Skip to main content Accessibility help
×
Home

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

  • R. van der Lem (a1), N. J. A. van der Wee (a1) (a2), T. van Veen (a1) and F. G. Zitman (a1)

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.

Copyright

Corresponding author

*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)

References

Hide All
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.
Asberg, M, Montgomery, SA, Perris, C, Schalling, D, Sedvall, G (1978). A comprehensive psychopathological rating scale. Acta Psychiatrica Scandinavica (Suppl.), 5–27.
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, 7578.
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, 11901196.
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, 601611.
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.
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, 308326.
DeMartinis, NA, Schweizer, E, Rickels, K (1996). An open-label trial of nefazodone in high comorbidity panic disorder. Journal of Clinical Psychiatry 57, 245248.
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, 409416.
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, 308315.
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), 4852.
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, 10871091.
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, 592602.
Fava, GA, Ruini, C, Rafanelli, C (2005). Sequential treatment of mood and anxiety disorders. Journal of Clinical Psychiatry 66, 13921400.
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, 577584.
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, 389399.
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, 225231.
Hamilton, M (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology 6, 278296.
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, 9799.
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, 215219.
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.
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.
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, 121127.
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.
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, 264267.
Livesley, WJ, Jackson, DW, Schroeder, ML (1991). Dimensions of personality pathology. Canadian Journal of Psychiatry 36, 557562.
Mittmann, N, Mitter, S, Borden, EK, Herrmann, N, Naranjo, CA, Shear, NH (1997). Montgomery-Asberg severity gradations. American Journal of Psychiatry 154, 13201321.
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, 265269.
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.
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.
Partonen, T, Sihvo, S, Lonnqvist, JK (1996). Patients excluded from an antidepressant efficacy trial. Journal of Clinical Psychiatry 57, 572575.
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, 191200.
Royston, P (2005). Multiple imputation of missing values: update. Stata Journal 5, 188201.
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, 119142.
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), 2233.
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, 16741681.
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, 13121320.
Stahl, SM (2000). Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline. Biological Psychiatry 48, 894901.
Stewart, JW, McGrath, PJ, Quitkin, FM (1992). Can mildly depressed outpatients with atypical depression benefit from antidepressants? American Journal of Psychiatry 149, 615619.
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, 13561364.
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, 16241632.
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, 289300.
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, 252259.
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, 115128.
Wells, KB (1999). Treatment research at the crossroads: the scientific interface of clinical trials and effectiveness research. American Journal of Psychiatry 156, 5–10.
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, 599607.
Zetin, M, Hoepner, CT (2007). Relevance of exclusion criteria in antidepressant clinical trials: a replication study. Journal of Clinical Psychopharmacology 27, 295301.
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, 8794.
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, 469473.
Zimmerman, M, Posternak, MA, Chelminski, I (2002 b). Symptom severity and exclusion from antidepressant efficacy trials. Journal of Clinical Psychopharmacology 22, 610614.
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, 577582.

Keywords

Type Description Title
WORD
Supplementary materials

Lem supplementary material
Appendix.doc

 Word (111 KB)
111 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed