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The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial.
J Clin Psychiatry. 2013 Dec; 74(12):1224-32.JC

Abstract

OBJECTIVE

The limitations of antipsychotic therapy in schizophrenia and schizoaffective disorder led to the investigation of the putative utility of pharmacologic augmentation strategies. The antitumor agent bexarotene via nuclear retinoid X receptor (RXR) activation might modulate numerous metabolic pathways involved in the pathogenesis of schizophrenia and schizoaffective disorder. This trial aimed to investigate efficacy and safety of add-on bexarotene to ongoing antipsychotic treatment of patients with schizophrenia or schizoaffective disorder.

METHOD

Ninety inpatients and outpatients that met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder participated in a 6-week, double-blind, randomized, placebo-controlled multicenter study. Bexarotene (75 mg/d) was added to ongoing antipsychotic treatment from October 2008 to December 2010. The reduction in the severity of symptoms on the Positive and Negative Syndrome Scale (PANSS) was a primary outcome. Secondary outcomes included general functioning, quality of life, and side effect scales.

RESULTS

Seventy-nine participants (88%) completed the protocol. Controlling for antipsychotic agents, a mixed model showed that patients who received adjunctive bexarotene had significantly lower PANSS positive scale scores compared to patients who received placebo (F = 8.6, P = .003; treatment arms × time, F = 2.7, P = .049), with moderate effect size (d = 0.48; 95% CI,0.04-0.93). Patients with mean or higher baseline PANSS positive scale scores and patients who did not take lipid-reducing agents revealed greater amelioration of positive symptoms (F = 7.4, P = .008). Other symptoms and secondary outcome measures were not affected by adjunctive bexarotene. Bexarotene was well tolerated, though 2 reversible side effects were reported: a significant increase in total cholesterol levels (P < .001) and a decrease in total thyroxine levels (P < .001).

CONCLUSIONS

Bexarotene might potentially be a novel adjuvant therapeutic strategy for schizophrenia, particularly for the reduction of positive symptoms. The potential benefits and risks of ongoing administration of bexarotene warrant further evaluation.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT00535574.

Authors+Show Affiliations

Division of Psychiatry, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24434091

Citation

Lerner, Vladimir, et al. "The Retinoid X Receptor Agonist Bexarotene Relieves Positive Symptoms of Schizophrenia: a 6-week, Randomized, Double-blind, Placebo-controlled Multicenter Trial." The Journal of Clinical Psychiatry, vol. 74, no. 12, 2013, pp. 1224-32.
Lerner V, Miodownik C, Gibel A, et al. The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial. J Clin Psychiatry. 2013;74(12):1224-32.
Lerner, V., Miodownik, C., Gibel, A., Sirota, P., Bush, I., Elliot, H., Benatov, R., & Ritsner, M. S. (2013). The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial. The Journal of Clinical Psychiatry, 74(12), 1224-32. https://doi.org/10.4088/JCP.12m08160
Lerner V, et al. The Retinoid X Receptor Agonist Bexarotene Relieves Positive Symptoms of Schizophrenia: a 6-week, Randomized, Double-blind, Placebo-controlled Multicenter Trial. J Clin Psychiatry. 2013;74(12):1224-32. PubMed PMID: 24434091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial. AU - Lerner,Vladimir, AU - Miodownik,Chanoch, AU - Gibel,Anatoly, AU - Sirota,Pinchas, AU - Bush,Ilan, AU - Elliot,Hadi, AU - Benatov,Ruben, AU - Ritsner,Michael S, PY - 2012/09/12/received PY - 2013/02/27/accepted PY - 2014/1/18/entrez PY - 2014/1/18/pubmed PY - 2014/4/9/medline SP - 1224 EP - 32 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 74 IS - 12 N2 - OBJECTIVE: The limitations of antipsychotic therapy in schizophrenia and schizoaffective disorder led to the investigation of the putative utility of pharmacologic augmentation strategies. The antitumor agent bexarotene via nuclear retinoid X receptor (RXR) activation might modulate numerous metabolic pathways involved in the pathogenesis of schizophrenia and schizoaffective disorder. This trial aimed to investigate efficacy and safety of add-on bexarotene to ongoing antipsychotic treatment of patients with schizophrenia or schizoaffective disorder. METHOD: Ninety inpatients and outpatients that met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder participated in a 6-week, double-blind, randomized, placebo-controlled multicenter study. Bexarotene (75 mg/d) was added to ongoing antipsychotic treatment from October 2008 to December 2010. The reduction in the severity of symptoms on the Positive and Negative Syndrome Scale (PANSS) was a primary outcome. Secondary outcomes included general functioning, quality of life, and side effect scales. RESULTS: Seventy-nine participants (88%) completed the protocol. Controlling for antipsychotic agents, a mixed model showed that patients who received adjunctive bexarotene had significantly lower PANSS positive scale scores compared to patients who received placebo (F = 8.6, P = .003; treatment arms × time, F = 2.7, P = .049), with moderate effect size (d = 0.48; 95% CI,0.04-0.93). Patients with mean or higher baseline PANSS positive scale scores and patients who did not take lipid-reducing agents revealed greater amelioration of positive symptoms (F = 7.4, P = .008). Other symptoms and secondary outcome measures were not affected by adjunctive bexarotene. Bexarotene was well tolerated, though 2 reversible side effects were reported: a significant increase in total cholesterol levels (P < .001) and a decrease in total thyroxine levels (P < .001). CONCLUSIONS: Bexarotene might potentially be a novel adjuvant therapeutic strategy for schizophrenia, particularly for the reduction of positive symptoms. The potential benefits and risks of ongoing administration of bexarotene warrant further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00535574. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/24434091/The_retinoid_X_receptor_agonist_bexarotene_relieves_positive_symptoms_of_schizophrenia:_a_6_week_randomized_double_blind_placebo_controlled_multicenter_trial_ L2 - http://www.psychiatrist.com/jcp/article/pages/2013/v74n12/v74n1212.aspx DB - PRIME DP - Unbound Medicine ER -