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Amisulpride

A Review of its Clinical Potential in Dysthymia

CNS Drugs volume 12, pages 471–483 (1999)Cite this article

Abstract

Amisulpride is a substituted benzamide derivative that selectively enhances dopaminergic neurotransmission; it is being developed as a potential treatment for the chronic mood disorder dysthymia. In placebo-controlled trials in patients with dysthymia ± major depression or those with major depression in partial remission, amisulpride 50 mg/day was more effective than placebo and had similar efficacy to imipramine 100 mg/day or amineptine 200 mg/day according to standard depression rating scales. Superiority of amisulpride over placebo was evident in the subgroup of patients with pure dysthymia and in those with dysthymia plus major depression in one study. In trials predominantly in patients with pure dysthymia, amisulpride 50 mg/day was as effective as amitriptyline 25 to 75 mg/day or fluoxetine 20 mg/day according to standard depression ratings.

Amisulpride 50 mg/day is generally well tolerated, with endocrine dysfunction the only notable adverse event. The most common endocrine events in female patients who received amisulpride 50 mg/day in clinical trials were menstrual dysfunction (2.0 to 12.3%), galactorrhoea (3.9 to 7.3%) and breast pain or enlargement (0.9 to 7.5%). The incidence of extrapyramidal symptoms with low dose amisulpride is similar to that with placebo. Nine percent of patients receiving amisulpride 50 mg/day discontinued treatment because of adverse events during clinical trials.

With the exception of endocrine events, amisulpride had a tolerability profile similar to that of placebo and was better tolerated (particularly for CNS and anticholinergic events) than imipramine 100 mg/day, amitriptyline 25 to 75 mg/day or amineptine 200 mg/day. Anorexia and nausea and vomiting were more common in fluoxetine 20 mg/day recipients than in amisulpride 50 mg/day recipients.

Conclusions: Data from a number of double-blind trials indicate that amisulpride is effective in the medium term treatment of dysthymia and is very well tolerated in most patients. Further efficacy and tolerability comparisons with the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors would be beneficial. The longer term tolerability profile of amisulpride has yet to be evaluated; nevertheless, the generally good tolerability of the drug is a potentially useful feature for treatment of a chronic disease such as dysthymia.

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References

  1. Willner P. The mesolimbic dopamine system as a target for rapid antidepressant action. Int Clin Psychopharmacol 1997; 12 Suppl. 3: S7–14

    Article  PubMed  Google Scholar 

  2. Rein W, Ayuso JL. Amisulpride: expert report on clinical documetation (dysthymia). Le Plessis-Robinson: Synthélabo Groupe, 1997. (Data on file)

    Google Scholar 

  3. Baldwin D, Rudge S, Thomas S. Dysthymia: options in pharmacotherapy. CNS Drugs 1995 Dec; 4: 422–31

    Article  CAS  Google Scholar 

  4. American Psychiatric Association, editor. Diagnostic and statistical manual of mental disorders IV. 4th ed. Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  5. Hellerstein DJ, Little SAS. Current perspectives on the diagnosis and treatment of double depression. CNS Drugs 1996 May; 5: 344–57

    Article  Google Scholar 

  6. Friedman RA, Kocsis JH. Pharmacotherapy for chronic depression. Mood Disorders 1996 Mar; 19(1): 121–32

    CAS  Google Scholar 

  7. Weissaman MM, Leaf PJ, Bruce ML, et al. The epidemiology of dysthymia in five communities: rates, risks, comorbidity, and treatment. Am J Psychiatry 1988; 145: 815–9

    Google Scholar 

  8. Regier DA, Narrow WE, Rae DS, et al. The defacto US mental and addictive disorders service system: Epidemiological Catchment Area prospective 1 -year prevalence rates of disorders and services. Arch Gen Psychiatry 1993; 50: 85–94

    Article  PubMed  CAS  Google Scholar 

  9. Horwath E, Johnson J, Klerman GL, et al. Depressive symptoms as relative and attributable risk factors for first-onset major depression. Arch Gen Psychiatry 1992; 49: 817–23

    Article  PubMed  CAS  Google Scholar 

  10. Robbins LN, Heizer JE, Weissman MM, et al. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984; 41: 949–58

    Article  Google Scholar 

  11. Scatton B, Claustre Y, Cudennec A, et al. Amisulpride: from animal pharmacology to therapeutic action. Int Clin Psychopharmacol 1997 May; 12 Suppl. 2: 29–36

    Article  Google Scholar 

  12. Perrault G, Depoortere R, Morel E, et al. Psychopharmacological profile of amisulpride: an antipsychotic drug with presyn-aptic D2/D3 dopamine receptor antagonist activity and limbic selectivity. J Pharmacol Exp Ther 1997 Jan; 280: 73–82

    PubMed  CAS  Google Scholar 

  13. Schoemaker H, Claustre Y, Fage D, et al. Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther 1997 Jan; 280: 83–97

    PubMed  CAS  Google Scholar 

  14. Dufour A, Desanti C. Pharmacokinetics and metabolism of amisulpride [in French]. Ann Psychiatr 1988; 3(3): 298–305

    Google Scholar 

  15. Guyon A, Assouly-Besse F, Biala G, et al. Potentiation by low doses of selected neuroleptics of food-induced conditioned place preference in rats. Psychopharmacology 1993 Mar; 110: 460–6

    Article  PubMed  CAS  Google Scholar 

  16. Ramaekers JG, Louwerens JW, Muntjewerff ND, et al. Psychomotor, cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic. J Clin Psychophannacol 1999 Jun; 19(3): 209–21

    Article  CAS  Google Scholar 

  17. Bianchetti G, Canal M, Rosenzweig P. Amisulpride: summary of human pharmacology and pharmacokinetics. Report no. 95-00679-EN-02. Le Plessis Robinson: Synthélabo Groupe, 1995. (Data on file)

    Google Scholar 

  18. Lecrubier Y, Boyer P, Turjanski S. Amisulpride versus imipramine and placebo in dysthymia and major depression. J Affect Disord 1997 Apr; 43: 95–103

    Article  PubMed  CAS  Google Scholar 

  19. Smeraldi E. Amisulpride versus fluoxetine in patients with dysthymia or major depression in partial remission: a double-blind, comparative study. J Affect Disord 1998; 48: 47–56

    Article  PubMed  CAS  Google Scholar 

  20. Boyer P, Lecrubier Y, Stalla-Bourdillon A, et al. Amisulpride versus amineptine and placebo for the treatment of dysthymia. Neuropsychobiology 1999; 39: 25–32

    Article  PubMed  CAS  Google Scholar 

  21. Ravizza L, AMILONG Investigators. Amisulpride in medium-term treatment of dysthymia: a six-month, double-blind safety study versus amitriptyline. J Psychophannacol 1999; 13(3): 248–54

    Article  CAS  Google Scholar 

  22. Gwirtsman HE, Blehar MC, McCullough JP, et al. Standardized assessment of dysthymia: report of a National Institute of Mental Health Conference. Psychophannacol Bull 1997; 33(1): 3–11

    CAS  Google Scholar 

  23. Lecrubier Y Phannacological interventions in dysthymia. Eur Psychiatry 1996; 11 Suppl. 3: 129s–33s

    Article  Google Scholar 

  24. Le Plessis-Robinson: Synthélabo Groupe, 1998. (Data on file)

  25. Bellino S, Barzega G, Bogetto F, et al. An open-label, randomized, prospective comparison of sertraline and amisulpride in the treatment of dysthymia in the elderly. Curr Ther Res Clin Exp 1997 Oct; 58: 798–808

    Article  CAS  Google Scholar 

  26. Rein W, Guerault E, Fleurot O. Amisulpride — clinical textual summary: dysthymia.c Groupe, 1997. (Data on file)

  27. Dreyfus JF, Rein W, Agoumi W, et al. Multicentre controlled study of amisulpride versus imipramine versus placebo for the treatment of dysthymia (chronic depressive neurosis). Le Plessis-Robinson: Synthélabo Groupe, 1997. (Data on file)

    Google Scholar 

  28. Demontrond V, Rein W, Theron M, et al. Multicentre controlled study of amisulpride-amineptine-placebo for the treatment of patients with dysthymia in primary care. Le PLessis-Robinson: Synthélabo Groupe, 1997. (Data on file)

    Google Scholar 

  29. Casadei G, Jori MC. Multicentre double-blind randomised trial to assess the efficacy and safety of amisulpride 50 mg/day compared with fluoxetine 20 mg/day in patients with dysthymia non responsive to placebo. Le Plessis-Robinson: Synthélabo Groupe, 1997. (Data on file)

    Google Scholar 

  30. Jori MC, Cesana BM, Casadei G. Multicentre, double-blind, randomized, comparative trial to assess safety and efficacy of amisulpride 50 mg/day versus amitriptyline 25–75 mg/day upon medium-tenn administration (6 months) in patients with dysthymia. Le Plessis-Robinson: Synthélabo Groupe, 1997. (Data on file)

    Google Scholar 

  31. Tracqui A, Mutter-Schmidt C, Kintz P. Amisulpride poisoning: a report on two cases. Hum Exp Toxicol 1995 Mar; 14: 294–8

    Article  PubMed  CAS  Google Scholar 

  32. Rein W, Favennec-Meidinger C. Amisulpride clinical textual summary (IV B). Le Plessis-Robinson: Synthèlabo Groupe, 1995, Report no. 95-00854-EN-00. (Data on file)

    Google Scholar 

  33. Harrison WM, Stewart JW. Pharmacotherapy of dysthymic disorder. In: Kocsis JH, Klein DN, editors. Diagnosis and treatment of chronic depression. New York: The Guilford Press, 1995: 124–45

    Google Scholar 

  34. Mason BJ, Kocsis JH, Leon AC, et al. Measurement of severity and treatmentresponse in dysthymia. Psychiatr Ann 1993; 23: 625–31

    Google Scholar 

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Stuart Noble & Paul Benfield

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Noble, S., Benfield, P. Amisulpride. CNS Drugs 12, 471–483 (1999). https://doi.org/10.2165/00023210-199912060-00005

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Keywords

  • Adis International Limited
  • Fluoxetine
  • Major Depression
  • Imipramine
  • Amitriptyline