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P.2.117 The clinical actions of risperidone
$228
P3 AnxieO, disorders and anxiolytics
representing positive, negative, extrapyramidal, and depressive symptoms on distinct latent dimensions was established in two independent samples of patients treated with different newer antipsychotics as compared to standard neuroleptics. Subsequently, effects of the different treatment strategies on the latent symptom dimensions were evaluated with particular emphasis on the improvement of depression. Study I (multi-centre, double-blind, parallel group design, n = 133) comprised acutely schizophrenic patients (DSM-III-R) with predominantly positive symptoms, randomly assigned to 6-week treatment with either amisulpride (mean daily dosage: 907 mg) or flupentixol (22.6 mg). Rating scales used in the present analysis were the BRMES, the BPRS, and the Simpson-Angus-Scale for the assessment of extrapyramidal symptoms. In study II (multi-eentre, double-blind, parallel group design, 6 weeks, n = 123) patients with combined psychotic and depressive symptoms (schizophrenia, schizoaffective disorder, depressive type, or maior depression with psychotic features, DSM-III-R) were randomly treated with either risperidone (6.9 rag) or a combination of halopefidol (9 mg) and amitriptylin (180 rag). Psychopathological ratings were carried out by means of the PANSS, the BRMES, and the Extrapyramidal Symptom Rating Scale (ESRS). In both studies, biperidene was allowed in case of EPS. For baseline psychopathology, five established subscales of the BPRS or PANSS, respectively, three subfactors of the BRMES derived from a first-order CFA, and ratings of EPS were subjected to a CFA. The goodness-of-fit of competing models was proved and for both data sets a consistent refined second-order model of three correlating factors (positive, negative, depressive) and a variable EPS-factor could be found (goodness-of-fit index > 0.95; Chi 2 > 0.05). One of the BRMES subscales ("retardation") showed highest loadings on the "negative" factor, whereas the remaining two BRMES subscales were related to the BPRS/PANSS "depression" subscale constituting a "depression" factor. The proposed model provides empirically based treatmenl comparisons on substantial symptom dimensions in a more reliable fashion than conventional analyses. The results of both studies will be discussed to illustrate the pragmatic validity of the present approach by substantiating differential treatment effects on depressive symptomatology in acutely psychotic patients.
~
Saliva levels of clozapine and desmethylclozapine
G. Dumortier 1, A. Lochu 2, p. Colen de Melo 2, A. Zerrouk 1, V. Van Nieuwenhuyse 1, D. Roche Rabreau 2, K. Degrassat 1 1 CHS de
Ville-Evrard, Pharmacological Department, Pharmacy, Neuilly/Marne, 2CHG de Lagny, Department of Psychiatry, Lagny-Marne la Vallde, France This study investigated the relationship between plasma concentrations of clozapine (CLZ) and desmethylclozapine (DMCLZ) and those of saliva in patients treated by clozapine. Patients were either inpatients or outpatients with schizophrenic DSM IV diagnosis (n = 14): (a) CLZ plasma and saliva levels averaged 336 4- 157 ng/ml (ranging from 90 to 580 ng/ml) and 159 4- 86 ng/ml (ranging from 40 to 364 ng/ml), respectively (r = 0.56, n = 14). (b) DMCLZ plasma and saliva levels averaged 196 4- 112 ng/ml (ranging from 55 to 481 ng/ml) and 109 4- 67 ng/ml (ranging from 40 to 250 ng/ml), respectively (r = 0.73, n = 14). (c) CLZ/DMCLZ ratios determined in plasma and saliva averaged 1.9 + 0.6 (ranging from 1.0 to 3.4) and 1.7 4- 0.6 (ranging from 1.0 to 3.2), respectively (r = 0.85, n = 14). As it was previously reported with many antipsychotic drugs (1,2,3), CLZ and DMCLZ saliva concentrations determination is a noninvasive and satisfactory method to check the compliance to the treatment, in particular with outpatients. The correlation between CLZ/DMCLZ ratio in plasma and whole saliva found in our patients (r = 0.85) is encouraging but further studies are necessary to precise its clinical interesL
References [1] May P.R., Van Punen T., Jenden M.D., Coradee Y., Dixson W.J. (1981)Chlorpromazine levels and the outcome of treatment in schizophrenic patients. Arch. Gen. Psychiatry, 38, 202-207. [21 Yamazumi S., Miura S. (1981) Haloperidol concentrations in saliva and serum:
Determination by radioimmunoassay method. Int. Pharmacopsychiatry, 16, 174-183. [3] Zohar J., Birmaher B., Schoenfeld H., Belmaker R. (1986). Salivary and blood levels of neuroleptics during outpatient maintenance treatment, lsr. Psychiatry Relat. Sci., 23, 123-128.
~ T h e
clinical actions of risperidone
S.R. Marder, G. Chouinard, J.M. Davis. West Los Angeles VA Med!cal
Center, Los Angeles, California, USA Combined data from the two double-blind trials of risperidone conducted in North America were analyzed. Factor analysis of scores on the P3sifive and Negative Syndrome Scale (PANSS) produced five factors (negative symptoms, positive symptoms, disorganized thought, uncona'olled hostility/excitement, and anxiety/depression). Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment week 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncon~xolled hostility/excitement, and anxiety/depression; 2 rag/day of rispefidone was significantly superior to haloperidol in reducing negative symptoms. Changes in factor scores at endpoint were unrelated to the occurrence of extrapyramidal side effects during treatment. The results suggest that risperidone has qualitatively different clinical effects from th3se of conventional neuroleptics.
P.3 Anxiety disorders and anxiolytics
•
Paroxetine in panic disorder
E Arias, J.J. Padin, M.A. Fermindez, M.S. Hem~ndez, M. Luengo.
Mental Health Unit, Santa Elena, Zamora, Spain The aim of this study was to analyze the efficacy and tolerability of paroxetine in the treatment of panic disorder. Methods: Eighty panic disorder outpatients, according to the DSM IV criteria, who consecutively initiated treatment were evaluated on the admission and six months later. Dosages were adjusted according to efficacy and tolerability. Reduction in the number of panic attacks and Clinical Global Impression (CGI) were the main efficacy indexes, changes in severity of Hamilton Depression Rating Scale (HDRS) and STAI-State were the secondary measure of outcome. Results: Ten patients dropped out by unknown reasons. 82% of the patients that fulfill the follow up of 6 months became panic attacks free, and 97% of the subjects experienced moderate to marked improvement in CGI. There were a significative reduction in severity of HDRS and STAIState. Agoraphobia, avoidance behavior, anticipatory anxiety, secondary depressive disorders and functional limitations improved too. Paroxetine's adverse effects were present in 40% of this sample, but they were transitory and mild, and they didn't obligate to treatment dropout. Acverse effects more prevalent were sexual problems (20%), gastrointestinal side effects (15%), nervousness (l 2%) and headache (9%). Conclusion: Thus, paroxetine was effective to reduce number of panic attacks and to improve other clinical manifestation in the majority of the patients, with a favourable tolerance.
~
Sertraline vs clomipramine in obsessive-compulsive disorder
R. A~ktn, M. Turan, A.S. t~itli, N. Kaya. Medical Faculty of Selguk
University Department of Psychiatry, 42080, Konya, Turkey" Objective: To compare the efficacy, safety and tolerability of sertraline 50 mg/day versus clomipramine 200 rag/day in the treatment of Obsessive-Compulsive Disorder (OCD). Method: Outpatients with DSM-IV defined OCD and scores of >on the 20 Yale-Brown Obsessive Compulsive Scale (YBOCS) and >4 (,n the Clinical Global Impression Severity Scale (CG1-S) were randomized to sertraline (n = 20) or clomipramine (n = 22) once daily for 8 weeks.
P3 AnxieO, disorders and anxiolytics
representing positive, negative, extrapyramidal, and depressive symptoms on distinct latent dimensions was established in two independent samples of patients treated with different newer antipsychotics as compared to standard neuroleptics. Subsequently, effects of the different treatment strategies on the latent symptom dimensions were evaluated with particular emphasis on the improvement of depression. Study I (multi-centre, double-blind, parallel group design, n = 133) comprised acutely schizophrenic patients (DSM-III-R) with predominantly positive symptoms, randomly assigned to 6-week treatment with either amisulpride (mean daily dosage: 907 mg) or flupentixol (22.6 mg). Rating scales used in the present analysis were the BRMES, the BPRS, and the Simpson-Angus-Scale for the assessment of extrapyramidal symptoms. In study II (multi-eentre, double-blind, parallel group design, 6 weeks, n = 123) patients with combined psychotic and depressive symptoms (schizophrenia, schizoaffective disorder, depressive type, or maior depression with psychotic features, DSM-III-R) were randomly treated with either risperidone (6.9 rag) or a combination of halopefidol (9 mg) and amitriptylin (180 rag). Psychopathological ratings were carried out by means of the PANSS, the BRMES, and the Extrapyramidal Symptom Rating Scale (ESRS). In both studies, biperidene was allowed in case of EPS. For baseline psychopathology, five established subscales of the BPRS or PANSS, respectively, three subfactors of the BRMES derived from a first-order CFA, and ratings of EPS were subjected to a CFA. The goodness-of-fit of competing models was proved and for both data sets a consistent refined second-order model of three correlating factors (positive, negative, depressive) and a variable EPS-factor could be found (goodness-of-fit index > 0.95; Chi 2 > 0.05). One of the BRMES subscales ("retardation") showed highest loadings on the "negative" factor, whereas the remaining two BRMES subscales were related to the BPRS/PANSS "depression" subscale constituting a "depression" factor. The proposed model provides empirically based treatmenl comparisons on substantial symptom dimensions in a more reliable fashion than conventional analyses. The results of both studies will be discussed to illustrate the pragmatic validity of the present approach by substantiating differential treatment effects on depressive symptomatology in acutely psychotic patients.
~
Saliva levels of clozapine and desmethylclozapine
G. Dumortier 1, A. Lochu 2, p. Colen de Melo 2, A. Zerrouk 1, V. Van Nieuwenhuyse 1, D. Roche Rabreau 2, K. Degrassat 1 1 CHS de
Ville-Evrard, Pharmacological Department, Pharmacy, Neuilly/Marne, 2CHG de Lagny, Department of Psychiatry, Lagny-Marne la Vallde, France This study investigated the relationship between plasma concentrations of clozapine (CLZ) and desmethylclozapine (DMCLZ) and those of saliva in patients treated by clozapine. Patients were either inpatients or outpatients with schizophrenic DSM IV diagnosis (n = 14): (a) CLZ plasma and saliva levels averaged 336 4- 157 ng/ml (ranging from 90 to 580 ng/ml) and 159 4- 86 ng/ml (ranging from 40 to 364 ng/ml), respectively (r = 0.56, n = 14). (b) DMCLZ plasma and saliva levels averaged 196 4- 112 ng/ml (ranging from 55 to 481 ng/ml) and 109 4- 67 ng/ml (ranging from 40 to 250 ng/ml), respectively (r = 0.73, n = 14). (c) CLZ/DMCLZ ratios determined in plasma and saliva averaged 1.9 + 0.6 (ranging from 1.0 to 3.4) and 1.7 4- 0.6 (ranging from 1.0 to 3.2), respectively (r = 0.85, n = 14). As it was previously reported with many antipsychotic drugs (1,2,3), CLZ and DMCLZ saliva concentrations determination is a noninvasive and satisfactory method to check the compliance to the treatment, in particular with outpatients. The correlation between CLZ/DMCLZ ratio in plasma and whole saliva found in our patients (r = 0.85) is encouraging but further studies are necessary to precise its clinical interesL
References [1] May P.R., Van Punen T., Jenden M.D., Coradee Y., Dixson W.J. (1981)Chlorpromazine levels and the outcome of treatment in schizophrenic patients. Arch. Gen. Psychiatry, 38, 202-207. [21 Yamazumi S., Miura S. (1981) Haloperidol concentrations in saliva and serum:
Determination by radioimmunoassay method. Int. Pharmacopsychiatry, 16, 174-183. [3] Zohar J., Birmaher B., Schoenfeld H., Belmaker R. (1986). Salivary and blood levels of neuroleptics during outpatient maintenance treatment, lsr. Psychiatry Relat. Sci., 23, 123-128.
~ T h e
clinical actions of risperidone
S.R. Marder, G. Chouinard, J.M. Davis. West Los Angeles VA Med!cal
Center, Los Angeles, California, USA Combined data from the two double-blind trials of risperidone conducted in North America were analyzed. Factor analysis of scores on the P3sifive and Negative Syndrome Scale (PANSS) produced five factors (negative symptoms, positive symptoms, disorganized thought, uncona'olled hostility/excitement, and anxiety/depression). Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment week 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncon~xolled hostility/excitement, and anxiety/depression; 2 rag/day of rispefidone was significantly superior to haloperidol in reducing negative symptoms. Changes in factor scores at endpoint were unrelated to the occurrence of extrapyramidal side effects during treatment. The results suggest that risperidone has qualitatively different clinical effects from th3se of conventional neuroleptics.
P.3 Anxiety disorders and anxiolytics
•
Paroxetine in panic disorder
E Arias, J.J. Padin, M.A. Fermindez, M.S. Hem~ndez, M. Luengo.
Mental Health Unit, Santa Elena, Zamora, Spain The aim of this study was to analyze the efficacy and tolerability of paroxetine in the treatment of panic disorder. Methods: Eighty panic disorder outpatients, according to the DSM IV criteria, who consecutively initiated treatment were evaluated on the admission and six months later. Dosages were adjusted according to efficacy and tolerability. Reduction in the number of panic attacks and Clinical Global Impression (CGI) were the main efficacy indexes, changes in severity of Hamilton Depression Rating Scale (HDRS) and STAI-State were the secondary measure of outcome. Results: Ten patients dropped out by unknown reasons. 82% of the patients that fulfill the follow up of 6 months became panic attacks free, and 97% of the subjects experienced moderate to marked improvement in CGI. There were a significative reduction in severity of HDRS and STAIState. Agoraphobia, avoidance behavior, anticipatory anxiety, secondary depressive disorders and functional limitations improved too. Paroxetine's adverse effects were present in 40% of this sample, but they were transitory and mild, and they didn't obligate to treatment dropout. Acverse effects more prevalent were sexual problems (20%), gastrointestinal side effects (15%), nervousness (l 2%) and headache (9%). Conclusion: Thus, paroxetine was effective to reduce number of panic attacks and to improve other clinical manifestation in the majority of the patients, with a favourable tolerance.
~
Sertraline vs clomipramine in obsessive-compulsive disorder
R. A~ktn, M. Turan, A.S. t~itli, N. Kaya. Medical Faculty of Selguk
University Department of Psychiatry, 42080, Konya, Turkey" Objective: To compare the efficacy, safety and tolerability of sertraline 50 mg/day versus clomipramine 200 rag/day in the treatment of Obsessive-Compulsive Disorder (OCD). Method: Outpatients with DSM-IV defined OCD and scores of >on the 20 Yale-Brown Obsessive Compulsive Scale (YBOCS) and >4 (,n the Clinical Global Impression Severity Scale (CG1-S) were randomized to sertraline (n = 20) or clomipramine (n = 22) once daily for 8 weeks.