- Email: [email protected]
P.2.115 Depressive symptoms in acute schizophrenia: Evaluation and outcome under new antipsychotics
P.2 Psychotic disorders and antipsychotics
~ T h e
German postmarketing surveillance of risperidone indaily practice: Gender differences with regard to demographic and treatment data
M. Albus, M. Linden, A. Klauder, M. Philipp. State Mental Hospital Haar, D 85540 Haar, Germany Methods: In the context of a German postmarketing surveillance on the long term use of risperidone in daily practice, gender differences with regard to demographic and treatment data during the first 3 months of risperidone administration investigated. Results: 886 schizophrenic patients (452 males and 432 females) were included in the study. More males were single compared to females. Although females were older than males with a longer duration of illness, they showed a higher level of psychosocial functioning. During pevions treatment females showed a higher rate of tardive dyskinesia, whereas male showed disturbed Kognition mor ofter. Druing treatment with risperidone the mean dosage of risperidone administeres was lower in females, however sigificantly only after 1 month (4.9 mg vs 4.6 rag). The percentage of patients discontinuing treatment as well as medication compliance did not differ beween the genders. Minus symptomatology was higher in men throughout the whole treatment period. Symptom improvement in plus and minus symptoms, in psychosocial functioning as well as in extrapyramidal side effects was significantly during the 3-month period, again without gender differences. As well, the therapeutic efficacy of risperidone was rated favorable in both groups. Coneulsion: Risperidone treatment during a 3-month-period was effichacious without differential effects on male and female schizophrenic patients.
~
D2 and 5 HT2A receptor binding of different doses of quetiapine in schizophrenics, a pet study
O. Gefvert 1, I.-M. Wieselgren 2, p. Hagstrrm 1, M. Bergstrrm 3 T. Lundberg 1, B. L~mgstrOm 3, F.A. Wiesel 2, L.H. Lindstrrm 1. 1Psychiatric Research Unit Vgisterds; 2 Uller~tker Hospital, Uppsala; 3 Uppsala University PET centre, Sweden Quetiapine ('Seroquel'), a dibenzothiazepine is a new anti-psychotic compound under development. In vitro data indicate that it has a similar receptor profile as that of clozapine, except for a much lower affinity for D4 and muscarinic cholinergic receptors. Method: We undertook a study in 5 schizophrenic patients. In 4 patients the dose of quetiapine was titrated up to 750 rag/day in one week. The dose was maintained for 21 days. At day 29 two PET scans were then performed two hours after dosing (at steady state) at 09.00 and 17.00. The ligand C I ~-raclopride was used to estimate D2 receptor binding in the striatum, and CJl-metylspiperone was used as ligand for 5 HT2A receptors in the frontal cortex. After the first two scans the dose of quetiapine was reduced to 450 mg/day and in 3 of these patients a further two PET scans were performed app. 8 days later at the steady state. The fourth patient had the dose of quetiapine further reduced to 300 rag/day before having two more PET scans. In the remaining patient, who was being well-controlled after titration to 450 mg/day, the dose was reduced to 300 mg/day and then to 150 mg/day with two PET scans at the last two levels at steady state... Results: Dose of quetiapine (rag) Number of patients (n) D~ (% striaturn) 5 HT2A(% frontal cortex)
150 1 0 38
31)0 2 0 57
450 3 31 74
750 4 43 76
Discussion: A consistent decrease of receptor blockade, on both D2 and 5 HT2A receptors, could be demonstrated with decreasing doses of quetiapine. The low values of D2 blockade at 150 mg and 300 mg are consistent with the clinical findings of these patients deteriorating after dose reduction. They either had to discontinue quetiapine (n = 1) or increase the dose again to achieve symptom control (n = 1). However higher occupancy values can not be ruled out in other patients, at these dose levels, as the low number of patients in this study will not take into the account the possibility of an inter individual variation of De occupancy.
$227
These data confirm the findings of our earlier study that quetiapine hinds to both D2 and 5 HT2A receptors, but with a higher level of occupancy and with a much more withstanding blockade of the serotonin receptors. From these data it is unlikely that quetiapine will cause EPS in the recommended dose range (150-750 rag). Thereby fulfilling one criterion of being an atypical neuroleptic. The lack of EPS has been proposed to be related to a dopamine D2 occupancy of less then 75% and at the maximum recommended dose (750 mg) is well below this level. This study has been sponsored by Zeneca Pharmaceuticals, England. ' Seroquel' is a trade mark and the property of Zeneca Ltd.
[ - ~
Aripiprazole, a new typical antipsychotic: Phase 2 clinical trial result
J.L. Petrie t, A.R. Saha 1, j.p. McE~oy 2.10tsuka America Pharmaceuticals, CNS Research, Rochville, Maryland, USA, 2john Umstead Hospital, Duke University, Bume~ NC 27509, USA Aripiprazole is a new atypical anlipsychotic now starting world wide Phase III development by Otsuka Pharmaceuticals. Receptor pharmacology showed that aripipazole is a postsynaptic dopamine receptor antagonist as well as presynaptic autoreceptor agonist. The latter action distinguishes aripiprazole from other currently available antipsychotic drugs. Aripirazole also demonstrated affinity for 5HT2 receptor. Aripiprazole has a T-max of 3-5 hr with a half life of 50-80 hr. A positron ,emission tomography (PET) study showed that aripiprazole enters the brain and its binding to the D2 receptor increases with increasing doses. Recently completed double-blind Phase II studies were conducted in a total of 410 acutely relapsing hospitalised schizophrenic patients. In study 31-93-202, aripiprazole was titrated up from 5 I:o 30 mg in 13 days while in study 31-94-202 fixed doses of 2, 10, and 30 mg/day were administered. Both studies were of 4 weeks duration, and haloperidol was t~sed as an active control. Based on the last observation carried forward (LOCF) analysis, in both studies aripiprazole was superior to placebo in improving the BPRS-total, BPRS-score, CGl-severity, and PANNS-total. Results of the fixed-dose study of 31-94-202 showed that all three aripiprazole doses (2, 10, and 30 mg/day) showed clinical effect in improving the symptoms of acute psychiatric exacerbation of schizophrenia and the 30 mg dose was consinstently more effective than the lower two doses. The 30 mg dose demonstrated a unique early onset of efficacy from week 1 on all efficacy variables including PANSS-negatiw~ score. Aripiprazole was well tolerated. Extrapyramidal syr~ptoms (EPS) as measured by standard scales were comparable to the placebo treatment. In the aripiprazole treatment groups there was no increase in prolactin level or in body weight. A favorable safety profile combined with data supporting efficacy in the treatment of the positive and uegative symptoms of schizophrenia, suggests that aripiprazole may represent an important advance in the management of psychotic disorders.
[
•
Depressive symptoms in acute schizophrenia: Evaluation and outcome under new antipsychotics
M.J. MiJller, O. Benkert. Department of Psychiatry; University of Mainz, Germany Depressive symptoms occur frequently during the course of psychotic disorders. Despite of their high clinical relevance, there is so far no commonly accepted guideline for evaluation and treatment of depressive symptomatology in more acute states of these disorders. However, recent studies with novel antipsychotics seem to yield promising results. Due to the complex nature of psychotic disorders, a substantial overlap of depressive and negative symptoms and the possible confounding with positive symptomatology and treatment-induced extrapyramidal sideeffects (EPS) may account for difficulties in discriminating treatment outcome with respect to depressive symptoms. Based on recent factor-analytical models of schizophrenic symptomatology, the present approach focused on depressive symptoms. Using confirmatory factor analysis (CFA, LISREL 7.20), a baseline model
$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.
~ T h e
German postmarketing surveillance of risperidone indaily practice: Gender differences with regard to demographic and treatment data
M. Albus, M. Linden, A. Klauder, M. Philipp. State Mental Hospital Haar, D 85540 Haar, Germany Methods: In the context of a German postmarketing surveillance on the long term use of risperidone in daily practice, gender differences with regard to demographic and treatment data during the first 3 months of risperidone administration investigated. Results: 886 schizophrenic patients (452 males and 432 females) were included in the study. More males were single compared to females. Although females were older than males with a longer duration of illness, they showed a higher level of psychosocial functioning. During pevions treatment females showed a higher rate of tardive dyskinesia, whereas male showed disturbed Kognition mor ofter. Druing treatment with risperidone the mean dosage of risperidone administeres was lower in females, however sigificantly only after 1 month (4.9 mg vs 4.6 rag). The percentage of patients discontinuing treatment as well as medication compliance did not differ beween the genders. Minus symptomatology was higher in men throughout the whole treatment period. Symptom improvement in plus and minus symptoms, in psychosocial functioning as well as in extrapyramidal side effects was significantly during the 3-month period, again without gender differences. As well, the therapeutic efficacy of risperidone was rated favorable in both groups. Coneulsion: Risperidone treatment during a 3-month-period was effichacious without differential effects on male and female schizophrenic patients.
~
D2 and 5 HT2A receptor binding of different doses of quetiapine in schizophrenics, a pet study
O. Gefvert 1, I.-M. Wieselgren 2, p. Hagstrrm 1, M. Bergstrrm 3 T. Lundberg 1, B. L~mgstrOm 3, F.A. Wiesel 2, L.H. Lindstrrm 1. 1Psychiatric Research Unit Vgisterds; 2 Uller~tker Hospital, Uppsala; 3 Uppsala University PET centre, Sweden Quetiapine ('Seroquel'), a dibenzothiazepine is a new anti-psychotic compound under development. In vitro data indicate that it has a similar receptor profile as that of clozapine, except for a much lower affinity for D4 and muscarinic cholinergic receptors. Method: We undertook a study in 5 schizophrenic patients. In 4 patients the dose of quetiapine was titrated up to 750 rag/day in one week. The dose was maintained for 21 days. At day 29 two PET scans were then performed two hours after dosing (at steady state) at 09.00 and 17.00. The ligand C I ~-raclopride was used to estimate D2 receptor binding in the striatum, and CJl-metylspiperone was used as ligand for 5 HT2A receptors in the frontal cortex. After the first two scans the dose of quetiapine was reduced to 450 mg/day and in 3 of these patients a further two PET scans were performed app. 8 days later at the steady state. The fourth patient had the dose of quetiapine further reduced to 300 rag/day before having two more PET scans. In the remaining patient, who was being well-controlled after titration to 450 mg/day, the dose was reduced to 300 mg/day and then to 150 mg/day with two PET scans at the last two levels at steady state... Results: Dose of quetiapine (rag) Number of patients (n) D~ (% striaturn) 5 HT2A(% frontal cortex)
150 1 0 38
31)0 2 0 57
450 3 31 74
750 4 43 76
Discussion: A consistent decrease of receptor blockade, on both D2 and 5 HT2A receptors, could be demonstrated with decreasing doses of quetiapine. The low values of D2 blockade at 150 mg and 300 mg are consistent with the clinical findings of these patients deteriorating after dose reduction. They either had to discontinue quetiapine (n = 1) or increase the dose again to achieve symptom control (n = 1). However higher occupancy values can not be ruled out in other patients, at these dose levels, as the low number of patients in this study will not take into the account the possibility of an inter individual variation of De occupancy.
$227
These data confirm the findings of our earlier study that quetiapine hinds to both D2 and 5 HT2A receptors, but with a higher level of occupancy and with a much more withstanding blockade of the serotonin receptors. From these data it is unlikely that quetiapine will cause EPS in the recommended dose range (150-750 rag). Thereby fulfilling one criterion of being an atypical neuroleptic. The lack of EPS has been proposed to be related to a dopamine D2 occupancy of less then 75% and at the maximum recommended dose (750 mg) is well below this level. This study has been sponsored by Zeneca Pharmaceuticals, England. ' Seroquel' is a trade mark and the property of Zeneca Ltd.
[ - ~
Aripiprazole, a new typical antipsychotic: Phase 2 clinical trial result
J.L. Petrie t, A.R. Saha 1, j.p. McE~oy 2.10tsuka America Pharmaceuticals, CNS Research, Rochville, Maryland, USA, 2john Umstead Hospital, Duke University, Bume~ NC 27509, USA Aripiprazole is a new atypical anlipsychotic now starting world wide Phase III development by Otsuka Pharmaceuticals. Receptor pharmacology showed that aripipazole is a postsynaptic dopamine receptor antagonist as well as presynaptic autoreceptor agonist. The latter action distinguishes aripiprazole from other currently available antipsychotic drugs. Aripirazole also demonstrated affinity for 5HT2 receptor. Aripiprazole has a T-max of 3-5 hr with a half life of 50-80 hr. A positron ,emission tomography (PET) study showed that aripiprazole enters the brain and its binding to the D2 receptor increases with increasing doses. Recently completed double-blind Phase II studies were conducted in a total of 410 acutely relapsing hospitalised schizophrenic patients. In study 31-93-202, aripiprazole was titrated up from 5 I:o 30 mg in 13 days while in study 31-94-202 fixed doses of 2, 10, and 30 mg/day were administered. Both studies were of 4 weeks duration, and haloperidol was t~sed as an active control. Based on the last observation carried forward (LOCF) analysis, in both studies aripiprazole was superior to placebo in improving the BPRS-total, BPRS-score, CGl-severity, and PANNS-total. Results of the fixed-dose study of 31-94-202 showed that all three aripiprazole doses (2, 10, and 30 mg/day) showed clinical effect in improving the symptoms of acute psychiatric exacerbation of schizophrenia and the 30 mg dose was consinstently more effective than the lower two doses. The 30 mg dose demonstrated a unique early onset of efficacy from week 1 on all efficacy variables including PANSS-negatiw~ score. Aripiprazole was well tolerated. Extrapyramidal syr~ptoms (EPS) as measured by standard scales were comparable to the placebo treatment. In the aripiprazole treatment groups there was no increase in prolactin level or in body weight. A favorable safety profile combined with data supporting efficacy in the treatment of the positive and uegative symptoms of schizophrenia, suggests that aripiprazole may represent an important advance in the management of psychotic disorders.
[
•
Depressive symptoms in acute schizophrenia: Evaluation and outcome under new antipsychotics
M.J. MiJller, O. Benkert. Department of Psychiatry; University of Mainz, Germany Depressive symptoms occur frequently during the course of psychotic disorders. Despite of their high clinical relevance, there is so far no commonly accepted guideline for evaluation and treatment of depressive symptomatology in more acute states of these disorders. However, recent studies with novel antipsychotics seem to yield promising results. Due to the complex nature of psychotic disorders, a substantial overlap of depressive and negative symptoms and the possible confounding with positive symptomatology and treatment-induced extrapyramidal sideeffects (EPS) may account for difficulties in discriminating treatment outcome with respect to depressive symptoms. Based on recent factor-analytical models of schizophrenic symptomatology, the present approach focused on depressive symptoms. Using confirmatory factor analysis (CFA, LISREL 7.20), a baseline model
$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.