Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder

Weiser, Mark; Levi, Linda; Burshtein, Shimon; Hagin, Michal; Matei, Valentin P.; Podea, D.M.; Miclutia, I.; Tiugan, A.; Păcală, Bogdan; Grecu, Iosif Gaboș; Noy, Adam; Zamora, Daisy; Davis, John M.

doi:10.4088/jcp.15m10498

Cited by 44 publications

(52 citation statements)

References 2 publications

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“…We found that the administration of adjunctive raloxifene significantly improved memory and attention compared to placebo, which is consistent with the findings of an earlier trial showing significant improvement in frontal cortex‐dependent memory and executive function with adjunctive raloxifene therapy in postmenopausal women with schizophrenia . Conversely, in a recent randomised‐controlled trial of 200 severely ill and decompensated postmenopausal women, raloxifene showed no significant cognitive benefit or symptom severity reduction as an adjunctive treatment compared to placebo (although the ability to detect cognitive improvement may have been limited by the extensive symptom severity in the sample). Overall, despite inconsistencies as to which specific clinical aspects of schizophrenia are ameliorated by raloxifene, it is clear that the SERM has potential as an adjunctive medication in the treatment of schizophrenia.…”

Section: Evidence That Sex Steroid Manipulations Can Be Useful Adjuncsupporting

confidence: 88%

Considering the role of adolescent sex steroids in schizophrenia

Owens

Murphy

Purves-Tyson

et al. 2018

J Neuroendocrinology

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Schizophrenia is a disabling illness that is typically first diagnosed during late adolescence to early adulthood. It has an unremitting course and is often treatment-resistant.Many clinical aspects of the illness suggest that sex steroid-nervous system interactions may contribute to the onset, course of symptoms and the cognitive impairment displayed by men and women with schizophrenia. Here, we discuss the actions of oestrogen and testosterone on the brain during adolescent development and in schizophrenia from the perspective of experimental studies in animals, human post-mortem studies, magnetic resonance imaging studies in living humans and clinical trials of sex steroid-based treatments. We present evidence of potential beneficial, as well as detrimental, effects of both testosterone and oestrogen. We provide a rationale for the necessity to further elucidate sex steroid mechanisms of action at different ages, sexes and brain regions to more fully understand the role of testosterone and oestrogen in the pathophysiology of schizophrenia. The weight of the evidence suggests that sex steroid hormones influence mammalian brain function, including both cognition and emotion, and that pharmaceutical agents aimed at sex steroid receptors appear to provide a novel treatment avenue to reduce symptoms and improve cognition in men and women with schizophrenia.

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Section: Evidence That Sex Steroid Manipulations Can Be Useful Adjuncsupporting

confidence: 88%

Considering the role of adolescent sex steroids in schizophrenia

Owens

Murphy

Purves-Tyson

et al. 2018

J Neuroendocrinology

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show abstract

“…Raloxifene was well tolerated and offers potential for its use in this difficult to treat patient cohort and follows on previous trials from the same centre showing an effect of adjunctive oestradiol 200mcg in symptom improvement, particularly positive symptoms (Kulkarni et al, 2015). However, other studies have failed to find a benefit for adjunctive raloxifene in improving cognitive symptoms in non-TR schizophrenia (Kulkarni et al, 2016, Weiser et al, 2017, or in improving symptom severity (Weiser et al, 2017).…”

Section: Alternatives To Clozapine In Trsmentioning

confidence: 59%

Treatment resistant schizophrenia – review and a call to action

Lally

Gaughran

2018

Ir. j. psychol. Med.

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Recovery rates in schizophrenia remain suboptimal with up to one-third resistant to standard treatments, a population prevalence of 0.2%. Clozapine is the only evidenced-based treatment for treatment resistant schizophrenia (TRS), yet there are significant delays in its use or it may not be trialled, potentially impacting the chance of recovery. Better outcomes with earlier use of clozapine may be possible. There is emerging evidence that early treatment resistance is not uncommon from the earliest stages of psychosis. In this review, we provide an update on TRS, its epidemiology and its management, with a specific focus on the optimal use and timing of clozapine and augmentation strategies for the one-third of patients who do not respond to clozapine.

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“…In perimenopausal and postmenopausal women (aged 40–70 years) with treatment‐resistant schizophrenia, raloxifene reduced symptom severity and improved likelihood of clinical response (Kulkarni et al, ). By contrast, another study found that severely ill, postmenopausal women with schizophrenia receiving adjunct raloxifene did not show symptom improvement and in fact experienced worsened positive and negative symptoms (Weiser et al, ). The authors concluded that while raloxifene may be beneficial for some patients, further research is needed to identify suitable subgroups for safe administration.…”

Section: Are Gonadal Steroid Hormones the Mediating Factor?mentioning

confidence: 96%

Sex differences in schizophrenia, bipolar disorder, and post‐traumatic stress disorder: Are gonadal hormones the link?

Gogos

Ney

Seymour

et al. 2019

British J Pharmacology

142

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In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident in schizophrenia, bipolar disorder, and posttraumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men. By contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that oestradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on oestradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders.

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Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder

Abstract: ClinicalTrials.gov identifier: NCT01280305.

Cited by 44 publications

References 2 publications

Considering the role of adolescent sex steroids in schizophrenia

Considering the role of adolescent sex steroids in schizophrenia

Treatment resistant schizophrenia – review and a call to action

Sex differences in schizophrenia, bipolar disorder, and post‐traumatic stress disorder: Are gonadal hormones the link?

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