Comparison of Efficacy and Safety Between Low-Dose Ziprasidone in Combination With Sertraline and Ziprasidone Monotherapy for Treatment-Resistant Patients With Acute Exacerbation Schizophrenia: A Randomized Controlled Trial

Hui Shi, Jing Xu, Xiaoe Lang, Hanjing Emily Wu, Mei Hong Xiu, Xiang Yang Zhang, Hui Shi, Jing Xu, Xiaoe Lang, Hanjing Emily Wu, Mei Hong Xiu, Xiang Yang Zhang

Abstract

Treatment-resistant schizophrenia (TRS) is a prevalent clinical problem with heterogeneous presentations. However, the clinical trial designs for new treatments are still lacking. This study aimed to assess the efficacy of ziprasidone plus sertraline in TRS patients as compared to ziprasidone monotherapy. We conducted a 24 weeks, randomized, controlled, double-blinded clinical research trial. 62 treatment-resistant patients with acute exacerbation SZ were randomly allocated to receive a usual dose of ziprasidone (120-160 mg/d) monotherapy (Control group) and 53 TRS inpatients were to receive a low dose of ziprasidone (60-80 mg/d) in combination with sertraline (ZS group). Treatment outcomes were measured by the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and Personal and Social Performance Scale (PSP) at baseline, week 4, 8, 12, and 24. Relative to control group, the patients in ZS group showed greater reductions in the following: PANSS positive symptom, negative symptom, total score, and HAMD total score. Additionally, the patients in ZS group had a greater increase in PSP total score. Notably, the reduction in HAMD was positively correlated with the reduction in PANSS total score. The reduction in CGI-S was a predictor for the improvement of psychosocial functioning in patients. Furthermore, the ZS group had a lower rate of side effects compared to the control group. Our findings suggest that a low dose of ziprasidone in combination with sertraline is an effective therapy for the clinical symptoms as compared to a usual dose of ziprasidone in the treatment-resistant patients with acute exacerbation SZ. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04076371.

Keywords: acute exacerbation; efficacy; schizophrenia; sertraline; treatment-resistant; ziprasidone.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Shi, Xu, Lang, Wu, Xiu and Zhang.

Figures

FIGURE 1
FIGURE 1
Flow diagram of included studies.
FIGURE 2
FIGURE 2
The trajectory of the PANSS total scores in each treatment group.

References

    1. Albayrak Y., Hashimoto K. (2017). Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders. Adv. Exp. Med. Biol. 964, 153–161. 10.1007/978-3-319-50174-1_11
    1. Ashby C. R., Jr., Edwards E., Harkins K. L., Wang R. Y. (1989). Differential Effect of Typical and Atypical Antipsychotic Drugs on the Suppressant Action of 2-methylserotonin on Medical Prefrontal Cortical Cells: A Microiontophoretic Study. Eur. J. Pharmacol. 166 (3), 583–584. 10.1016/0014-2999(89)90382-8
    1. Best M. W., Law H., Pyle M., Morrison A. P. (2020). Relationships Between Psychiatric Symptoms, Functioning and Personal Recovery in Psychosis. Schizophr Res. 223, 112–118. 10.1016/j.schres.2020.06.026
    1. Bouchette D., Fariba K., Marwaha R. (2021). Ziprasidone.
    1. Cheng Z., Yuan Y., Han X., Yang L., Cai S., Yang F., et al. (2019). An Open-Label Randomised Comparison of Aripiprazole, Olanzapine and Risperidone for the Acute Treatment of First-Episode Schizophrenia: Eight-Week Outcomes. J. Psychopharmacol. 33 (10), 1227–1236. 10.1177/0269881119872193
    1. Conley R. R., Tamminga C. A., Bartko J. J., Richardson C., Peszke M., Lingle J., et al. (1998). Olanzapine Compared with Chlorpromazine in Treatment-Resistant Schizophrenia. Am. J. Psychiatry 155 (7), 914–920. 10.1176/ajp.155.7.914
    1. Correll C. U., Rubio J. M., Inczedy-Farkas G., Birnbaum M. L., Kane J. M., Leucht S. (2017). Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic Monotherapy in Schizophrenia: Systematic Overview and Quality Appraisal of the Meta-Analytic Evidence. JAMA Psychiatry 74 (7), 675–684. 10.1001/jamapsychiatry.2017.0624
    1. Daniel D. G., Zimbroff D. L., Potkin S. G., Reeves K. R., Harrigan E. P., Lakshminarayanan M. (1999). Ziprasidone 80 Mg/day and 160 Mg/day in the Acute Exacerbation of Schizophrenia and Schizoaffective Disorder: A 6-week Placebo-Controlled Trial. Ziprasidone Study Group. Neuropsychopharmacology 20 (5), 491–505. 10.1016/S0893-133X(98)00090-6
    1. Demjaha A., Egerton A., Murray R. M., Kapur S., Howes O. D., Stone J. M., et al. (2014). Antipsychotic Treatment Resistance in Schizophrenia Associated with Elevated Glutamate Levels but Normal Dopamine Function. Biol. Psychiatry 75 (5), e11–3. 10.1016/j.biopsych.2013.06.011
    1. Doogan D. P., Caillard V. (1988). Sertraline: A New Antidepressant. J. Clin. Psychiatry 49 (Suppl. l), 46–51.
    1. Flanagan R. J., Lally J., Gee S., Lyon R., Every-Palmer S. (2020). Clozapine in the Treatment of Refractory Schizophrenia: A Practical Guide for Healthcare Professionals. Br. Med. Bull. 135 (1), 73–89. 10.1093/bmb/ldaa024
    1. Galling B., Vernon J. A., Pagsberg A. K., Wadhwa A., Grudnikoff E., Seidman A. J., et al. (2018). Efficacy and Safety of Antidepressant Augmentation of Continued Antipsychotic Treatment in Patients with Schizophrenia. Acta Psychiatr. Scand. 137 (3), 187–205. 10.1111/acps.12854
    1. Gillespie A. L., Samanaite R., Mill J., Egerton A., MacCabe J. H. (2017). Is Treatment-Resistant Schizophrenia Categorically Distinct from Treatment-Responsive Schizophrenia? A Systematic Review. BMC Psychiatry 17 (1), 12. 10.1186/s12888-016-1177-y
    1. Gregory A., Mallikarjun P., Upthegrove R. (2017). Treatment of Depression in Schizophrenia: Systematic Review and Meta-Analysis. Br. J. Psychiatry 211 (4), 198–204. 10.1192/bjp.bp.116.190520
    1. Guy W. (1976). “Clinical Global Impression,” in ECDEU Assessment Manual for Psychopharmacology (Rockville: US Department of Health, Education, and Welfare; ), 217–222.
    1. Hamilton M. (1960). A Rating Scale for Depression. J. Neurol. Neurosurg. Psychiatry 23 (1), 56–62. 10.1136/jnnp.23.1.56
    1. Helfer B., Samara M. T., Huhn M., Klupp E., Leucht C., Zhu Y., et al. (2016). Efficacy and Safety of Antidepressants Added to Antipsychotics for Schizophrenia: A Systematic Review and Meta-Analysis. Am. J. Psychiatry 173 (9), 876–886. 10.1176/appi.ajp.2016.15081035
    1. Howes O. D., McCutcheon R., Agid O., de Bartolomeis A., van Beveren N. J., Birnbaum M. L., et al. (2017). Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am. J. Psychiatry 174 (3), 216–229. 10.1176/appi.ajp.2016.16050503
    1. Huhn M., Nikolakopoulou A., Schneider-Thoma J., Krause M., Samara M., Peter N., et al. (2019). Comparative Efficacy and Tolerability of 32 Oral Antipsychotics for the Acute Treatment of Adults with Multi-Episode Schizophrenia: A Systematic Review and Network Meta-Analysis. Lancet 394 (10202), 939–951. 10.1016/S0140-6736(19)31135-3
    1. Kane J., Honigfeld G., Singer J., Meltzer H. (1988). Clozapine for the Treatment-Resistant Schizophrenic. A Double-Blind Comparison with Chlorpromazine. Arch. Gen. Psychiatry 45 (9), 789–796. 10.1001/archpsyc.1988.01800330013001
    1. Kane J. M., Khanna S., Rajadhyaksha S., Giller E. (2006). Efficacy and Tolerability of Ziprasidone in Patients with Treatment-Resistant Schizophrenia. Int. Clin. Psychopharmacol. 21 (1), 21–28. 10.1097/01.yic.0000182114.65134.81
    1. Kay S. R., Fiszbein A., Opler L. A. (1987). The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia. Schizophr Bull. 13 (2), 261–276. 10.1093/schbul/13.2.261
    1. Lehman A. F., Lieberman J. A., Dixon L. B., McGlashan T. H., Miller A. L., Perkins D. O., et al. (2004). Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition. Am. J. Psychiatry 161 (2 Suppl. l), 1–56.
    1. Leucht S., Cipriani A., Spineli L., Mavridis D., Orey D., Richter F., et al. (2013). Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis. Lancet 382 (9896), 951–962. 10.1016/S0140-6736(13)60733-3
    1. Lewis S. W., Barnes T. R., Davies L., Murray R. M., Dunn G., Hayhurst K. P., et al. (2006). Randomized Controlled Trial of Effect of Prescription of Clozapine versus Other Second-Generation Antipsychotic Drugs in Resistant Schizophrenia. Schizophr Bull. 32 (4), 715–723. 10.1093/schbul/sbj067
    1. Loebel A. D., Khanna S., Rajadhyaksha S., Siu C. O., Giller E., Potkin S. G. (2007). Ziprasidone in Treatment-Resistant Schizophrenia: A 52-week, Open-Label Continuation Study. J. Clin. Psychiatry 68 (9), 1333–1338. 10.4088/jcp.v68n0902
    1. McEvoy J. P., Lieberman J. A., Stroup T. S., Davis S. M., Meltzer H. Y., Rosenheck R. A., et al. (2006). Effectiveness of Clozapine versus Olanzapine, Quetiapine, and Risperidone in Patients with Chronic Schizophrenia Who Did Not Respond to Prior Atypical Antipsychotic Treatment. Am. J. Psychiatry 163 (4), 600–610. 10.1176/appi.ajp.163.4.600
    1. Mizuno Y., McCutcheon R. A., Brugger S. P., Howes O. D. (2020). Heterogeneity and Efficacy of Antipsychotic Treatment for Schizophrenia with or without Treatment Resistance: A Meta-Analysis. Neuropsychopharmacology 45 (4), 622–631. 10.1038/s41386-019-0577-3
    1. Morosini P. L., Magliano L., Brambilla L., Ugolini S., Pioli R. (2000). Development, Reliability and Acceptability of a New Version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to Assess Routine Social Functioning. Acta Psychiatr. Scand. 101 (4), 323–329. 10.1111/j.1600-0447.2000.tb10933.x
    1. Mulholland C., Lynch G., King D. J., Cooper S. J. (2003). A Double-Blind, Placebo-Controlled Trial of Sertraline for Depressive Symptoms in Patients with Stable, Chronic Schizophrenia. J. Psychopharmacol. 17 (1), 107–112. 10.1177/0269881103017001713
    1. Park S., Yi K. K., Kim M. S., Hong J. P. (2013). Effects of Ziprasidone and Olanzapine on Body Composition and Metabolic Parameters: An Open-Label Comparative Pilot Study. Behav. Brain Funct. 9, 27. 10.1186/1744-9081-9-27
    1. Popli A. P., Fuller M. A., Jaskiw G. E. (1997). Sertraline and Psychotic Symptoms: A Case Series. Ann. Clin. Psychiatry 9 (1), 15–17. 10.1023/a:1026274123689
    1. Potkin S. G., Kane J. M., Correll C. U., Lindenmayer J. P., Agid O., Marder S. R., et al. (2020). The Neurobiology of Treatment-Resistant Schizophrenia: Paths to Antipsychotic Resistance and a Roadmap for Future Research. NPJ Schizophr. 6 (1), 1. 10.1038/s41537-019-0090-z
    1. Rammes G., Eisensamer B., Ferrari U., Shapa M., Gimpl G., Gilling K., et al. (2004). Antipsychotic Drugs Antagonize Human Serotonin Type 3 Receptor Currents in a Noncompetitive Manner. Mol. Psychiatry 9 (9), 846818–818. 10.1038/sj.mp.4001490
    1. Richelson E. (1994). Pharmacology of Antidepressants-Characteristics of the Ideal Drug. Mayo Clin. Proc. 69 (11), 1069–1081. 10.1016/s0025-6196(12)61375-5
    1. Samara M. T., Dold M., Gianatsi M., Nikolakopoulou A., Helfer B., Salanti G., et al. (2016). Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-Analysis. JAMA Psychiatry 73 (3), 199–210. 10.1001/jamapsychiatry.2015.2955
    1. Seeger T. F., Seymour P. A., Schmidt A. W., Zorn S. H., Schulz D. W., Lebel L. A., et al. (1995). Ziprasidone (CP-88,059): A New Antipsychotic with Combined Dopamine and Serotonin Receptor Antagonist Activity. J. Pharmacol. Exp. Ther. 275 (1), 101–113.
    1. Vauth R., Carpiniello B., Turczyński J., Ivanov M., Cherubin P., Lahaye M., et al. (2020). Relationship Between Clinical Outcomes Measures and Personal and Social Performance Functioning in a Prospective, Interventional Study in Schizophrenia. Int. J. Methods Psychiatr. Res., e1855. 10.1002/mpr.1855
    1. Velthorst E., Fett A. J., Reichenberg A., Perlman G., van Os J., Bromet E. J., et al. (2017). The 20-Year Longitudinal Trajectories of Social Functioning in Individuals with Psychotic Disorders. Am. J. Psychiatry 174 (11), 1075–1085. 10.1176/appi.ajp.2016.15111419
    1. Viskin S. (1999). Long QT Syndromes and Torsade de Pointes. Lancet 354 (9190), 1625–1633. 10.1016/S0140-6736(99)02107-8
    1. Vita A., Barlati S. (2018). Recovery from Schizophrenia: Is it Possible? Curr. Opin. Psychiatry 31 (3), 246–255. 10.1097/YCO.0000000000000407
    1. Volavka J., Czobor P., Sheitman B., Lindenmayer J. P., Citrome L., McEvoy J. P., et al. (2002). Clozapine, Olanzapine, Risperidone, and Haloperidol in the Treatment of Patients with Chronic Schizophrenia and Schizoaffective Disorder. Am. J. Psychiatry 159 (2), 255–262. 10.1176/appi.ajp.159.2.255
    1. Wallwork R. S., Fortgang R., Hashimoto R., Weinberger D. R., Dickinson D. (2012). Searching for a Consensus Five-Factor Model of the Positive and Negative Syndrome Scale for Schizophrenia. Schizophr. Res. 137 (1-3), 246–250. 10.1016/j.schres.2012.01.031
    1. Zhang M. Y. (1984). Treatment Emergent Symptom Scale (TESS). Shanghai Arch. Psychiatry 2, 24.

Source: PubMed

3
Iratkozz fel