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Correspondence |
Regional Secure Unit, West London Mental Health NHS Trust, Southall UB1 3EU, UK. E-mail: lelemanjiri{at}hotmail.com
Windmill Lodge, West London Mental Health NHS Trust, London
We noted the findings of Kasper et al (2005) and their conclusion that ‘escitalopram was efficacious in treatment of social anxiety disorder’ with interest. They reported a difference of 7.3 (P=0.005) on the Liebowitz Social Anxiety Scale (LSAS) from baseline to week 12, favouring escitalopram over placebo. They suggested that this difference was comparable to three previous studies that reported the efficacy of paroxetine in the treatment of social anxiety disorder (Stein et al, 1998; Allgulander, 1999; Baldwin et al, 1999).
Unfortunately, without the confidence interval (CI), reliable interpretation of the above difference is not possible. Hence we calculated the standardised effect size, which was 0.22 (95% CI 0.01–0.43). Although the lower limit of the CI is not reassuring, by convention, the point estimate of 0.22 can be interpreted as ‘small’.
We appreciate that small effect sizes can be clinically relevant, especially if the condition treated is common and the putative treatment is easily available, cheap and without adverse effects. In addition, the given treatment must perform better than other options. We compared the above effect size with the effect sizes for the three studies quoted above. These were 0.83 (95% CI 0.53–1.13), 1.36 (95% CI 0.90–1.80) and 0.38 (95% CI 0.14–0.61), respectively.
We then looked at the number needed to treat (NNT) based on the responders as per the Clinical Global Impression–Improvement (CGI–I) scores. The NNT for the study by Kasper et al (2005) is 7 (95% CI 4–20) and for the comparative studies, 4 (95% CI 3–6), 2 (95% CI 2–3) and 3 (95% CI 3–4), respectively. van der Linden et al (2000) reported a meta-analysis of the effectiveness of serotonin reuptake inhibitors (SSRIs) in the treatment of social anxiety disorder. They found a collective NNT of 4 (responders on CGI–I) and a mean effect size for all SSRIs of 1.0 (the SSRI/placebo difference at endpoint on the LSAS). None of the ten SSRI studies in the meta-analysis included escitalopram.
It is tempting to suggest that the placebo response in the study of Kasper et al (2005) was high and distorts results. However, if randomisation is presumed to have been successful, an equivalent placebo effect would have occurred in the escitalopram group. The impressive P values reported by Kasper et al (2005) are likely to be because their study was overpowered and they used analysis of covariance (ANCOVA) which is known to have greater statistical power.
Based on our analysis, among the different SSRI medications escitalopram is less likely to be effective in the treatment of social anxiety disorder. We suggest that P values can mislead and should not be interpreted as measures of magnitude of effect.
REFERENCES
Allgulander, C. (1999) Paroxetine in social anxiety disorder: a randomized placebo-controlled study. Acta Psychiatrica Scandinavica, 100, 193 -198.[Medline]
Baldwin, D., Bobes, J., Stein, D. J., et al
(1999) Paroxetine in social phobia/social anxiety disorder.
Randomised, double-blind, placebo-controlled study. Paroxetine Study Group.
British Journal of Psychiatry,
175, 120
-126.
Kasper, S., Stein, D. J., Loft, H., et al
(2005) Escitalopram in the treatment of social anxiety
disorder: randomised, placebo-controlled, flexible-dosage study.
British Journal of Psychiatry,
186, 222
-226.
Stein, M. B., Liebowitz, M. R., Lydiard, R. B., et al (1998) Paroxetine treatment of generalised social phobia (social anxiety disorder) – a randomised controlled trial. JAMA, 26, 707 -713.
van der Linden, G. J., Stein, D. J. & van Balkom, A. J. (2000) The efficacy of the selective serotonin reuptake inhibitors for social anxiety disorder (social phobia): a meta-analysis of randomized controlled trials. International Clinical Psychopharmacology (suppl.), 2, S15 -S23.
Department of General Psychiatry, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria. E-mail: sci-genpsy{at}meduniwien.ac.at
University of Stellenbosch, Cape Town, South Africa and University of Florida, Gainesville, Florida, USA
H. Lundbeck A/S, Copenhagen, Denmark
Lundbeck (Switzerland) Ltd, Glattbrugg, Switzerland
The original study was sponsored by H. Lundbeck A/S.
We thank Drs Lele and Joglekar for drawing our attention to the absence of the 95% CIs for the primary efficacy end-point (treatment effect measured as the difference in the Liebowitz Social Anxiety Scale (LSAS) scores from baseline) in our article on the treatment of social anxiety disorder with escitalopram (Kasper et al, 2005). The treatment difference between escitalopram and placebo was 7.3 (95% CI 2.2–12.4) with a standardised effect size of 0.30 (95% CI 0.09–0.51).
When comparing the results of this trial with the literature we looked at the size of the effect of the active treatment, that is, the adjusted change from baseline in LSAS scores, not the standardised effect size. These values are 33.0 (Allgulander, 1999), 29.4 (Baldwin et al, 1999) and 30.5 (Stein et al, 1998), which are comparable to the 34.5 change in our study with escitalopram (Kasper et al, 2005). The main difference between these studies is the placebo response, which was largest in our study.
In interpreting differences in placebo response rate (and hence standardised effect sizes) it is important to recognise differences in study design. One of the paroxetine studies (Allgulander, 1999) was a small (n=92) single-centre trial with a 40% placebo withdrawal rate (compared with 18% for paroxetine) and patients were also required to have been treated for at least 2 weeks. These factors may be responsible for the small placebo effect with the last observation carried forward (LOCF) analysis. In the studies of Allgulander (1999) and Stein et al (1998) patients were not excluded if they had comorbid depression, which was the case in our study. Finally, in our escitalopram study the mean baseline LSAS scores in the placebo and treatment groups (95.5 and 96.3) were higher than in the paroxetine studies (70.4 and 78.5 in Allgulander, 1999; 78.0 and 83.5 in Stein 83.5 in Stein et al, 1998; and 86.1 and 87.6 in Baldwin et al, 1999).
We would like to emphasise the appropriate powering of our study. ANCOVA is overpowered if the distribution is skewed but our data are fairly normally distributed. Allgulander (1999) state that their data were skewed and non-parametric tests were used.
In line with the results of our study additional recent data
(Lader et al, 2004)
confirm the efficacy of escitalopram in social anxiety disorder. In a 24-week
study the placebo response was 43.4 compared with 60.8 with 20 mg escitalopram
and 53.1 with 20 mg paroxetine (mean change from baseline). The treatment
difference (observed cases) between escitalopram and placebo was 17.4 (95% CI
11.5–23.2) with a standardised effect size of 0.77 (95% CI
0.51–1.03). The treatment difference for escitalopram and paroxetine
(observed cases) was 7.71 (95% CI 2.0–13.4) in favour of escitalopram
with a standardised effect size of 0.34 (95% CI 0.09–0.59). After 12
weeks the number needed to treat (NNT) based on the responders as per Clinical
Global Impression–Improvement (CGI–I 
2, LOCF) scores for
Kasper et al (2005)
was 6.4 (95% CI 4–19) and 4.8 (95% CI 3–10) for Lader et
al (2004). To judge a
single medication based on the NNT it is necessary to consider all available
studies and, based on the evidence published in the literature, we therefore
do not agree with the statement of Drs Lele and Joglekar that paroxetine is
superior to escitalopram for the treatment of social anxiety disorder.
REFERENCES
Allgulander, C. (1999) Paroxetine in social anxiety disorder: a randomized placebo-controlled study. Acta Psychiatrica Scandinavica, 100, 193 -198.[Medline]
Baldwin, D., Bobes, J., Stein, D. J., et al
(1999) Paroxetine in social phobia/social anxiety disorder.
Randomised, double-blind, placebo-controlled study. Paroxetine Study Group.
British Journal of Psychiatry,
175, 120
-126.
Kasper, S., Stein, D. J., Loft, H., et al
(2005) Escitalopram in the treatment of social anxiety
disorder: randomised, placebo-controlled, flexible-dosage study.
British Journal of Psychiatry,
186, 222
-226.
Lader, M., Stender, K., Burger, V., et al (2004) Efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder: randomised, double-blind, placebo-controlled, fixed-dose study. Depression and Anxiety, 19, 241 -248.[CrossRef][Medline]
Stein, M. B., Liebowitz, M. R., Lydiard, R. B., et al (1998) Paroxetine treatment of generalised social phobia (social anxiety disorder) – a randomised controlled trial. JAMA, 26, 707 -713.
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