Background: Results from randomized controlled trials (RCTs) are considered to give the most reliable information on treatment outcome (efficacy). Yet, the generalizability of efficacy results to daily practice (effectiveness) might be diminished by the design of RCTs. The STAR*D trial approached daily practice as much as possible, but still has some properties of an RCT. In this study, we compare results from treatment of major depressive disorder (MDD) in routine clinical practice to those of RCTs and STAR*D. Methods: Effectiveness in routine clinical practice was compared with efficacy results from 15 meta-analyses on antidepressant, psychotherapeutic and combination treatment and results from STAR*D. Data on daily practice patients and treatments were derived from a routine outcome monitoring (ROM) system. Treatment outcome was defined as proportion of remitters (MADRS ≤10) and within-group effect size. Results: From ROM, 598 patients suffering from a MDD episode according to the MINI-plus were included. Remission percentages were lower in routine practice than in meta-analyses for all treatment modalities (32 vs.40–74%). Differences were less explicit for antidepressants (21 vs. 34–47%) than for individual psychotherapy (27 vs. 34–58%; effect size 0.85 vs. 1.71) and combination therapy (21 vs. 45–63%), since only 60% of the meta-analyses for antidepressants showed significant differences with ROM, while for psychotherapy and combination treatment almost all meta-analyses showed significant differences. No differences in effectiveness were found between routine practice and STAR*D (antidepressants 27 vs. 28%; individual psychotherapy 27 vs. 25%; combination treatment 21 vs. 23%, respectively). Conclusions: Effectiveness of treatment for mild-to-moderate MDD in daily practice is similar to STAR*D and significantly lower than efficacy results from RCTs.

Fava GA, Tomba E: New modalities of assessment and treatment planning in depression: the sequential approach. CNS Drugs 2010;24:453–465.
IJff MA, Huijbregts KM, van Marwijk HW, Beekman AT, Hakkaart-van Roijen L, Rutten FF, Unutzer J, van der Feltz-Cornelis CM: 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. BMC Health Serv Res 2007;7:34.
Tunis SR, Stryer DB, Clancy CM: Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA 2003;290:1624–1632.
Mulder RT, Frampton C, Joyce PR, Porter R: Randomized controlled trials in psychiatry. Part II: their relationship to clinical practice. Aust N Z J Psychiatry 2003;37:265–269.
Licht RW, Gouliaev G, Vestergaard P, Frydenberg M: Generalisability of results from randomised drug trials: a trial on antimanic treatment. Br J Psychiatry 1997;170:264–267.
Wells KB: Treatment research at the crossroads: the scientific interface of clinical trials and effectiveness research. Am J Psychiatry 1999;156:5–10.
Rothwell PM: External validity of randomised controlled trials: ‘to whom do the results of this trial apply?’. Lancet 2005;365:82–93.
Hamilton M: Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6:278–296.
Pigott HE, Leventhal AM, Alter GS, Boren JJ: Efficacy and effectiveness of antidepressants: current status of research. Psychother Psychosom 2010;79:267–279.
de Beurs BE, den Hollander-Gijsman ME, van Rood YR, van der Wee NJ, Giltay EJ, van Noorden MS, van der Lem R, van FE, Zitman FG: Routine outcome monitoring in the Netherlands: practical experiences with a web-based strategy for the assessment of treatment outcome in clinical practice. Clin Psychol Psychother 2011;18:1–12.
Asberg M, Montgomery SA, Perris C, Schalling D, Sedvall G: A comprehensive psychopathological rating scale. Acta Psychiatr Scand Suppl 1978;271:5–27.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J: An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–571.
Entsuah AR, Huang H, Thase ME: Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry 2001;62:869–877.
Davidson JR, Meoni P, Haudiquet V, Cantillon M, Hackett D: Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms. Depress Anxiety 2002;16:4–13.
Stahl SM, Entsuah R, Rudolph RL: Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Biol Psychiatry 2002;52:1166–1174.
Einarson TR, Arikian SR, Casciano J, Doyle JJ: Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors, and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials. Clin Ther 1999;21:296–308.
Storosum JG, Elferink AJ, van Zwieten BJ, van den BW, Gersons BP, van Strik R, Broekmans AW: Short-term efficacy of tricyclic antidepressants revisited: a meta-analytic study. Eur Neuropsychopharmacol 2001;11:173–180.
Nelson JC: A review of the efficacy of serotonergic and noradrenergic reuptake inhibitors for treatment of major depression. Biol Psychiatry 1999;46:1301–1308.
Steffens DC, Krishnan KR, Helms MJ: Are SSRIs better than TCAs? Comparison of SSRIs and TCAs: a meta-analysis. Depress Anxiety 1997;6:10–18.
Bech P, Cialdella P, Haugh MC, Birkett MA, Hours A, Boissel JP, Tollefson GD: Meta-analysis of randomised controlled trials of fluoxetine v. placebo and tricyclic antidepressants in the short-term treatment of major depression. Br J Psychiatry 2000;176:421–428.
Thase ME, Entsuah AR, Rudolph RL: Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001;178:234–241.
de Maat SM, Dekker J, Schoevers RA, de Jonghe F: Relative efficacy of psychotherapy and combined therapy in the treatment of depression: a meta-analysis. Eur Psychiatry 2007;22:1–8.
Thase ME, Greenhouse JB, Frank E, Reynolds CF, III, Pilkonis PA, Hurley K, Grochocinski V, Kupfer DJ: Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations. Arch Gen Psychiatry 1997;54:1009–1015.
Wexler BE, Cicchetti DV: The outpatient treatment of depression: implications of outcome research for clinical practice. J Nerv Ment Dis 1992;180:277–286.
Montgomery SA: A meta-analysis of the efficacy and tolerability of paroxetine versus tricyclic antidepressants in the treatment of major depression. Int Clin Psychopharmacol 2001;16:169–178.
Kasper S, Zivkov M, Roes KC, Pols AG: Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline. Eur Neuropsychopharmacol 1997;7:115–124.
Beasley CM Jr, Nilsson ME, Koke SC, Gonzales JS: Efficacy, adverse events, and treatment discontinuations in fluoxetine clinical studies of major depression: a meta-analysis of the 20-mg/day dose. J Clin Psychiatry 2000;61:722–728.
Thase ME, Haight BR, Richard N, Rockett CB, Mitton M, Modell JG, VanMeter S, Harriett AE, Wang Y: Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials. J Clin Psychiatry 2005;66:974–981.
Minami T, Wampold BE, Serlin RC, Kircher JC, Brown GS: Benchmarks for psychotherapy efficacy in adult major depression. J Consult Clin Psychol 2007;75:232–243.
Becker BJ: Synthesizing standardized mean-change measures. Br J Math Stat Psychol 1988;41:257–278.
Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M: Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006;163:28–40.
Thase ME, Friedman ES, Biggs MM, Wisniewski SR, Trivedi MH, Luther JF, Fava M, Nierenberg AA, McGrath PJ, Warden D, Niederehe G, Hollon SD, Rush AJ: Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry 2007;164:739–752.
Landelijke Stuurgroep Richtlijn Ontwikkeling in de GGZ: Multidisciplinaire richtlijn voor diagnostiek en behandeling van volwassen cliënten met een depressie, herziene versie. Stuurgroep Richtlijnen, Trimbos Instituut, 2005.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC: The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):22–33.
Hawley CJ: Depression rating scales can be related to each other by simple equations. Int J Psychiatry Clin Pract 1998;2:215–219.
Mittmann N, Mitter S, Borden EK, Herrmann N, Naranjo CA, Shear NH: Montgomery-Asberg severity gradations. Am J Psychiatry 1997;154:1320–1321.
Zimmerman M, Posternak MA, Chelminski I: Defining remission on the Montgomery-Asberg depression rating scale. J Clin Psychiatry 2004;65:163–168.
Carmody TJ, Rush AJ, Bernstein I, Warden D, Brannan S, Burnham D, Woo A, Trivedi MH: The Montgomery Asberg and the Hamilton ratings of depression: a comparison of measures. Eur Neuropsychopharmacol 2006;16:601–611.
Hawley CJ, Gale TM, Sivakumaran T: Defining remission by cut off score on the MADRS: selecting the optimal value. J Affect Disord 2002;72:177–184.
Bandelow B, Baldwin DS, Dolberg OT, Andersen HF, Stein DJ: What is the threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder? J Clin Psychiatry 2006;67:1428–1434.
Altman DG: Practical Statistics for Medical Research. Oxford, Chapman and Hall, 1991, pp 229–276.
Altman DG: Practical Statistics for Medical Research. Oxford, Chapman and Hall, 1991, pp 179–228.
Stewart JW, McGrath PJ, Quitkin FM: Can mildly depressed outpatients with atypical depression benefit from antidepressants? Am J Psychiatry 1992;149:615–619.
Wisniewski SR, Rush AJ, Nierenberg AA, Gaynes BN, Warden D, Luther JF, McGrath PJ, Lavori PW, Thase ME, Fava M, Trivedi MH: Can phase III trial results of antidepressant medications be generalized to clinical practice? A STAR*D report. Am J Psychiatry 2009;166:599–607.
van der Lem R, van der Wee N, van Veen T, Zitman FG: The generalisability of antidepressant efficacy trials to routine psychiatric out-patient practice. Psychol Med 2011;41:1353–1363.
Zimmerman M, Posternak MA, Chelminski I: Symptom severity and exclusion from antidepressant efficacy trials. J Clin Psychopharmacol 2002;22:610–614.
Leonard KL: Is patient satisfaction sensitive to changes in the quality of care? An exploitation of the Hawthorne effect. J Health Econ 2008;27:444–459.
Demyttenaere K, Adelin A, Patrick M, Walthere D, Katrien de B, Michele S: Six-month compliance with antidepressant medication in the treatment of major depressive disorder. Int Clin Psychopharmacol 2008;23:36–42.
Bech P: Struggle for subtypes in primary and secondary depression and their mode-specific treatment or healing. Psychother Psychosom 2010;79:331–338.
McKenzie N, Marks I: Routine monitoring of outcome over 11 years in a residential behavioural psychotherapy unit. Psychother Psychosom 2003;72:223–227.
McKay R, McDonald R: Expensive detour or a way forward? The experience of routine outcome measurement in an aged care psychiatry service. Australas Psychiatry 2008;16:428–432.
Jacobson NS, Truax P: Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. J Consult Clin Psychol 1991;59:12–19.
Schmitz N, Hartkamp N, Franke GH: Assessing clinically significant change: application to the SCL-90-R. Psychol Rep 2000;86:263–274.
Barkham M, Stiles WB, Connell J, Twigg E, Leach C, Lucock M, Mellor-Clark J, Bower P, King M, Shapiro DA, Hardy GE, Greenberg L, Angus L: Effects of psychological therapies in randomized trials and practice-based studies. Br J Clin Psychol 2008;47:397–415.
Moleiro C, Beutler LE: Clinically significant change in psychotherapy for depressive disorders. J Affect Disord 2009;115:220–224.
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