Raloxifene as an Adjuvant Treatment of the Negative Symptoms of Schizophrenia in Post-menopausal Women

Summary

The efficacy of raloxifene versus placebo was compared over a six-month period, as an adjuvant treatment of the negative symptoms of schizophrenia in a group of 80 post-menopausal women. The aim of the study is to analyze whether raloxifene has an effect on the positive and negative symptoms of schizophrenia, and on psychopathological symptoms in general, and on social and neuropsychological functioning, and to study the influence of genetic polymorphisms in treatment response.

Timeline

Start

2011-07

Primary completion

2014-07

Completion

2014-07

Publications

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• Background Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, Day R, Bertelsen A. Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study. Psychol Med Monogr Suppl. 1992;20:1-97. doi: 10.1017/s0264180100000904. No abstract available.
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• Background Seeman MV, Lang M. The role of estrogens in schizophrenia gender differences. Schizophr Bull. 1990;16(2):185-94. doi: 10.1093/schbul/16.2.185.
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• Background Huber TJ, Rollnik J, Wilhelms J, von zur Muhlen A, Emrich HM, Schneider U. Estradiol levels in psychotic disorders. Psychoneuroendocrinology. 2001 Jan;26(1):27-35. doi: 10.1016/s0306-4530(00)00034-2.
• Background Di Paolo T, Bedard F, Bedard PJ. Influence of gonadal steroids on human and monkey cerebrospinal fluid homovanillic acid concentrations. Clin Neuropharmacol. 1989 Feb;12(1):60-6. doi: 10.1097/00002826-198902000-00008.
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• Background Moses EL, Drevets WC, Smith G, Mathis CA, Kalro BN, Butters MA, Leondires MP, Greer PJ, Lopresti B, Loucks TL, Berga SL. Effects of estradiol and progesterone administration on human serotonin 2A receptor binding: a PET study. Biol Psychiatry. 2000 Oct 15;48(8):854-60. doi: 10.1016/s0006-3223(00)00967-7.
• Background DonCarlos LL, Azcoitia I, Garcia-Segura LM. Neuroprotective actions of selective estrogen receptor modulators. Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S113-22. doi: 10.1016/j.psyneuen.2009.04.012.
• Background Kulkarni J, Riedel A, de Castella AR, Fitzgerald PB, Rolfe TJ, Taffe J, Burger H. Estrogen - a potential treatment for schizophrenia. Schizophr Res. 2001 Mar 1;48(1):137-44. doi: 10.1016/s0920-9964(00)00088-8.
• Background Akhondzadeh S, Nejatisafa AA, Amini H, Mohammadi MR, Larijani B, Kashani L, Raisi F, Kamalipour A. Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Sep;27(6):1007-12. doi: 10.1016/S0278-5846(03)00161-1.
• Background Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, Burger H. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry. 2008 Aug;65(8):955-60. doi: 10.1001/archpsyc.65.8.955.
• Background Bottlender R, Jager M, Groll C, Strauss A, Moller HJ. Deficit states in schizophrenia and their association with the length of illness and gender. Eur Arch Psychiatry Clin Neurosci. 2001 Dec;251(6):272-8. doi: 10.1007/pl00007545.
• Background Lindamer LA, Buse DC, Lohr JB, Jeste DV. Hormone replacement therapy in postmenopausal women with schizophrenia: positive effect on negative symptoms? Biol Psychiatry. 2001 Jan 1;49(1):47-51. doi: 10.1016/s0006-3223(00)00995-1.
• Background Castle D, Sham P, Murray R. Differences in distribution of ages of onset in males and females with schizophrenia. Schizophr Res. 1998 Oct 9;33(3):179-83. doi: 10.1016/s0920-9964(98)00070-x.
• Background Häfner H. Gender differences in first-episode of schizophrenia. In Frank ed, gender and its effects in Psychopathology. American Psychiatric Press, Washington 2000
• Background Chlebowski RT, Kuller LH, Prentice RL, Stefanick ML, Manson JE, Gass M, Aragaki AK, Ockene JK, Lane DS, Sarto GE, Rajkovic A, Schenken R, Hendrix SL, Ravdin PM, Rohan TE, Yasmeen S, Anderson G; WHI Investigators. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med. 2009 Feb 5;360(6):573-87. doi: 10.1056/NEJMoa0807684.
• Background MacGregor JI, Jordan VC. Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev. 1998 Jun;50(2):151-96.
• Background Huang Y, Huang YL, Lai B, Zheng P, Zhu YC, Yao T. Raloxifene acutely reduces glutamate-induced intracellular calcium increase in cultured rat cortical neurons via inhibition of high-voltage-activated calcium current. Neuroscience. 2007 Jun 29;147(2):334-41. doi: 10.1016/j.neuroscience.2007.04.037. Epub 2007 Jun 1.
• Background Littleton-Kearney MT, Ostrowski NL, Cox DA, Rossberg MI, Hurn PD. Selective estrogen receptor modulators: tissue actions and potential for CNS protection. CNS Drug Rev. 2002 Fall;8(3):309-30. doi: 10.1111/j.1527-3458.2002.tb00230.x.
• Background Jarkova NB, Martenyi F, Masanauskaite D, Walls EL, Smetnik VP, Pavo I. Mood effect of raloxifene in postmenopausal women. Maturitas. 2002 May 20;42(1):71-5. doi: 10.1016/s0378-5122(01)00303-6.
• Background Wong J, Seeman MV, Shapiro H. Case report: raloxifene in postmenopausal women with psychosis: preliminary findings. Am J Geriatr Psychiatry. 2003 Nov-Dec;11(6):697-8. doi: 10.1176/appi.ajgp.11.6.697. No abstract available.
• Background Kulkarni J, Gurvich C, Lee SJ, Gilbert H, Gavrilidis E, de Castella A, Berk M, Dodd S, Fitzgerald PB, Davis SR. Piloting the effective therapeutic dose of adjunctive selective estrogen receptor modulator treatment in postmenopausal women with schizophrenia. Psychoneuroendocrinology. 2010 Sep;35(8):1142-7. doi: 10.1016/j.psyneuen.2010.01.014. Epub 2010 Feb 19.
• Background Usall J, Huerta-Ramos E, Iniesta R, Cobo J, Araya S, Roca M, Serrano-Blanco A, Teba F, Ochoa S. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2011 Nov;72(11):1552-7. doi: 10.4088/JCP.10m06610. Epub 2011 Aug 23.
• Background Zavratnik A, Zegura B, Marc J, Prezelj J, Pfeifer M. XbaI polymorphism of the estrogen receptor alpha gene influences the effect of raloxifene on the endothelial function. Maturitas. 2010 Sep;67(1):84-90. doi: 10.1016/j.maturitas.2010.05.011. Epub 2010 Jul 6.
• Background Zavratnik A, Prezelj J, Kocijancic A, Marc J. Exonic, but not intronic polymorphisms of ESR1 gene might influence the hypolipemic effect of raloxifene. J Steroid Biochem Mol Biol. 2007 Apr;104(1-2):22-6. doi: 10.1016/j.jsbmb.2006.10.009. Epub 2007 Mar 12.
• Background Zhang ZL, He JW, Qin YJ, Huang QR, Liu YJ, Hu YQ, Li M. Association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006 Apr;23(2):129-33.
• Results Chua WL, de Izquierdo SA, Kulkarni J, Mortimer A. Estrogen for schizophrenia. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004719. doi: 10.1002/14651858.CD004719.pub2.
• Huerta-Ramos E, Labad J, Cobo J, Nunez C, Creus M, Garcia-Pares G, Cuadras D, Franco J, Miquel E, Reyes JC, Marco-Garcia S; RALOPSYCAT Group; Usall J. Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial. Eur Arch Psychiatry Clin Neurosci. 2020 Sep;270(6):729-737. doi: 10.1007/s00406-019-01079-w. Epub 2019 Nov 14.
• Usall J, Huerta-Ramos E, Labad J, Cobo J, Nunez C, Creus M, Pares GG, Cuadras D, Franco J, Miquel E, Reyes JC, Roca M; RALOPSYCAT Group. Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A 24-Week Double-Blind, Randomized, Parallel, Placebo-Controlled Trial. Schizophr Bull. 2016 Mar;42(2):309-17. doi: 10.1093/schbul/sbv149. Epub 2015 Nov 20.

Drugs

Indications

No indication recorded.