Clozapine treatment and psychosocial rehabilitation on schizophrenia longitudinal study on positive and negative symptoms in neuroleptic non responder patients

P.3 Psychotic disorders and antipsychotics neocortex, the dorsal septal nucleus, ventral hippocampus and a slight (10%) lowering of total brain weight. Both the frontal cortex and the entorhinal cortex have been implicated in tasks requiring focusing, or sustaining of attention. The abnormalities in these regionsmay,therefore, well be related to the observeddeficits.

IP.3.045I Clozaplne treatment and psychosocial rehabilitation on schizophrenia longitudinal study on positive and negative symptoms In neuroleptic nonresponder patients S. Marchetti, L. Palagini, P. Pietrini, S. Starnini, L. Giuntoli 1, A. Parrini2, M. Guazzelli. Clinica Psichiatrica, Universita di Pisa via

Roma67,56100, Pisa, Italy; 1 Cooperativa Humanitas, Prato; 2 USL9, Prato A longitudinal study is now in progress to investigate clinical course of positive and negative symptomsin schizophrenic patients (pts)participating in a long-term psychosocial rehabilitation program in a Residential Community (Cooperativa Humanitas) in Tuscany. PIsare currently treated with neuroleptics under the responsibility of the psychiatrist who sent the pt to the community. PIs are clinically evaluated at admission (TO), after 6 months (Tl), and after 1 (TI) and 2 (T3) yrs by using BPRS, Andreasen SANS and SAPS and COTES(Comprehensive Occupational TherapyEvaluation Scale). Clinicalresponseis defined as 25% reduction on BPRS at n. Actually 19 pts completed first 2 yrs of program; five of them at TO were considered neuroleptic non responders and received clozapine(dailydosage 233.3 ± 57.7) (groupA). The daily dosageof 14 pts with classic neuroleptics (haloperidol, tioridazine, clorpromazine and pimozide) was 132.2 ± 128.4mg/cpzequivalents (group B); No hematological abnormalities were detectedduringtreatement. At TOgroupB comparedto group A showedno significant differences on age (28.5 ± 5 vs 29.4 ± 5), illness duration (11.8 ± 4.7 vs 11.2 ± 4.6), BPRS (74.1 ± 14.2 vs 62.2 ± 19.4), SANS and SAPS areas and COTEStotal score (82.5 ± 16.6vs 79.0 ± 18.5). Group A pts showeda significant reductionon SANSarea 3 at T2 (4.4 ± 0.5 vs 3.4 ± 0.5 (p < 0.05), on SANS area 4 at T2 and T3 (4.6 ± 0.5 vs 3.6 ± 0.5, vs 2.8 ± 0.8 (p < 0.05), on SAPS area 3 at TI and T3 (4.0 ± 1.4 vs 3.2 ± 2.1, vs 2.4 ± 0.5 (p < 0.05) and on COTES total score at TI, T2 and T3 (79.0 ± 18.5 vs 61.0 ± 20.0, vs 57.4 ± 27.9, vs 41.0 ± 17.6 (p < 0.05»). Group B pts showeda significant reductionon BPRStotal score at Tl, T2 and T3 (74.1 ± 14.2 vs 69.7 ± 13.5, vs 66.4 ± 14.3,vs 61.4 ± 15.8 (p < 0.05)), on SANS area 3 at Tl, T2 and T3 (4.6 ± 0.6 vs 3.9 1.2, vs 3.5 ± 1.3, vs 3.6 ± 1.2 (p < 0.05), on SANS area 4 at Tl, T2 and T3 (4.4 ± 0.7 vs 3.9 ± 1.1, vs 3.5 ± 1.3, vs 3.5 ± 1.3 (p < 0.05)), on SAPS area 3 at Tl, T2 and T3 (4.6 ± 1 vs 3.9 ± 1, vs 3.8 ± 1, vs 3.6 ± 1 (p < 0.05)) and on COTEStotal score, at Tl , T2 and T3 (82.5 ± 16.6 vs 64.8 ± 20.4, vs 58.3 ± 25.2, vs 50.6 ± 24.7 (p < 0.05»). At T3, three clozapinetreated pts and eight classic neuroleptic treated pts were responders. Response to psychosocial rehabilitation was observed both on neuroleptic responderand no responder schizophrenics. Long-term administrationof clozapinewaseffective in threeout of fiveneuroleptic refractory pts. The treatmentwithclozapineto the.six classicneuroleptic no responders would further verify the efficacy of the drug in during psychosocial rehabilitation.

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I P.3.046I Effects of clozaplne on medial prefrontal cortical cells: A presynaptlcal hypothesis G. Gobbi, A. Barbieri I, L. Janiri 1, E. Tempesta2, S. De Risio I. Department of Neuroscience "Bernard B. Brodie", University of Cagliari, Italy; 1 Institute of Psychiatry, Catholic University of Sacred Heart, Rome, Italy; 2 Institute of Pharmacology, Catholic University of Sacred Heart, Rome, Italy Clozapine is the first antipsychotic drug which has been proven in controlled clinical trials to be more effective in decreasing positive and negative symptoms with respect to typical neuroleptic drugs. Clozapine has the additional advantage of producing minimal extrapyramidal symptoms and virtuallyno provencases of tardivedyskinesia. It's likelythat understanding the biological basis of clozapinewill provide some information about the pathophysiology and even the etiology of schizophrenia. In this study, we report the microiontophoretic effects of clozapine and L-sulpiride on dopaminergic medial prefrontal cortical cells (mPFc) of Wistarrats.Coiontophoresis of othersubstances suchas I-phenilbiguanide (PBG) (5-HT3 agonist), (+-) DOl (5-HTI and 5-HTlc agonist), SKF 38393 (01 agonist), quinpirole (02 agonist), LY 171555 (02 agonist) was employedin order to test the receptor interactions of clozapine. The microiontophoresis of dopamine (OA) produced a suppression of mPFc cell's firing; it was antagonized by clozapine (80.7% of tested cells), L-sulpiride (60%) and Clozapine coejectedwith NaCI (60%). C!ozapine blocked DOl-induced inhibitions and PBG-induced inhibitions both in 66.6% of tested cells. SKF 38393 and LY 171555 haven't significant effects on DA-responsive cells. Our resultconfirmthe effectof clozapineand L-sulpirideon dopamine mPFc cells and the lack of inhibitory effects of LY 171555 and SKF 38393. As NaC! is able to block the D2a receptor subtype, clozapine effects are likely to be exerted at the D2b receptor subtype level. Therefore the prefrontal dopamine inhibition can be mediated especially by this D2 receptorsubpopulation. OUT study showsthe antiserotoninergic activity of clozapine on mPFc. According to the 5-HT receptorspectruminvestigated, clozapineshowed anti- 5-HT2/5-HT3 properties. Particularly the anti-5-HT3 effect is in agreement with previousfindings, which pointedtowards a majorrole for 5-HT3receptors in DA regulation (Ashbyet al., 1991). How this mechanism of actions of clozapine as an effective drug on negative schizophrenic symptoms fits the hypothesis of the DA system hypofunction. Further study investigate if the action of clozapine on D2b is a presynapticalor postsynaptical effect. If clozapinewould act on D2b receptor presynaptically and would increase the level of dopamine in mPFc, we could explainthe acute increaseof DA release in the cortex after clozapine administration (as demonstrated with in vivo microdialysis) (Meltzer and Gudelsky, 1992). References Ashby Jr C.R., Minabe Y., Edwards E., Wang R.Y. (1991) Comparison effects of various typical and atypical antypsychotic drug on the suppression action of 2-methilserotonin on medial prefrontal cell in the rat. Synapse 8, 155-161. Meltzer H.Y., Gudelsky G.A. (1992) Dopaminergic and serotoninergic effects of clozapine. Implications for a unique clinical profile. Arzneimittel-Forsch. 42, 268-272.

References

I P.3.047I

[I] Kerstin S. (1992): Comparison of quality of life with standard of living in schizophrenics outpatients. British Journal of Psychiatry. 161: 797-801. [2] Ba G. (1993): Continuing forum: model of psychosocial rehabilitation for chronic psychiatric patients. The Italian Journal of Psychiatry and Behavioural Sciences, 4, I: 47-48.

H.J. Koponen. Moisio Hospital, FIN-50500 Mikkeli, Finland

Risperidone Inthetreatment of psychosis and concomitant buccollnguo-mastlcatory dyskinesia

Conventional neuroleptics are widely used in the treatment of schizophreniaand other psychoses. Althoughthey are effective in the treatment of positive symptoms, such as delusions and hallucinations, their usefulness is more limited when the negative symptoms, such as emotional withdrawal and affective blunting are concerned. The emergence of extrapyramidal side-effects and the risk of tardivedyskinesiaare also major problems. Risperidone is a newatypicalneuroleptic witha potent serotonin5-HT2 and dopamine D-2-antagonist activity and an established antipsychotic