RSS-Feed abonnieren
DOI: 10.1055/s-2004-815471
Combination of Clozapine and Amisulpride in Treatment-Resistant Schizophrenia - Case Reports and Review of the Literature
Publikationsverlauf
Received: 16. 8. 2002
Revised: 6. 11. 2002
Accepted: 4. 12. 2002
Publikationsdatum:
29. Januar 2004 (online)
![](https://www.thieme-connect.de/media/pharmaco/200401/lookinside/thumbnails/10.1055-s-2004-815471-1.jpg)
Background: The clinical outcome of patients suffering from schizophrenic psychoses has been considerably improved by atypical antipsychotics like clozapine and amisulpride. In patients whose symptomatology cannot be ameliorated by monotherapy, it might be necessary to combine two atypical antipsychotics.
While clozapine interacts with a variety of neurotransmitter receptors, amisulpride predominantly binds with high affinity to D3/D2-dopamine receptors. Combination can be considered if a supplementary dopamine-receptor blockade is desired.
Methods: We report on the therapy of 15 patients using a combination regimen of amisulpride and clozapine. Data were collected from patient records. The case reports document previous treatment attempts, describe the reason for the combination therapy, and determine its effect.
Results: Major (six cases) or at least marked (eight cases) improvement of previously treatment-resistant positive and negative symptoms could be achieved by using a mean clozapine dose of 375 mg/day (serum level 0.38 mg/l) and an amisulpride dose of 527 mg/day. Additionally, by reducing the clozapine dose compared to monotherapy by 24 %, a significant reduction of side effects was observed.
Conclusions: The combination of amisulpride with clozapine considerably enriches the therapeutic arsenal in cases of severe schizophrenic psychoses. Additional prospective studies are needed in order to systematically evaluate this new treatment strategy.
References
- 1 Adler G, Grieshaber S, Faude V, Thebaldi B, Dressing H. Clozapine in patients with chronic schizophrenia: Serum level, EEG and memory performance. Pharmacopsychiatry. 2002; 35 190-194
- 2 Barnes T R, McEvedy C J, Nelson H E. Management of treatment resistant schizophrenia unresponsive to clozapine. Br J Psychiat - Suppl. 1996; 31 31-40
- 3 Bennett M R. Monoaminergic synapses and schizophrenia: 45 years of neuroleptics. J Psychopharmacol. 1998; 12(3) 289-304
-
4 Bleuler E. Handbuch der Psychiatrie. Spezieller Teil. 4. Abteilung. 1911:
Dementia praecox oder die Gruppe der Schizophrenien . - 5 Bottlender R, Jager M, Hofschuster E, Dobmeier P, Moller H J. Neuroleptic malignant syndrome due to atypical neuroleptics: three episodes in one patient. Pharmacopsychiatry. 2002; 35(3) 119-121
- 6 Buchanan R W. Clozapine: efficacy and safety. Schizophr Bull. 1995; 21(4) 579-591
- 7 Caccia S. Biotransformation of post-clozapine antipsychotics: pharmacological implications. Clin Pharmacokinet. 2000; 38(5) 393-414
- 8 Chong S A, Remington G. Clozapine augmentation: safety and efficacy. Schizophr Bull. 2000; 26(2) 421-440
- 9 Chue P, Welch R, Snaterse M. Combination risperidone and quetiapine therapy in refractory schizophrenia. Can J Psychiatry - Revue Canadienne de Psychiatrie. 2001; 46(1) 86-87
- 10 Cooke C, de Leon J. Adding other antipsychotics to clozapine. J Clin Psychiat. 1999; 60(10) 710
- 11 Croissant B, Hermann D, Olbrich R. Saving potential of clozapine due to combination with amisulpride. Psychopharmakotherapie. 2002; 8(3) 128-130
- 12 de Groot I W, Heck A H, van Harten P N. Addition of risperidone to clozapine therapy in chronically psychotic inpatients. J Clin Psychiat. 2001; 62(2) 129-130
- 13 Delcker A, Schoon M L, Oczkowski B, Gaertner H J. Amisulpride versus haloperidol in treatment of schizophrenic patients-results of a double-blind study. Pharmacopsychiatry. 1990; 23(2) 125-130
- 14 Deniker P. The neuroleptics: a historical survey. Acta Psychiat Scand Suppl. 1990; 358 83-87
- 15 Duval A M, Goldman D. The new drugs (chlorpromazine & reserpine): administrative aspects. 1956. Psychiat Serv. 2000; 51(3) 327-331
- 16 Freudenreich O, Goff D C. Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current combinations. Acta Psychiat Scand. 2002; 106 323-330
- 17 Friedman J, Ault K, Powchik P. Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine. Biol Psychiat. 1997; 42(6) 522-523
- 18 Green A I, Schildkraut J J. Should clozapine be a first-line treatment for schizophrenia? The rationale for a double-blind clinical trial in first-episode patients. Harv Rev Psychiat. 1995; 3(1) 1-9
- 19 Grohmann R, Koch R, Schmidt L G. Extrapyramidal symptoms in neuroleptic recipients. Agents Actions - Suppl. 1990; 29 71-82
- 20 Gupta S, Sonnenberg S J, Frank B. Olanzapine augmentation of clozapine. Ann Clin Psychiat. 1998; 10(3) 113-115
- 21 Hellewell J S. Treatment-resistant schizophrenia: reviewing the options and identifying the way forward. J Clin Psychiat. 1999; 60 Suppl 23 14-19
- 22 Henderson D C, Goff D C. Risperidone as an adjunct to clozapine therapy in chronic schizophrenics. J Clin Psychiat. 1996; 57(9) 395-397
- 23 Horacek J. Novel antipsychotics and extrapyramidal side effects. Theory and reality. Pharmacopsychiatry. 2000; 33 Suppl 1 34-42
- 24 Koshino Y. Algorithm for treatment-refractory schizophrenia. Psychiat Clin Neurosci. 1999; 53 Suppl S9S13
- 25 Kraepelin E. Dementia precox and paraphrenia. 8. Edinburgh; E. and S. Livingstone 1919
- 26 Lecrubier Y, Azorin M, Bottai T, Dalery J, Garreau G, Lemperiere T. et al . Consensus on the practical use of amisulpride, an atypical antipsychotic, in the treatment of schizophrenia. Neuropsychobiology. 2001; 44(1) 41-46
- 27 Leucht S, Pitschel-Walz G, Engel R R, Kissling W. Amisulpride, an unusual ”atypical” antipsychotic: A meta-Analysis of randomized controlled trials. Am J Psychiat. 2002; 159 180-190
- 28 Mann K, Bartels M, Bauer H, Gaertner H J. Amisulpride - an open clinical study of a new benzamide in schizophrenic patients. Pharmacopsychiatry. 1984; 17(4) 111-115
- 29 Marsalek M. Tardive drug-induced extrapyramidal syndromes. Pharmacopsychiatry. 2000; 33 Suppl 1 14-33
- 30 Meltzer H Y. An overview of the mechanism of action of clozapine. J Clin Psychiat. 1994; 55 Suppl B 7-52
- 31 Meyer J M, Simpson G M. From chlorpromazine to olanzapine: a brief history of antipsychotics. Psychiat Serv. 1997; 48(9) 1137-1139
- 32 Miller D D. Review and management of clozapine side effects. J Clin Psychiat. 2000; 61 Suppl 8 14 - 17; discussion 18 -17; discussion 18 - 19
- 33 Moeller H J. Amisulpride: a review of its efficacy in schizophrenia. Acta Psychiat Scand Suppl. 2000; 400 17-22
- 34 Moore N A. Behavioural pharmacology of the new generation of antipsychotic agents. Br J Psychiat Suppl. 1999; 38 5-11
- 35 Pantelis C, Barnes T R. Drug strategies and treatment-resistant schizophrenia. Aust N Z J Psychiat. 1996; 30(1) 20-37
- 36 Pantelis C, Barnes T R. Drug strategies and treatment-resistant schizophrenia. Aust N Z J Psychiat. 1996; 30(1) 20-37
- 37 Prior T I, Chue P S, Tibbo P, Baker G B. Drug metabolism and atypical antipsychotics. Eur Neuropsychopharmacol. 1999; 9(4) 301-309
- 38 Raskin S, Katz G, Zislin Z, Knobler H Y, Durst R. Clozapine and risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation. Acta Psychiat Scand. 2000; 101(4) 334-336
- 39 Rein W, Coulouvrat C, Dondey-Nouvel L. Safety profile of amisulpride in short- and long-term use. Acta Psychiat Scand Suppl. 2000; 400 23-27
- 40 Rein W, Turjanski S. Clinical update on amisulpride in deficit schizophrenia. Int Clin Psychopharmacol. 1997; 12 Suppl 2 S19-27
- 41 Scatton B, Claustre Y, Cudennec A, Oblin A, Perrault G, Sanger D J. et al . Amisulpride: from animal pharmacology to therapeutic action. Int Clin Psychopharmacol. 1997; 12 Suppl 2 S29-36
- 42 Sethi K D. Movement disorders induced by dopamine blocking agents. Semin Neurol. 2001; 21(1) 59-68
- 43 Shen W W. A history of antipsychotic drug development. Compr Psychiat. 1999; 40(6) 407-414
- 44 Shiloh R, Zemishlany Z, Aizenberg D, Radwan M, Schwartz B, Dorfman-Etrog P. et al . Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study. Br J Psychiat. 1997; 171 569-573
- 45 Stahl S M. Antipsychotic polypharmacy, Part 1: Therapeutic option or dirty little secret?. J Clin Psychiat. 1999; 60(7) 425-426
- 46 Stahl S M. Antipsychotic polypharmacy: evidence based or eminence based?. Acta Psychiat Scand. 2002; 106 321-322
- 47 Stahl S M. Antipsychotic polypharmacy: squandering precious recources?. J Clin Psychiat. 2002; 63(2) 93-94
- 48 Stephenson C M, Pilowsky L S. Psychopharmacology of olanzapine. A review. Br J Psychiat Suppl. 1999; (38) 52-58
- 49 Stern R G, Schmeidler J, Davidson M. Limitations of controlled augmentation trials in schizophrenia. Biol Psychiat. 1997; 42(2) 138-143
- 50 Stubbs J H, Haw C M, Staley C J, Mountjoy C Q. Augmentation with sulpiride for a schizophrenic patient partially responsive to clozapine. Acta Psychiat Scand. 2000; 102(5) 390 - 393; discussion 393 -393; discussion 393 - 394
- 51 Taylor C G, Flynn S W, Altman S, Ehmann T, MacEwan G W, Honer W G. An open trial of risperidone augmentation of partial response to clozapine. Schizophr Res. 2001; 48(1) 155-158
- 52 Wirshing D A. Adverse effects of atypical antipsychotics. J Clin Psychiat. 2001; 62 Suppl 21 7-10
- 53 Wirshing D A, Wirsshing W C, Kysar L, Berisford M A, Goldstein D, Pashdag J. et al . Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiat. 1999; 60 358-363
- 54 Young C R, Bowers M B Jr, Mazure C M. Management of the adverse effects of clozapine. Schizophr Bull. 1998; 24 381-390
- 55 Young C R, Longhurst J G, Bowers M B Jr, Mazure C M. The expanding indications for clozapine. Exp Clin Psychopharmacol. 1997; 5(3) 216-234
Dr. med. Mathias Zink
Central Institute of Mental Health
P.O. Box: 12 21 20
D-68072 Mannheim
Germany
Fax: +49-621-23429
Telefon: +49-621-1703-0
eMail: zink@kv.zi-mannheim.de