
• 32 Knegtering H, van den Bosch R, Castelein S et al. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?. Psychoneuroendocrinology 2008; 33: 711-717
• 33 Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol 2011; 26: 130-140
• 34 de Boer MK, Wiersma D, Bous J et al. A randomized open-label comparison of the impact of aripiprazole versus risperidone on sexual functioning (RAS study). J Clin Psychopharmacol 2011; 31: 523-525
• 35 Bushe CJ, Bradley A, Pendlebury J. A review of hyperprolactinaemia and severe mental illness: are there implications for clinical biochemistry?. Ann Clin Biochem 2010; 47: 292-300
• 36 Lee BH, Kim YK, Park SH. Using aripiprazole to resolve antipsychotic-induced symptomatic hyperprolactinemia: a pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 714-717
• 37 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: 1978-1981
• 38 Jeong HG, Lee MS, Lee HY et al. Changes in sexual function and gonadal axis hormones after switching to aripiprazole in male schizophrenia patients: a prospective pilot study. Int Clin Psychopharmacol 2012; 27: 177-183