Successful use of adjuvant raloxifene treatment in clozapine-resistant schizophrenia.

Sir,

Treatment with estrogen supplementation can be beneficial in women with schizophrenia.[1] However, systemic side effects limit the use of synthetic estrogen derivatives for treating schizophrenia. Raloxifene, a selective estrogen receptor modulator, has been advocated as a safer option because of its agonistic activity in the brain and bone in contrast to the antagonistic activity on breast.[2] Recently, the benefit of adjunctive treatment with raloxifene has been demonstrated in postmenopausal women with schizophrenia.[3] However, the potential role for raloxifene in premenopausal women with schizophrenia is yet to be established. In this letter, we describe the first report of a premenopausal woman with schizophrenia whose symptoms improved after adjuvant treatment with raloxifene.

Ms. B, a 17-year-old girl with paranoid schizophrenia, presented to us with a 3-year history of continuous illness characterized by delusion of persecution, auditory hallucination, thought broadcast, and decline in academic performance. Over the past 3 years, she had been treated with adequate trials of risperidone (8 mg/day), olanzapine (22.5 mg/day), and clozapine (600 mg/day—clozapine had to be stopped because of leucopenia) with only minimal improvement in symptoms. Her ongoing treatment regimen during February 2011 before the addition of raloxifene was: quetiapine 325 mg/day, amisulpiride 600 mg/day, chlorpromazine 100 mg/day, trihexyphenidyl hydrochloride 2 mg/day, lorazepam 2 mg/day, and vitamin B12 supplements. With this she showed partial improvement in her positive symptoms. However, hallucinatory behaviour, agitation, restlessness, attention difficulties, and asocialization persisted. She was treated with add-on raloxifene 120 mg/day. After 2 weeks of add-on raloxifene, Ms. B showed marked reduction in restlessness, agitation, and hallucinatory behavior. Her attention span improved as reflected by her ability to read newspaper and magazines, perform simple calculations, and write few sentences. Moreover, she started interacting with her relatives spontaneously and involved herself in household chores as well. In April 2011, after 2 months of treatment with 120 mg/day raloxifene, she had passage of blood clots during menstrual period. Blood investigations revealed that her bleeding, clotting, and prothrombin times were within normal limits. However, because of concern expressed by the relatives related to thrombosis risk, the dose of raloxifene was reduced to 60 mg/day. She persisted to maintain the clinical improvement after 4 months of treatment with raloxifene 60 mg/day.

This case report suggests a promising role for adjuvant raloxifene in premenopausal women with schizophrenia. Interestingly, estrogen has been postulated to have protective effects in young women also. For example, Cohen et al.[4] demonstrated that early menarche was found to predict later age-at-onset of psychosis in women. Also, early menarche was observed to be associated with better clinical outcome.[5] Given our observation that this patient maintained clinical improvement with 60 mg/day of raloxifene treatment (in contrast to 120 mg/day advocated for postmenopausal women), it is possible that premenopausal women might require lower dosage. In summary, this first time case report of striking clinical benefits of adjuvant raloxifene supports compelling need for further systematic studies in premenopausal women with schizophrenia.