Advertisement

Clinical Drug Investigation

, Volume 31, Issue 1, pp 61–71 | Cite as

Pirlindole in the Treatment of Depression

A Meta-Analysis
  • Ana Macedo
  • Eva Leiria
  • Augusto Filipe
Original Research Article

Abstract

Background: Depressive disorders are common health problems. Both preclinical and clinical studies have shown that pirlindole, a tetracyclic compound, is suitable for the management of depression; however, a systematic review is needed to accurately select randomized controlled trials (RCTs) for a meta-analysis that will provide more consistent and accurate results regarding the efficacy and tolerability of the drug.

Objectives: To evaluate the efficacy and frequency of adverse events with pirlindole in comparison with active comparators (monoamine oxidase inhibitors [MAOIs], tricyclic antidepressants, tetracyclic antidepressants, and selective serotonin reuptake inhibitors [SSRIs]) for the treatment of major depression.

Methods: Data were searched through MEDLINE (via PubMed), EMBASE, the Cochrane Central Register of Controlled Trials and a manual search through the sponsor’s available archives (1966 to 30 August 2010). The metaanalysis was performed using the Mantel-Haenszel technique and analysing data through Comprehensive Meta-Analysis software version 1.0.23. Studies were included if they were RCTs evaluating the efficacy and number of reported adverse events with pirlindole in comparison with active comparators for the treatment of major depression in adults. Placebo-controlled trials were excluded to minimize study heterogeneity.

Results: This systematic review included ten published articles and one nonpublished report corresponding to a total of 13 clinical trials in the adult population. Two RCTs were excluded from the meta-analysis because the comparator was placebo. Two more studies were excluded, one because randomization could not be confirmed and the other because it described follow-up data on patients from a study that had already been included in the meta-analysis. Therefore, only nine RCTs were included in the meta-analysis. No differences were found between pirlindole and its active comparators with regard to the percentage of patients whose clinical condition improved by 50% according to the Hamilton Depression Rating Scale (HDRS) [odds ratio (OR) 1.52; 95% confidence interval [CI] 0.92, 2.51; p = 0.11] and Hamilton Anxiety Rating Scale (HARS) [OR 1.15; 95% CI 0.69, 1.90; p = 0.59]. With regard to the improvements in HDRS and HARS, the results were favourable for patients treated with pirlindole (depression: absolute value 0.18; 95% CI −0.01, 0.37; p = 0.06; anxiety: absolute value 0.26; 95% CI 0.03, 0.48; p = 0.03).

Conclusion: This systematic review and meta-analysis showed that all RCTs included reported efficacy outcomes for pirlindole comparable to those of its comparators, and that pirlindole was significantly better in terms of reducing anxiety symptoms. However, the analysis of these results should take into account the quality of the original included articles, which had a mean Jadad trial quality score of 3.7 (out of 5). Therefore, further clinical trials should be conducted to evaluate the benefits of pirlindole.

Keywords

Bipolar Disorder Fluoxetine Tyramine Active Comparator Moclobemide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Grupo Tecnimede markets pirlindole in Portugal and funded the conduct of this meta-analysis and the preparation of this article.

Ana Macedo, MD, PhD, and Eva Leiria, MS, work as scientific advisers at KeyPoint, Consultoria Científica, Lda. Augusto Filipe, MD, is an employee of Grupo Tecnimede and reviewed the final manuscript. The authors have no other conflicts of interest that are directly relevant to the content of this meta-analysis.

The authors wish to thank Ana Maria Tomé, PharmD, and Inês Moital for assistance in the revision of the article and Liliana Coelho for assistance in the management of the manuscript submission and bibliographic research.

References

  1. 1.
    WHO. Mental health [online]. Available from URL: http://www.who.int/mental_health/management/depression/ definition/en/ [Accessed 2010 May 17]Google Scholar
  2. 2.
    Eaton W, Shao H, Nestadt G, et al. Population-based study of first onset and chronicity in major depressive disorder. Arch Gen Psychiatry 2008; 65: 513–20PubMedCrossRefGoogle Scholar
  3. 3.
    Bschor T, Adli M. Continuing medical education: treatment of depressive disorders. Dtsch Arztebl Int 2008; 105: 782–92PubMedGoogle Scholar
  4. 4.
    Möller H-J, Volz HP. Drug treatment of depression in the 1990s: an overview of achievements and future possibilities. Drugs 1996; 52: 625–38PubMedCrossRefGoogle Scholar
  5. 5.
    Möller H-J, Müller WE, Volz HP. Psychopharmakotherapie: ein Leitfaden für Klinik und Praxis. 2nd ed. Stuttgart Berlin Köln: Kohlhammer, 2000Google Scholar
  6. 6.
    Patkar AA, Pae C, Masand P. Transdermal selegiline: the new generation of monoamine oxidase inhibitors. CNS Spectr 2006; 5: 363–75Google Scholar
  7. 7.
    Lotufo-Neto F, Trivedi M, Thase ME. Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and broforamine for the treatment of depression. Neuropsychopharmacology 1999; 20: 226–47PubMedCrossRefGoogle Scholar
  8. 8.
    Fowler JS, Logan J, Azzaro AJ, et al. Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157. Neuropsychopharmacology 2010; 35: 623–31PubMedCrossRefGoogle Scholar
  9. 9.
    Bortolato M, Chen K, Shih JC. Monoamine oxidase inactivation: from pathophysiology to therapeutics. Adv Drug Deliv Rev 2008; 60: 1527–33PubMedCrossRefGoogle Scholar
  10. 10.
    Johnston JP. Some observations upon a new inhibitor or monoamine oxidase in brain tissue. Biochem Pharmacol 1968; 17: 1285–97PubMedCrossRefGoogle Scholar
  11. 11.
    Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry 2007; 68Suppl. 8: 35–41PubMedGoogle Scholar
  12. 12.
    Pacher P, Kecskemeti V. Trends in the development of new antidepressants: is there a light at the end of the tunnel? Curr Med Chem 2004; 11: 925–43PubMedCrossRefGoogle Scholar
  13. 13.
    Youdim MBH, Bakhle YS. Monoamine oxidase: isoforms and inhibitors in Parkinson’s disease and depressive illness. Brit J Pharmacol 2006; 147: S287–96CrossRefGoogle Scholar
  14. 14.
    Stahl SM, Felker A. Monoamine oxidase inhibitors: a modern guide to an unrequited class of antidepressants. CNS Spectr 2008; 13: 855–70PubMedGoogle Scholar
  15. 15.
    Bruhwyler J, Liégeoist JF, Géczy J. Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties. Pharmacol Res 1997; 30: 23–33CrossRefGoogle Scholar
  16. 16.
    De Wilde J, Mertens C, Dorpe JV, et al. Double-blind randomized controlled pilot study of the efficacy and tolerability of pirlindole, a reversible inhibitor monoamine oxidase A, and mianserin, in the treatment of depression. Hum Psychopharmacol 1997; 12: 41–6Google Scholar
  17. 17.
    Schäpperle O, Eckmann F, Immich H. A double-blind comparison of pirlindole with amitriptyline and imipramine. In: Pichot P, Berner P, Wolf R, et al., editors. Psychiatry: the state of the art. Vol. 3. Pharmacopsychiatry. New York: Plenum Press, 1983: 297–302Google Scholar
  18. 18.
    Tanghe A, Geerts S, Van Dorpe J, et al. Double-blind randomised controlled study of the efficacy and tolerability of two reversible monoamine oxidase A inhibitors, in the treatment of depression. Acta Psychiatrica Scandinavica 1997; 96: 134–41PubMedCrossRefGoogle Scholar
  19. 19.
    Silverstone T. Introduction to a new generation of antidepressant drugs: pirlindole. Psicopatologia 1987; 7: 432–6Google Scholar
  20. 20.
    Lehmann E, Kinzler E, Stuckmann A, et al. A double-blind comparative study on the use of 225mg pirlindole and 150mg desipramine in the treatment of depressive inpatients. In: Pichot P, Berner P, Wolf R, et al, editors. Psychiatry: the state of the art. Vol. 3. Pharmacopsychiatry. New York: Plenum Press, 1983: 321–7Google Scholar
  21. 21.
    Renfordt E. A comparison of pirlindole and amitriptyline in a double-blind controlled study. In: Pichot P, Berner P, Wolf R, et al, editors. Psychiatry: the state of the art. Vol. 3. Pharmacopsychiatry. New York: Plenum Press, 1983: 311–7Google Scholar
  22. 22.
    Blaha L. A double-blind comparative study of pirlindole and amitriptyline in thirty depressive patients. In: Pichot P, Berner P, Wolf R, et al, editors. Psychiatry: the state of the art. Vol. 3. Pharmacopsychiatry. New York: Plenum Press, 1983: 303–9Google Scholar
  23. 23.
    Saletu B, Grünberger J, Rajna P, et al. Examining pharmaco EEG-based predictions about the antidepressant action of pirlindole by double blind clinical trials. In: Pichot P, Berner P, Wolf R, et al, editors. Psychiatry: the state of the art. Vol. 3. Pharmacopsychiatry. New York: Plenum Press, 1983: 291–6Google Scholar
  24. 24.
    Pöldinger W. Pirlindole: results of an open clinical study in out-patients and of a double-blind study against maprotiline. In: Pichot P, Berner P, Wolf R, et al, editors. Psychiatry: the state of the art. Vol. 3. Pharmacopsychiatry. New York: Plenum Press, 1983: 3: 283–9Google Scholar
  25. 25.
    De Wilde JE, Geerts S, Van Dorpe J, et al. A double-blind randomised placebo-controlled study of the efficacy and safety of pirlindole, a reversible monoamine oxidase A inhibitor, in the treatment of depression. Acta Psychiatrica Scandinavica 1996; 94: 404–10PubMedCrossRefGoogle Scholar
  26. 26.
    Geerts S, Vandekerckhovev K, Bruhwyler J, et al. Pirlindole versus fluoxetine in the treatment of major depression: a controlled double-blind medium-term study. Prior Velho: Grupo Tecnimede, 2000. (Data on file)Google Scholar
  27. 27.
    Zapletálek M, Libiger J, Kaspárkova I, et al. Pyrazidol in the treatment of endogenous depression: a controlled study. Activ Nerv Sup 1981; 23: 200–2Google Scholar
  28. 28.
    Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1–12PubMedCrossRefGoogle Scholar
  29. 29.
    Diversity and heterogeneity [online]. Available from URL: http://www.cochrane-net.org/openlearning/HTML/ mod13-4.htm [Accessed 2003 Nov 18]Google Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.KeyPoint, Consultoria Científica, LdaMirafloresPortugal
  2. 2.Medical DepartmentGrupo TecnimedeSintraPortugal

Personalised recommendations