DOI: http://dx.doi.org/10.18203/2349-3933.ijam20201618

Clinical efficacy and safety of lurasidone in schizophrenia: 8 week randomized double blind active controlled trial

Unnati Saxena, Anuradha Nischal, Anil Nischal, Abbas Ali Mahdi, Manu Agarwal, Adarsh Tripathi

Abstract


Background: Schizophrenia comprises a group of disorders with heterogeneous etiologies, it includes patients whose clinical presentations, treatment response, and courses of illness vary. This study was carried to study the clinical efficacy and safety of Lurasidone versus Risperidone on psychopathology and cognition in patients with first episode of schizophrenia.

Methods: Patients diagnosed with first episode of schizophrenia were enrolled in the study. Patients were randomized to 80 mg/d (n = 27) of Lurasidone or 6mg/d (n = 27) of Risperidone. Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores, Schizophrenia cognition rating scale (SCoRS). IL-6 estimation was done and safety assessment was done using UKU side effect rating scale.

Results: During the eight weeks of study; significant improvement was observed in PANSS total and all its subscale scores with both Lurasidone and Risperidone. Mean change in PANSS scores were not significant between the groups (-32.93 vs -35.33 p>0.05). Mean change in SCoRS scores were significantly higher in Lurasidone group as compared to risperidone group (-8.43 vs -2.34, p<0.001). Significant reduction in the IL-6 levels with both the groups but mean change in IL-6 levels were not significant between the group (-10.47 vs -8.31, p>0.05). UKU side effect rating scores were significantly higher with Risperidone as compared to Lurasidone (p<0.001).

Conclusions: Lurasidone is as effective as Risperidone in improving psychopathology in patient of schizophrenia. Lurasidone proved more efficacious in improving cognition as compared to Risperidone. Both the treatment modalities are efficacious in lowering IL-6 levels. Lurasidone causes less adverse effects as compared to Risperidone.


Keywords


IL-6, Lurasidone, Positive and negative syndrome scale, Risperidone, Schizophrenia, SCoRS

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References


Rasgon LN, Hendrick VC, Sadock BS. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry, 7th ed. Am J Psychiatry. 2002;159(2):327.

Kaplan HI, Sadock BJ. Synopsis of psychiatry: Behavioral sciences clinical psychiatry. Williams & Wilkins Co; 2015:294-295.

Rang H, Dale M, Ritter M, Flower R, Henderson G. Hyde, M. Rang and Dale’s Pharmacology. 2012:237-45.

Muller N, Riedel M, Ackenheil M, Schwarz MJ. The role of immune function in schizophrenia: An overview. Eur Arch Psychiatry Clin Neurosci. 1999.

Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E. Inflammatory Cytokine Alterations in Schizophrenia: A Systematic Quantitative Review. Biol Psychiatry. 2008;63(8):801-8.

Brunton L, Chabner B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Twelfth Ed. McGraw Hill Professional; 2010.

Ishibashi T, Horisawa T, Tokuda K, Ishiyama T, Ogasa M, Tagashira R, et al. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Experimental Therapeutics. 2010 Jul 1;334(1):171-81.

Loebel A, Cucchiaro J, Sarma K, Xu L, Hsu C, Kalali AH, et al. Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia: a randomized, double-blind, placebo- and active-controlled trial. Schizophr Res. 2013;145(1-3):101-9.

Citrome L. Lurasidone for schizophrenia : a review of the efficacy and safety profile for this newly approved second-generation antipsychotic . Int J Clin Pr. 2011;65(2):189-210.

Cruz MP. Lurasidone HCl (Latuda), an oral, once-daily atypical antipsychotic agent for the treatment of patients with schizophrenia. Pharmacy Therapeutics. 2011 Aug;36(8):489-92.

Ishiyama T, Tokuda K, Ishibashi T, Ito A, Toma S, Ohno Y. Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. European J Pharmacol. 2007 Oct 31;572(2-3):160-70.

Enomoto T, Ishibashi T, Tokuda K, Ishiyama T, Toma S, Ito A. Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. Behav Brain Res. 2008;186(2):197-207.

Harvey PD, Siu CO, Hsu J, Cucchiaro J, Maruff P, Loebel A. Effect of lurasidone on neurocognitive performance in patients with schizophrenia. Eur Neuropsychopharmacol. 2013;23(11):1373-82.

Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin. 1987 Jan 1;13(2):261-76.

Keefe RSE, Poe M, Walker TM, Kang JW, Harvey PD. The schizophrenia cognition rating scale: An interview-based assessment and its relationship to cognition, real-world functioning, and functional capacity. Am J Psychiatry. 2006;163(3):426-32.

Efird J. Blocked Randomization with Randomly Selected Block Sizes. Int J Env Res Public Heal. 2011;8(1):15-20.

Loebel A, Cucchiaro J, Silva R, Mao Y, Xu J, Pikalov A, et al. Efficacy of lurasidone across five symptom dimensions of schizophrenia: Pooled analysis of short-term, placebo-controlled studies. Eur Psychiatry. 2015;30(1):26-31.

Citrome L, Cucchiaro J, Sarma K, Phillips D, Silva R, Tsuchiya S, et al. Long-term safety and tolerability of lurasidone: a 12-month , double-blind in active-controlled study. Int Clin Psychopharmacol. 2012;27:165–76.

Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, et al. Comparative Ef fi cacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia : A Multiple-Treatments Meta-Analysis. Lancet. 2013;382(9896):940.

Green M, Kern R, Heaton R. Longitudinal studies of cognition and functional outcome in schizophrenia : implications for MATRICS. Schizophr Res. 2004;72(1):141-51.

Harvey PD, Ogasa M, Cucchiaro J, Loebel A, Keefe RSE. Performance and interview-based assessments of cognitive change in a randomized , double-blind comparison of lurasidone vs ziprasidone. Schizophr Res. 2011;127(1):188-94.

Keefe R, Atkins A, Davis V, Spagnola N, Hilt D, Dgetluck N, et al. The schizophrenia cognition rating scale: Reliability, validity and sensitivity. Schizophr Bull. 2015;41:S51-2.

Harvey PD, Siu CO, Ogasa M, Loebel A. Effect of lurasidone dose on cognition in patients with schizophrenia : Post-hoc analysis of a long-term, double- blind continuation study. Schizophr Bull. 2015;166(1):334-8.

Schmitt A, Bertsch T, Tost H, Bergmann A, Henning U, Klimke A, et al. Increased serum interleukin-1beta and interleukin-6 in elderly, chronic schizophrenic patients on stable antipsychotic medication. Neuropsychiatr Dis Treat. 2005;1(2):171-7.

Naudin J, Mège JL, Azorin JM, Dassa D. Elevated circulating levels of IL-6 in schizophrenia. Schizophr Res. 1996;20(3):269-73.

Frommberger UH, Bauer J, Haselbauer P, Fräulin A, Riemann D, Berger M. Interleukin ­ 6 ­ ( IL ­ 6 ) plasma levels in depression and schizophrenia : comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci. 1997;247(4):228-33.

Kubistova A, Horacek J, Novak T. Increased interleukin-6 and tumor necrosis factor alpha in first episode schizophrenia patients versus healthy controls. Psychiatr Danub. 2012;24(SUPPL. 1):153-6.

Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC. Changes in serum interleukin-2,-6, and-8 levels before and during treatment with risperidone and haloperidol: Relationship to outcome in schizophrenia. J Clin Psychiatry. 2004;65(7):940-7.