Introduction: Data from the three available placebo-controlled trials with fixed doses of escitalopram in the acute therapy of DSM-IV major depressive disorder (MDD) were pooled. The hypothesis tested was that escitalopram 10 mg/d might be an effective dose in moderate MDD, whereas escitalopram 20 mg/d might be needed in severe depression. Methods: The Montgomery-Asberg Depression Scale with all 10 items was used at baseline to differentiate between moderate (score range 22 to 29) and severe (scores ≥ 30) major depression. The MADRS6 was selected as the primary efficacy parameter, using a standardised effect size of 0.40 as indicator of clincally significant response. Results: After 8 weeks of therapy, escitalopram 10 mg was superior to placebo, with a standardised effect size above 0.40 for patients with moderate depression, but not for those with severe depression. In contrast, 20 mg escitalopram was superior to placebo, with a standardised effect size above 0.40 in severe depression, but not in moderate depression. The MADRS6 showed response (standardised effect sizes above 0.40) for moderate depression after two weeks of treatment with 10 mg escitalopram and in severely depressed patients after 4 weeks with 20 mg escitalopram. Conclusion: Escitalopram 10 mg/d was the optimal dose for the treatment of moderate DSM-IV MDD, while escitalopram 20 mg/d was an effective dose in patients with moderate to severe depression.
References
-
1 American Psychiatric A ssociation. Diagnostic and statistical manual of mental disorders. Fourth edition (DSM-IV). Washington DC; American Psychiatric Association 1994
-
2
Bagby R M, Ryder A G, Schuller D R, Marshall M B.
The Hamilton Depression Rating Scale: Has the gold standard become a lead weight?.
Am J Psychiatry.
2004;
161
2163-2177
-
3
Barbui C, Hotopf M.
Amitryptiline v the rest: still the leading antidepressant after 40 years of randomised clinical trials.
Br J Psychiatry.
2001;
178
129-144
-
4
Bech P, Cialdella P, Haugh M, Birkett M A, Hours A, Boissel J P, Tollefson G D.
A meta-analysis of randomised controlled trials of fluoxetine versus placebo and tricyclic antidepressants in the short-term treatment of major depression.
Br J Psychiatry.
2000;
176
421-428
-
5
Bech P, Tanghøj P, Cialdella P, Friis A H, Pedersen A G.
Escitalopram dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression.
Int J Psychopharmacol.
2004;
7
283-290
-
6 Bech P. Pharmacological treatment of depressive disorders: A review. In: Maj M, Sartorius N. (eds) Depressive disorders in psychiatry. Chichester; Wiley, second edition 2002
-
7
Bulpitt C J.
Medical statistics: meta-analysis.
Lancet.
1988;
2
93-94
-
8
Burke W J, Gergel I, Bose A.
Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients.
J Clin Psychiatry.
2002;
63
331-336
-
9
Chen F, Larsen M B, Sánchez C, Wiborg O.
The S-enantiomer of R,S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors.
European Neuropsychopharmacology.
2005;
15
193-198
-
10 Cohen J. Statistical power analysis for the behavioural sciences. Mahwah, NJ; Lawrence Erlbaum 1988
-
11
Colonna L, Reines E H, Andersen H F.
A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive patients with major depressive disorder.
Curr Med Res Opin.
2005;
21
1659-1668
-
12
Demyttenaere K, Mesters P, Boulanger B, Dewe W, Delsemme M H, Gregoire J, Van Ganse E.
Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine.
J Affect Disord.
2001;
65
243-252
-
13
Fabre L F, Abuzzahab F S, Amin M, Claghorn J L, Mendels J, Petrie W M. et al .
Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo.
Biol Psychiatry.
1995;
38
592-602
-
14
Faries D, Herrera J, Rayamajhi J, DeBrota D, Demitrack M, Potter W Z.
The responsiveness of the Hamilton Depression Rating Scale.
J Psychiatr Res.
2000;
34
3-10
-
15
Gorman J, Korotzer A, Su G.
Efficacy Comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials.
CNS Spectr.
2002;
7 (4 Suppl 1)
40-44
-
16
Gram L F.
Fluoxetine.
N Eng J Med.
1994;
331
1354-1361
-
17
Kragh-Sorensen P, Hansen C E, Baastrup P C, Hvidberg E F.
Self-inhibiting action of nortryptilin’s antidepressive effect at high plasma levels.
Psychopharmacologia.
1976;
45
306-312
-
18
Lepola U M, Loft H, Reines E H.
Escitalopram (10-20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care.
Int Clin Psychopharmacol.
2003;
18
211-217
-
19
Licht R W, Qvitzau S, Allerup P, Bech P.
Validation of the Bech-Rafaelsen Melancholia Scale and the Hamilton Depression Scale in patients with major depression: is the total score a valid measure of illnes severity?.
Acta Psychiatr Scand.
2005;
111
144-199
-
20
Mittmann N, Mitter S, Borden E K, Herrmann N, Naranjo C A, Shear N H.
Montgomery-Asberg severity gradations.
Am J Psychiatry.
1997;
154
1320-1321
-
21
Moncrieff J, Kirsch I.
Efficacy of antidepressants in adults.
BMJ.
2005;
331
155-157
-
22
Moncrieff J.
Are antidepressants overrated? A review of methodological problems in antidepressant trials.
J Nerv Ment Dis.
2001;
189
288-295
-
23
Montgomery S A, Asberg M.
A new depression scale designed to be sensitive to change.
Br J Psychiatry.
1979;
134
382-389
-
24
Müller M J, Szegedi A, Wetzel H, Benkert O.
Moderate and severe depression. Gradations for the Montgomery-Asberg Depression Rating Scale.
J Affect Disord.
2000;
60
137-140
-
25 Ninan P T, Ventura D, Wang J. Escitalopram is effective and well tolerated in the treatment of severe depression. Data presented at the 156th Annual Meeting of the American Psychiatric Association, 17 - 22 May 2003, San Francisco, CA. Further details available at http://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id= scsr/SCSR_SCT-MD-26_final.pdf.
-
26
Olsen R L, Mortensen E L, Bech P.
Prevalence of major depression and stress indicators in the Danish general population.
Acta Psychiatr Scand.
2004;
109
96-103
-
27
O’Sullivan R L, Fava M, Augustin C, Baer L, Rosenbaum J F.
Sensitivity of the six-item Hamilton Depression Rating Scale.
Acta Psychiatr Scand.
1997;
95
379-384
-
28
Peto R.
Why do we need systematic overviews of randomised trials.
Stat Med.
1987;
6
233-244
-
29 Preskorn S H. Recent dose-effect studies regarding antidepressants. In: Balant LP, Benitez J, Dahl SG. (eds) Clinical pharmacology in psychiatry: finding the right dose of psychotropic drugs. Brussels; European Commission 1998: pp 45-61
-
30
Reisby N, Gram L F, Bech P, Sihm F, Krautwald O, Elley J, Ortmann J, Christiansen J.
Clomipramine: Plasma levels and clinical effects.
Communications in: Psychopharmacology.
1979;
3
341-351
-
31
Rifkin A.
SSRI optimal dose remains at issue.
J Clin Psychiatry.
1997;
58
87-88
-
32
Sánchez C, Bøgesø K P, Ebert B, Reines E H, Braestrup C.
Escitalopram versus citalopram: the surprising role of the R-enantiomer.
Psychopharmacology.
2004;
174
163-176
-
33
Schmid J E, Koch G, La Vange L M.
An overview of statistical issues and methods of meta-analyses.
J Biopharm Stat.
1991;
1
103-120
-
34
Stein D J, Andersen H F, Goodman W K.
Escitalopram for the treatment of GAD: Efficacy across different subgroups and outcomes.
Ann Clin Psychiatry.
2005;
17
71-75
-
35
Wade A, Lemming O M, Hedegaard K B.
Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care.
Int Clin Psychopharmacol.
2002;
17
95-102
-
36 World Health O rganisation. International Classification of Diseases, tenth revision (ICD-10). Diagnostic criteria for research. Geneva; World Organisation; Geneva 1993
Professor Per Bech
Psychiatric Research Unit
Frederiksborg General Hospital
3400 Hillerød
Denmark
Phone: +45 48 29 32 52
Fax: +45 48 26 38 77
Email: pebe@fa.dk
