Acetaminophen as Adjuvant to Risperidone in Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
-
Somaye Arabzadeh
,
Atefeh Zeinoddini
,
Seyed-Ali Mostafavi
,
Mehdi Hamedi
,
Abolfazl Ehyaii
,
Ali Ghaleiha
,
Arefeh Zeinoddini
,
Shahin Akhondzadeh
Abstract
Objective: Although the pathogenesis of schizophrenia is still uncertain, a variety of predisposing mechanisms have been implicated including inflammatory cascades. The present study was conducted to investigate the effectiveness of acetaminophen as a cyclooxygenase inhibitor in treating patients with schizophrenia.
Method: A double-blind clinical trial was performed on 52 patients with chronic schizophrenia. Patients received risperidone (up to 6 mg/day) plus either acetaminophen (975mg/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 post therapy.
Results: Compared to the placebo group, the acetaminophen group showed no significant difference in any subtypes of PANSS. Moreover, the side effect profiles of the 2treatment regimens were not significantly different.
Conclusion: Acetaminophen adjuvant to risperidone showed no significant effect in ameliorating symptoms of schizophrenia.
Fillman SG, Cloonan N, Catts VS, Miller LC, Wong J, Mccrossin T, et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 2013; 18: 206-214.
Kirkpatrick B, Miller BJ. Inflammation and schizophrenia. Schizophr Bull 2013; 39: 1174-1179.
Akhondzadeh S. The 5-ht hypothesis of schizophrenia. IDrugs 2001; 4: 295-300.
Korschenhausen DA, Hampel HJ, Ackenheil M, Penning R, Muller N. Fibrin degradation products in post mortem brain tissue of schizophrenics: A possible marker for underlying inflammatory processes. Schizophr Res 1996; 19: 103-109.
Muller N, Schwarz M. Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotox Res 2006; 10: 131-148.
Muller N, Schwarz MJ. Cox-2 inhibition in schizophrenia and major depression. Curr Pharm Des 2008; 14: 1452-1465.
Muller N, Riedel M, Scheppach C, Brandstatter B, Sokullu S, Krampe K, et al. Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry 2002; 159: 1029-1034.
Akhondzadeh S, Tabatabaee M, Amini H, Ahmadi Abhari SA, Abbasi SH, Behnam B. Celecoxib as adjunctive therapy in schizophrenia: A double-blind, randomized and placebo-controlled trial. Schizophr Res 2007; 90: 179-185.
Muller N, Krause D, Dehning S, Musil R, Schennach-Wolff R, Obermeier M, et al. Celecoxib treatment in an early stage of schizophrenia: Results of a randomized, double-blind, placebo-controlled trial of celecoxib augmentation of amisulpride treatment. Schizophr Res 2010; 121: 118-124.
Baheti T, Nischal A, Nischal A, Khattri S, Arya A, Tripathi A, et al. A study to evaluate the effect of celecoxib as add-on to olanzapine therapy in schizophrenia. Schizophr Res 2013; 147: 201-202.
Rapaport MH, Delrahim KK, Bresee CJ, Maddux RE, Ahmadpour O, Dolnak D. Celecoxib augmentation of continuously ill patients with schizophrenia. Biol Psychiatry 2005; 57: 1594-1596.
Laan W, Grobbee DE, Selten JP, Heijnen CJ, Kahn RS, Burger H. Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: Results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2010; 71: 520-527.
Lai AY, Todd KG. Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines. Glia 2006; 53: 809-816.
Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci U S A 1998; 95: 15769-15774.
Levkovitz Y, Mendlovich S, Riwkes S, Braw Y, Levkovitch-Verbin H, Gal G, et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 2010; 71: 138-149.
Khodaie-Ardakani MR, Mirshafiee O, Farokhnia M, Tajdini M, Hosseini SM, Modabbernia A, et al. Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study. Psychiatry Res 2014; 215: 540-546.
Schnitzer TJ. Update of acr guidelines for osteoarthritis: Role of the coxibs. J Pain Symptom Manage 2002; 23: S24-30; discussion S31-24.
Prescott LF. Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 1980; 10 Suppl 2: 291s-298s.
Botting RM. Mechanism of action of acetaminophen: Is there a cyclooxygenase 3? Clin Infect Dis 2000; 31 Suppl 5: S202-210.
Ghanem CI, Perez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. Pharmacol Res 2016; 109: 119-131.
Falloon I, Watt DC, Lubbe K, Macdonald A, Shepherd M. N-acetyl-p-amino-phenol (paracetamol, acetaminophen) in the treatment of acute schizophrenia. Psychol Med 1978; 8: 495-499.
Sharifi V, Asadi SM, Mohammadi MR, Amini H, Kaviani H, Semnani Y, et al. Reliability and validity of persian version of Structured Clinical Interview for Axis I DSM-IV Disorders (SCID). advances in Cognitive Science. 2004; 6: 10-22.
Arabzadeh S, Amini H, Tehrani-Doost M, Sharifi V, Noroozian M, Rahiminejad F. Correlation of neurological soft signs and neurocognitive performance in first episode psychosis. Psychiatry Res 2014; 220: 81-88.
Kay SR, Fiszbein A, Opfer LA. The positive and negative syndrome scale (panss) for schizophrenia. Schizophr Bull 1987; 13: 261-276.
Bordbar F, Reza M, Abdollahian E, Hojjat K, Samaric AA. Effects of selegiline on negative symptoms in schizophrenia: A double-blind clinical trial. Iranian Journal of Psychiatry and Clinical Psychology 2008; 14: 131-139.
Chouinard G, Margolese HC. Manual for the extrapyramidal symptom rating scale (esrs). Schizophr Res 2005; 76: 247-265.
Zeinoddini A, Ahadi M, Farokhnia M, Rezaei F, Tabrizi M, Akhondzadeh S. 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.
Amrollahi Z, Rezaei F, Salehi B, Modabbernia AH, Maroufi A, Esfandiari GR, et al. Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania. J Affect Disord 2011; 129: 327-331.
Akhondzadeh S, Ahmadi-Abhari SA, Assadi SM, Shabestari OL, Kashani AR, Farzanehgan ZM. Double-blind randomized controlled trial of baclofen vs. Clonidine in the treatment of opiates withdrawal. J Clin Pharm Ther 2000; 25: 347-353.
Hamilton M. A rating scale for depression. Journal of neurology, neurosurgery, and psychiatry 1960; 23: 56.
Arabzadeh S, Ameli N, Zeinoddini A, Rezaei F, Farokhnia M, Mohammadinejad P, et al. Celecoxib adjunctive therapy for acute bipolar mania: A randomized, double-blind, placebo-controlled trial. Bipolar Disord 2015; 17: 606-614.
Abbasi SH, Mohammadinejad P, Shahmansouri N, Salehiomran A, Beglar AA, Zeinoddini A, 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.
Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. Faseb j 2008; 22: 383-390.
Feldberg W. Possible association of schizophrenia with a disturbance in prostaglandin metabolism: A physiological hypothesis. Psychol Med 1976; 6: 359-369.
Sommer IE, Van Westrhenen R, Begemann MJ, De Witte LD, Leucht S, Kahn RS. Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: An update. Schizophr Bull 2014; 40: 181-191.
Yokota O, Terada S, Ishihara T, Nakashima H, Kugo A, Ujike H, et al. Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 715-721.
| Files | ||
| Issue | Vol 13 No 1 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Acetaminophen Cyclooxygenase Inflammation PANSS Schizophrenia | ||
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