An open study of risperidone liquid in the acute phase of schizophrenia

An open‐label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty‐eight patients (M/F: 50/38; age: 18–74 years;, mean±SD =32±16 years) meeting DSM‐IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC‐ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1±2.9 ng/ml) were higher than those in nonresponders (5.9±1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity. Copyright © 2005 John Wiley & Sons, Ltd.

[1]  O. Ohmori,et al.  Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6 , 2005, International clinical psychopharmacology.

[2]  R. Yoshimura,et al.  Clinical response to antidepressant treatment and 3-methoxy-4-hydroxyphenylglycol levels: mini review , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[3]  D. Naber,et al.  Risperidone in the Treatment of Acute Schizophrenia , 2004, Journal of clinical psychopharmacology.

[4]  R. Yoshimura,et al.  Plasma levels of homovanillic acid and the response to risperidone in first episode untreated acute schizophrenia , 2003, International clinical psychopharmacology.

[5]  J. Gauillard,et al.  Long-term pharmacoclinical follow-up in schizophrenic patients treated with risperidone Plasma and red blood cell concentrations of risperidone and its 9-hydroxymetabolite and their relationship to whole blood serotonin and tryptophan, plasma homovanillic acid, 5-hydroxyindoleacetic acid, dihydroxyp , 2002, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[6]  R. Yoshimura,et al.  Possible Relationship between Combined Plasma Concentrations of Risperidone plus 9-Hydroxyrisperidone and Extrapyramidal Symptoms , 2001, Neuropsychobiology.

[7]  G. Currier,et al.  Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. , 2001, The Journal of clinical psychiatry.

[8]  T. Terao,et al.  Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement. , 2000, International clinical psychopharmacology.

[9]  T. Terao,et al.  Inhibitory effects of clozapine and other antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells , 2000, Psychopharmacology.

[10]  R. Ownby,et al.  A Double‐Blind Study of Lorazepam versus the Combination of Haloperidol and Lorazepam in Managing Agitation , 1998, Pharmacotherapy.

[11]  W. Dubin,et al.  Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. , 1997, The American journal of emergency medicine.

[12]  J. Dingemanse,et al.  Determination of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in human plasma by a simple and rapid high-performance liquid chromatography assay. , 1996, Journal of pharmaceutical sciences.

[13]  G. Meco,et al.  Combined serotonin‐5‐HT2 and dopamine‐D2 antagonism in schizophrenia: Clinical, extrapyramidal and neuroendocrine response in a preliminary study with risperidone (R 64 766) , 1990 .

[14]  P. Janssen,et al.  Pilot Clinical Investigation of Risperidone in the Treatment of Psychotic Patients , 1990, Pharmacopsychiatry.

[15]  J. Bodkin Emerging uses for high-potency benzodiazepines in psychotic disorders. , 1990, The Journal of clinical psychiatry.

[16]  J. Overall,et al.  Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. , 1989, The American journal of psychiatry.

[17]  S. Heylen,et al.  The efficacy of the D2 and 5-HT2 antagonist risperidone (R 64 766) in the treatment of chronic psychosis An open dose-finding study , 1989, Schizophrenia Research.

[18]  W. Dubin,et al.  Pharmacotherapy of psychiatric emergencies. , 1986, Journal of clinical psychopharmacology.

[19]  T. Ishizaki,et al.  Determination of free 3-methoxy-4-hydroxyphenylglycol with several other monoamine metabolites in plasma by high-performance liquid chromatography with amperometric detection. , 1984, Journal of chromatography.

[20]  D. Weinberger,et al.  Clonazepam treatment of chronic schizophrenia: negative results in a double-blind, placebo-controlled trial. , 1982, The American journal of psychiatry.