CASE REPORT Beneficial effects of add-on raloxifene in schizophrenia A case report Eesha Sharma & Dhanya Raveendranathan & Venkataram Shivakumar & Naveen Jayaram & Naren P. Rao & Ganesan Venkatasubramanian Received: 20 September 2011 / Accepted: 16 January 2012 / Published online: 31 January 2012 # Springer-Verlag 2012 Abstract The role of estrogens in schizophrenia has been proposed from the observation of schizophrenia occurring later and with symptom severity being lesser in women. Utility of estrogens in treatment of psychoses, though seen to be useful, comes with inherent risks of neoplasias, given its agonistic action on breast and endometrium. This risk can be overcome with use of selective estrogen receptor modulators, like raloxifene. Raloxifene has been used in schizophrenia, with improvement in symptoms and cognitive functions. We report the use of raloxifene as an adjunctive treatment, with risperidone, in treatment-resistant form of schizophrenia. The patient, a 29-year-old woman, over a 7-month follow- up period, showed significant improvement in socio- occupational functioning, with reduction in symptom severity. Keywords Schizophrenia . Selective estrogen receptor modulators . Raloxifene Introduction The role of estrogen in brain functioning is vital, with estrogen receptors being found in various areas of the brain. Their presence in the limbic system confers a neuromodulatory influence on emotions (Riecher-Rossler 2002). Its role in regulating blood flow and glucose metabolism in brain also makes it a neuroprotectant (Garcia-Segura et al. 2001). In the context of psychosis, it possibly acts as a psychoprotectant by modulating the monoaminergic neurotransmission and its effects on dopamine, serotonin and GABA (Garcia-Segura et al. 2001). The relation between estrogen and schizophrenia is robustly supported by the more frequent occurrence of late- onset schizophrenia, after age 40, in women—a finding attrib- uted to the loss of ovarian function (Riecher-Rossler 2002). Though the prevalence of schizophrenia is equal among men and women, women have a lesser symptom severity. Further supporting this link, estrogens used as adjunctive treatment have been seen to ameliorate both psychotic symptoms and cognitive deficits (Shivakumar and Venkatasubramanian 2011; Wong et al. 2003). However, estrogens pose a high risk/benefit ratio due to agonistic action on breast and uterine endometrium, resulting in neoplasias. Selective Estrogen Receptor Modulators (SERMs), like raloxifene and tamoxi- fene, with agonistic action on brain and anti-estrogenic action on breast and uterus, overcome the non-specific effects of estrogens. Few studies have reported the successful use of SERMs, especially raloxifene, as an adjunctive therapy in schizophrenia and other psychoses, with improvement in symptoms and cognitive status (Kulkarni et al. 2008; Usall et al. 2011; Wong et al. 2003). Here, we report a case of early-onset schizophrenia which responded well to add-on Raloxifene. Case report Ms. M, a 29-year-old single woman, was diagnosed with paranoid schizophrenia and presented with a four years duration, acute onset, continuous illness characterized by E. Sharma : D. Raveendranathan : V. Shivakumar : N. Jayaram : N. P. Rao : G. Venkatasubramanian (*) The Metabolic Clinic in Psychiatry, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, India e-mail: venkat.nimhans@yahoo.com Arch Womens Ment Health (2012) 15:147–148 DOI 10.1007/s00737-012-0259-1