Abstract
Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0–6; baseline: 42.0±2.3; mean±SeM), SAPS (64.5±4.8) and SANS (55.0±4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0±3.5; SAPS: 36.1±6.7; SANS: 42.5±5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel. Our results suggest that seroquel may be a well tolerated drug with some antipsychotic properties, exhibiting no extrapyramidal side effects that could be of use in the treatment of schizophrenic patients with positive symptomatology. Further double-blind studies with higher doses, in order to test presumably better efficacy, and with monitoring of plasma levels, are needed to extend the present results.
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References
Alphs LD, Meltzer HY, Bastiani B (1991) Side effects of clozapine and their management. Pharmacopsychiatry 24:46
Andermann B, Griffith RW (1977) Clozapine-induced agranulocytosis: a situation report up to August 1976. Eur J Clin Pharmacol 11:199–201
Axelsson R, Nilsson A, Christensson E, Björk A (1991) Effects of amperozide in schizophrenia. An open study of a potent 5-HT2 receptor antagonist. Psychopharmacology 104:287–292
Baldessarini RJ, Frankenburg FR (1991) Clozapine. A novel antipsychotic agent. N Engl J Med 324:746–754
Balsara J, Jadhav JH, Chandorkar AG (1979) Effects of drugs influencing central serotonergic mechanisms on haloperidol-induced catalepsy. Psychopharmacology 62:67–69
Bersani G, Grispini A, Marini S, Pasani A, Valducci M, Ciani (1986) Neuroleptic-induced extrapyramidal side effects: clinical perspectives with ritanserin (R 55667), a new selective 5HT2 receptor blocking agent. Curr Ther Res 40:492–499
Casey DE (1989) Serotonergic aspects of acute extrapyramidal syndromes in nonhuman primates. Psychopharmacol Bull 25:457–459
Cohen BM, Keck PE, Satlin A, Cole JO (1991) Prevalence and severity of akathisia in patients on clozapine. Biol Psychiatry 29:1215–1219
Costall B, Fortune DH, Naylor RJ, Marsden CD, Pycock C (1975) Serotonergic involvement with neuroleptic catalepsy. Neuropharmacology 14:859–868
Czobor P, Volavka J (1992) Level of haloperidol in plasma is related to electroencephalographic findings in patients who improve. Psychiatry Res 42:129–144
Fabre L, Slotnick V, Jones V, Murray G, Malick J (1990) ICI 204.636. A novel atypical antipsychotic. Early indications for safety and efficacy in man. Abstracts of the 17th CINP Congress, vol II, Kyoto, Japan, p 223
Fink M (1969) EEG an human psychopharmacology. Annu Rev Pharmacol 9:241–258
Galderisi S, Mucci A, DiGregorio MR, Bucci P, Maj M, Kemali D (1990) C-EEG brain mapping in DSM -III schizophrenics after acute and chronic haloperidol treatment. Eur Neuropsychopharmacol 1:51–54
Gerlach J (1991) New antipsychotics: classification, efficacy and adverse effects. Schizophr Bull 17:289–309
Goldstein JM, Litwin LC, Sutton DB, Malick JB (1993) Seroquel: electrophysiological profile of a potential atypical antipsychotic. Psychopharmacology 112:293–298
Haller E, Binder RL (1990) Clozapine and seizures. Am J Psychiatry 147:1069–1071
Herrmann WM, Irrgang U (1983) An absolute must in clinico-pharmacological research: pharmaco-electro-encephalography, its possibilities and limitations. Pharmacopsychiatry 16:134–142
Itil TM (1977) Qualitative and quantitative EEG findings in schizophrenia. Schizophr Bull 3:61–79
Kane J, Honigfeld G, Singer J, Meltzer HY, Clozaril Collaborative Study Group (1988) Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 45:789–796
Koukkou M, Angst J, Zimmer D (1979) Paroxysmal EEG activity and psychopathology during the treatment with clozapine. Pharmacopsychiatry 12:173–183
Krupp P, Barnes P (1989) Leponex-associated granulocytopenia: a review of the situation. Psychopharmacology 99:S118–121
Lieberman JA, Kane JM, Johns CA (1989) Clozapine: guidelines for clinical management. J Clin Psychiatry 50:329–338
Lindström LH (1988) The effect of long-term treatment with clozapine in schizophrenia: a retrospective study in 96 patients treated with clozapine for up to 13 years. Acta Psychiatr Scand 77:524–529
Matejcek M (1982) Vigilance and the EEG: psychological, physiological and pharmacological aspects. In: Herrmann WM (ed) EEG in drug research. Gustav Fischer Verlag, Stuttgart, New York, pp 405–508
Meltzer HY, Matsubara S, Lee JC (1989) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D1, D2 and serotonin2 pKi values. J Pharmacol Exp Ther 251:238–246
Migler BM, Warawa EJ, Malick JB (1993) Seroquel: behavioral effects in conventional and novel tests for atypical antipsycotic drug. Psychopharmacology 112:299–307
Povlsen UJ, Noring U, Fog R, Gerlach J (1985) Tolerability and therapeutic effect of clozapine. Acta Psychiatr Scand 71:176–185
Reyntjens A, Gelders YG, Hoppenbrouwers M-LJA, Van den Bussche G (1986) Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin-S2 receptor blocker. Drug Dev Res 8:205–211
Saller CR, Salama AI (1993) Seroquel: biochemical profile of a potential atypical antipsychotic. Psychopharmacology 112:285–292
Seroquel Investigator's Brochure (1993) Zeneca Pharmaceuticals
Tiihonen J, Nousiainen U, Hakola P, Leinonen E, Tuunainen A, Merraala E, Paanila J (1991) EEG abnormalities associated with clozapine treatment. Am J Psychiatry 148:1406
Van Tol HHM, Wu CM, Guan HC et al. (1992) Multiple dopamine D4 receptor variants in the human population. Nature 358:149–152
Wetzel H, Wiedemann K, Holsboer F, Benkert O (1991) Savoxepine: invalidation of an “atypical” neuroleptic response pattern predicted by animal models in an open clinical trial with schizophrenic patients. Psychopharmacology 103:280–283
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Wetzel, H., Szegedi, A., Hain, C. et al. Seroquel (ICI 204 636), a putative “atypical” antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters. Psychopharmacology 119, 231–238 (1995). https://doi.org/10.1007/BF02246165
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DOI: https://doi.org/10.1007/BF02246165