Duloxetine Add-On to Risperidone for Treatment of Negative Symptoms in Patients with Stable Schizophrenia: Randomized Double-Blind Placebo-Controlled Study

M.-R. Nikbakhat; S. Arabzadeh; A. Zeinoddini; Z. Khalili; F. Rezaei; P. Mohammadinejad; A. Ghaleiha; S. Akhondzadeh

doi:10.1055/s-0042-101557

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2016; 49(04): 162-169
DOI: 10.1055/s-0042-101557

Original Paper

Duloxetine Add-On to Risperidone for Treatment of Negative Symptoms in Patients with Stable Schizophrenia: Randomized Double-Blind Placebo-Controlled Study

Authors

M.-R. Nikbakhat^*

¹Department of Pharmacology, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
S. Arabzadeh^*

²Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
A. Zeinoddini^*

²Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
Z. Khalili

²Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
F. Rezaei

³Qods Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran
P. Mohammadinejad

²Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
A. Ghaleiha

⁴Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran
S. Akhondzadeh

²Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Introduction: Although the pathogenesis of symptoms of schizophrenia is largely unknown, a variety of neurotransmitters are implicated, including serotonin and norepinephrine. Here we investigate the effectiveness of duloxetine as a serotonin-norepinephrine inhibitor in the treatment of negative symptoms.

Methods: We performed a double-blind clinical trial on 64 patients with stable schizophrenia and no prominent symptoms of depression. Patients received risperidone (up to 6 mg/day) plus either duloxetine (60 mg/day) or placebo. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) at the onset of the trial, and at 2, 4, 6 and 8 weeks of therapy.

Results: Compared to the placebo group, the duloxetine group showed significantly higher improvement in negative symptoms (p<0.001), PANSS total (p<0.001), and the general psychopathology subscale scores (p=0.001), but no significant difference in positive symptoms (p=0.13). The side effect profiles of the 2 treatment regimens were not significantly different.

Discussion: Duloxetine adjuvant to risperidone seems to be a tolerable and efficacious treatment for primary negative symptoms of schizophrenia.

Key words

duloxetine - SNRI - schizophrenia - clinical trial

Full Text

References

References
1 Ananth J, Djenderdjian A, Shamasunder P et al. Negative symptoms: psychopathological models. J Psychiatry Neurosci 1991; 16: 12-18
2 Fenton WS, McGlashan TH. Natural history of schizophrenia subtypes. II. Positive and negative symptoms and long-term course. Arch Gen Psychiatry 1991; 48: 978-986
3 Orsel S, Akdemir A, Dag I. The sensitivity of quality-of-life scale WHOQOL-100 to psychopathological measures in schizophrenia. Compr Psychiatry 2004; 45: 57-61
4 Norman RM, Malla AK, McLean T et al. The relationship of symptoms and level of functioning in schizophrenia to general wellbeing and the Quality of Life Scale. Acta Psychiatr Scand 2000; 102: 303-309
5 Kirkpatrick B, Fenton WS, Carpenter Jr WT et al. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull 2006; 32: 214-219
6 Terevnikov V, Joffe G, Stenberg JH. Randomized controlled trials of add-on antidepressants in schizophrenia. Int J Neuropsychopharmacol 2015; 18
7 Galderisi S, Merlotti E, Mucci A. Neurobiological background of negative symptoms. Eur Arch Psychiatry Clin Neurosci. 2015
8 Abbasi SH, Behpournia H, Ghoreshi A et al. The effect of mirtazapine add on therapy to risperidone in the treatment of schizophrenia: a double-blind randomized placebo-controlled trial. Schizophr Res 2010; 116: 101-106
9 Murphy BP, Chung YC, Park TW et al. Pharmacological treatment of primary negative symptoms in schizophrenia: a systematic review. Schizophr Res 2006; 88: 5-25
10 Akhondzadeh S, Gerami M, Noroozian M et al. A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 1810-1815
11 Akhondzadeh S, Ghayyoumi R, Rezaei F et al. Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial. Psychopharmacology (Berl) 2011; 213: 809-815
12 Amiri A, Noorbala AA, Nejatisafa AA et al. Efficacy of selegiline add on therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Hum Psychopharmacol 2008; 23: 79-86
13 Ghaleiha A, Noorbala AA, Farnaghi F et al. A double-blind, randomized, and placebo-controlled trial of buspirone added to risperidone in patients with chronic schizophrenia. J Clin Psychopharmacol 2010; 30: 678-682
14 Buchanan RW, Freedman R, Javitt DC et al. Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. Schizophr Bull 2007; 33: 1120-1130
15 Bennett AC, Vila TM. The role of ondansetron in the treatment of schizophrenia. Ann Pharmacother 2010; 44: 1301-1306
16 Akhondzadeh S. The 5-HT hypothesis of schizophrenia. IDrugs 2001; 4: 295-300
17 Yamamoto K, Hornykiewicz O. Proposal for a noradrenaline hypothesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 913-922
18 Stahl S. Stahl’s Essential Pharmacology. 4th ed. New York: Cambridge University Press; 2013: 305 308, 309
19 Mico U, Bruno A, Pandolfo G et al. Duloxetine as adjunctive treatment to clozapine in patients with schizophrenia: a randomized, placebo-controlled trial. Int Clin Psychopharmacol 2011; 26: 303-310
20 Englisch S, Knopf U, Scharnholz B et al. Duloxetine for major depressive episodes in the course of psychotic disorders: an observational clinical trial. J Psychopharmacol 2009; 23: 875-882
21 Schueler YB, Koesters M, Wieseler B et al. A systematic review of duloxetine and venlafaxine in major depression, including unpublished data. Acta Psychiatr Scand 2011; 123: 247-265
22 Cipriani A, Koesters M, Furukawa TA et al. Duloxetine versus other anti-depressive agents for depression. Cochrane Database Syst Rev 2012; 10: CD006533
23 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261-276
24 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56-62
25 Zeinoddini A, Ahadi M, Farokhnia M et al. L-lysine as an adjunct to risperidone in patients with chronic schizophrenia: a double-blind, placebo-controlled, randomized trial. J Psychiatr Res 2014; 59: 125-131
26 Jafari S, Ashrafizadeh SG, Zeinoddini A et al. Celecoxib for the treatment of mild-to-moderate depression due to acute brucellosis: a double-blind, placebo-controlled, randomized trial. J Clin Pharm Ther 2015;
27 Zeinoddini A, Sorayani M, Hassanzadeh E et al. Pioglitazone adjunctive therapy for depressive episode of bipolar disorder: a randomized, double-blind, placebo-controlled trial. Depress Anxiety 2015; 32: 167-173
28 Abbasi SH, Mohammadinejad P, Shahmansouri N et al. Simvastatin versus atorvastatin for improving mild to moderate depression in post-coronary artery bypass graft patients: A double-blind, placebo-controlled, randomized trial. J Affect Disord 2015; 183: 149-155
29 Arabzadeh S, Ameli N, Zeinoddini A et al. Celecoxib adjunctive therapy for acute bipolar mania: a randomized, double-blind, placebo-controlled trial. Bipolar Disord 2015; 17: 606-614
30 Emadi-Kouchak H, Mohammadinejad P, Asadollahi-Amin A et al. Therapeutic effects of minocycline on mild-to-moderate depression in HIV patients: a double-blind, placebo-controlled, randomized trial. Int Clin Psychopharmacol 2015; 31: 20-26
31 Mohammadinejad P, Arya P, Esfandbod M et al. Celecoxib versus diclofenac in mild to moderate depression management among breast cancer patients: a double-blind, placebo-controlled, randomized trial. Ann Pharmacother 2015; 49: 953-961
32 Chouinard G, Margolese HC. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophr Res 2005; 76: 247-265
33 Leon AC. Multiplicity-adjusted sample size requirements: a strategy to maintain statistical power with Bonferroni adjustments. J Clin Psychiatry 2004; 65: 1511-1514
34 Wernicke JF, Gahimer J, Yalcin I et al. Safety and adverse event profile of duloxetine. Expert Opin Drug Saf 2005; 4: 987-993
35 Mazeh D, Shahal B, Saraf R et al. Venlafaxine for the treatment of depressive episode during the course of schizophrenia. J Clin Psychopharmacol 2004; 24: 653-655
36 Thibaut F, Ribeyre JM, Dourmap N et al. Plasma 3-methoxy-4-hydroxyphenylglycol and homovanillic acid measurements in deficit and nondeficit forms of schizophrenia. Biol Psychiatry 1998; 43: 24-30
37 Nibuya M, Kanba S, Sekiya U et al. Schizophrenic patients with deficit syndrome have higher plasma homovanillic acid concentrations and ventricular enlargement. Biol Psychiatry 1995; 38: 50-56
38 Bodkin JA, Siris SG, Bermanzohn PC et al. placebo-controlled, multicenter trial of selegiline augmentation of antipsychotic medication to treat negative symptoms in outpatients with schizophrenia. Am J Psychiatry 2005; 162: 388-390
39 Carpenter Jr WT, Breier A, Buchanan RW et al. Mazindol treatment of negative symptoms. Neuropsychopharmacology 2000; 23: 365-374
40 Yasuno F, Suhara T, Ichimiya T et al. Decreased 5-HT1A receptor binding in amygdala of schizophrenia. Biol Psychiatry 2004; 55: 439-444
41 Akhondzadeh S, Malek-Hosseini M, Ghoreishi A et al. Effect of ritanserin, a 5HT2A/2C antagonist, on negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 1879-1883
42 Akhondzadeh S, Mohammadi N, Noroozian M et al. Added ondansetron for stable schizophrenia: a double blind, placebo controlled trial. Schizophr Res 2009; 107: 206-212
43 Khodaie-Ardakani MR, Seddighi S, Modabbernia A et al. Granisetron as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study. J Psychiatr Res 2013; 47: 472-478
44 Zhang ZJ, Kang WH, Li Q et al. Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled study. Schizophr Res 2006; 88: 102-110