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Effect of adjunctive raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial

Kulkarni, Jayashri, Gavrilidis, Emorfia, Gwini, Stella M., Worsley, Roisin, Grigg, Jasmin, Warren, Annabelle, Gurvich, Caroline, Gilbert, Heather, Berk, Michael and Davis, Susan R. 2016, Effect of adjunctive raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial, JAMA psychiatry, vol. 73, no. 9, pp. 947-954, doi: 10.1001/jamapsychiatry.2016.1383.

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Title Effect of adjunctive raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial
Author(s) Kulkarni, Jayashri
Gavrilidis, Emorfia
Gwini, Stella M.
Worsley, Roisin
Grigg, Jasmin
Warren, Annabelle
Gurvich, Caroline
Gilbert, Heather
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Davis, Susan R.
Journal name JAMA psychiatry
Volume number 73
Issue number 9
Start page 947
End page 954
Total pages 8
Publisher American Medical Association
Place of publication Chicago, Ill.
Publication date 2016-09
ISSN 2168-622X
2168-6238
Summary IMPORTANCE: A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects. OBJECTIVE: To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis. INTERVENTIONS: Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed. RESULTS: Of the 56 participants (mean [SD] age, 53 [7.7] years; age range, 40-70 years; mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37; 95% CI, -11.64 to -1.10; P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79; 95% CI, 1.46 to 22.97; P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72; 95% CI, -6.83 to -0.61; P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92; 95% CI, -3.83 to 0.00; P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups. CONCLUSIONS AND RELEVANCE: Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00361543.
Language eng
DOI 10.1001/jamapsychiatry.2016.1383
Field of Research 110399 Clinical Sciences not elsewhere classified
Socio Economic Objective 920199 Clinical Health (Organs
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, American Medical Association
Persistent URL http://hdl.handle.net/10536/DRO/DU:30085590

Document type: Journal Article
Collection: School of Medicine
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