What to expect from a third step in treatment resistant depression: A prospective open study on escitalopram

Abstract

Objectives. Only few studies investigated treatment strategies for treatment resistant depression (TRD). The objective of this multicentre study was to evaluate TRD patients who did not respond to at least two antidepressants. Methods. A total of 417 patients, who failed to respond to a previous retrospectively assessed antidepressant (AD1), were firstly included in a 6-week venlafaxine treatment (AD2); secondly, those who failed to respond were treated for further 6 weeks with escitalopram (AD3). Results. Out of 417 patients who had failed to respond to previous treatment (AD1), 334 completed treatment with venlafaxine to prospectively define TRD. In the intent to treat (ITT) population in the first phase of the trial (AD2), responders to venlafaxine were 151 (36.21%) out of which remitters were 83 (19.90%). After phase one, 170 non-responders, defined as TRD, were included in the second phase and 157 completed the course. Of the 170 ITT entering the second phase (AD3), responders to escitalopram were 71 (41.76%) out of which remitters were 39 (22.94%). After the third treatment, patients showed a dropout rate of 7.65% and a rate of presence of at least one serious adverse event of 19.18%. Conclusions. Relevant rates of response and remission may be observed after a third line treatment in patients resistant to two previous treatments. A relevant limitation of this study was represented by the design: naturalistic, non-randomized, open-label, without a control sample and with unblinded raters.

Key words::

• major depressive disorder
• antidepressants
• pharmacotherapy
• resistant depression
• escitalopram

Acknowledgements

None to declare.

Statement of Interest

Dr Souery has received grant/research support from GlaxoSmithKline and Lundbeck; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen and Lundbeck. Dr Calati, Dr Juven-Wetzler, Dr Gailledreau, Dr Modavi, Dr Sentissi and Dr Pitchot declare no conflict of interest. K. Papageorgiou received honoraria from RB Pharmaceuticals. Prof. Papadimitriou has served on speakers/advisory boards and/or has received consultancy fees for participation in research and in clinical expert groups, as well as unrestricted grants for the 1st Department of Psychiatry of Athens University Medical School of which he is the Chairman, from various Pharmaceutical Industry Companies including Eli Lilly, Bristol Myers Squibb, Sanofi, Wyeth, AstraZeneca, Servier, GAP, Specifar, Elpen, Pfizer, Organon, Janssen and Lundbeck. Prof. Dikeos has been on speakers or advisory boards for, and/or has received consultancy fees for participation in research and for participation in clinical expert groups from various Pharmaceutical Industry Companies including AstraZeneca, Boehringer, Bristol Myers Squibb, Eli Lilly, Genesis Pharma, GlaxoSmithKline, Janssen, Lundbeck, Organon, Sanofi, UniPharma, and Wyeth; he has also received unrestricted grants from Lilly and AstraZeneca for the Sleep Research Unit of Eginition Hospital (Athens University), of which he is director. Prof. Montgomery has been a consultant or served on Advisory boards: AstraZeneca, Bionevia, Bristol Myers Squibb, Forest, GlaxoSmithKline, Grunenthal, Intellect Pharma, Johnson & Johnson, Lilly, Lundbeck, Merck, Merz, M’s Science, Neurim, Otsuka, Pierre Fabre, Pfizer, Pharmaneuroboost, Richter, Roche, Sanofi, Sepracor, Servier, Shire, Synosis, Takeda, Theracos, Targacept, Transcept, UBC, Xytis and Wyeth. Prof. 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, Janssen and Neuraxpharm. Prof. Zohar has received grant/research support from Lundbeck, Servier and Pfizer, has served as a consultant or on advisory boards for Servier, Pfizer, Solvay and Actelion, and has served on speakers’ bureaus for Lundbeck, GSK, Jazz and Solvay. Prof. Mendlewicz is a member of the Board of the Lundbeck International Neuroscience Foundation and of Advisory Board of Servier. Prof. Serretti is or has been consultant/speaker for: Abbott, Astra Zeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Pfizer, Sanofi, Servier.

This study was supported by an unrestricted grant from Lundbeck for the Group for the Study of Resistant Depression (GSRD). Lundbeck had no further role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. All authors were actively involved in the design of the study, the analytical method of the study, the selection and review of all scientific content. All authors had full editorial control during the writing of the manuscript and finally approved it.

Supplementary material available online

Supplementary Table I–IV.