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A Risk-Benefit Assessment of Sulpiride in the Treatment of Schizophrenia

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  • Risk-Benefit Assessment
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Summary

Sulpiride is a substituted benzamide with a selective action on receptors of the dopamine D2-like family, and clinical and pharmacological data suggest that it could be considered to be an atypical antipsychotic.

Sulpiride penetrates the blood-brain barrier poorly because of its low lipid solubility. It is mainly excreted unchanged in the urine, and accumulation of the drug could occur in patients with renal dysfunction and possibly in elderly patients with declining glomerular filtration rate. At low dosages (50 to 150 mg/day), sulpiride produces a disinhibiting and antidepressant effect, which is probably related to its action on D2 presynaptic autoreceptors, thus facilitating dopaminergic neurotransmission.

Data have confirmed the efficacy of sulpiride in patients with acute or chronic schizophrenia during both short and long term treatment, but long term, placebocontrolled trials are still lacking.

It is still doubtful whether sulpiride is more effective than typical antipsychotics for the treatment of negative symptoms. Data from clinical studies are controversial; the majority of authors indicate that sulpiride produces a better recovery rate from negative than from positive symptoms at low doses, but it shows a similar efficacy either on negative and positive symptoms at higher doses.

The safety profile of sulpiride is similar to that of typical antipsychotics, although the frequency of adverse effects seems to be globally lower. Extrapyramidal reactions appear generally to be mild. Autonomic effects occur less frequently with sulpiride than with typical antipsychotics, showing no clinically relevant influence on cardiovascular parameters and, on the whole, good tolerability in elderly patients.

Sulpiride is known to induce prolactin elevation in both serum and CSF, which may be associated with impotence in men and diminished gonadal function in women; these effects appear to be dosage-dependent.

Sulpiride can be considered to be an atypical antipsychotic, considering its action on negative, defective symptoms, its partial activity against positive symptoms, and its low incidence of extrapyramidal adverse effects.

Sulpiride could find its specific therapeutic role in elderly patients with schizophrenia, as it shows a good margin of safety between therapeutic dosages and toxic concentrations.

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References

  1. Meitzer HY. Effect of neuroleptics on the schizophrenic syndrome. In: Dahl SG, Gram LF, Paul G, et al., editors. Clinical pharmacology in psychiatry. Berlin, Heidelberg: Springer-Verlag, 1987: 255–65

    Chapter  Google Scholar 

  2. Kane JM, Mayerhoff D. Do negative symptoms respond to pharmacological treatment? Br J Psychiatry 1989; 155: 115–8

    Google Scholar 

  3. Arndt S, Allinger RJ, Andreasen NC. The distinction of positive and negative symptoms: the failure of a two dimensional model. Br J Psychiatry 1991; 158: 317–22

    Article  PubMed  CAS  Google Scholar 

  4. Dahal SG. Pharmacokinetics of neuroleptic drugs and the utility of plasma level monitoring. In: Acasey DE, Christensen AV, editors. Psychopharmacology: current trends. Berlin, Heidelberg: Springer-Verlag, 1988: 34–6

    Chapter  Google Scholar 

  5. Meitzer HY, Zureick J. Negative symptoms in schizophrenia: a target for new drug development. In: Dahl SG, Gram LF, editors. Clinical pharmacology in psychiatry. Berlin, Heidelberg: Springer-Verlag, 1989: 68–77

    Chapter  Google Scholar 

  6. Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry 1994; 151: 825–35

    PubMed  CAS  Google Scholar 

  7. Meitzer HY. Atypical antipsychotic drugs. In: Bloom FE, Kupfer DJ, Dahl SG, editors. Psychopharmacology: the fourth generation of progress. New York: Raven Press Ltd, 1995: 1277–86

    Google Scholar 

  8. Kervin RW. The new atypical antipsychotic. Br J Psychiatry 1994; 164: 141–8

    Article  Google Scholar 

  9. Jenner P, Theodoru A, Marsden CD. Specific receptors for substituted benzamide drugs in brain. Adv Biochem Psychopharmacol 1982; 35: 109–41

    PubMed  CAS  Google Scholar 

  10. Jackson DM, Mohell N, Bengtsson A, et al. What are atypical neuroleptics and how do they work? In: Brunello N, Mendlewicz J, Racagni G, editors. New generation of antipsychotic drugs: novel mechanisms of action. Basel: Karger, 1993: 27–38

    Google Scholar 

  11. Jenner P, Marsden CD. The substituted benzamides — a novel class of dopamine antagonists. Life Sci 1979; 25: 479–86

    Article  PubMed  CAS  Google Scholar 

  12. Caley FC, Weber SS. Sulpiride: an antipsychotic with selective dopaminergic antagonist properties. Ann Pharmacother 1995; 29: 152–60

    PubMed  CAS  Google Scholar 

  13. Sedval G, Farde L. Chemical brain anatomy in schizophrenia. Lancet 1995; 346: 743–49

    Article  Google Scholar 

  14. Sokoloff P, Giros B, Martres MP, et al. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 1990; 347: 146–51

    Article  PubMed  CAS  Google Scholar 

  15. Farde L, Nordstrom A, Wiesel FA. Positron emission tomography analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Arch Gen Psychiatry 1992; 49: 538–44

    Article  PubMed  CAS  Google Scholar 

  16. Motohashi N, Takashima M, Mataga N, et al. Effects of sulpiride and oxipertine on the dopaminergic systems in the rat striatum. Neuropsychobiology 1992; 25: 29–33

    Article  PubMed  CAS  Google Scholar 

  17. Ossowska K, Karcz M, Wardas J, et al. Striatal and nucleus accumbens D1/D2 receptors in neuroleptic catalepsy. Eur J Psychopharmacol 1990; 182: 327–34

    Article  CAS  Google Scholar 

  18. Crow TJ. Two syndromes of schizophrenia as one pole of the continuum of psychosis: a concept of the nature of pathogen and its genomic locus. In: Henn FA, De Lisi LE, editors. Handbook of schizophrenia. Vol. 2. The neurochemistry and neuropharmacology of schizophrenia. New York: Elsevier, 1987; 17–48

    Google Scholar 

  19. Carpenter WT, Buchanan RW. Schizophrenia. N Engl J Med 1994; 330: 681–90

    Article  PubMed  Google Scholar 

  20. Serra G, Forgione A, D’Aquila PS, et al. Possible mechanism of antidepressant effect of L-sulpiride. Clin Neuropharmacol 1990; 13(l): 76–83

    Article  Google Scholar 

  21. Petit M, Zann M, Lesieur P, et al. The effect of sulpiride on negative symptoms of schizophrenia. Br J Psychiatry 1987; 150: 270–1

    Article  PubMed  CAS  Google Scholar 

  22. Alfredsson G, Harnryd C, Wiesel FA. Effects of sulpiride and chlorpromazine on autistic and positive psychotic symptoms in schizophrenic patients-relationship to drug concentrations. Psychopharmacology 1985; 85: 8–13

    Article  PubMed  CAS  Google Scholar 

  23. Colonna L. Antideficit properties of neuroleptics. Acta Psychiatr Scand 1994; 89 (380 Suppl.): 77S–82S

    Article  Google Scholar 

  24. Mucci A, Nolfe G, Maj M. Levosulpiride: a review of its clinical use in psychiatry. Pharmacol Res 1995; 31(2): 95–101

    Article  PubMed  CAS  Google Scholar 

  25. Bressolle F, Bress J, Faure-Jeantis A. Absolute bioavailability, rate of absorption and dose proportionality of sulpiride in humans. J Pharm Sci 1992; 81: 26–32

    Article  PubMed  CAS  Google Scholar 

  26. Shinkuma D, Hamaguchi T, Kobayashi M, et al. Effects of food intake and meal size on the bioavailability of sulpiride in two dosage forms. Int J Clin Pharmacol Ther Toxicol 1990; 28: 440–2

    PubMed  CAS  Google Scholar 

  27. Lenhard G, Kieferdorf U, Berner G, et al. The importance of pharmacokinetic data on sulpiride: results of a bioequivalence study of two sulpiride 200mg preparations following oral administration. Int J Clin Pharmacol Ther Toxicol 1991; 29: 231–7

    PubMed  CAS  Google Scholar 

  28. Wiesel FA, Alfredsson G, Ehrnebo M, et al. The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects. Eur J Clin Pharmacol 1980; 17: 385–91

    Article  PubMed  CAS  Google Scholar 

  29. Alfredsson G, Bjerkenstedt L, Edman G, et al. Relationships between drug concentrations in serum and CSF, clinical effects and monoaminergic variables in schizophrenic patients treated with sulpiride or chlorpromazine. Acta Psychiatr Scand 1984; 311: 49–74

    Article  CAS  Google Scholar 

  30. Wagstaff AJ, Fitton A, Benfield P. Sulpiride: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in schizophrenia. CNS Drugs 1994; 2(4): 313–33

    Article  Google Scholar 

  31. Mauri MC, Leva P, Coppola MT, et al. L-sulpiride in young and elderly negative schizophrenics: clinical and pharmacokinetics variables. Prog Neuropsych Biol Psychiatry 1994; 18(2): 355–66

    Article  CAS  Google Scholar 

  32. Bres J, Bressolle F. Pharmacokinetics of sulpiride in humans after intravenous and intramuscular administrations. J Pharm Sci 1991; 80: 1119–24

    Article  PubMed  CAS  Google Scholar 

  33. Blanco JM, Sanchez C, Diaz JA, et al. Ensayo clínico con dogmatil y placebo en esquizofrenicos crónicos estudio de 89 enfermes con applicación de la escala de Harris, Letemendia y Willems. Arch Neurobiol 1972; 35: 3–22

    Google Scholar 

  34. Toru M, Shimazono Y, Miyasaka M, et al. A double-blind comparison of sulpiride with chlorpromazine in chronic schizophrenia. J Clin Pharmacol 1972; 12: 221–9

    CAS  Google Scholar 

  35. Cassano GB, Castrogiovanni P, Conti L, et al. Sulpiride versus haloperidol in schizophrenia: a double blind comparative trial. Curr Ther Res 1975; 17: 189–201

    PubMed  CAS  Google Scholar 

  36. Asada S, Ishimaru T, Kubo S, et al. Étude des effets cliniques du sulpiride et de la perphenazine chez 82 schizophrènes par la méthode du double aveugle. Encephale 1976; 11: 73–83

    Google Scholar 

  37. Bratfos O, Haug JO. Comparison of sulpiride in psychoses: a double-blind multicentre study. Acta Psychiatr Scand 1979; 60: 1–9

    Article  PubMed  CAS  Google Scholar 

  38. Edwards JG, Alexander JR, Alexander MS, et al. Controlled trial of sulpiride in chronic schizophrenic patients. Br J Psychiatry 1980; 137: 522–9

    Article  PubMed  CAS  Google Scholar 

  39. Rao VAR, Bailey J, Mirkin A, et al. A clinical and pharmacodynamic evaluation of sulpiride. Psychopharmacology 1981; 73: 77–80

    Article  PubMed  CAS  Google Scholar 

  40. Harnryd C, Bjerkenstedt L, Bjork G, et al. Clinical evaluation of sulpiride in schizophrenic patients: a double blind comparison with chlorpromazine. Acta Psychiatr Scand 1984; 69Suppl. 311: 7–30

    Article  Google Scholar 

  41. Munk-Andersen E, Behnke K, Heltberg J, et al. Sulpiride versus haloperidol, a clinical trial in schizophrenia: a preliminary report. Acta Psychiatr Scand 1984; 69 Suppl.: 31–41

    Article  Google Scholar 

  42. Dreyfus JF. Essai comparatif multicentrique en double insu du dogmatil et de la chlorpromazine dans le traitement de la psychose aiguë. Sem Hop 1985; 61(19): 1322–6

    Google Scholar 

  43. Gerlach J, Behnke K, Heltberg J, et al. Sulpiride and haloperidol in schizophrenia: a double-blind cross-over study of therapeutic effect, side effects and plasma concentrations. Br J Psychiatry 1985; 147: 283–8

    Article  PubMed  CAS  Google Scholar 

  44. Lepola U, Koskinen T, Rimon R, et al. Sulpiride and perphenazine in schizophrenia: a double-blind clinical trial. Acta Psychiatr Scand 1989; 80: 92–6

    Article  PubMed  CAS  Google Scholar 

  45. Soni SD, Mallik A, Schiff A. Sulpiride in negative schizophrenia: a placebo-controlled double-blind assessment. Hum Psychopharm 1990; 5: 233–8

    Article  Google Scholar 

  46. Svestka J, Rysanek R, Ceskova E, et al. Cross-over comparison of the therapeutic effects of sulpiride and perphenazine in schizophrenic and schizoaffective psychoses. Act Nerv Super 1989; 31: 35–6

    CAS  Google Scholar 

  47. Mahadevan K, Gadhvi HM, Suri AK, et al. A multicentre comparison of oral zuclopenthixol dihydrochloride and oral sulpiride in the treatment of acute schizophrenia. Br J Clin Res 1991; 2: 13–20

    Google Scholar 

  48. Yamagami S, Hirayama E, Okuno M, et al. A single-blind evaluation of bromperidol and sulpiride in the treatment of schizophrenic patients [in Japanese]. Yakuri to Chiryo 1991; 19: 4667–77

    Google Scholar 

  49. Nishikawa T, Tanaka M, Tsuda A, et al. Prophylactic effects of neuroleptics in symptom-free schizophrenics: a comparative dose-response study of timiperone and sulpiride. Biol Psychiatry 1989; 25: 861–6

    Article  PubMed  CAS  Google Scholar 

  50. Borenstein P, Champion C, Cujo P. Un psychotrope original: le Dogmatil. Sem Hop 1969; 45(19): 1301–14

    PubMed  CAS  Google Scholar 

  51. Brion S, Guerin R. Étude clinique d’un groupe de psychoses traitées par un nouveau psychotrope. Gaz Med 1970; 77(14): 3125–8

    Google Scholar 

  52. Cenac-Thaly H, Charbaut J, Ageorges MA, et al. Étude clinique du Dogmatil et hypothèses neurologiques sur son mode d’action. Gaz Med 1970; 77(14): 3106–20

    Google Scholar 

  53. Merceron M, Combet R, Mourot H. Apport original dans le traitement des psychoses: le ‘Dogmatil’, antipsychotique psychotonique. Psychol Med 1971; 3(2): 1–6

    Google Scholar 

  54. Delaunay J, Guibert S. Le dogmatil dans le traitement ambulatoire des psychotiques chroniques. Inform Psych 1974; 50(9): 965–8

    Google Scholar 

  55. Szymonowicz R. Le dogmatil au long cours en psychiatrie lourde. Sem Hop 1983; 59(19): 1468–70

    PubMed  CAS  Google Scholar 

  56. Nishiura M. Clinico-pharmacological studies on sulpiride. Curr Ther Res 1976; 20: 164–72

    PubMed  CAS  Google Scholar 

  57. Lecubrier Y, Douillet P. Neuroleptics and bipolar dopaminergic hypothesis of schizophrenia. In: Ackenheil M, Matussek N, editors. Special aspects of psychopharmacology. Paris: Expansion Scientifique Française, 1983: 375–82

    Google Scholar 

  58. Brenner HD, Denck SJ, Goldstein MJ, et al. Defining treatment refractoriness in schizophrenia. Schizophr Bull 1990; 16: 551–61

    PubMed  CAS  Google Scholar 

  59. Alberts JL, Francois F, Josserand F. Étude des effets secondaires rapportés a l’occasion de traitements par dogmatil. Sem Hop 1985; 61(19): 1351–7

    Google Scholar 

  60. Achiron A, Zoldan Y, Melamed E. Tardive dyskinesia induced by sulpiride. Clin Neuropharmacol 1990; 13(3): 248–52

    Article  PubMed  CAS  Google Scholar 

  61. Fava GA. Sulpiride and tardive dyskinesia. CNS Drugs 1995; 3(3): 237

    Article  Google Scholar 

  62. Schwartz M, Moguillansky L, Lanyi G, et al. Sulpiride in tardive dyskinesia; J Neurol Neurosurg Psychiatry 1990; 53: 800–2

    Article  PubMed  CAS  Google Scholar 

  63. Miller LG, Jankovic J. Sulpiride-induced tardive dystonia. Mov Disord 1990; 5(1): 83–4

    Article  PubMed  CAS  Google Scholar 

  64. Mielke DH, Gallant DM, Kessler C. An evaluation of a unique new antipsychotic agent, sulpiride: effects on serum prolactin and growth hormone levels. Am J Psychiatry 1977; 134(12): 1371–5

    PubMed  CAS  Google Scholar 

  65. Chieli T, Cocchi D, Fregman GB, et al. Neuroleptic induced prolactin rise: influence of pharmacological alterations of different neurotransmitter systems. Experimentia 1980; 36: 463–5

    Article  CAS  Google Scholar 

  66. Nir I, Herzog P, Wislicki L. Suspected adverse drug reactions reported in 1980 by practitioners and hospitals. Drug Monitoring Centre, Department of Clinical Pharmacology, Ministry of Health, Jerusalem, 1980; P10

    Google Scholar 

  67. Weizman A, Maoz B, Treves I, et al. Sulpiride-induced hyper-prolactinemia and impotence in male psychiatric outpatients. Prog Neuropsych Biol Psychiatry; 1985; 9: 193–8

    Article  CAS  Google Scholar 

  68. Levkovitz H, Abramovitch Y, Nitzan I. Leukocytosis related to the therapeutic dosage of sulpiride. Biol Psychiatry 1994; 35(12): 963

    Article  PubMed  CAS  Google Scholar 

  69. Baldessarini RJ, Viguera AC. Neuroleptic withdrawal in schizophrenic patients. Arch Gen Psychiatry 1995; 52: 189–92

    Article  PubMed  CAS  Google Scholar 

  70. Baldessarini RJ. Risks and implications of interrupting maintenance psychotropic drug therapy. Psychother Psychosom 1995; 63: 137–4

    Article  PubMed  CAS  Google Scholar 

  71. Van Putten T, May PRA. ‘Akinetic’ depression in schizophrenia. Arch Gen Psychiatry 1978; 35: 1101–7

    Article  PubMed  Google Scholar 

  72. Csernansky JG, Newcomer JG. Maintenance drug treatment for schizophrenia. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: the fourth generation of progress. New York: Raven Press, 1994: 1267–75

    Google Scholar 

  73. Bressolle F, Bres J, Mourad G. Pharmacokinetics of sulpiride after intravenous administration in patients with impaired renal function. Clin Pharmacokinet 1989; 17(S): 367–73

    Article  PubMed  CAS  Google Scholar 

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Mauri, M.C., Bravin, S., Bitetto, A. et al. A Risk-Benefit Assessment of Sulpiride in the Treatment of Schizophrenia. Drug-Safety 14, 288–298 (1996). https://doi.org/10.2165/00002018-199614050-00003

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