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General and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders: a report by the WPA section of pharmacopsychiatry

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Abstract

Current gold standard approaches to the treatment of depression include pharmacotherapeutic and psychotherapeutic interventions with social support. Due to current controversies concerning the efficacy of antidepressants in randomized controlled trials, the generalizability of study findings to wider clinical practice and the increasing importance of socioeconomic considerations, it seems timely to address the uncertainty of concerned patients and relatives, and their treating psychiatrists and general practitioners. We therefore discuss both the efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders. We explain and clarify useful measures for assessing clinically meaningful antidepressant treatment effects and the types of studies that are useful for addressing uncertainties. This includes considerations of methodological issues in randomized controlled studies, meta-analyses, and effectiveness studies. Furthermore, we summarize the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties, and differences between studies using antidepressants and/or psychotherapy. We also address the differential effectiveness of antidepressant drugs with differing modes of action and in varying subtypes of depressive disorder. After highlighting the clinical usefulness of treatment algorithms and the divergent biological, psychological, and clinical efforts to predict the effectiveness of antidepressant treatments, we conclude that the spectrum of different antidepressant treatments has broadened over the last few decades. The efficacy and clinical effectiveness of antidepressants is statistically significant, clinically relevant, and proven repeatedly. Further optimization of treatment can be helped by clearly structured treatment algorithms and the implementation of psychotherapeutic interventions. Modern individualized antidepressant treatment is in most cases a well-tolerated and efficacious approach to minimize the negative impact of otherwise potentially devastating and life-threatening outcomes in depressive disorders.

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Notes

  1. Augmentation treatment: efficiency amplification of an antidepressant treatment with a substance that alone does not exert sufficient antidepressant activity to be used as a monotherapy.

  2. The mode of action of bupropion is discussed as a dopamine and noradrenaline reuptake inhibitor (DNRI), but there are now four PET scan studies in humans showing only a ~20% occupation of dopamine transporters with clinically relevant doses and no clear evidence of NE reuptake inhibition. This may be due to the fact that its affinity is 10–100 times less for the NE transporter than the DA transporter in rodents [135]. Nevertheless, it increases both norepinephrine and serotonin transmission [169].

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Conflicts of interest

T.C. Baghai accepted paid speaking engagements and acted as a consultant for Astra-Zeneca, Glaxo-Smith-Kline, Janssen-Cilag, Organon, Pfizer and Servier. M. Bauer has received Grant/Research Support from The Stanley Medical Research Institute, NARSAD and the European Commission (FP7). He is a consultant for AstraZeneca, Lilly, Servier, Lundbeck, Bristol-Myers Squibb and Otsuka, and has received Speaker Honoraria from AstraZeneca, Lilly, GlaxoSmithKline, Lundbeck, GlaxoSmithKline, Bristol-Myers Squibb and Otsuka. D. Baldwin holds or has held grants from Cephalon, GlaxoSmithKline, Lilly, Lundbeck, Pharmacia and Wyeth; has received honoraria from AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Lundbeck, Pharmacia, Pierre Fabre, Pfizer, Servier and Wyeth; and has served on advisory boards for AstraZeneca, GlaxoSmithKline, Grunenthal, Lilly, Lundbeck, Organon, Pierre Fabre, Pfizer and Servier. P. Blier received honoraria for speaking engagements, advisory boards, and/or investigator-initiated grants from Angelini, Astra-Zeneca, Bristol Myers Squibb, Eli Lilly, Euthymics, Janssen, Labopharm, Lundbeck, Merck, Organon, Pfizer, Pierre Fabre, Schering-Plough, Servier, Takeda, Wyeth. G.M.Goodwin holds or has held grants from Bailly Thomas charity, Medical Research Council, NIHR, Servier; has received honoraria from AstraZeneca, BMS, Lundbeck, Sanofi-Aventis, Servier, holds shares in P1vital ltd; has served on advisory boards for AstraZeneca, BMS, Boehringer Ingelheim, Cephalon, Janssen-Cilag, Lilly, Lundbeck, P1Vital, Servier, Shering Plough, Wyeth and acted as an expert witness for Lilly and Servier. K.N. Fountoulakis has received grant/research support from Eli Lilly, Bristol-Myers Squibb, and Servier; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb and Servier, Janssen, and has given lectures for AstraZeneca, Eli Lily, Janssen, Servier, and Bristol-Myers Suibb. S. Kasper has received grant/research support from Eli Lilly, Lundbeck, Bristol-Myers Squibb, GlaxoSmithKline, Organon, Sepracor and Servier; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Lundbeck, Pfizer, Organon, Schwabe, Sepracor, Servier, Janssen, and Novartis; and has served on speakers’ bureaus for AstraZeneca, Eli Lily, Lundbeck, Schwabe, Sepracor, Servier, Pierre Fabre, and Janssen. U.F. Malt has been paid for lecturing about treatment of mood disorders by Astra-Zeneca, GSK; Lilly and Lundbeck; and received honorarium by the Norwegian government’s Directorate of Health, for beeing member of task forces providing national treatment guidelines for Depression and Bipolar disorders respectively. D. Stein has received research grants and/or consultancy honoraria from Abbott, Astrazeneca, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Takeda, Tikvah, and Wyeth. H.-J. Möller has received grant/research support, is member of advisory boards or has served as a speaker for AstraZeneca, Bristol-Myers Squibb, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, Merck, Novartis, Organon, Pfizer, Sanofi-Aventis, Schering-Plough, Schwabe, Sepracor, Servier and Wyeth. B.E. Leonard, and M. Versiani had no conflicts of interest to declare.

This supplement was not sponsored by outside commercial interest. It was funded entirely by the authors.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of Munich, Nußbaumstraße 7, 80336, Munich, Germany

    Thomas C. Baghai & Hans-Jürgen Möller

  2. Department of Psychiatry and Psychotherapy, University Regensburg, Universitätsstraße 84, 93053, Regensburg, Germany

    Thomas C. Baghai

  3. Department of Psychiatry, University of Ottawa, Ottawa, Canada

    Pierre Blier

  4. University Department of Psychiatry, University of Southampton, Southampton, UK

    David S. Baldwin

  5. University Hospital Carl Gustav Carus, Dresden, Germany

    Michael Bauer

  6. University Department, Warneford Hospital, Oxford, UK

    Guy M. Goodwin

  7. 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Kostas N. Fountoulakis

  8. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria

    Siegfried Kasper

  9. National University of Ireland, Galway, Ireland

    Brian E. Leonard

  10. Department of Neuropsychiatry and Psychosomatic Medicine, Oslo University Hospital, Oslo, Norway

    Ulrik F. Malt

  11. MRC Unit of Anxiety Disorders, University of Stellenbosch, Cape Town, South Africa

    Dan Stein

  12. Department of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Marcio Versiani

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for the Section of Pharmacopsychiatry, World Psychiatric Association

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Correspondence to Thomas C. Baghai.

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The Section of Pharmacopsychiatry World Psychiatric Association is given in the Appendix.

Appendix: Section of Pharmacopsychiatry World Psychiatric Association

Appendix: Section of Pharmacopsychiatry World Psychiatric Association

Altamura C, Andreassen OA, Aarsland D, Baghai TC, Baldwin DS, Baron D, Bauer M, Belmaker RH, Blier P, Boyer P, Bunney WE, Burrows G, Fleischhacker W, Flores D, Fountoulakis KN, Gattaz WF, Goodwin G, Heinze G, Hindmarch I, Hoschl C, Kasper S, Sorensen PK, Langer SZ, Leonard B, Lopez-Ibor JJ, Malt U (co-chair), Millet B, Möller HJ (chair), Monti J, Müller-Oerlinghausen B, Okasha A, Olie JP, Paykel ES, Racagni G, Renshaw P, Rosenberg R, Rutz W, Saletu B, Sedvall G, Singh B (secretary), Stein DJ, Tandon R, Versiani M, Vieta E, Wegener G, Zohar J.

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Baghai, T.C., Blier, P., Baldwin, D.S. et al. General and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders: a report by the WPA section of pharmacopsychiatry. Eur Arch Psychiatry Clin Neurosci 261 (Suppl 3), 207–245 (2011). https://doi.org/10.1007/s00406-011-0259-6

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