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The generalizability of antidepressant efficacy trials to routine psychiatric out-patient practice

Published online by Cambridge University Press:  16 November 2010

R. van der Lem ,
N. J. A. van der Wee ,
T. van Veen  and
F. G. Zitman
R. van der Lem*
Affiliation:
Leiden University Medical Center/Rivierduinen, Department of Psychiatry, Leiden, The Netherlands
N. J. A. van der Wee
Affiliation:
Leiden University Medical Center/Rivierduinen, Department of Psychiatry, Leiden, The Netherlands Leiden Institute for Brain and Cognition, Leiden, The Netherlands
T. van Veen
Affiliation:
Leiden University Medical Center/Rivierduinen, Department of Psychiatry, Leiden, The Netherlands
F. G. Zitman
Affiliation:
Leiden University Medical Center/Rivierduinen, Department of Psychiatry, Leiden, The Netherlands
*
*Address for correspondence: Drs. R. van der Lem, LUMC, Department of Psychiatry, Albinusdreef 2, PO box 9600, 2300 RC Leiden, The Netherlands. (Email: r.van_der_lem@lumc.nl)
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Abstract

Background

Generalizability of antidepressant efficacy trials (AETs) to daily practice is questioned because of their very stringent patient selection. This study aims to determine eligibility for AETs of out-patients suffering from major depression in a routine out-patient setting and investigates influence of eligibility on treatment outcome.

Method

Data collection (n=1653) was performed through routine outcome monitoring by independent trained research nurses. The Mini-International Neuropsychiatric Interview Plus and the Dimensional Assessment of Personality Pathology, short Dutch version were used for diagnostic assessment and personality pathology screening. The Montgomery–Asberg Depression Rating Scale (MADRS) was used for assessment of baseline severity and treatment outcome. Eligibility was assessed by stepwise application of commonly used exclusion criteria. Influence of eligibility on treatment outcome was investigated in a subsample of the 1653 patients who had at least one follow-up assessment (n=626). Eligible and non-eligible patients were compared on proportion of response (50% reduction) and remission on MADRS (MADRS⩽10).

Results

Altogether, 17–25% of the patients were eligible for AETs. The most common reasons for exclusion would be ‘not meeting minimum baseline severity’ and ‘presence of co-morbid Axis I disorder’. Eligible and non-eligible patients did not differ in treatment outcome. Only ‘meeting the minimum baseline severity’ is associated with remission.

Conclusions

The majority of ‘real life’ out-patients are not eligible for AETs. However, the influence of eligibility on treatment outcome seems to be small. This suggests that stringent patient selection by eligibility criteria is not the major reason for lack of generalizability of AETs. Exclusion of less severely depressed patients from the analyses resulted in better treatment outcome. Milder depression is highly prevalent in daily practice and more research into treatment effectiveness in milder depression is warranted.

Keywords

Antidepressant efficacy trialseligibility generalizabilitymajor depressionroutine outcome monitoring
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 7 , July 2011 , pp. 1353 - 1363
Copyright
Copyright © Cambridge University Press 2010

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References

Anderson, I, Pilling, S, Barnes, A, Bayliss, L, Bird, V (2009). The NICF guideline on the treatment and management of depression in adults. National Collaborating Centre for Mental Health and National Institute for Health and Clinical Excellence: The British Psychological Society and The Royal College of Psychiatrists.Google Scholar
Asberg, M, Montgomery, SA, Perris, C, Schalling, D, Sedvall, G (1978). A comprehensive psychopathological rating scale. Acta Psychiatrica Scandinavica (Suppl.), 5–27.CrossRefGoogle ScholarPubMed
Benkert, O, Szegedi, A, Philipp, M, Kohnen, R, Heinrich, C, Heukels, A, van der Vegte-Senden, M, Baker, RA, Simmons, JH, Schutte, AJ (2006). Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder. Journal of Clinical Psychopharmacology 26, 75–78.CrossRefGoogle ScholarPubMed
Bielski, RJ, Ventura, D, Chang, CC (2004). A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. Journal of Clinical Psychiatry 65, 1190–1196.CrossRefGoogle ScholarPubMed
Carmody, TJ, Rush, AJ, Bernstein, I, Warden, D, Brannan, S, Burnham, D, Woo, A, Trivedi, MH (2006). The Montgomery Asberg and the Hamilton ratings of depression: a comparison of measures. European Neuropsychopharmacology 16, 601–611.CrossRefGoogle ScholarPubMed
de Beurs, E, den Hollander-Gijsman, ME, van Rood, YR, van der Wee, NJ, Giltay, EJ, van Noorden, MS, van der Lem, R, van Fenema, E, Zitman, FG (2010). Routine outcome monitoring in the Netherlands: practical experiences with a web-based strategy for the assessment of treatment outcome in clinical practice. Clinical Psychology & Psychotherapy. Published online: 17 March 2010. doi:10.1002/cpp.696.Google Scholar
de Beurs, E, Rinne, T, van Kampen, D, Verheul, R, Andrea, H (2009). Reliability and validity of the Dutch Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF), a shortened version of the DAPP-Basic Questionnaire. Journal of Personality Disorders 23, 308–326.CrossRefGoogle ScholarPubMed
DeMartinis, NA, Schweizer, E, Rickels, K (1996). An open-label trial of nefazodone in high comorbidity panic disorder. Journal of Clinical Psychiatry 57, 245–248.Google ScholarPubMed
Derubeis, RJ, Hollon, SD, Amsterdam, JD, Shelton, RC, Young, PR, Salomon, RM, O'Reardon, JP, Lovett, ML, Gladis, MM, Brown, LL, Gallop, R (2005). Cognitive therapy vs medications in the treatment of moderate to severe depression. Archives of General Psychiatry 62, 409–416.CrossRefGoogle ScholarPubMed
Detke, MJ, Lu, Y, Goldstein, DJ, Hayes, JR, Demitrack, MA (2002). Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. Journal of Clinical Psychiatry 63, 308–315.CrossRefGoogle ScholarPubMed
Dinan, TG (2001). Efficacy and safety of weekly treatment with enteric-coated fluoxetine in patients with major depressive disorder. Journal of Clinical Psychiatry 62 (Suppl. 22), 48–52.Google ScholarPubMed
Donders, AR, van der Heijden, GJ, Stijnen, T, Moons, KG (2006). Review: a gentle introduction to imputation of missing values. Journal of Clinical Epidemiology 59, 1087–1091.CrossRefGoogle ScholarPubMed
Fabre, LF, Abuzzahab, FS, Amin, M, Claghorn, JL, Mendels, J, Petrie, WM, Dube, S, Small, JG (1995). Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biological Psychiatry 38, 592–602.CrossRefGoogle ScholarPubMed
Fava, GA, Ruini, C, Rafanelli, C (2005). Sequential treatment of mood and anxiety disorders. Journal of Clinical Psychiatry 66, 1392–1400.CrossRefGoogle ScholarPubMed
Golden, RN, Nemeroff, CB, McSorley, P, Pitts, CD, Dube, EM (2002). Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression. Journal of Clinical Psychiatry 63, 577–584.CrossRefGoogle ScholarPubMed
Goldstein, DJ, Lu, Y, Detke, MJ, Wiltse, C, Mallinckrodt, C, Demitrack, MA (2004). Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. Journal of Clinical Psychopharmacology 24, 389–399.CrossRefGoogle ScholarPubMed
Goldstein, DJ, Mallinckrodt, C, Lu, Y, Demitrack, MA (2002). Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. Journal of Clinical Psychiatry 63, 225–231.CrossRefGoogle ScholarPubMed
Hamilton, M (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology 6, 278–296.CrossRefGoogle ScholarPubMed
Hatcher, S (2008). The STAR*D trial: the 300 lb gorilla is in the room, but does it block all the light? Evidence Based Mental Health 11, 97–99.CrossRefGoogle Scholar
Hawley, CJ, Gale, TM, Smith, VRH, Sen, P (1998). Depression rating scales can be related to each other by simple equations. International Journal of Psychiatry in Clinical Practice 2, 215–219.CrossRefGoogle ScholarPubMed
IJff, MA, Huijbregts, KM, van Marwijk, HW, Beekman, AT, Hakkaart-van Roijen, L, Rutten, FF, Unutzer, J, van der Feltz-Cornelis, CM (2007). Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial. British Medical Care, Health Service Research 7, 34.CrossRefGoogle Scholar
Karasu, TB, Gelenberg, A, Merriam, A, Wang, P (2000). Practice Guideline for the Treatment of Patients with Major Depressive Disorder (2nd edn). Arlington, VA: American Psychiatric Association.Google Scholar
Langworth, S, Bodlund, O, Agren, H (2006). Efficacy and tolerability of reboxetine compared with citalopram: a double-blind study in patients with major depressive disorder. Journal of Clinical Psychopharmacology 26, 121–127.CrossRefGoogle ScholarPubMed
Lesser, IM, Leuchter, AF, Trivedi, MH, Davis, LL, Wisniewski, SR, Balasubramani, GK, Petersen, T, Stegman, D, Rush, AJ (2005). Characteristics of insured and noninsured outpatients with depression in STAR(*)D. Psychiatric Services 56, 995–1004.CrossRefGoogle ScholarPubMed
Licht, RW, Gouliaev, G, Vestergaard, P, Frydenberg, M (1997). Generalisability of results from randomised drug trials. A trial on antimanic treatment. British Journal of Psychiatry 170, 264–267.CrossRefGoogle ScholarPubMed
Livesley, WJ, Jackson, DW, Schroeder, ML (1991). Dimensions of personality pathology. Canadian Journal of Psychiatry 36, 557–562.CrossRefGoogle ScholarPubMed
Mittmann, N, Mitter, S, Borden, EK, Herrmann, N, Naranjo, CA, Shear, NH (1997). Montgomery-Asberg severity gradations. American Journal of Psychiatry 154, 1320–1321.Google ScholarPubMed
Mulder, RT, Frampton, C, Joyce, PR, Porter, R (2003). Randomized controlled trials in psychiatry. Part II: their relationship to clinical practice. Australian and New Zealand Journal of Psychiatry 37, 265–269.CrossRefGoogle ScholarPubMed
Mulder, RT, Joyce, PR, Frampton, CM, Luty, SE, Sullivan, PF (2006). Six months of treatment for depression: outcome and predictors of the course of illness. American Journal of Psychiatry 163, 95–100.CrossRefGoogle ScholarPubMed
National Taskforce Guideline Development in Mental Health Care (2005). Multidisciplinary guideline for diagnostics and treatment for adult patients suffering from depression, revised version. Utrecht: Trimbos Institute.Google Scholar
Partonen, T, Sihvo, S, Lonnqvist, JK (1996). Patients excluded from an antidepressant efficacy trial. Journal of Clinical Psychiatry 57, 572–575.CrossRefGoogle ScholarPubMed
Posternak, MA, Zimmerman, M, Keitner, GI, Miller, IW (2002). A re-evaluation of the exclusion criteria used in antidepressant efficacy trials. American Journal of Psychiatry 159, 191–200.CrossRefGoogle Scholar
Royston, P (2005). Multiple imputation of missing values: update. Stata Journal 5, 188–201.CrossRefGoogle Scholar
Rush, AJ, Fava, M, Wisniewski, SR, Lavori, PW, Trivedi, MH, Sackeim, HA, Thase, ME, Nierenberg, AA, Quitkin, FM, Kashner, TM, Kupfer, DJ, Rosenbaum, JF, Alpert, J, Stewart, JW, McGrath, PJ, Biggs, MM, Shores-Wilson, K, Lebowitz, BD, Ritz, L, Niederehe, G (2004). Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. Controlled Clinical Trials 25, 119–142.CrossRefGoogle Scholar
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 22–33.Google ScholarPubMed
Shelton, RC, Haman, KL, Rapaport, MH, Kiev, A, Smith, WT, Hirschfeld, RM, Lydiard, RB, Zajecka, JM, Dunner, DL (2006). A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder. Journal of Clinical Psychiatry 67, 1674–1681.CrossRefGoogle ScholarPubMed
Sir, A, D'Souza, RF, Uguz, S, George, T, Vahip, S, Hopwood, M, Martin, AJ, Lam, W, Burt, T (2005). Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. Journal of Clinical Psychiatry 66, 1312–1320.CrossRefGoogle ScholarPubMed
Stahl, SM (2000). Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline. Biological Psychiatry 48, 894–901.CrossRefGoogle ScholarPubMed
Stewart, JW, McGrath, PJ, Quitkin, FM (1992). Can mildly depressed outpatients with atypical depression benefit from antidepressants? American Journal of Psychiatry 149, 615–619.Google ScholarPubMed
Trivedi, MH, Pigotti, TA, Perera, P, Dillingham, KE, Carfagno, ML, Pitts, CD (2004). Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder. Journal of Clinical Psychiatry 65, 1356–1364.CrossRefGoogle ScholarPubMed
Tunis, SR, Stryer, DB, Clancy, CM (2003). Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. Journal of the American Medical Association 290, 1624–1632.Google ScholarPubMed
Uher, R, Farmer, A, Maier, W, Rietschel, M, Hauser, J, Marusic, A, Mors, O, Elkin, A, Williamson, RJ, Schmael, C, Henigsberg, N, Perez, J, Mendlewicz, J, Janzing, JG, Zobel, A, Skibinska, M, Kozel, D, Stamp, AS, Bajs, M, Placentino, A, Barreto, M, McGuffin, P, Aitchison, KJ (2008). Measuring depression: comparison and integration of three scales in the GENDEP study. Psychological Medicine 38, 289–300.CrossRefGoogle ScholarPubMed
Uher, R, Maier, W, Hauser, J, Marusic, A, Schmael, C, Mors, O, Henigsberg, N, Souery, D, Placentino, A, Rietschel, M, Zobel, A, Dmitrzak-Weglarz, M, Petrovic, A, Jorgensen, L, Kalember, P, Giovannini, C, Barreto, M, Elkin, A, Landau, S, Farmer, A, Aitchison, KJ, McGuffin, P (2009). Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. British Journal of Psychiatry 194, 252–259.CrossRefGoogle ScholarPubMed
van Kampen, D, de Beurs, E, Andrea, H (2008). A short form of the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ): the DAPP-SF. Psychiatry Research 160, 115–128.CrossRefGoogle Scholar
Wells, KB (1999). Treatment research at the crossroads: the scientific interface of clinical trials and effectiveness research. American Journal of Psychiatry 156, 5–10.CrossRefGoogle ScholarPubMed
Wisniewski, SR, Rush, AJ, Nierenberg, AA, Gaynes, BN, Warden, D, Luther, JF, McGrath, PJ, Lavori, PW, Thase, ME, Fava, M, Trivedi, MH (2009). Can phase III trial results of antidepressant medications be generalized to clinical practice? A STAR*D report. American Journal of Psychiatry 166, 599–607.CrossRefGoogle Scholar
Zetin, M, Hoepner, CT (2007). Relevance of exclusion criteria in antidepressant clinical trials: a replication study. Journal of Clinical Psychopharmacology 27, 295–301.CrossRefGoogle ScholarPubMed
Zimmerman, M, Chelminski, I, Posternak, MA (2004 a). Exclusion criteria used in antidepressant efficacy trials: consistency across studies and representativeness of samples included. Journal of Nervous and Mental Disease 192, 87–94.CrossRefGoogle ScholarPubMed
Zimmerman, M, Mattia, JI, Posternak, MA (2002 a). Are subjects in pharmacological treatment trials of depression representative of patients in routine clinical practice? American Journal of Psychiatry 159, 469–473.CrossRefGoogle ScholarPubMed
Zimmerman, M, Posternak, MA, Chelminski, I (2002 b). Symptom severity and exclusion from antidepressant efficacy trials. Journal of Clinical Psychopharmacology 22, 610–614.CrossRefGoogle ScholarPubMed
Zimmerman, M, Posternak, MA, Chelminski, I (2004 b). Derivation of a definition of remission on the Montgomery-Asberg depression rating scale corresponding to the definition of remission on the Hamilton rating scale for depression. Journal of Psychiatric Research 38, 577–582.CrossRefGoogle Scholar
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