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Adjunctive raloxifene improves outcomes in women with refractory schizophrenia

Raloxifene hydrochloride, a selective estrogen receptor modulator with mixed agonist and antagonist activity, reduced illness severity and increased likelihood of clinical response in women with treatment-resistant schizophrenia, according to recent findings.

“Estradiol therapy has been shown to reduce psychotic symptoms in women with treatment-resistant schizophrenia in most placebo-controlled randomized clinical trials. However, concerns regarding potential adverse effects on breast tissue and the endometrium have driven the investigation of drugs exhibiting estrogenic activity, with selectivity for the brain, to treat women with refractory schizophrenia,” Jayashri Kulkarni, MBBS, PhD, of Alfred Hospital and Monash University Central Clinical School, Monash University, Melbourne, Australia, and colleagues wrote.

Jayashri Kulkarni

To assess efficacy of adjunctive raloxifene therapy in women with treatment-resistant schizophrenia, researchers conducted a 12-week, double-blind, placebo-controlled randomized clinical trial among 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite stable antipsychotic doses. Study participants received 120 mg of raloxifene hydrochloride (n = 26) or placebo (n = 30) per day for 12 weeks. Assessments occurred every 2 weeks. Mean age of the study cohort was 53 years.

Compared with placebo, individuals who received raloxifene had greater reductions in Positive and Negative Syndrome Scale (PANSS) total scores (P = .02) and an increased probability of clinical response (P = .01).

PANSS general symptom scores were also significantly lower among individuals who received raloxifene, compared with placebo (P = .02).

Among participants who completed the full 12-week trial, PANSS positive symptom scores did not statistically significantly change (P = .05).

Changes in mood, cognition and reproductive hormone levels did not differ between treatment groups.

Rates of adverse events did not differ between groups.

“Our results support growing evidence that, in this patient group, raloxifene is a promising, well-tolerated adjunctive treatment with potential future application in clinical practice. Although consideration of sex, age, and other heterogeneous factors in schizophrenia should always drive treatment decision making, this investigation represents an important development regarding the evidence base for central nervous system-estrogenic agents and schizophrenia tractability,” the researchers concluded. – by Amanda Oldt

Disclosure: Kulkarni reports being employed by the Alfred Hospital and receiving research grants from Jansen Cilag, AstraZeneca, and Eli Lily Pharmaceuticals for other research. Please see the full study for a list of all authors’ relevant financial disclosures.