Abstract
Schizophrenic patients in long-term neuroleptic monotherapy with clozapine (n=100) and perphenazine, flupenthixol or zuclopentixol (controls,n=100) were evaluated for extrapyramidal side effects (EPS) (blind) as well as other side effects and mental condition (non-blind). In both groups the patients had received neuroleptic treatment for a total of 14 years (median) and the present antipsychotic (clozapine or control drug) for 5 years. Thus the clozapine-treated patients had previously received traditional neuroleptics for 9 years (median). The study was both retrospective (0.3–19 years for clozapine, 0.3–24 years for control drug, by means of chart information) and prospective (1 year, with video-controlled evaluation of EPS). There was a significantly lower prevalence of tardive dyskinesia (TD) in clozapine treated patients than control patients, although prior to this treatment there were more TD patients in the clozapine group (P<0.05). This lower level of TD in the clozapine group was related to a lower induction of new cases (P<0.001) and a tendency towards greater disappearance of TD in the clozapine than in the control group (P=0.07). Clozapine treated patients without TD had started clozapine and ceased traditional neuroleptics at an earlier age than those with TD. Parkinsonian signs were seen in 33% of the clozapine patients versus 61% of the control patients, mainly as hypokinesia; tremor in 3% versus 11% and rigidity in 0 versus 19%. Psychic akathisia was found in 14% versus 40% and motor akathisia in 7% versus 29% of the patients, all differences significantly in favor of clozapine. Clozapine treated patients also had less neuroleptic-induced emotional indifference and depression, but more autonomic side effects than controls.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Casey DE (1989) Clozapine: neuroleptic-induced EPS and tardive dyskinesia. Psychopharmacology 99 [suppl]:47–53
Casey DE (1995) The nonhuman primate model: focus on dopamine D2 and serotonin mechanisms. In: Fog R, Gerlach J, Hemmingsen R (eds) Schizophrenia. An integrated view. Munksgaard, Copenhagen, pp 287–297
Clozapine Study Group (1993) The safety and efficacy of clozapine in severe treatment-resistent schizophrenic patients in the UK. Br J Psychiatry 163:150–154
Cohen BM, Keck PE, Satlin A, Cole JO (1991) Prevalance and severity of akathisia in patients on clozapine Biol Psychiatry 29:1215–1219
Dave M (1994) Clozapine-related tardive dyskinesia: a case report. Biol Psychiatry 35:886–887
Doepp S, Muddeberg C (1975) Extrapyramidale symptom unter clozapin. Nervenarzt 46:589–590
Fitton A, Heel RC (1990) Clozapine: a review of its pharmacological properties, and therapeutic use in schizophrenia. Drugs 40:722–747
Gerlach (1979) Tardive dyskinesia. Dan Med Bull 26:209–245
Gerlach J, Koppelhus P, Helweg E, Monrad A (1974) Clozapine and haloperidol in a single-blind cross-over trial: therapeutic and biochemical aspects in the treatment of schizophrenia. Acta Psychiatr Scand 50:410–424
Gerlach J, Casey DE, Korsgaard S (1986) Tardive dyskinesia: epidemiology, pathophysiology and pharmacology. In: Shah NS, Donald AG (eds) Movement disorder. Plenum Press, New York, pp 119–147
Gerlach J, Korsgaard S, Clemmesen P, Lund Lauersen A-M, Magelund G, Noring U, Povlsen UJ, Bech P, Casey DE (1993) The St Hans Rating Scale for extrapyramidal syndromes: reliability and validity. Acta Psychiatr Scand 87:244–252
Glazer WM, Morgenstern H, Niedzwiecki D, Hughes J (1988) Heterogeneity of tardive dyskinesia: a multivariate analysis. Br J Psychiatry 152:253–259
Glazer WM, Morgenstern H, Doucette JT (1991) The prediction of chronic persistent versus intermittent tardive dyskinesia: a retrospective followup study. Br J Psychiatry 158:822–828
Guy W (1976), ECDEU Assessment Manual for Psychopharmacology. US Dept of Health and Human Services publication (ADM) 76-338, Rockville, pp 534–535
Kane J, Woerner M, Lieberman J et al. (1986) Tardive dyskinesias and drugs. Drug Dev Res 9:41–51
Kane J, Honigfeld G, Singer J, Meltzer H and the Clozaril Collaborative Study Group (1988) Clozapine for the treatment resistant schizophrenia: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45:789–796
Kane JM, Woerner MG, Pollack S, Safferman AZ, Lieberman JA (1993) Does clozapine cause tardive dyskinesia? J Clin Psychiatry 54:327–330
Kurz M, Hummer N, Oberbauer H, Fleischhacker WW (1995) Extrapyramidal side effects of clozapine. Psychopharmacology 118:52–56
Levin H (1992) Should chronic treatment-refractory akathisia be an indication for the use of clozapine in schizophrenic patients. J Clin Psychiatry 53:248–251
Lieberman J, Johns C, Coopet T, Pollack S, Kane J (1989) Clozapine pharmacology and tardive dyskinesia. Psychopharmacology 99 [suppl]:54–59
Lieberman JA, Saltz BL, Johns CA, Pollack S, Borenstein M, Kane J (1991) The effects of clozapine on tardive dyskinesia. Br J Psychiatry 158:503–510
Lingjærde O, Ahlfors UG, Bech P, Dencker ST, Elgen K (1987) The UKU side effect rating scale: a new comprehensive scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand 76 [suppl]:1–100
Meltzer HY (1992) Dimensions of outcome with clozapine. Br J Psychiatry 160 [suppl]:46–53
Meltzer HY, Luchins DJ (1984) Effect of clozapine in severe tardive dyskinesia: a case report. J Clin Psychopharmacol 4:286–287
Meltzer HY, Bastani B, Young Kwon K, Ramirez LF, Burnett S, Sharpe J (1989) A prospective study of clozapine in treatment-resistant schizophrenic patients: I. preliminary report. Psychopharmacology 99 [suppl]:68–72
Meltzer HY, Burnett S, Bastani B, Ramirez LF (1990) Effects of six months of clozapine treatment on the quality of life of chronic schizophrenic patients. Hosp Commun Psychiatry 41:892–897
Overall JE, Gorham DR (1962) The brief psychiatric rating scale (BPRS). Psychol Rep 10:799–812
Owens DGC, Johnstone EC, Frith CD (1982) Spontaneous involuntary disorders of movement: their prevalence, severity and distribution in chronic schizophrenics with and without treatment with neuroleptics. Arch Gen Psychiatry 39:452–461
Pickar D, Owen RR, Litmen RE, Konicki PE, Gutierrez R, Rapapoty MH (1992) Clinical and biological response to clozapine in patients with schizophrenia. Arch Gen Psychiatry 49:345–353
Simpson G, Lee JH, Shrivastava RK (1978) Clozapine in tardive dyskinesia. Psychopharmacology 56:75–80
Stille G, Lauener H, Eichenberger E (1971) The pharmacology of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4] diazepine (clozapine). II Pharmaco 26:603–625
Tamminga CA, Thaker GK, Moran M, Kakigi T, Gao X-M (1994) Clozapine in tardive dyskinesia: observations from human and animal model studies. J Clin Psychiatry 55 [9 (suppl B)]:102–106
Thomas P, Lalaux N, Rogelet P (1993) Lasting dystonia with clozapine. In: Abstracts from 9th World Congress of Psychiatry, Rio, Brazil, p 191
Waddington JL, Youssef HA, Dolphin C, Kinsella A (1987) Cognitive dysfunctions, negative symptoms and tardive dyskinesia in schizophrenia: their association in relation to topography of involuntary movements and criterion of their abnormality. Arch Gen Psychiatry 44:907–912
Wulff HR, Schlichting P (1988) Medstat: statistical program for the analysis of the results of controlled therapeutic trials and other types of clinical research. ASTRA Group A/S, Albertslund, Denmark
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Peacock, L., Lublin, H., Gerlach, J. et al. Clozapine versus typical antipsychotics a retro- and prospective study of extrapyramidal side effects. Psychopharmacology 124, 188–196 (1996). https://doi.org/10.1007/BF02245620
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245620